Shaw's Textbook of Gynaecology [17 ed.] 9788131254110

Table of contents :
Shaw's Textbook of Gynecology, 17th Edition
Half Title
Title Page
Copyright
Dedication
Preface to the 17th Edition
Preface to the 16th Edition
Preface to the 10th Edition
Table of Content
Chapter 1 Approach to a Gynaecological Patient
Chapter 2 Anatomy of Female Genital Tract
Chapter 3 Normal Histology of Ovary and Endometrium
Chapter 4 Physiology of Ovulation and Menstruation
Chapter 5 Development of Female Reproductive Organs and Related Disorders
Chapter 6 Puberty, Adolescence and Related Gynaecological Problems
Chapter 7 Menopause and Related Problems
Chapter 8 Breast and Gynaecologist
Chapter 9 Sexual Development and Disorders of Sexual Development
Chapter 10 Common Disorders of Menstruation
Chapter 11 Abnormal Uterine Bleeding (AUB)
Chapter 12 Primary and Secondary Amenorrhoea
Chapter 13 Fibroid Uterus
Chapter 14 Endometriosis and Adenomyosis
Chapter 15 Hormonal Therapy in Gynaecology
Chapter 16 Infertility Male and Female
Chapter 17 Ectopic Gestation
Chapter 18 Acute and Chronic Pelvic Pain
Chapter 19 Temporary and Permanent Methods of Contraception
Chapter 20 Medical Termination of Pregnancy
Chapter 21 Genital Prolapse
Chapter 22 Displacements of the Uterus
Chapter 23 Diseases of the Broad Ligament, Fallopian Tubes and Parametrium
Chapter 24 Benign Diseases of the Ovary
Chapter 25 Benign Diseases of the Vulva
Chapter 26 Benign Diseases of the Vagina
Chapter 27 Pelvic Inflammatory Disease
Chapter 28 Tuberculosis of the Female Genital Tract
Chapter 29 Sexually TransmiHed Diseases Including HIV Infection
Chapter 30 Diseases of the Urinary Tract
Chapter 31 Urinary Fistula and Stress Urinary Incontinence
Chapter 32 lniuries of the Genital Tract and Intestinal Tract
Chapter 33 Preinvasive and Invasive Carcinoma of Cervix
Chapter 34 Cancer of the Body of the Uterus
Chapter 35 Pathology of Ovarian Tumours and Benign Ovarian Tumours
Chapter 36 Ovarian Malignancies
Chapter 37 Vulval and Vaginal Cancer
Chapter 38 Gestational Trophoblastic Diseases
Chapter 39 Radiation Therapy, Chemotherapy and Palliative Care for Gynaecological Cancers
Chapter 40 Imaging Modalities in Gynaecology
Chapter 41 Endoscopy in Gynaecology
Chapter 42 Maior and Minor Operations in Gynaecology
Chapter 43 Obesity and its Significance in Gynaecology
Chapter 44 Instruments Used in Gynaecology
Index

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HOWKINS & BOURNE

SHAW'S TEXTBOOK OF GYNAECOLOGY

HOWKINS & BOURNE

SHAW'S TEXTBOOK OF GYNAECOLOGY Edited by

Sunesh Kumar, MD (AIIMS) Professor and Chief Gynae Oncdlogj Services, Depa rtment of Obstetr-lc.;:s ancJ Gynaecology, All India lnstitut f ed1cal Sciences, New Delhi

eritus Editars

S, FRCOG (LOND) edor Professor and Head, bstetrics and Gynaecology ge Medica l College, New Delhi

Shirish N

ry,

, DGO, FICS, FIC, FICOG

er-i us Professor, Formerly Dean and Med1cal Advisor, Nowrosjee Wadia Ma terni ty Hospi ta l, Mumbai Past Presiden t, FOGSI

ELSEVIER

ELSEVIER RELX India Pvt. Ltd. RegisiL'red Offit:e: 818, lndraprakash Building, 8th Floor, 21, Barakhamba Road, New Delhi- II 0001 Cements with o~anir.ations such as the Copyright Clearance Center and the Copyright Licensing Aj,>ency, can be found at our website: w·ww.ciSC\·i cr.•merase chain reacLion (PC R) staining has been extensively utilized in the diagnosi.~ of various infections.

SPECIAL TESTS HANGING DROP PREPARATION ln women complaining leucon·hoea, the discharge collected from the postel'ior fornix on the blade of the speculum should be suspended in saline and submitted to microscopic ex;unination. ormal 'oaginal discharge shows the presence of exfoliated 'oaginal epithelial cells and the presence of large rod-like lacLObacilli known as Doderlein's bacilli. A fresh suspension of the discharge may reveal the motile flagellated o•-ganisms known as TridwmQIWS vagina.l.is. Another common cause of \'llginal infection is fungal infection or vll{,riual cmulidir~:>i:>, this can also be detected f•·om a microscopic examination of the vaginal discharge. To the suspension of the vaginal discharge, add an eq ua l amount of 10% KOH soluti on. Place a drop of the mi xtu re o n a slide, cover it with a cover sli p, wa nn the slide and exa mine it under the low power of the microscope. T he KO H dissolves all cellular debris, leaving be hi nd the mo re resista nt yeast-like organisms. Typical h)•p hae o r m>•celia and b udding spores can be easil)' detec ted. Many C about60%-70% of precancer and cance•· of the cen~x and less than 70% of endomeu·ial cance•: Reliability of the repon depends on the slide preparation and tl1e skiU of the C) LOiogist. Although a single test yields as much as 10%-15% false-negathe reading, it is reduced to only 1% with repeated tests. A false-positive finding is reponed in the presence of infection. A yearly negative Pap sme;u· for 3 years is assuring, and thereafter 5-yearly test is adequate. Th e Pap smear should be obtained before vaginal examination, because the nngers may remove tl1 e desquamated cervical cells and give a false-negative repo rt, lubrica m may prevent de tec ti o n of orga nisms a nd a ny vaginal bleedin g during exa min atio n may preclude a prope r visua li zati o n of th e ce rvix. T he patient s ho uld no t have inte rco urse or to uch fo r 24 ho urs befo re the Pap test. T he bes t time to do Pap smear is a ro und ov ulatio n, b ut any other time can a lso do. T he patient is placed in th e do rsal position, with the lab ia parted, and Cusco's self- retaining spec ulu m is gemly introd uced witho ut the use of lubrican t or jelly. The cervix is exposed; the sq uamoco lu mnar ju nction is now scraped with Ayre's spatula by rotating tl1e spatula all around (Fig. 1.8 0). The scrapings are evenly spread onto a glass slide and immediately fixed by dipping the slide in the jar containing equal parts of 95% ethyl alcohol and ether. After fixing it for 30 minutes, the slide is air-d•;ed and stained with Pap or shon stain. The slide is considered satisfact011, if endocen'ical cells are seen. To improve the predictive valve, endocen'ix is also scraped with a brush and added to the slide. owadays, a fixative spray (cytospray) is a\oailable and can be used conveniently in an office set-up. For honnonal cytological evaluation, the scrapings are taken from the upper lateral pan of the vaginal walls; tlwee types of cells are found in the normal smear: (i) the basal and pa•-abasal cells are small, •·otmded and basophilic wi th la •-ge nuclei; (ii) the cells from th e mi ddle layer are squamous cells, tra nsparent a nd basophilic witl1 vesicular nuclei; a nd (iii) th e cells from th e s uperficial la>•e •· are acidop hilic with charac teris ti c p yknoti c nuc lei. ln add ition, endome tri al cells, histiocytes, blood cells a nd bacteri a ca n be seen . Malignant cells a re hyperc hro ma ti c with a great increase in c hro matin co nte nt. Th e n uclei va11' in size a nd th e re is usua lly o nly a s ma ll amo unt of C)'top lasm in the un d iffe re miatecl malign am cell (Figs 1.9 and 1.1 0). T he nucle us/cytoplasmic ratio is increased in malignant cells. Papru1icolaou classincation: Grade l Grade ll

Screening for Cancer

First described b) Papanicolaou and Traut in 1943, this screening test is often •·efen·ed to as the 'Pap test' or a surfuce biopsy or exfoliative C) tology (C) to logy is a Greek word, meaning swdy of cells). It forms a pan of the routine gynaecological examination in women. All sexually active

7

Grade Ill Grade IV Grade V

Nonnal cells (Fig. 1.9) Slightl) abnonnal, suggestive of inflammatOI") change; repeat smear after treating tl1e infection A more se•ious t} pe of abnonnality, usuall> indicative of the need for biopsy Distinctly abnonnal, possibly malignruu and dennitely requi•·ing biopsy Malignant cells seen (Fig. 1.1 0)

8

SHAW'S TEXTBOOK OF GYN AECOLOGY

R gure 1.8 (A) Papanicolaou sampling devices. Left to right: Cervix -Brush, Cytobrush, wooden spatula, plastic spatula, tongue blade and cotton swab applicator. (B) Pap smear with a brush. (Source for (A): From Agure 16, Pre-prooedure. Prooedure ConsUlt. Pap Smear. Editors: Michael L Tuggy and Jorge Garcia; Source tor (B): From Figure 1, Pre-prooedure. Procedure Consult. Papanicolaou Testing. Editors: Todd W Thomsen and Gary S Setnik.) 0 Scan to play How to take pap smear

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J Rgure 1.9 Normal cervical smear showing superficial (pink) and intermediate (blue/green) exfoliated cervical cells (low power magnification). (Source: From Agure 20·5, ian Symonds a"~d Sab.,.-atnam Arul tology us ing a thin preparation is s uperior to Pap smear (Fig. I. II ). T he liq uid is used to screen for papilloma virus. Cervical ca ncer screening is described in Fig. 1.12. This is described in detail in Chapter 33. Outer metJ1ocls of cervical screening are also described in Chapter 33.

VISUAL INSPECTION AFTER ACETIC ACID APPLICATION (VIA) Gross inspection of cen·ix after application of 3% or 5% acetic acid for I minute helps in detecting acetowhite area which may harbour Cl / neoplasia.

CHAPTER 1 - APPROACH TO A GYNAECOLOGICAL PATIENT

Table 1.5

• • • • •

9

Bethesda Classification

Sample-adequate, unsatisfactory Squamous cell abnonnalities Atypical squamous cells (ASC) Atypical squamous cells of undetermined significance ASCUS ASC-cannot exclude high grade lesion ASC-H Low- grade squamous intraepithell al lesion (LSIL) Hlghijrade squamous intraepithellal lesion (HSIL) Squamous cell carcinoma Adenocarcinoma

S01.rce: Bethesda G.Jideines.

Rgur e 1.10 Illustration of pathological grades of epidennoid cells in the squamocolumnar junction of the cervix. Cells arising in this location were produced by a unifonn cell- scraping technique. Classification of cell types is based upon thorough study, eval uation of cell characteristics and pathological features and Is final ly correlated wit h corresponding histological studies of t he tissue. No attempt is made to classify cell s exfoliated from other tissue areas, such as the endometrium. The squamocolumnar junction Is a vital zone to the female because this is the focal point where cancer arises. Grading of cell~ depends upon knowledge of origin of cell sample, on securing a rich concentration of cells, and of greatest importance, correct correlation with histological fi ndings.

Figure 1.11 Liquid -based cytology classified as epithelial cell abnormality, IOWiJrade squamous lntraeplt hellal lesion (LSiL) . Note particularly the cells in the centre. They have enlarged nuclei compared with those in the cell s to the left and below. This feature is required for a diagnosis of LSIL. The nuclear contours are irregular. One cell to the right of centre is binucleated, a common feature in LSIL. (Source: From Figtre 12-1, Barbara S Apgar, Gregory L Brotzman and Mar1< Spczer: Copoooopy: Prnc.,les and Practice, 2nd Ed. Saunders Else>Aer, 2008.)

PAP smear (liquid-based cytology with HPV testing), start with sexual activity at 30 years or any time after 2 1 years

Table 1.4 Comparison of Different Classification System for Pre-Invasive Lesion Papsm e ar

Dysplasia

CIN

Bethesda

II Ill

M ild

IV

Moderate

II

HSIL

v

Severe

Ill

HSIL

LS IL

L, low; H, high; SIL, squamous lntraepithellal lesion.

Figure 1.12

Cervical cancer screening.

10

SHAW'S TEXTBOOK OF GYN AECOLOGY

SCHIUER TEST (VISUAL INSPEOION AFTER LUGOL'S IODINE APPLICATION - VIU) 0 Scan to play VIA and VILI This test detects tl1e presence of glycoge n in the superficial cells of tl1e vaginal epitJ1elium. The vagi nal wall is stained wilh Ltago l's iodine (Lugol's iodine contains 5% iodine and 10% potassium iodide in water [l g iodine + 2g KI]). The vaginal epiilielium takes mahogan) brown colour in Lhe presence of gl)cogen. Unstained areas (nega tive LesL) are abnormal and require biopsy for hisLological exa mination.

CYTOHORMONAL EVALUATION The ovarian hormones oesu·ogen and progesterone influence ilie vagin al mucosa; thus, the epitltelial cells exfoliaLed in the vagina reflect the influence of the pt"C\'• camy, and the cleft between the labia is therefore conspicuous. At puberty, pudenda! hair appear o n the mons veneri , the outer surface of the labia majora and in some cases on th e skin of the perine t:Lm as well. T h e inner

LABIA MINORA Th e labia minora are thin folds of skin which encl ose ve ins an d e lastic tissue and lie on the inner aspect of the labia majora. T he vasc ular labia minora are erec tile during sexual activity; they do not contain any sebaceotts glands or hair follicles (Fig. 2.4). Ameriorly, they enclose the cliLOris to fo rm the prepuce on the upper surface and the frenulum on iL~ und ersurface. Posteriorly, they join tO form the fo 111~ chette. The fourc h ette is a tlli n fold of skin, iden tified when th e labia are separated, and it is often rorn during parturition. The fossa navicnlaris is the small hollow between th e hyme n and the fo urchette. Labia minora is homologous with the ven u·a l aspect of the penis. The clitoris is an erec tile organ and consists of a glans, covered by tl,e frenulum and prepuce , an d a body whi ch is ubcutaneous; it corresponds to th e penis and Ls attached LO the und ersurface of the symph}•sis pubis by th e suspenso11• ligament. ormally, the clitoris is 1- 11/1 cm long and 5 mm

13

14

SHAW'S TEXTBOOK OF GYN AECOLOGY

Uterus

Ovary Rgure 2.1 General view of internal genital organs showing t he normal uterus and ovaries.

Mons pubis (wneris)

Prepuce Frenum Vestibule _ ,._,1---,f+.Labium minus -~i----+1 l.!l--1+-+1'Vaginal introitus -..,.-+--1--SI

Figure 2.3 Hi stological section of the labium majus showing squamous epit helium with hair follicle and sebaceous gland {X 55).

Clitoris Labium majus External urethral orific.e Opening of Bartholin's duct

1-+- -- -

Hymen Perineum

A

8

Virginal Rgure 2.2

Septate

Cribriform

Parous

(A) Anatomy of the vulva. (B) Variations of the hymen.

in width. Clitoris o f more than 3.5 on in le ngth and I em

in width is called clitoro megaly, and occurs in virilism due to excess o f androge n ho nno ne. The clitoris is well supplied with nerve endings and is e xu·emely sensitive . Dlll·ing coiLUs, it becomes e rect a nd pla)S a conside rable pan in inducing orgasm in the female. The clito•·is is highl)' vascular. An injury to the clitoris causes profuse bleeding and can be very painful.

Figure 2.4 Histological section of the labium minus showing squamous epithelium. Note complete absence of hair follicles and sebaceous and sweat glands.

The ve~tibule is the space I) ing be twee n the anterio r and the inner aspects of the labia minora a nd is bounded posterioliy by the vaginal in troitus. The I'Xf t'rrUllurintt ')' 11U!lt iLIS iies immediatel) posterio r to the clito •is. The vaginal orifice lies poste,;or to th e meatus and is surrounded by the hp nen. In virgins, the h)lne n is re p•-esellled b)• a thin membra ne cove red o n each surface by sq uamous e pithelium. It genera lly has a small eccenu·ic opening, which is usua lly not wide

CHAPTER 2 - ANATOMY OF FEMALE GENITAL TRACT

enough to admit the fin gertip. Coitus resul ts in the rupture of tl1e hymen; the resulting lace rations are radially arranged and are multiple. Occasionally, coital n.apwre can cause a brisk hae mo rrhage. During childbirtll, further lacerations occur: tl1e h)lnen is wide!) SU'etched and subsequently is represe nted b) the tags of skin kn own as the carunculae myrtiformes. \\'ith the populaait) of tll e use of intemal sanital")' tampons, the loss of in tegait) of tlle hpnen is no longer an evide nce of loss of virginity. The ' 'ulval tissues respond to ho nn ones, especially oestrOgen , during m e childbeaa·ing)ears. After menopause, auophy due to oestrogen deficiency m akes me vulval skin tl1inner and drier, and this m ay lead to atrophi c '~alvitis and itching. Mons jJUbiJ is an at·ea which overl aps the symphysis pubis and contains f.n. At puberty, abundant hair grow over it.

BARTHOLIN'S GlAND Bartl1oli n 's gland li es posterolaterall y in relatio n to the vagi nal otifice, deep to the b ul bospongiosus m uscle and supe rficial to tl1e o uter layer of tJ1e u·iangu lar ligament. It is e mbedded in the erec til e tissue of tJ1e vestib ular b ulb at its posterior ex u·em it)'· It is norma lly impa lpable when healtl1y, but can be readil)' palpated be twee n the finger and the tl1U mb when en larged b)' inflammation. Its vascu lar bed accounts for me brisk bleeding, which always accompan ies its removal. Its duct passes forwards and inwards to open, external to the hymen, on tl1e inne r side of the labium minus. The gland measures about 10 mm in di.'lmeter and lies near tllejunction of the middle and posterior thirds of tlle labium majus. The duct of the gland is about 25 mm lo ng and a min mucous secretio n can be expressed from it by pressure upon me gland. Barth olin's gland and its duct are infected in acute gonorrhoea, when the a·eddened mo urn of the duct can easily be disti nguished on tl1e inner surface of m e labiwn minus to one side of tl1e vaginal o aifice below the level of tl1e hpnen. Bat·tllolin's gland is a compound racemose gland and its acini are lined by low columnar epitllelium (Fig. 2.50 ) . The epitheliwn of the duct is cubical near the acini, but becomes

Rgure 2.5 Bartholin's gland. Low-power view showing the structure of a oompound racemose gland with acini lined by low columnar epithelium (x92). 0 Scan to play Barthol in's abscess

15

u·ansitional and finally squamo us near tl1e mouth oftl1e d uct. The function of tl1e gland is to sec rete lubricating mucous dwing coitus. The labia majora j o in at the posterior commisSttre and merge imperceptibl) into tl1e peainea.un.

THE VAGINA The vagina is a fibronnLSCular passage mat connects tl1e Lllerus to me introitLLS. The lower end of the vagina lies at the level of the h) men a nd of the inu·oitus \'llginae. It is surrounded at tllis point by tl1e erectile tissue of tl1e bulb, which corresponds to tl1e corpus spongiosum of the male. The direction of the \':!gina is approxim ately parallel tO me plane of tl1 e brim of tl1e u·ue pelvis; the vagina is slightl y curved forwards from above downwards, and its anterior and postetior walls lie in a close co nta ct. It is notofun ifotm cali bre, being nea rly twi ce as capacious in i t.~ upper part and somewhat flask shaped. T he vaginal ponio n of the cervix projects into its upper e nd and leads to the fo rma tio n of th e anterio •~ poste ri or and latera l forn ices. T he dep th of th e forn ices depends upon the deve lopmen t of the portio vagina lis of the cervix. In girls before pube r1.)' and in e lderly women in whom the ute nts has undergone postmenopausal atroph)', me fornices are shallow whe reas in women wim congenital elongation of the portio vaginalis of tl1e cervix, the fornices are deep. The vagina is attached to the cervix at a higher leve l posteriorly than elsewhere, and this makes the posterior fornix the deepest o f the fo rnices and tl1e posterior \':!gina! wall lo nger than tl1e anterio r. The posterior wall is 4.5 inch ( 11.5 em) lo ng, whereas Ll1e antet;or wall measures 3.5 in ch (9 em). Transve rse folds which are present in m e \'3ginal walls of nulliparae a llow the \':!gi na to stretch and dilate during coitLLS and pat1.ut·itio n. These folds are pa 11.ly o bliterated in women who have bome ma ny children. In the a nteri or \':lgi nal wall, tllree sulci caa1 be disting uished. One lies immediately above the meatus aa1d is called ~ubmeaJal>ulctl> ( Fig. 2.6). About 35 mm above this

Rgure 2.6 A case of prolapse In which the cervix has been drawn down. Parameatal recess, hymen, submeatal sulcus, paraurethral recess, oblique vaginal fold , transverse sulcus of the anterior vaginal wall, arched rugae of the vaginal wall and bladder sulcus.

16

SHAW'S TEXTBOOK OF GYN AECOLOGY

sulcus in tl1e ameli or vaginal wa ll is a second sulc us, known as the transver:.e vaginal sulws, which corresponds approximately to the junction of the urethra and the bladder. fLLrtller upwards is tl1e bltuhkr sulcus, indicating tl1e junction of tl1e bladder to tl1e an tetior vaginal wall. The vaginal mucosa is lined by nonkeratized squamous epithelium which consists of a basal layer of cuboidal cells, a middle la)er of prickle cells and a superficial layer of comified cells (Fig. 2. 7). In the newborn, the epitheliwn is almost transitional in t)pe and cornified cells are scanty until puberty is reached. No glands open into the vagina, and the \'3ginal secretion is derived partly from tl1e mucous discharge of the ce•vix and partly from transudation through tl1e vaginal epithelium. The subepithelial layer is

Epithelium

Submucous la~r

Smooth muscle (inner circular and outer longitudinal)

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--

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--=---~-= -==-~---

}

External fibrous layer (endopelvic tascia)

Rgure 2. 7 (A) Low-power {X36) microscopic appea-ance of the vaginal wall showing the corrugated squamous epithelium and bundles of plain muscle cells subjacent to the vascular subepithelial layer. (B) Structure of the vaginal wall. (Courtesy for (A): Dr Sardeep Mathur, AJIMS.)

vasc ular and contains much erectile tissue. A muscle layer consisting of a complex interlac ing lattice of plain muscle lies external to the subepithelial layer, whereas the large vessels lie in the connective tissues surrounding the vagina. If the female fews is exposed LO diethylstilboestrol (DES) taken b) the mother during pregnancy, columnar epithelium appears in the upper two-thirds of vaginal mucosa, which can develop vaginal adenosis and vaginal cancer during adolescence. The keratinization of vaginal mucosa occurs in prolapse due to the exposure of vagina to the outside and ulcer may form over the \'3ginal mucosa (decubitus ulcer). The keratized mucosa appears skin-like and brown. Menopause causes atrophy of tl1e vagina. The vagiual .~ecretion is small in amount in healthy women and consists of white coagulated material. Wh en it is examined under a microscope, sq uamous cells sh ed from the vaginal epi thelium and Doderlein's bacilli alo ne are fo und. Duderlein~ !Jacillt.t.l is a large Gra m-positive rods haped organism, whi ch grows a nae robicall y on ac id media. T he vaginal sec retion is ac id ic cl ue to tl1e presence of lac tic ac id, and tl1is ac id it)' inhi b its th e growth of pa ul oge nic organ isms. T he pl-1 of th e vagina ave rages abo ut 4.5 du ring reprod ucti ve life. T he ac id it)', which is undo ub ted!)' oestrogen dependent, fa lls afte r me nopause to ne utt·a t or even a lkaline. Before pubert)', the pH i.~ abo ut 7. This high p l-1 before puberty and after menopause explains the tendency for the development of mi xed organism infections in these age groups. The synthesis of lactic acid is probably influenced by either enzrme or bacterial activit) {Doderlein 's) on the glycogen of the epithelial cells, which itself is dependem on the presence of oestrogen, so that its deficiem activity can be boosted b) the administration of oral or local oestrogen. During the pue•·pe•·ium and also in cases of leucorrhoea, tl1e acidity of the \'llgina is reduced and pathogenic organisms are then able to survive. The squamous cells of the vagina and cervix stain a deep brown colour after being painted with iodine solution, owi ng to the presence of glycogen in healthy cells (positive Schiller's test). Ln a posUllenopausal woma n, because of tl1e absence of or low glycogen-conta ini ng superficial cells, Schiller's test becomes negative. T he vagina l epithelium is under tl1 e ova rian hormo nal infl ue nces of oestrogen and progestero ne. Oesu-ogen proliferates the gl)'cogen-containing supe rficial cells and progestero ne causes prolife ratio n of ime rm ediate cells. Lack of these ho rm ones in a me nopa usal woman leaves only the basal cells with a thi n vagina l mucosa. T he abno•mal and malignant cells also do no t con tain gi)'COgen and do not take up lhe stain. Similarly, these abnormal cells turn wh ite with acetic ac id d ue tO coagulation of protein. These areas are selected for biopsy in the detection of cancer.

RELATIONS OF VAGINA ANTERIOR RELATION In its lower half. the vagina is close!) related tO tl1e urethra and the paraurethral glands {Skene's wbules), so closely in faCL tl1at the urethr0\'3ginal fascia is a fused struCLure and only separable by a sharp dissection. In its upper half, tl1e

CHAPTER 2 - ANATOMY OF FEMALE GENITAL TRACT

vagina is related to the b ladder in the region of the u·igone, and here the vesical and vaginal fasc iae are easily separable by a blunt dissection via the vesicovaginal space. There is a considerable vasc ular and lymph atic imercommunication between the vesical and the vaginal vessels, a sinister relationship having a bearing on Lhe surgery of a malignam disease of Lh is area.

POSTERIOR RELATIONS The lower third of the \'llgina is re lated 1.0 Lhe perineal body, the middle third 1.0 the ampulla of the reCLum and the upper third to the anterior \\'llll of the pouch of Douglas, which comains la•·ge and small bowel loops. This partition dividing the vagina from the pe•·itOneal cavity is tl1e thinnest a•·ea in the whole pe•·itOneal surface and, tl1erefore, a site of election for poim ing and opening of pelvic abscess or th e productio n of a h ernia or enterocele. T his is also an ideal site for colpocem esis in th e d iagn osis of ectOpic pregnancy. Pouch of Douglas (Fig. 2.8) is a pe rito neal cul-de-sac in the rec tovaginal space in the pelvis. IL is bo unded anterio rl)' by the peritone um cove rin g the pos te rio r vaginal wall and posLerio rl )' b)' tl1e peritone um covering the sigmoid colon and the recwm. Laterall y, th e uterosacral ligame nts limi t its bo undary whereas th e floor is Lhe reflection of the peritoneum o f the pe rito neal cavity. The endometriotic nod ules and metasmtic growth of an ovarian cance r are fe lt in tl1 e pouch of Douglas, so also pelvic inflammatOI') mass. The u1.erosacral ligaments are thickened and become nodular in advanced cancer cervix. LATERAL RELATIONS The la1.eral relations f•·om below upwa rds are the cavernous tissue of the vestibule; the supe •·ficia l muscles of the pe•·ineum; the u·iangu lar liga ment and at about 2.5 em from the inu·oitus t11 e Je,>aLOr ani, lateral tO which is tl1e ischio•·ectal fossa. Above the levator lies the endopelvic cellular tissue, and its condensation , called Mackenrodt's ligament, on tl1 e either side. The ureter traverses this

17

tissue in the urete ric ca na l and is abou t 12 mm anterolateral to the lateral fo rnix.

SUPERIOR RELATIONS 1l1e cervix with its four fornices - amerior, posterior and two lateral- are related to tl1 e uLerine vessels, Mackenrodt's ligament and the ~.u·e ter. PosLe•io rl), surrounding the pouch of Douglas lie the uterosacral ligaments which can be identified o n vaginal examination, especiall)• if thickened by disease such as endomeu·iosis and cance r ce rvix. Squamocolumnar j unction, also known as u-ansitional zone, is clinically a ' ery important junction where the squamous epithelium lining tl1e vagina merges witllthe columnar epithelium of tl1e endocervix and is 1-10 mm (Fig. 2.9) . Here, tl1e constant cellular activiLy of tl1e cells takes place, and the cells are highly sensitive to irritants, mutagens and viral agents such as papilloma virtL5 16, 18. T hese agents cause nuclear changes tl1at ca n evenLUall y lead tO dysplasia and carcinoma cervix, which is the most co mmon malignancy of tl1e female geniLal tra ct in Ind ia. Squamocolumnar junction is of two types: first one is embryo nic when columnar epithelium spreads over the exte rna l os. Afte r pube rt)\ metaplasia of colu mnar epitl1e liu m unde r the infl uence of oestroge n brings sq uamous epitheliu m close to Lhe ex ternal os, thus creati ng a u·ansitional zone be twee n the two j unc tions. In women exposed to DES in utero, tl1is zone is well outside the os, spreading over tl1e \'llgi nal vau lt. In a menopausal woman, it gets indrawn inside tlle os. During pregnancy and with oral conu-aceptives, it pouts o uL of os. The squamoco lumnarjunction is well outside me external os dLLring tl1 e reprod uctive period, and in Pap smear tl1is area is scraped and tl1 e C) tolog) of its cells swdied for the nuclear changes, in me scree ning programme for ca nce r cervix. Dw·ing pregnane), tl1e ex1.e m al os becomes patulous and the squamocolumnar junction is well exposed all round. Pap smear> ields the most accu rate C) tological findings. ln menopausal women, the cervix sh•·inks and the squamocolumnar junction gets indrawn into the cervical canal.

Columnar epithelium

Pouch of Douglas Figure 2.8 Pouch of Douglas showing uterosacral ligaments as upper border.

Uterosacral ligament

Figure 2.9 Squamocolumnar junction. In the 'ideal' cervix, the original squamous epithelium abuts the columnar epithelium. (Soun::e: Hacker NF, Ganbone JC, Hobel CJ, Hacker CW'ld Moore's Essentials ot Obstetres ard Gynecology, 5th ed Pliladelphia: Elsevier, 201 0.)

18

SHAW'S TEXTBOOK OF GYN AECOLOGY

lt is therefore not easily accessib le, and ill exposed to the vagina, for visua l inspection. This explains high false-negative findings in Pap smear in older women. Giving oestrogen locally or orall) or prostaglandin E (misoprosLOI) pessary allows this junction to pout out and improves t11e efficacy of t.he Pap smear C) to log). The squamocolumnarjunction is SLUdied colposcopically when t.he Pap smear shows abnormal cells, and t11e abnormal areas are biopsied fo•· cancer detection.

THE UTERUS The uterus is py.-iform in shape and measures approximate!)' 9 em in length, 6.5 em in width and 3.5 em in tl1ickness. It is divided anatom icall y and fun ction all y into body and ce1vix. It weighs I o unce (60 g). T he line of division correspo nds to the level ofth e intern al os, and here the muco us membra ne lining the cavity of the uter us beco mes con tinuo us witl1 that of th e cervical ca nal (Fig. 2.1 0). At thi s level, the pe ri to ne um of the front of t11e ute rus is reflected o n to the bladde r, a nd the uterine artery, after passing a lmost tra nsverse!)' ac ross the pe lvis, reac hes tl1e uterus, tu rns at r ight angle and passes vertically upwards a long the latera l wa ll of the u terus. T he ce1vix is divided into vagina l and supravaginal portions. The fundus of the uterus is that part of the corpus uteri which lies above the insertion of the fallopian tubes. The cavity of t11e uterus communicates above wit11 t11e openings of the fallopian tubes, and by way of t11eir abdominal ostia is in direct con tin uit) with t11e peritOneal cavity. The uterine caviL) is triangular in shape witll a capacity of 3 mL. The lower angle is formed by the internal os. The lateral angle connecting to the fallopian tube is called t11e cornual end. The wall of the uterus consistS of tluee layers, t.he peritoneal co,·ering called pe•·imetrium, tl1e muscle layer or myomeu·ium and t.he mucous membrane or endomeu·ium. The ute•·us is capable of distension during pregnancy, haematometra as well as with distended media du.-i ng hysteroscopic examination. Otherwise tl1e two walls are in opposition.

Infundibulum

Intramural (Interstitial) par t

PERITONEAL COVERING The peritoneal covering of the utems is incomplete. Anteriorly, t11e whole bod) of t11e ULerus is covered witll peritoneum. 1l1e peritoneum is reflected on to t11e bladder at t11e level of t.he imemal os. ll1e cen1x of t11e uterus has t11erefore no peritoneal covering ameliorl). Post.e•iorl), tl1e whole body of t.he uterus is covered b) pelitoneum, as is the supravaginal portion oft.he cen·ix. The pel"itoneum is reflected from t.he supravaginal portion of t.he eel"\ ix on to the poste•·iorvaginal wall in tl1e region of t.he postelior fomix. The peritOneal la)er is incomplete laterally because of the insertion of t.he fallopian tubes, t.he row1d and ovarian ligaments into t.he uterus, and below t.his level tl1e two sheets of peritoneum, which constitute t.he broad ligament, leave a tl1in bare area laterall y on each side.

MYOMETRIUM T he myome u·ium is the thickest of t11e t11ree laye rs ofthe wall of the ute n.ts. ln the cen>ix, the m>•ometrium consists of plain muscle tissue together witJ1 a large amo unt of fibrous tissue, which gives it a hard consistency. T he muscle fibres and fibro us tissues are mixed togctJlcrwithout an orderl)' arrangemenL ln tJ1e bod)' of tJ1e utenJS, tJ1e myomeuium measures aboutl 0-20 mm in tJ1 ickness, and tJ1ree layers can be d istingu ished which are best marked in tJ1e pregnam and puerperal uterus. The extemal layer lies immediately beneath the peritonewn and is longitudinal, tJ1e fibres passing from t11e cervix anteriorly over tl1e ft.uldus to reach tJ1e posterior surface of the cervix. ll1is la)er is Lhin and cannot easily be identified in ilie nulliparous uterus. The main function of tJ1is layer is a dem.ISor action during tJ1e expulsion oftJle fetus. The middle layer is t.he thickest of the tJwee and consists of bLUldles of muscle sepamted b) a connecti'e tissue, the exact amow1t of whid1 varies with age; plain muscle tissue is best marked in tl1e childbearing pe•iod, especially during pregnancy whereas before pubeny and after menopause it is much less plentiful. There is a tendency for tJ1e muscle bundles to imerlace, and as t.he blood vessels supplying blood to the uterus are dist.libuted in the connective tissues, tJ1e calibre of the vessels is in part controlled by tJ1e conu•er is therefore in part haemostatic, tl1ough its exp ulsive role is equally importa nt. T his layer is clesclibed as living ligal!tm~ of the uteno, and is responsible for comrol of bleeding in the thi rd stage of labo ur. Inefficient contrac tion and re u·act.i on of these muscle fib res ca use prolonged labo ur and atOni c postpartwn haemo •Thage (PI)I-1). T he inner muscle la>•er COI1Sists of circula r fib res. T he layer is never we ll marked and is best rep rese med by tl1 e circ ular mt.ISc le fibres around the in te rnal os a nd tJ1e ope nings of the fallopian tubes. It can be regarded as sp hin cteric in action. The myomeui um is th ickest at the fund us ( 1-2 em) and thinnest at tJ1e cornual end (3-4 mm), one should t11erefore be careful during curettage and endometrial ablation not to perforate tJ1e com ual end.

-4::::~-- Cervical canal

Vaginal cervix or (portio vaginalis)

Rgure 2.10 A nulliparous uterus showing the anatomical structures.

ENDOMETRIUM The endomeu·ium or mucot.IS membrane lining tJ1e ca'~t:)' of the uterus has a different structure from that of tl1e enclocervix. It is described in Chapter 3, ' onnal histology ofOvaryand Endometdum'.

CHAPTER 2 - ANATOMY OF FEMALE GENITAL TRACT

The cer vix is spind le shaped and measures 2.5 em or a little more. It is bounded above by the internal os and below by the external os (Fig. 2. 10). The mucosal lining of tJ1e cervix differs from that of the body of tJ1e uterus by tJ1e absence of a submucosa. The endocervix is lined by a single la)er of high columnar ciliated epitJ1elium \vith spindle-shaped nuclei I) ing adjacent to the basement membrane with abundam C)LOplasm and mucin. The direction of the cilia is downwards towarcls the external os. The glanometrium LO open into tlle endometdal cavil). It is the shortest part oftlle tube, its lengtll being the th ick.ness of tJ1e uterine mLLScle, about 18 mm. It is also the narrowest part, its intemal diameter being I mm or less so tJ1aL only tJ1e finest cannula can be passed imo it during falloscopy examination. There ru·e no

22

SHAW'S TEXTBOOK OF GYN AECOLOGY

the others and is attached to the region of tJ1e ovary. This fimbria embraces the ovar>• at ovulatio n, picks up t11e ovum and carries it to tJ1e ampullary portion.

longiwdinal muscle fibres here but the circular fibres are well deve loped. 2. The i~lltmu~ comprises the nex t and inner part of the tube and represents abo ut o ne-third of Lh e LOtal length, i.e. 35 mm. It is narrow but a li Llie wider than the in terstitial part and its lumen has a diameter of 2 mm. Its muscle wall contains both longiwdinal and circular fibres, and it is covered by peritoneum except for a small inferior bare area related to the broad ligament. It is relatively suaighL 3. TIU! ampul/it is tJ1e lateral, widest and longest part of the tube and comprises rough I) two-tJ1 irds of the tube, measuring 2.5-3 inch (60-75 mm) in length. Here me mucosa is a•·borescem witJ1 man> complex folds (Fig. 2.15). Fe•·tiliation occurs in tJ1e ampu llary portion of the fullopian wbe. 4. The fimbriated e.\1rt'mity or infimdibulwn is where the abdominal ostium opens into me pe•·iLOneal cavity. The fimbriae are motile and almost prehensile, and e•"Uoy a considerable r·a nge of movement and action. One fimbria- tJ1e ovadan fimb1ia- is larger and longer than

The fallopian tube represents the crania l e nd of the Miille 1ian dueL and its lumen is continuous witJ1 t11e ca\~1)' of the uterus. Consequent!), spe•matoLoa and tJ1e fertilized ovum can pass along the tube. Fl uids such as d)eS a nd gases such as carbon dioxide may be injected mrough the ULerus and by me way of tJ1e fallopian tubes imo me pe•·iwneal cavity, and by mese means tJ1e patency of tJ1e fallopian tubes can be investigated clinically by a d)e test (Fig. 2. 16). The fallopian tubes lie in the upper part of me broad ligamen lS and are covered witJ1 pedtoneum except along a tJ1in area inferiorly, which is left bare by the reflection of the pe•itoneum to fom1 the two layers of tJ1e broad ligamenL The blood supply of tJ1 e fa llopia n tube is main ly derived from the tubal branches of the ova lian artery, but tJ1 e anastomos· ing branch of the uterine artery s uppli es its inner parL Unlike the vermiform append ix, the fa llopian tube does not become ga ngrenous when ac utely inflamed, as it has two so urces of b lood supp ly whi ch reac h it a t opposite ends. The lymp ha tics of the fa ll opian tube communicate with tJ1e lym· phatics of tJ1e fundus of the ULerus and witJ1 those of th e ovary, and me)' drain along tJ1 e in fund ib ulopelvic ligament to the para-aortic glands near tJ1e origin of the ovarian artery from t.he aorta. Some drain into the pelvic glands. The fallopian tubes have three layers: sero us, muscular and mucous. The serous la)er consists of l11e mesotJ1elium of tJ1e pedtoneum. Intervening between th e mesotJ1elium and me muscle Ia) er is a well- concealed by t11e upper end of the labia minora. umerous periuretl1ral glands surround tl1e urethra and open b) till)' duelS into iiS lumen. These are analogues of Lhe prosLaLe in males. The parauremral glands of Skene are imporLanL paired glands which lie alongside me floor of Lhe urethra and open by tiny duelS close to me external meatus. The glands when infeCLed form periuretlual abscess and cysiS. The proximal tu·etlwa derives blood supply from me inferior vesical anery and distal uret11ra from in temal pudendal ane•l'· The veins drain into t11e vesical plexus and intemal pudendal vein. T he uretlwa is innervated by the internal pudendal nerve. T he uretlwa is developed from the cloaca. T he proximity of tl1e uret11 ra to the vagina makes it suscep ti ble to infection sp reading from the lower ge niLal tract. T he commonest infec ti ve orga nisms are N. go norrhoea, Chlam>•dia u-ac homatis and trichomonads. T he ure t11ral swab, cultw·e and uri ne Cl ~turc can iden ti fy Lhe o rganisms.

THE BLADDER The bladder is a smooLh muscle organ witl1 a body and a trigone. It lies between Lhe spnphysis pubis in from and t11e uterus behind, being separated from tl1e uterus by t11e uterovesical peritoneum. It is a pelvic organ with a capacity to hold 500-600 mL of urine. The bladder distends upwards with a fixed base at tl1e Lrigone, and t11en becomes palpable abdominal!). The bladder has an apex, a base, a supe•·ior and L\1'0 inferolaLeral surfaces. The neck of the bladder (internal Ulinary sphincter) lies abo1e the lev~nor ani muscles, so mal me raised abdominal pressure transmitS me pressure equall)' Lo Lhe bladder and itS neck, hence mainLaining urinal")' cominence dur-ing coughing and sneezing. Ameriorly, lies tl1e cave of Reuius (t'Cu·opubic space). Posteriorly, iLis in proximity to tl1e uterus and supt·avaginal portion of the cervix, sepamted from them by t11e uterovesical pouch of peritone um. T he ureters en ter tl1e bladde r obliquely, and t11e area be tween tl1e ure te ric openin gs and the inte rnal urinar y sphincter fo rms a fixed tri angular a rea called u·igo ne. T he apex is co nti nuo us witl1 tJ1e urac hus. T he b ladder receives b lood suppl)' from the s uperior and inferior vesical arteries, and the pub ic branc h of the infe rior epigastric anery. T he venous plex us drains in to in te m al iliac vein. T he lymphatics dra in into interna l and extemal iliac glands.

NERVESUPPLY The spnpathetic outflow is from first and second ltunbar segmeniS of tl1e spinal cord which inhibiiS conu-act.ions of me detrusor (bladder) mtLScle and main Lains internal sphincteric contraction. The pa•-as)lnpathetic outflow from 52, 53 and 5 I stimulates tl1e detnLSor muscle and relaxes tl1e internal sphincter, tlnLS initiating micw•·ition. The sensory

nerve fibres reach the cenu·al nervous system via the splanchnic nerves (pa1ies produce ho rmo nes respo nsible for matumtio n of the Graafian fo llicle, ovulati on, mensu·uatio n and ma in tenance o f pregnat1cy in the ea rly weeks of gestation. The ste roidal honno nes at·e oestrogen and progestemne. Oesuugen is mainly secreted

46

SHAW'S TEXTBOOK OF GYNAECOLOGY

by the Graafian follicle in the follicular phase (preovulatory phase). A small arnoun tis also secreted by the corpus luteum in the premensu·ual phase. Progesterone is secreted b)' the corpus Imeum, and the absence o f progesterone in the premenstmal phase denotes anovulation. The comrol of these hormones is described in Chapter 4. Inhibin is a nonsteroidal hormon e presenL in the Graafian follicle. It is a protein that inhibits FSH and stimulates Ll-1 secretion by the atue•ior pituitary. Excess of inhibin see n in poi)C)'Stic ovarian disease ( PCOD) is responsible fo r the high level of LH. The other hormones whi ch the ovary produces in small amounts are testosterone and androstenedione, mainly secreted by th e stromal cells and stimulated b)' LH. Androstenedione gets converted pe•ipherally into oestrone through aromati£ation in the f). This reaction disappears after O\Uiation under p•·ogesterone influence. Under tl1e influence of p•·ogesterone, the cel'\·ical mucus becomes thick

~

Rgure 3.15 Microscopic appearance of dried cervical mucus showing the 'fern appearance'. (Sru~: htlp://g}'flOOCI'lline.ccm/cefVical_cy::le.htm.)

and tenacious and impeneu·able to sperms and bacte•ia. T he detai ls of cervical mucus are clesclibed in Chapter 16. Endocervical li ning does not ex hibit cyclical changes li ke the endomeu·ium. In pregnancy, however, adenomawus h)•perplasia may occw·, and decidua l changes are seen in 10% of tlle patients. Oral combined hormonal pills over tl1e years also ca use hyperplasia of endocervical e pitl1e lium and an abnorma l ' Pap smear'. Lately, an increased incidence of endocervical carcinoma has been observed in young women who have been on honnonal contraception use. Contrary to tl1is, the pills cause au·ophic e ndometrium in the body uterus.

PROCESS OF FERTIUZATION Cenain changes are necessa•1' before the p•·ima•)' OOC)'I.e catl mature for fertili.~:ation. Oogonia that enter the prophase of tlle first meiotic division are known as primat-y oocytes, whereas tl1ose oogonia whi ch do not begin the first meiotic division and not surrounded by granulosa layer undergo atrophy. At puberty, under the LH SUI·ge, p•·imary oocyte completes the first meiotic division and gives rise LO secondal)' oocyte, containing most of the cytOplasm, 23X chromosomes and a small polar body. This secondary oocyte completes its second meiotic divisio n only after fertilization, and gives o ut second polar body. T hus, the first stage of mawratio n of the oocyte occurs within tl1e Graafian foll icle, b ut t11e second d ivis ion occurs only after tl1e ferti li zation in the fa llopian wbe.

KEY POINTS • The ova.-y of tl1e newbom has about 2 million p•imordial foUicles. These are reduced to abo ut 400,000 at pubert). atul of these around 400 are available during the reproducti' e lifespan. • C)clic cl1anges in the Graafian follicle- leading to ovulation. corpus lute um formation and mensu·uation a.·e under tl1e conu·ol of the h) pot11alamus, which conu·ols tl1e release of gonadotropins from the atHerior pituita•)'·

CHAPTER 3 - NORMAL HISTOLOGY Of OVARY AND ENDOMETRIUM

• Oesu·ogen causes regeneralion of the endomeuium and leads to proliferalive phase. Progesterone is responsible for secretory transfonnation of the endomeu·ium, rendering it favourable for implamalion of fcrti li Led ovum. • Peak level of 40-75 ng/ m L of Lll is noted j ust before ovul ati on. • In the presem-day practice, se ti alultrasound monitoring of th e Graafian fo llicle is the most preferred method LO detect ovulation in patienlS undergo ing u·eatmem for infertility. • l::ndomeu·ial histology is useful to diagnose endomeu·ial tuberculosis, endomeu·ial cancer and honnonal d)Sfunclion. • l::ndomeuial thicknessofS-12 mm is considered normal in the premensu·ual phase. In posunenopausal women, enclomeuialthickness should not exceed 4 mm. • L H surge is an im portant indicator of imminent ovu· lation.

47

SELf-ASSESSMENT I. Deso·ibe the microscopic appearance of the endomeuium during the proliferative phase. 2. Describe the histological appearance of th e endomeuium in the sec retOt) ' phase. 3. Describe the e ndometrial changes during pregnancy. 4. What is the significance of cervical mucus changes in feni lity practice?

SUGGESTED READING Berek and :--'o,~•k'• Textbook of C,na~-colg>. Ada, hi EY, I Iiiiard PA (ed>) . :--'o,-ak's G)llCCOiogy. 151h ed. Phihtdelphia, PA, Williams & \\"lll:.in>. 2014. Mishdl DR J r, Oavajan V (eds) . Infertility. Contmception and Reproducti\ C Endocrinology. 2nd Ed. Or.tdcll, NJ, ~kxlical Economics Book> Or.-tdell, 1986. ' ov-.tk E, Nov-.1k ER (eds). Textbook of Gynecology. 4th Ed. Baltimore, Philadelphia, PA, Williams & Wilkins, 1952.

Physiology of Ovulation and Menstruation

Hypothalcmic-Pituitary-Ovorian Axis 48 Ovarian Steroidogenesis 51 Physiology of Menstruation 54 Feed bock Mechanism in the H- P-o Axis 56 Leptin 58

Menstruation 58 Menstrual Fluid in 'Stem Cell' Therapy 60 Key Points 60 Self-Assessment 60

C)•clical mensu·uaLion and reprod ucLive func Lions in a woman occur as a resu lL of fine in Leraction between hypoLhalamus and anLerior piLUiLary. Hormone prod uction (follicle-stimulaLing hormone [FSH] and lu te inizing hormone (LH]) from anterior pituiLary in turn is responsible for follicular maturaLion, ovulaLion, corpus luteum formaLion and producLion of oesLrogen and progesterone honnones from oval'). Therefore, an understanding of hypothalamic-pilllital')-'-arian (H-P-0) axis is imponam for knowing ph)siolog> of reproduction and managemem of \ and the intemction of various honnones. • S)ntlletic analogues ofGnRH , FSH and LH are used in infertilit) and amenorrhoea. • Oesu·ogen and progeste•"One ha' e specific I"Oies in mensu·ual C)cle and in the de,elopment of genital organs. • Oilier honnones pa•·ticipate in the maintenance of normal mensuuation. • LH surge is the key marker of imminent o' ulation. • LH causes maturation of Grnafian follicle, meiosis of ovum before ovulation, ovulation and development of corpus luteum. • Leptin appeal'S to have a rol e in the development and onset of puberty. • Menstrual fluid is rece ntly discovered LO co ntain stem cells and may prove useful in s te m cell the rapy. Only yo ung women are s uitab le for donation.

SELF-ASSESSMENT KEY POINTS • Neuroendocrinolog) with its \'3SL hormonal network is ke) to nom1almenstrual C)Cies a nd reproductive function in a woman. • H)pothalamus, with its pulsatile secretion of GnRH (decapeptide), is the main neuroendoc•·ine gland a nd regulator> factor in the chain of H- P- 0 axis. The higher conical ce nu-es can modif) or influence h) pothalamic secretion. • Pulsatile secretion of Gn RH resultS in secretion of FSH and LH from anterior piwitary gland. • FSH and LH secreted from ante•·ior pituitary in turn results in follicular matumtion and ovulation, which in turn a•·e •·esponsible for secretion of oestrogen and progesterone from ova•)'· • Proliferative phase of endometrium represents oestroge ni c acti o n of ovary. • Progestero ne ca uses secretory endom e trium only if the Iauer is plimed with oestroge n.

l. Desclibe tl1e neuroe ndocrine co ntm l of mensm.ta l cycle . 2. Desc•ibe tl1e fom1ation and pt"Ocesses that lead to the formation of Graafian follicles. 3. Desclibe the mechanism of ovulatio n. 4. Desclibe tl1 e microscopic appearnnce of endometrium dLLring tl1 e valious phases of menstrual cycle.

SUGGESTED READING Bloom FE. :\euroendocrinc mechanism.: cells and systems. In Yen SCC.Jaffe RB (eds) . Rcproduc li\e Endocrinology. Philadelphia, WB Saunders Co. 1991: 2-24. Plant Thl. Krey LC, Moo>.>yj et al. 1l>e arcuate nude us and the control of the gonadotropin and prolactin ..ecretion in the female rhesus monkey. Endocrinology 1978; 102: 52-62. Rabin D, McNeil LW. Pituitary and gonadal desensitization after con· tinuous h.ue::inizing honnonc releasing hormone infusion in nonnal females.] Clin Endocrinol Mc1ab 1980; 51: 873-6. Schwanze~Fukuda M. PfalfDW. Origin of Luteinizing hormone rele-;c;ing hormone neurons. Nau orc 1989; 338: 161-4. Soules MR, Steiner RA, Cohen M cl al. Noctumal slowing of pulsatile luteinizing hormone M:Crccion in wo•ncn dllring 1hc follicular phase of the mcns1rual ~yclc. J Clin Endocrinol Me1ab 1985; 61:43-9.

Development of Female Reproductive Organs and Related Disorders

Developmen t of the Female Genital Organs 6 1

Wollfion Duct Anomalies 73 Renal Tract Abnormalities 73

Development of the Ovaries 64 Malformati ons of the Rectum and Anal Conal 73

Key Points 7 4 Sell-Assessment 7 4

Anoma lies o f Mi:dle rian duc ts are seen in 1%-2% of females. Most a no malies do not have any effect on menstrual o r rep rod uctive function and remain undiagnosed. However, some of th e a no malies can cause recurrent abortions, preterm delivery, malpresemations or other obstetric complications. Mens trual irregulatities are Lmcommon with these anomalies but at times can caLLSe haematocolpos, C)clical pain in abdome n, etc. Knowledge of a natomical development of ge nital o rgan s is helpful in unde rstanding these condi tions.

DEVELOPMENT OF THE FEMALE GENITAL ORGANS Urogenital diiTer·enti ation is a complex process involving genetic, honnonal and environmenta l influences. T he genital and urin ary systems develop in close relationship, so developmental e n·o t-s in bo th these systems often coexist. lf a u·ansver-se secti on is cut th ro ugh th e upper part of t11e coelom ic caviL)' of an emb ryo of 8 wee ks, the primitive mesen tery is seen to prqject in to t11e coelo mic cavity posteriorly near the mid li ne. O n each side of the p rimitive mesenter)', ano tJ1er projec tion, the intermed iate cell mass, can be distinguished. On t11e inne r side of the intennediate ceU mas~, b)' the end of the 8th week, a ridge has appeared- the genital ridge. The Wolffian body witJ1 primitive tubules and primitive glomeruli occ upies th e rest of the intermediate mass (Figs 5. 1 and 5.2).

DEVELOPMENT OF URINARY SYSTEM l11e primitroe uritWT)' sy.stem consists of the pronephros, the meso nephros o r Wo lfllan bOd) and t11 e metanephros, which gives rise to tl1e pet·manent kidney. Each of t11ese systems is derived from the urogenital plates of the pt·imitive somites.

ln the human fe male, the pro nep hros disappears, and the Wolffian body is rep rese nted by the su·aight tub ules of tl1e epoophoron, or o rgan of Rose nmit lle r, found in the mesosalpinx of an adult whereas the tubules o f t11e paroophoron represe nt tJ1e relics of the re na lwbules o f L11e Wolffian system. and the Gartner's duct represents L11e Wo lffian duct (Fig. 5.3). The metanephros gives rise to t11 e tubules of the permanent lddne) whereas the ureter and re nal peh~s are fonned from a di, et·ticulum from the lowe r e nd of t11e Wolffian dueL In an em bt)O, two tidges appea r between fifth and eighth week, mesonephric (Wolffian) and paramesonephric ducts. The form er disappears in females, and tJ1e latter, paramesonephri c duct (Mullet·ian), develops into female genital organs. The Mi:tllerian duct is fonned as a •·esult of invagination of th e mesothelium of tJ1e coelomic cavity on tl1 e venu·al pan of the interm ediate cell mass. The invagination extends from the proneph ros region above to the sacral region below, and bo th ducts tenn inate in tJ1e primi tive cloaca. T he position of the Mulleria n d uct is of im portance, for it lies ventral to the Wolffia n d uct o n th e o uter s urface of t11e intermed iate cell ma\is. In hum an e mbr)•O, tl1e cauda l pa rts of the two MCtll eri an ductS fuse to form tl1e uterus, whe reas the uppe r pa ns re ma in as t11 e fallopian tubes (Fig. 5.:3).

DEVELOPMENT OF THE UTERUS, CERVIX AND VAGINA The uterus can be ide ntified as ea rly as by t11e end of Ll1e 3rd month. Uterus, fallopian tubes and most of Ll1e vagina are derived from the M i:tllerian duct in t11e absence of Y chromosome. The upper e nd of the ML:tlle rian duct becomes t11e alxlominal ostium of the fallopian tube, and it is not uncommo n for small accesso•1 ostia to be foLUld (Fig. 5. 1). In tl1 e 7th week of inu-a ute t·ine life (IUL) of t11e e mbi)O, a n invagination of coelomi c mesothe lium occurs

61

62

SHAW'S TEXTBOOK OF GYNAECOLOGY

___ ___ ,..,.._ X....

X

...

lndiflerenl gonad

""'

(

----+

Mesonephros - - - - _ . . . ,-t---11 WoiHian duct - - - -----1 Mullerian duct ---:-:-;-:--H

Bladder

. ........ ....

·:'..

.::c.

.:. •·...

Genital tubercle -~"'---~_.__....___ Figure 5.3

·.·

Rectum

Development of genital tract -und ifferentiated stage.

Ovary

------{}j

_ _ _ _.::) Remnants of ________:-: mesonephros

Tube

Uterus

UGS Rgure 5.1 Diagram of urogenital system: X - intermediate cel l mass, shaded area is the genital ridge. (1) lnfundibulopelvic ligament, (2) ovary, (3) ovarian ligament and (4) round ligament. Dotted outline is Wolflian duct (Gartner's duct~ (a) Pronephros , (b) epoophoron and (c) mesonephros. Solid block is MOIIerlan ducts. Q) Fimbria, QQ fallopian tube, QiQ uterus, (iv) upper three-fourths of the vagina. UGS - urogenital sinus.

Kidney - --1 Gartner's - - ---tH duel Bladder Clitoris--~..-

R gure 5.4

Paroophoron (distal tubules of the mesonephros)

Epoophoron (proximal tubules of the mesonephros)

Female genital tract development.

close to the primitive gonad in the upper lateral portion of the intennedi ate cell mass; this is called the Mullerian duct (paramesonephric duct). As the two Mullerian ductS, one o n either side, develop and grow caudally. they approach each other in the midline after crossing the Wolffian duct (meso nephric duct} a nd fuse (Figs 5. 1 and 5.2 ). The cranial-free pan of the MCalleria.n ductS deve lops into fa llopian tubes. The midd le fused portion forms the ute rus and cervix, and the cauda l fused ponion forms the upper one-thi rd of vagina. ln itia ll)', the in terve ni ng sep ta are prese n t b u t la te r d isappea r as a s ing le continuous passage. Tlms, the 1Wmwl development of the Miilii'Tian ~)·~tem comprises organogeuf'~i~, fu~ion rmd later sf'jJifd re~orption.

1:1- - - - Gartnefs duct (vestigial remnant)

Rgure 5.2 Remnants of t he mesonephric (Wolflian) ducts that m ay persist In the anterolateral vag ina or adjacent to the uterus w it hin t he broad ligament or mesosal pinx.

The muscle wall of the uterus is differentiated from mesoblastic tissues, and during the 5th month, a circular la)er of muscle can be distinguished. The longitudinal muscles of uterus can be recogniLed during the 7th month, and this muscle layer is continuous morphologically with the plain muscle tissue of the ovarian ligament, tl1e roLmd ligament and tl1e muscle fibres fo und in the uterosacra l ligaments (Fig. 5.5). In the ea rly stage of the developmen t, the cervix of the uterus is longer and thi cker tha n the bOd)', and tJ1is proportion persistS until p uberty. T he proportion may persist in adult life, when the uterus is described as infantile in type.

CHAPTER 5 - DEVELOPMENT OF FEMALE REPRODUCTIVE ORGANS AND RELATED DISORDERS

Wolffian duct (mesonephric duct) Mullerian duct

11.-~1+-t"----

Mullerian vaginal cords

Figure 5.5 MUllerian and Wolffian systems.

The cervical glands can be recognized in the 6th month, whereas the glands of the body of th e uterus develop only during the last mon th of IUL, although primiti ve glands are prese nt a t tl1e 4th month. T he primit.ive clolU'll is d ivided by the fo 1mation of the w·orectal sep tum into a ventra l pan, the urogen ital sinus (UGS) and a dorsal pan, the rectum. T he urorectal septum ulti ma tel)' deve lops into the pe rineal body.

DEVELOPMENT Of VAGINA The lower ends of the MCIIIeiian duelS tem1inate in t11e ttrogenital sinus, into the posterior part of which t11ey project as a solid Ml'IIIerian tubercle. A solid vaginal cord resulls from proliferation of cells at t11e caudal tip of fused Miilleiian ducts. the cord elongates to meet the bilateral endodennal evaginalions (sinovaginal bulbs) from t11e posterior aspect of urogenital sin us below, and botl1 fuse tO form vaginal plate. Vagina is formed by rne subsequent canali.t.ation of rne vaginal cord followed by epirnelialization wirn cells de1·ived from urogenital sinus. Recent proposals hold that only t11e upper one-third of vagina is fonned from MiiJlel'ian ducts and the lower vagina develops from rne vaginal plate of lll'ogenital sinus. The hymen is the embryologic septum between the sinovaginal bulbs above and t11e urogenital sinus below.

DEVELOPMENT Of THE EXTERNAL GENITAL ORGANS (Figs 5.6 and 5.7) T he cloaca becomes d ivided in to two pa ns by tl1e deve lopment of the m orectal septum , wh ich originalt)' consists of two fo lds which project on eac h side and then fuse caudally to divide the cloaca into a dorsal pan, tl1 e recwm, and a

Fused paramesonephric ducts

Bladder

Genital

tubercle

Vagina plate

Sinovaginal bulb Rg~.re

5.6

63

Development of the lower genital organs.

SHAW'S TEXTBOOK OF GYN AECOLOGY

Urogenital groove

Genital swelling

A

Glans cli tori dis

Vestibule

4'---1-- - - - Labium minora Genl tal - - - - 1 - --\+ fold

'+.. ! - - - - - - Labium majora

c

B

Figure 5.7 Development of the external genitalia.

venu-al ponion, the urogenital sinus. The p•imitive cloaca is closed b)' the cloacal membrane, which can be recognized very early in the de,elopmem of the embryo and from which the vessels of the allantois are developed. The primitive intestines enter th e dorsal pan of the cloaca. Both Wolffian ducts, both Mi:.Uerian dueLS and the allamois, from which the bladder and the urethra are differemiated, enter the urogenital sinus. Originall y, the u reter arises from the lower end of the Wolffian duct nea r th e openi ng of the duct in to th e urogeni tal sin us. Subseq uentl y, as a resul t of the growth of tl1e surround ing mesoblasti c ti ssues, the ure te r is d isplaced cra ni al! )' so that it e nters tl1 e uroge ni tal sinus indepenclen tl )' of the Wolffia n d ueL. T his d isplace me nt of tl1e ure ter expla ins the aberrant L)•pe of ure te r which is some ti mes encountered in gynaecological s w·gery. T he part of the urogenita l sinus wh ich lies ven u·al to the mo uths of tl1e Wo lffian ducts becomes clifferemiated into the bladder, whereas tl1e al lantois is rep resented by the urach us passing upwards from the apex of the bladder to the umbilicus. Before tl1e 9tll week, it is not possible to recognize the fetal sex by exLemal genitalia. ll1e clitolis deve lops from the genital tubercle, whid1 appears about the 5th week and is o liginally a bilateral sLructure de lived from mesoderm. From the region of tl1e genital tubercle, a genital fold passes backwards lateral tO the urogenital sinus to fonn the labium majus (scrotum in the male). Between the ge nital folds lies the urogenital or

anterior pan of the cloacal membrane, which breaks down to form the labia minora (6th week). The vestibule and urethra are tl1us derived from the ame•·ior pan of tl1e urogenital sinus, and Bartholin's glands and Skene's parauretlu-al glands a•·e developed ft-om downgrowths of the urogenital sinus. T he female uret11ra represents tl1e uppe•· part of tl1e ma le uretlu-a, and the pa ra- and periuretl1ral glands are homologous to t11 e male prostate. The external genitalia are recogni:t.able by the 12tll week of IUL In females, ure tl1ral groove rema ins ope n LO fo rm the ves tibul e.

DEVELOPMENT OF THE OVARIES Ovaries begin to develop by the 5th wee k. T he ovarian d ifferemia tion is determ ined b)' the presence of a dete nn inant located on tl1e gene of tl1e short ann of X-c hromosome, a lthough tl1e alllosomes are a lso involved in tl1e ovarian clevelopmenL Two intact sex chromosomes (XX) are necessary for tl1e development of t11 e ovaries. The genital l'idge extends from tl1e pronephric region above to the sacml region below, and, in itS earliest fonn, is represented b) an e longated vertical prominence. Very soon it develops a mesente11 of its own, the mesov:uium, by which it is attached to imermediate cell mass. The infundibulopeh·ic fold passes upwarcls from the upper pole of the ovary and contains the O\>arian vessels. The ovari:m

CHAPTER 5 - DEVELOPMEN T OF FEMALE REPRODUCTIVE ORGANS AND RELATED DISORDERS

vessels of an adu l4 a tising from the abdom inal aorta, ill ustrate tl1e original lumbar position of tl1e upper part of the genital ridge. The genital fold of peritOneum passes downwards from the lower pole of the ovary tO the region of the internal abdominal ring. The MCtllerian duct originally lies on the outer aspect of tlle genital ridge but crosses tlle genital fold below. As tJ1e Ml:tllerian duct o ·osses tl1e genital fold, the two su·uctures fuse, and after muscle tissue has fonned around the Ml:tllet·ian duct, it passes into the tissues of tlle genital fold. The part of tlle genital fold lying proximal to its point of intersection with the Mullerian duct becomes tlle ovarian ligament, whereas the distal portion becomes tl1e round ligament (Fig. 5.1 ). This corresponds to tl1e gubernaculum of the ma le. The ovaries are developed by the 12th week. Undescended ovaries. At birth , t11e ovaries are located at tl1e pelvic brim. T hey g•·ad uall y descend tO the pelvis by puben.y. Undescended ovaries ( rare) are associated witl1 absent Mt"tllerian system in as much as 40% cases and t.mi co rnuate uterus in 20% cases, and ca n co nfuse the t.~ traso und sca nning. The undescended ova ries are at risk of ma lignanC)' as witJ1 un desce nded testes. It is a rare condition. Th e ovaries can be located b)' ultraso und sca nning, comp med tomograp h)' (CT) and magne tic resonance imaging (MRl ). The significance of undesce nded ovaries is as fo llows: • They are associated witJ1 tJ1e Mitllerian d uct anomalies and ma) ad\ersel) influence the menstrual and reproductive fu nCLio ns. • Ovulation monitoring ma) be difficuiL • Ov;u·ian pain ma) be misimerpreted as appendicitis or intestinal pain. • 0\mental tlefecll of the urogenital sinus m ay manifest in the form of defective development of the u•·in ary bladder, hymen and the perine um. Structura l homologues in males and females are discussed in Table 5. 1. Mullerian duct anomalies: Some anoma li es are detected at b irth, i.e. ex terna l ge nita l orga ns. Some may be detected a t puberty wh ile investi ga ting fo r primary amenorrhoea. Some are revealed durin g invcsLiga tio ns of infertili ty and repeated pregnane>' losses. AILho ugh a greaL n umber of anomalies of the ute rus have been desc ribed, tJ1ese can be broadly gro uped as fo llo ws: I. Agenesis 2. A110malies arising out of defects in vertical fusion (Fig. 5.8; see also Fig. 5.16) between lhe downgrowing fused Miille 1i an dueLS and the upgrowing de rivative fro m the

Structural Homologues in Males and Females Male

Female

Detennlnl ng Factors

Germ cells

Spermatozoa

Oogonia

Sex chromosomes

Coelomic epithelium

Sertoll cells

Granulosa cel ls

Mesenchyme

Leydig cells

Theca cells rete ovarii

Paramesonephric duct (M ullerian)

Hydatid testis

Fallopian tubes, uterus and upper three ·fourths of vagina

Mesonephric duct (WoiHian)

Vas deterens sem inal vesicles

Epoophoron Paroophoron Gartner's Testosterone MIF duct

Gonadal

Ductal

epididymis

Absence of Y-chromosome

External genitalia Lower vagina Skene's tubercles Bartholin 's gland

Urogenital sinus

Prostrate Cowper's glands

Genital tubercle

Penis

Clitoris

Urogenital folds

Corpora spongiosa

Labia minora

Genital folds

Scrotum

Labia majora

Bladder. urethra prostrate, bulbourethral glands

Lower portion of vagina, Bartholin's gland, paraurethral gland, url nlrf bladder, urethra

Urogenital s inus

Presence or absence of testosterone and dlhydrotestosterone

--------------------------~--------------

CHAPTER 5 - DEVELOPMENT OF FEMALE REPRODUCTIVE ORGANS AND RELATED DISORDERS

67

Rgure 5.8 (A) Hysteroscopy showing septum In t he uterus d ividing the uterine cavity. (B) Hysterosalpingography film of the same patient. (Courtesy (A): Dr Shyam Desai, Mumbal.)

urogen ital s in us. These may manifest as (a) obstructive lesions or (b) nonobSLructive lesions. 3. Anomalies ari~ing out of defects of lateml fiuion or resorption resu lti ng in dup lication defects. These ma)' manifest as (a) obstmcLive lesions or (b) nonobstmctive lesions.

Figure 5.9 Haematocolpos. The Illustration shows the distended vagina filled with blood.

Congrmital defect~ am OCf ur bec(I'IISP of till' follmuing: (a) Failure of initial descent- agenesis. (b) Failure of vertical fusion - u-ansverse vaginal septum, imperforate h)lnen. (c) Failure of late•-al fusion -this ma)' result in complete or partial duplication, which may be either S)1nmeu'ical or as)lnmetrical. )lnmetrical fusion defects would lead to bicomuate uterus or uterus didelphys whereas the as)lnmetrical fusion defects would result in one well-de, eloped ute•·ine hom with the other being .-udimentary. Noncommunicating hom of the ute•·us is an example of obstructive defect. (d) Defects in the resorption of the septum - example, septate UleiUS.

DETAILED CONSIDERATION OF MULLERIAN DEFECTS (a) Verticalftt~ion defects 1. Vagi1wl atmia: Sim pson ( 1976) stated that vaginal

atresia is a cond ition in whi ch the lower portion of the vagina is rep resented me re ly by fibrous tissue, whereas the contiguo us superior s u·uctures (uterus) are well differentiated. 2. 1'rwt~'Ver..e vagiual ~eptmn: It occ urs in the upper portion of vagina in 50%, midd le portion in 30%40% and lower portion in 10% cases. (a) Imperforate hymen - this is entirely of urogenital origin. Failure of canalization may lead to formation of a mucocolpos; this ma)• be recognized in earl) infanC) and get treated. However, the anomal) often continues unrecognized Lllltil pubert), when amenorrhoea in the presence of seconda11' sexual cha•-acters, C)clic abdominal discomfon, lll·inary S)lnptoms (retention of

Rgure 5.10 Suprapubic bulge caused by haematocolpos.

urine) and ofte n the palpation of a midline h ypogastric lump leads LO th e examination of the externa l genitalis, parting of th e labia reveals the presence of a te ll ta le b luish b ul ging membrane in th e region ofthe hymen that points to the di agnosis of hae matocolpos. A sim p le cruciate incision fo llowed by excision of th e tags of h)•men allows drainage of the retained menstrual b lood. The ope ration should be performed under aseptic conditions and under an adequate antibiotic cover to avoid any ascending infection. The vagina regains its wne very quickly (Figs 5.9-5. 11). (b) Congtmital abJetlce of vagina- M t~dlerian agenesis (absent vagina) INTRODUGION

The commonS) non) ms in clinical usage include Mullerian agenesis (MA), Ma)er-Rokitanskr-KusLer-Hauser (MRKH )

68

SHAW' S TEXTBOOK OF GYNAECOLOGY

Rgure 5.11 Vaginal introitus showing the bulging membrane caused by haematocolpos.

Figure 5.14 CT showing haem atometra and haematocolpos. (Courtesy: Dr Parveen Gulati, New Delhi.)

S) ndrome and vagina l age nesis. This condition , though commo n I) re fe n·ed to as congtmillll absnw• of tiU! vagina -a misno mer, is u·taly a deve lopme ma l defect o f the MCallerian dueLS resulting in t11 e co nditio n desc ribed as the 1\tlRKH ~yndrome. The MRKH syndrome occurs in 1:5000-1:20,000 wom en a t b irth, and is d iagnosed in approximate!)' 1:1500 gynaecologic ad missions.

Rgure 5.12 Imperforate hymen causing haematocolpos, haematornetra and haematosalpinx.

Rgure 5.13 Imperforate hymen - ultrasonography showing haematocolpos (distended vagin a) and haematometra (distended uterus). (Courtesy: Dr Rajeev H Kothari, Mumbal.)

DEFINING FEATURES Clinicall y identifi ed by th e absence of structures derived from Muller-i an dueLS, namely th e uterus, cerv ix and upp er vagina, 25% patienLS may have a sh ort vaginal pouch. Rudim en tary wbes are often prese nt. The gonads a re ovat·ies. The kal") Ot) pe is XX; the disorde r see ms to be an accide n t of developme nt. 1n clinical practice, t11 e wo rking diagnosis fo r an y individual prese nting with primary a me no rrhoea, fe minine seco ndary se xual charac te ristics and a n abse m vag ina is MRKH sy ndro me (Griffin e t al., 1976), with a fam ilia lte nde nq • in ute rus is prese n t in o nly 7 %- 8% cases. CHARAOERISTIC FEATURES • Congeni tal absence of uterus and vagina (smal l rudimentary ULedne bulbs are usually present). • Norm al ova tia n function, including ovul ati on. • Sex of real"ing- fema le. • PhenOt) pic sex - fe male (nonna l development o f breasts, bod) propo rtio ns, ha ir distri bution and externa l ge ni ta lia). • Ge ne tic sex- fe ma le (46, XX- ka ryo type) . • Freq uent associatio n with other co nge ni ta l a noma lies, ske letal a nd spine abnormalities (20%-30%) urologic abnorm alities s uch as ma lrota ti o n of ki d ney, ec topic ki d ne)' (horseshoe kidn ey, pelvi c ki d ne>•) and ano malies of tuinaty-collecti ng system needLO be invesLiga ted forby intrave nous pyelogram or ulu·aso und (40%).

CHAPTER 5 - DEVELOPMENT OF FEMALE REPRODUCTIVE ORGANS AND RELATED DISORDERS

DIFFERENTIAL DIAGNOSIS • Imperforate hymen • Transverse vaginal septum • Complete androgen insensitivity syndrome {testicular feminization S) ndrome) Imperforate h)lnen can be detected by observing the vaginal outlet. On performing t11e Valsalva manoeuvre, the membrane bulges. Peh·ic sonograph)' reveals presence of haematocolpos and intemal genitalia. Transverse septum reveals presence of a short 'oagina, absence of bulging on Valsalva manoeuvre. Testicular feminit.ation or androgen insensitivity S)•ndrome closely mimics one another, and efforts to dilfer·entiate between these two have therapeutic bearings.

INVESTIGATIONS • Pelvis and abdomen ultrasound - pelvic organs and kidneys. • 3-D ulu·asoun d is very precise in detecting these malformations (100% sensitive and specific) , less costly than MRI. One sho uld move on to MRl only if any do ubt prevails. • MRI gives more precise defin ition of pelvic viscera. • Karyot)•pe. • Laparoscopy (invasive proced ure) may be avo ided, exti1·pation of t11e M("allerian remnants is not necessary unless it is causing problems such as fibroids, haemawmetra. endometriosis or symptOmatic hemiation into the inguinal canal. • Radioloro -descending P> elography to delineate urinary tract anomalies, X-r11) L-S spine. MANAGEMENT • onsurgical met11ods - act by imermiuem pressure on the perineum. • Frank's nonsurgical method of active dilatation using graduated 'oaginal dilators of 0.5-1.0 inch diameter and 4-5 inches in length is used to apply constam pressure LO tl1e vaginal dimple for 20 minutes t.i.d. for 6-8 weeks LO achieve clinicall y acceptable results. Nonnal sexual function is possible in over 75% individuals. To main tain patency, vaginal di lator use shoul d be con tinued until regular sex ual inte rcourse begins. Other modificatio ns of Frank's artificia l vagina incl ude Ingram's bicycle seat stool used for 2 ho urs dai ly to ma inta in co nsta nt perineal pressure. J affe successfully modified Frank's di lation techn ique by using increasing sizes of syringe conta iners. Oestrogen creams he lp in vagina l ep ithelia l u·ansformation. • Surgical metl10d of vaginop lasty- to be delayed ti ll the marriage or until the patient becomes sexually active. The Mclndoe operation of vaginoplasty using split· t11ickness skin graft spread over a mould and held in place in an artificial space created between the bladder in from and the rectum behind has been successfully performed and has served functional use. Surgeons have also successfull> used fresh amniotic membrane graft to line tl1e 'oaginal space. HIV testing of the donor is required. Another surgical procedure which is simple to perfonn has been devised by Williams using labial

69

skin. However, tl1e axis of the artificial vagina poin ts directly backwards. • Tissue expansion vaginoplasty using tissue expander has also been tried with success. Water balloon is employed. • Shirodkar used a section of the Sigmoid colon LO prepare an artificial 'oagina, but this method was technically difficult to perform, and the mucus secretion caused discomfort; hence, this metl10d is not curTently practiced. Transveru vaginal uptum can be very easily mistaken for congenital absence of the vagina. It is a rare condition having an incidence of I :84,000 gynaecologic visits. The clinical symptoms will depend entire!)' on whetl1er the septum is imperfor-ate or otherwise. In case of a perforated sepwm, mensu·uation occurs and no difficul ty is suspected until the tim e of marriage when apareunia may lead the patient to seek consultation, o r at the tim e of pregnancy. If tl1e seplllm is im perforate, the symp toms of a menorrhoea and those res ulting fro m mucocolpometra may call for a tten ti o n . Ul u·asonography helps to arrive a t the diagnosis. T he co mmonest site for the occ urre nce of a transverse seplllm is the junction of the upper and middle tl1ird of tl1 e vagina. Treatment consist~ of e ither manual di latation from the micrope rforation or surgical excision of the septum. If the sep tum is th ick and wide, reanastomosis of the upper a nd lower vag ina may be d iffintlt; it may require skin grafting to cover t11e intervening raw area. Arulrog~tnic imm~itivil)' syntfroml' - originally described as testicular feminit.ation S) ndrome- needs to be differentiated from the Mfallerian duct anomaly causing MRKH syndrome. which also presents with amenont1oea and absent uter·us. Androgen insensiti,·ity S) ndrome is a genetically transmitLed androgen receptor defect in a 46 XY indi'~dual with testes and nonnal testosterone levels. These indi,~duals present with amenorrhoea, they have no inter· nal male or female genitalia (absent LllentS), nor·mal female external genitalia, an absent or shallow vagina, a nonnal female phenotype with well-developed breastS, and scanty body h air. Ultrasound/ MRI examination coupled with a karyotype XY helps to setLle the diagnosis. The abnotmal gonads are prone to ma ligna ncy, so these sho uld be removed surgicall y at an early date, soon after sex ual maturit)' has been ac hi eved.

(b)

Latemlfu~ion

defects - these include partial o r co mplete

dup licati on. 1. Double or ~eptt1te vogi1w- th is rna>• occ ur with an en-

tire I)' norma l fallopia n tubes, uterus and cervix, or with d up lica tion of th e ute rus. T he longitudin al antero-posterior septum may be partial or complete, extend ing right down to the vaginal o utlet. Generally, both sides are patent, but in rare instances the septum may deviate from tl1e centre and fuse with one lateral vaginal wall so tl1at one side of the "agina and uterus are obstructed and there is unilater-al haemawcolpos. The asymptomatic longiwdinal sepwm may only come LO light when the patient complains of soiling her clothes in spite of using a tampon dur·ing menses. Examination may re,eal a septum with Mullerian

70

SHAW'S TEXTBOOK OF GYN AECOLOGY

duplication, where in her placemem of the tampon in one vagina can not prevent egress from the other side, or it may be detected after marriage when it ma> be a cause of dyspareunia, or become apparent onl) at the Lime of labo ur. Symptomatic septum requires excision. A thick septum can be vel") vascular. Complete Nonfusion of the Mullerian Ducts Results in Duplication of the Genital Tract

2. Duplicatio11 of the ttll'nt~ -- of one S)Ste m ma> coexist with the anomal) o f o th er S)Ste m. • Although genital U I % of naecological patie nt~ a \tructi' e Su rgery in lnfcnility. In: Sarai~a U B, Rao KA, chattetjcc A (c-wlogit feature> of the .cptum in thi> abnonnal uterus. Am J O b.tel C,necol 1995: I 72: I 05. Daly DC. Walter. CA. Soto-Albor. C. I l)'>leroscopic meuoplasty: Smgicalaechnique and ob.tctric outcome. Fertil Steril 1983;39:623. Eli Reshef. Sanfilippo JS. I l)'>lero>pan FP (eds). Current Therapy i11 Obstetric; o~nd G)1lCOOIO!,'Y· 5th e d . Philad elphia: W. B. Sau nders Compan)': 2000. p. 77. £ ,-ans Tl\. Poland M. Bo\ing RL. \'aj,~nal malfonnarions. Am J Obstea Gynecol198 1:14 1:910. Fedele L, Bianchi S, March ini M, ea al. L'lar-.uanocau o-.tl aspects of e ndornt:uiurn in infcnilc women '"it h septate urerus . Ferti l Steril 1996;65:750- 2. Frank RT. Form ation ofaraifidal v S, Di Spiezio Sard o A, ct al. Th e ESIIRE/ ESGE consensus on the clas.sifi cation of fe male genital tract congenital anorn aliL~. ll um Reprod Oxf En gl. 201 3;28(8):2032-2044. doi:IO. I093/ hum rcp/ det098. llorner I !A, Li T C, Gookc ID, cl al. The septate ut erus: A re,ie w of man agem ent ould reproou cthc ou tcome. Fe nil Stcril 2000;73: I. Ingram JN. The biqcle >eat>tOOI in the treatmen t of \-agin al agen esis and >lenO>i>: A preliminary report. Am J Obstel G~11ecol 1982; 140:867- 73. lso-ael R. Man:h G\1. I l)>tero>ears of age ( 10%). Primary amen orrhoea and delayed puberty: Causes for these conditions can be broadly divided into h)pogonadal and eugonadal 'oalieties. Patients with h)pogonadism may have hypergonadotropism seconda•)' to ova•·ian failure (Turner) or hypogonadism as a result of Failure of maturation of the hypothalamic-pituitai)'-{)Wrian relationship. The eugonaclal 'oadety consists of patients with evidence of steroidogenesis but delayed menarche. In tl1is group the possibility of prima•)' ame no n·hoea due to other causes s uch as Mt~dl erian developmental ano malies leading to o utflow obstn.•ction, less com mon!)• testi cul ar femini zation synd rome (a nd roge n insensitivit)•), fa ilure of developme nt of the positi ve feedback mechanism in s pite of adequate e ndogenous oesu·ogen production and hype rprolac tinaemia often resulLi ng from a pitui tary neoplas m (p rolactinoma) s houl d be suspected. Ma lnutrition and anorexia nervosa are o tl1er causes. Details are described in chapter on Amenorrhoea. Aetiology of delayed puberty: • Commonly, it is familial or idiopaiJ1ic (60%). • Kallmann S)ndrome- 1-l)pOthalamic and pituitary inadequacy. Cr. MR1 of sella turcica, FSH, LH level con finn tlle diagnosis. • Ovru;;m causes - Tumer S) ndrome, Swyer syndrome, resistant 0\'' be contributory causes. Infections such as encephalitis, meningitis and h)drocephalus have also been implicated. Clinical features of prerocious puberty: The commonest variety termed constitlllional precocity tends to run in families. lL must be bome in mind that this diagnosis is one of exclusion. Long-tenn follow-up is recommended as some of me cerebral conditions come to light o nl y in adulthood. Sexual precocity is consistent witJ1 a normal reproductive function, and is not related to ea rly onset of menopause. In tJ1ese chi ldren, tJ1e seq uence of eve nts of sexual maturation fo llows t11e norm al standard pattern. T he growth sp urt occurs at an earlier age, so the re is a transient but short-lived increase in height. As the epiphysis of tlt e long bones fuse early under premature oestrogen effects, there is an eventual stunting of the height. Intellec tual, psychosex ual and emo tional development co•,·espond to the chronological age; hence, tltese youngsters and their fami lies have to face potentially difficult social and emotional situations. McCune-Albright S) ndrome affects about 5% of children with precocious pubert). Multiple cystic bone lesions are seen. Cafe-au-la it spots on the skin may be evident at birm. Mensm.ation sets in earl) independent of t11e customruy sequence events of thelarche and ad re narc he preceding menru·che. This is atuibuted LO the autonomous production of oestrogens by the ovaries. Eventual fertility remains unimpaired and t11e adult height attained. ln every case of sexual precocity, the possibility of ru1 underlying functional hormone-secreting tumour of the ova•y must be entertained and its possibility excluded. InvestigatiollS: The following investigations are recommended: l. Radiograph of the wrist to establish bone age. 2. T hyroid function tests- T~. T 4• and TSH. TSH s timula tes FSH receptors. 3. EEG and CAT/M RI sca n ofLhe s kull. 1. Adrenal function tests LO exclude he te rosex ual precocity. 5. Pelvic sonograp h)' LO exclude pelvic neoplasms. 6. GnRl-1 Lest to exclude aULonomous ovarian cysts from those secondary to gonadotrOpin stimulation. Gn RH test - i.v. 20 meg/ kg GnRI-1 - estimate LH level 30 minu tes latet~ level > 9.2 IU/ L indicates u·ue precocio us p uberty (GnRH related). 7. FSH, LH, oesu·ogen levels.

Management: Precocious puberty is a disturbing development for t11e parents and child. All efforts must be Lmdertaken to detect the under!) ing cause. However, t11e cause may not be apparent and rna> be detected only late•· in life. Pru·ents should be counselled according!)'· Parents should be wamed t11at the child is vulnerable to sexual assault and needs careful supervision.

A proper treatment sho uld be instituted for hypothyro idism, adrenal hyperplasia and surgical intervention for u.tmOLll'S of t11e ov;uy, adrenals or of neurological origin. Drug treaunen t of constitutional precocity includes: I. l•1i· depot medrox)progesterone acetlue (DMPA) 100-

200 mg. i.m. eve!") 2-4 weeks to induce regression ofmese chru1ges and cessation of mensu·uation. It is however not vel)' efficient in inhibiting bone growth. Treaunem depresses adrenocortical and h) pomalamic-pituita•)' activities. Instead of i•1iection, daily or qclical progestogen avoids i•1iections, but are not convenient. 2. Cyproterone acetate exerts antiandrogenic and antigonadotropin effects. Oral administration of 70-150 mg/ m2 / da)' has been found to be superior to DMPA It also helps in increase of height and stature. Adrenal suppression is a known side effect. 3. GnRl-1 agonists ( Buserelin) form t11 e mainstay of the treatment in present-day practice. T he month ly adm inistra tion of depot prepamti ons allows p ubertal develop ment LObe a n·ested te mporarily until the full height potential has been ac hieved and the child reaches t11e appropliate age for t11 e onse t of pubert)'· • Buserelin I 00 meg nasal spray daily. • Leuprolide 7.5 mg montJ1 Iy. A single implant of histrelineffect lasts for I year. • Triptorelin 11.25 mg 3 monthly for I year witJ1 calcium and viwnin D to prevent osteoporosis 20 meg. ln precocious pubert), future reproductive capacity is not compromised and premature menopause is not documented. Calcium and ' 'itamin D supplementation is required to prevent drug-related osteoporosis.

ADOLESCENT CONTRACEPTION This is a complex subject. Cultu•'ts. lleallh Care for Adolc.ccms. WashingtOn, D.C., ACOC. 2003 Education Pamphlet>. Be~kJS. Ada.>hi EY. llillard PA (eds). On Pubcn). l'\omk'• Gtnaecology. 12th Ed. Philadelphia, Williams & Wilkin.>, 1996. Dehm1>orr.~'o" dc~WaaiiiA. Regulatioll of puberty. lk'.>t Pr.tct Re-s Oi11 Endocrinol Mclab 2002; 16: I. Droegcmucllcr W, llcrbst AL, Mishdl DR, Slcnchcvcr MA (eels). Pedi>llric J.:ynccology. Comprehensive Gynccolof..'Y· l$1 Ed. USA, CV Mosby & Co. 1987; 231. Gordon J 0, Spcrolf L. Abllonnal pub)"'drome. In: Otmpbell S, (cd). Mmwgrmi'nl of tl" Mmofxwst and PosJ.?nmopausaJ Yra?l. Lancaster, England: ~HP Pn."M Ltd; 1976: 12. LindT, Otmeron EC. l lunter WM, el al. A prospective controlled trial of six forms of hormone "'placement therapy g iven 10 postrnenopausal women. Drj Obstet (;yntltcol. 1979;86: I. Lobo RA, Picker J II. Wild RA, el al. Metabolic impact of adding medroxyprogesterone acetate to conjugated estrogen thc:mpy in postmenopausal women . The Menopause Study Croup. Obstrt Gynet:ol. 1994;84:987-995. Newcombe PA, Longnecke r M P, Storer llE, et al. Long-tcnn hormone replacement therapy and risk of breast ca•"cr in postmenopausal women. Am] J..pidemiol. 1995; 142:788-795. Utian WI I, Schiff I. 1A.\1S.Callupsurvey on wom en's knowledge, inforrnation, wurct.~ and attitutlt.~ to menopause and honnonc replacement therdpy. Mtnoptwst. 1994; 1:39-48.

Breast and Gynaecologist

Congenital Deformities 99 Benign Tumours 100 Breast Cancer 102

Key Points I 05 Sell-Assessment I 05

T he breast is a n essentia l part of gynaecological examination and should be included in the ge nera l exam ination of every woman coming witJ1 a gynaecological problem. A rou tine breast examinatio n may discover a breast lump, hithe r1.o no t recognized by tJ1 e woman. Breast examination becomes ma ndatory in an ovarian tumour suspected to be a metastatic growth. During infe r1.ility work-up, galaCtorrhoea may poim to h)'Perprolacti naemia as a cause of infertility. ln prinlary amenorrhoea, ill-deve lo ped breasrs suggest hypothalamic-pilllitat') cause whe reas well-developed secondary sex characters indicate a local ge nital cause for ame norrhoea. Regular breast examinatio n is esse ntial in a woman on honnonal replacemem tJ1erapy (Figs 8. 1-8.3) . HORMONAL EFFEOS ON THE BREASTS Breast tissues, glandu lar, ductal as well as me Sl.11)ma respond to and remain sensitive to ovarian hor·mones throughout the r-eproducti'e period and also after menopause. Therefore, excess of ovarian hormones and antihormones play a major role in breast diseases.

CONGENITAL DEFORMITIES

interferes with tl1e woman's ac uvrues. Chronic mastalgia is desc ribed whe n pain lasts fo r more tJ1 an 6 momhs, and requires in vesti gati o ns. TREATMENT Treaunent (Fig. 8. 1) comprises the fo llowing: • Analgesics- nonsteroidal antt-inflammatorrd n.rg; (NSAIDs) . • Evening primrose oil capsule (Wellwome n capsule) containing gamma linoleic acid or gamole nic acid 3 g daily relieves pain in 70%. Occasional nausea a nd headache are tJ1e side effects. • Oana.t.ol 100 mg b.i.d. produces severe androge nic side effectS in some, and is expensi,e. Although it is 70% ef.. fective, cost and side effectS ma>• preclude some woman taking mem. Vitamin B6 benefits few women. • Bromocriptine 2.5 mg b.i.d.: Nausea, vom iting and giddin ess may occur, and because of these side effects, complian ce is poor with danaLOI and bromocriptine. About45% success is reponed. Cabergoli11e i~ IIJ11g-arti11g with less side effects. ( Destin ex 0.25 mg twice a week.) • Trunoxifen 10 mg has less side effectS, but endomeuial h yperplasia and in rare cases, ca ncer has been reported.

Congenital deformiti es include an abse m or an extra nipple, supern ume rat)' breasts, ap lasia or hypoplasia, someLimes uni latera l. ln Turner S)'ndro me, and in some cases of primal')' amenorrhoea, oestrogen tJ1 crapy may develop breastS and reduce me risk of osteoporosis. Trmww mul infectiou are mainly confined to breastfeeding puerperal women. Cracked nipples wi ll be healed wim Masse a ·eam. Mastitis requires a nalgesic, ho t fomentation and antibiotics. An abscess will require incisio n and drainage.

MASTALGIA Painful breast seen in )Otmg wome n is ofte n cyclical, but in older women it is usually ac> dical. C)•clical mastalgia is the breast pain occun·ing for a few da)S before menstruation. Severe mastalgia lasts more than 7 days, requires drugs and

F~ure 8.1 Milk-producing structures and ducts in the human breast (simplified cross-section).

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SHAW'S TEXTBOOK OF GYN AECOLOGY

Figure 8.2

Sell-palpation of breasts.

• Gonadotropin-re leasing hormo ne (G nRH ) analogue (gosere li n) 3.6 mg as month ly depot it"Uection is effec tive but in fl uences the menstrua l cycle (ame no n·hoea) and causes os teopo rosis on prolonged use. Sho n.-term therap)' is useful, but very expens ive. • Testosterone uncleca no1 Mild requires assurance and observation

~

Analgesic

Tietze syndrome _ _ _---, NSAIDs, anaesthetic+ ~ steroid injection Moderate requires treatment

l

Evening Primrose oil 3 g

. +

l

Investigation (cancer)

l

Treat

Vitamin 86 100 mg daily

No 1mprovement Danazol 100 mg bid

~

Bromocriptine 2.5 mg bid

- - - ---1 No response L------

1 .

+

Goserelin 3.6 mg monthly injection

or severe

.

l

Testosterone undecanoate 40 mgbid

-----.

Tamoxifen 10 mg daily

Figure 8.4 Treatment of mastalgia.

PREMENSTRUAL MASTALGIA It is u·eated with toremifene, which is an selective estrogen receptor modulator and belongs to the tamoxifen group of drugs; 60 mg dail) is given only in r.he luteal phase. It improves mastalgia in 60% cases. It has lesser side effectS as compared to tamoxifen (Fig. 8. 1).

BREAST CANCER Breast cancer is the commonest can cer in woman and accountS for 10% of all breast problems presented at the clinic. Breast car·cinoma is more prevalent in elderly women, and needs prompt investigations and treatment comprising surgery followed by rad iothe rapy and chemotherapy, as the need be. Certain hi gh-risk cases have been recognized and will need regu lar sc reenin g. These are as follows: • Fi:nnilifll hiltor:y. A fam il y history of breast cancer in first, second degree relatives suggest that genetic factor is responsible for development of breast carcinoma. BRCAl and BRCA2 genes mutatio ns may be fo und in 3-8% cases. Presence of these mutations indicates a higher risk of development of breast cance r in othe r family members. • A woman with ovaria n cancer is at a high risk of breast cancer and vice versa. Both malignancies share common aetiological factors and have common o ncogen s. • A woman with ovarian cancer sho uld be screened for breast tumour, as the ovarian wmour could be a metastasis from the breast. • Agl'. After the age of60 >ears, 50% breastiLUnps prove to be malignant. In childbea•ingage, 15% ofiLUnpsare malignatlt. • PariI)'. ullipadty,late first pregnancy (after age of30 yrs) and nonlactation are the high-risk factors.

• Obese women too have a propensity for breast cancer. • Early menarche and late menopause with greater number of menstrual C)cles and shorter cycles expose r.he breast tissues to oesu·ogen hormones and make them susceptible to the development of breast cancer. Endogenous as well as exogenous oestrogens are carcinogenic. Lately, p•·ogestogens also ha'e pro,·ed carcinogenic. • The risk of breast cancer is high in young women on oral comraceptive pills. The •isk decreases I 0 years after the stoppage of honnones. However, can cer is well differentiated in these women. • S11wking. It encow-ages pcriductal mastitis and atypical growth. It is also immtmosuppressive. Alcohol too may be a factor. • Honnoues. It is strongly suspected that combined oral comraceptives (COC) containing hi gh-potency progestogen given for more than 4 )'Ca rs to a woman yo unger tha n 25 years and befo re he r first pregnancy may predispose her to breast ca nce r at a late r age and the risk is two- to fivefo ld. One shoul d be ca reful in prescribing COC to )'Otlllg women. Progestogen-only pill (POP), while protecting against benign tumours, increases th e risk in elderly women. T he risk decreases after 10 years of stoppage of oral conu·aceptive pills. Low-dose COC may have a lower risk. The risk is related to the d uration of COC intake. Lately, COC is considered a higher dsk factor than oestrogen alo ne because of progestogen content. Breast cancer is the main concern while prescdbing hormo ne replacementthempy (I IRT) r.o a menopausal woman. A woman on HRT should be screened regularly for breast lump, and mammography should be done every 1-2 )Cars. HRT should not be administered for more than 10 )Cars.

CHAPTER 8 - BREAST AND GYNAECOLOGIST

Fortunately, breast cancer following HRT is of low malignant "potential" with good prognosis. It may be prudent not to recommend HRT to a woman treated for breast cancer. It is equally important tO carefully monitor a woman on tamoxifen for breast and uterine cancers. It is suggested that vitamin A may be protective. Obesity increases the risk of cancer becattSe of pet;pheral conversion of oesu·ogen. Raloxifene is safe agai tlSt endomeu;al cancer but causes thrombosis.

CUNICAL FEATURES Very often, the fit"Sl thing a woman feels is a lump in her breast. Nipple discharge and pain come later. The lump feels firm , irregular and fixed in t11e later stage. Axillat-y lymph nodes become palpable in the advanced stage. The ot11cr breastShould also be palpated.

INVESTIGATIONS (Figs 8.5- 8.7) Clinical fJrtljJat.ion is not I 00% accurate for detec ti ng cancer. In patients younge r than 40 )'Cars, 50% cases can be missed. Between the age of 40 and 49 years, accuracy is 80%; between 50 and 59 )'Ca rs, 90%; and over 60 years, accuracy is 95%. Self-examination increases t.he awareness in a woman and brings her to the doctor at an early stage for the treatment. Ex amination by physician supp lementsself-examination(Figs 8.2 and 8.:3).

Mammography is indicated in the following cases: • Older and high-risk women. • To assure nonnalit) when a woman has cancer phobia. • If a lump is present.

• Prior to HIIT; Yearly/ 2-yearly screening between the age of 45 and 60 years is cost-effective. Contrairulicatiom. Mammography is conu-ainclicated in pregnane) because of the risk of radiation. Using onl) mammograph) as an investigation tool is unreliable in 50% women below the age of 40 years becattSe of cletlSe breast tissue. Mammog•-aph) identifies cancer in 75% cases between 10 and 19 )ears of age, and reliability increases with age. It must be mentioned tllat ime•·pretation of mammography findings may be difficult if a woman had previous breast surgeq•. Similarly, HRT also interferes with mammographic screening. Mammography should include two views of both breasts: mediolateml obliquf' vinu and cranioCtJttdnl view. Regular mammog•-aphy can reduce the mo•·tality of cancer by 30%. The findings include:

• • • • • • •

Altera tion in density of breast tissue Microcalcifica ti on Thickening of skin Presence of fibro us s u·eaks Nipp le alterati o n Detection of fibroade no ma, lymph nodes, galactocele C)•Sts and solid wm o ur.

Ultrmowul imt~ring, using 10-MH:t. probe, is useful in all age groups, especially before the age of 35 years when mammography may not be reliable. Ulu-asouncl differentiates cystic from solid malignanttumotLr. It is required in young women, pregnant and lactating woman, and in duct papilloma. Ultrasound, hO\\" ever. fails to ident.il) microcalcification, which is the hall mark of

Breast lump • Clinical examination • Mammography • Ultrasound • FNAC

• MRI (sometimes)

!i4alignancy suspect~

~ Age 30 years

Excisiona I biopsy and frozen section

~

~

~

Excisional biopsy and histology

Observe Painful or increase in size

Malignant

~ Radical surgery. lumpectomy followed by radiotherapy, chemotherapy if required

~

Resection and histology

•

No hormonal therapy thereafter

•

Follow-up Figt.We 8.5

103

Investigation and treatment of breast lump.

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SHAW'S TEXTBOOK OF GYN AECOLOGY

• Tru-mt biopsy removes a core of tissue for frozen section, histology and receptor swdy. A big tumour requires excisional biopsy.

SCREENING Screenjng is an important tool tO identif} women at higher tisk of developing breast cancer. It a llo"s for early detection and timely channeli.a~tion of modalities of treatment best suited for the patienL A patiem must be evaluated on the basis of certain risk factors to determine whether referrals :u·e needed for genetic testing and for consideration of chemoprevention and/ or prophylactic surgery. Major factors used to determine a risk category, based on a patiem's histOIJ', ar·e as follows:

Figure 8.6 CC view- mammography cranlocaudal view.

• Personal histor/' of ovaria n, peritoneal (including tubal) or breast cancer • Family h is to r/' of breast, ovarian o r peri to neal cancer • Genetic predisposition (if the patient's BRCA Status is kn own) • Radiotherapy of the chest be tween t11 e age of I 0 and 30 years

AVERAGE RISK • Age under 40 years - No screening fo r average-risk women who :u·e younger tl1an 40 years. Among women younger than 40 yeat·s, the incidence ofbrea~t can cer is low. • Age between 40 and 49 years- For women who decide tO initiate screening in their 40s, a screening mammography every 2 ye:u·s is performed. • Age between 50 and 74 years - Breast cancer screening with m:unmograph) for avemge-ris k women aged between 50 and 7 1 )Cars. We t)picall) screen evet}' 2 yeat-s. • Age 75 years and older - Women older than 74 )'eat'S should be offered screening on I)' if their life expectat1cy is at least iO )Cars. Rgure 8.7 MLO - mammography mediolateral oblique view.

HIGH RISK As per American College of Obstetrics and G)'naecology

early cancer. In the cancer of breast, O\'Sanian R, BlairSL, Bul'>tein llj, CyrA, e1 al. NCCN Guidelines Insights Bre-ast Canc~r. Vcl'>ion 1.2016.] ' all . ComprCtnc Nci\V. 2015;13(12):1475-S.~.

Mango V, Bryce Y, Morris EA. Gianotti E, Pinker K. ACOG p~dCIICC bulletin July 0 I 7: brt:""..stcancer risk assessment and t.erccnmg m a•erage.. risk women. Br J Radiol. 2018;24:201 70907. Speroff L, Fri11. MA. Oinical G)'llecologic Endocrinoq,') and lnferulny. &h ~-d. Phibdclphia: Lippincou \\'illia111> & Wilkin>. 2011:621-672. Sule EA, Ehcmade F. Management ofpregrum9 a>>OCi&L-d breast cancer hilh chemotherapy in a den;loping country. lmj Surg C:bt: Rep. 2015 ;17:117-20.

Sexual Development and Disorders of Sexual Development

Principles of Sexual Development I 06 Factors Influencing Designation of Sex I 09 Disorders of Female Sexual Differentiation 112 Masculinization 114

Virilism 114 Hirsutism 116 Key Points 120 Sell-Assessment 120

Sex differentiation is a comp lex process comp rising a cascade of even lS that begin with the undifferemiated (potentiall)' bisexual) go nad up to the 6Lh week of inu·auterine life and end up with the developmem of the specific gonads and their corresponding in te m al and external genital organs. Genetic arul lwmwnal injlumces are t!Ut TTUtin determiTUmt~ in tl~~t development of stx, (titlwugh other f(lctnrs TrUly modifj• its devtiofJment. The environmemal and teratogenic facwrs, such as ionit.ing radiation, viral infection, chemical agents, immtmological disturbances, hormones and nuu;tional deficiencies. pia) a role in sexual differentiation. ew insights into the biolog) of sexual developmem and advances in chromosome analysis have encouraged clinicians to determine sex of the individual at an early age and institute prompt treaunem of the intersexual state to enable the individual to lead a more normal life. The expanding knowledge and recognition of imersexual states have h elped to develop a classification of abnormal sexual development based on gonadal and genital anatomy, chr·ornosornal nndings and specific identifiable genetic/metabolic defects. T he knowl edge of e mbryology is necessa1)' to understand how congenital malformations occ ur in I% offemale pop ul a ti on.

PRINCIPLES OF SEXUAL DEVELOPMENT (Fig. 9 . 1) The deve lopment of no1mal male and female genital organs and tracts is detenn ined by several factors, all ofwhidl are time specific during emb1yogenesis. In the 5th week ofinu-auterine life. the undifferemiated gonad comains cortex and medulla. The critical period for gonad,·\! developmem is at fr7 weeks of emb1yogenesis when Y chromosome promotes male gonadal development. 1l1e external genital organs (phenotype) stan. developing atiOtJ1 week and read1 completion by 16th week. The genetic sex is detennined at fei·tiliLation, but the gonads remain undifferentiated until 6 weeks of intrauterine life. First, the sex chromosomes determine whether the

106

indifferem gonad (w·ogenita l ridge) wi ll differemiate imo a tes tis or an ovary. Y chromosome develops a ma le gonad and absence ofY and presence of XX chromosome deve lop ovaries. lf the gonad is ma le, ge nes associated with the Y chromosome imeract with other compo nents of the somatic cells in the primitive gonad and initiate development along t11e male lines. The elaboration of the H-Y amigen complex in tJ1e short arm of Y chromosome, known as sex-detennining region Y (SRY) , induces testicular developmenL Senoli cells in the developing testis produce Miille iian-i nhibiting substance (MIS) that causes regression of the Mulledan (paramesonepluic) ducts. In me abse nce of tvUS, the Mullel'ian ducts de,elop passive!)' to fonn the fallopian tubes, Lllerus and upper '-agina. Female imernal organs and external genitalia de,elop partially witJ1out the need of O\ 200 ng/ mL). LH is raised, but FSH is nonnal. Chromosome sllld) reveals XY chromosomes (Fig. 9.8A and B).

MANAGEMENT • Once diagnosed, it is impo•·tam to u-ace me location of the testes and perfonn gonadectOm)'• because testes are liable to undergo malignancy in 10%-30% cases. The conu·ove1'Sial point is as lO when to perform gonadectomy. lt is prefen·ed to remove the testes in puberty when tl1e correct diagnosis is made ( 16-18 years).

SUPERFEMALE (TRIPLE X CHROMOSOME) The presence of an extm X is not uncommon because it is quite compatible with complete femin ine normali ty. There is, however, a we ll-recognized u·ip le X syndrome in which t11e patiem, who is often mentally subn ormal, suffers from scanty or irregular menstruation and infertility. Clinical examination ma) reveal hypoplasia of the genital tracL The importance of chromosomal studies in such a patiem is obvious. and iLS determination plays an imponam role in me investigations and management.

MALE PSEUDOHERMAPHRODITE Testicular feminit.ing S)ndrome, initially described by No•·ris in 1953, is now designated as eit11er complete androgen insensitivity S)•ndrome (CAIS) or pa•·tial androgen insensitivity S)•nch-ome (PAIS), and t11is reflectS the aetiology. incidence is 1:2000 to I :60,000.

AETIOLOGY The peripheral receptOJ'S for testos•ero ne are absem or are seamy or they fui l to respond to tes•oste•·one. The external genitalia are of female phenotype. Chromosome is XY, and the testes are located along its line of descent in the abdom inal cavity o r in inguina l ca na l, and are maldeveloped. The Wo lffian d uct fa ils to deve lop because of absence of tes tosterone recepLOrs. Testes prod uce MlF, so the Mt~dl er ian S)'Stem fai ls to deve lop. However, the lower portion of tl1 e vagina derived from sinovaginal bulb appears as a dimple of 1-2 em in length. There is often a strong familial tendency to this disorder, and several cases may appear in the same family and in different generations, and tl1e condition is attributed to X-linked recessive gene. Unless there is a famil) history, or childhood inguinal hemia comaining the testis, the condition is not diagnosed until pu bert). The girl is t)•pically feminine and tall. The pubic and axillar)' hair are seamy, but the breasts are developed because of oestrogen derived from peripheral comersion of androstenedione. The

Figure 9.8 (A) Ambiguous genitalia In a child with XY karyotype and partial androgen insensitivity. (B) Male pseudohermaphrodite showing micropenis with labioscrotal gonads. (Source (A): Hack« NF, Gambone JC , Hobel CJ, Hacker and Moore's Essentials of Obstetrics and Gynecobgy, 5th ed Pl"iladelphia: Bsevier, 2010. Courtesy: (B) Dr &mesh kuma-, AIIMS)

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• These patients will •·equire oestrogen therapy for the development of the bt·easts and to prevent osteoporosis. • If she plans to matT)', vaginoplasty should be done. If sufficient length of vagina pt-evails, \'llginal dilators may be effecthe in stretching its length. The reproducti'e function is not possible O\'ll t·ies and uterus.

"~th

Some breast development

absem

PARTIAL ANDROGEN INSENSITlVITY SYNDROME

Very long arms

ln PAlS, few receptors respond to testosterone, and the clinical features are variable. Some presem at birth witl1 ambiguO IL~ genitalia, and chromosome study reveals XY chromosomes. Others presem at puberty with lack of virilization in a boy, or signs of virilization in a girl with ptimary amenorrhoea. The treaLtnent is based on the sex in which the child is reared, psychological behaviour and t11e amo unt of virilization. If the chi ld is reared as female, it is best to perform gonadectOm)' in childh ood to avo id virilization. ln a boy, tes tosterone will help. T he reproductive function rema ins poor.

)----.'4- Less-developed

testes

ENZYME ERRORS IN ANDROGEN PRODUCTION T he production of testosterone from the testes requires enzymes, the most important of which is 5-alpha-reducrase. This enzyme converts testosterone into DHT, which is capable of acting on pel'ipheral target tissues to produce male phenotype. Absence of this enqme results in female phenotype and male pseudohermaphroditism.

MASCULINIZAnON KLINEFELTER SYNDROME Klinefelter syndrome is seen in I :500 males. The patiem with this rare disorder external!) resembles a male in general body conformity, the penis is smaU or normal in size; the testes are small, but as a rule are normaUy placed. Sterili ty is commo n, gynaecomastia is frequently present (Fig. 9.'1 ), Lh e voice ma)' be high pitched, and me appearance ma)' be e unucho id. The patient is often mentally defective or deli nquent. Most of tl1ese individuals are sex ch romatin posiLive li ke females because of t11e extra X chromosome. Genetic ana i)'Sis reveals tl1e ir karyotype to be 47XXY. Tes ti cul ar b iopS)' usuall y reveals hya li ne dege nerati on of the sem iniferous tubu les and overgrowth of Leydig cells, as a result of whi ch sterility is so often the presenting symptOm ( Fig. 9.9). Sole-to-p ubic lengLI1 is more than nonnal. T he pe1'S0n should be bred as male and should n ot be told about chromosomal abnonnality. Testosterone may help. The breasts may need surgical excision.

VIRIUSM Vit·ilism is charactet·it.ed by hirsutism and some of the male appearances, and au·oph) of tlte breasts. In patients exhibiting virilism. me chromosomal and gonadal sex is female and the accessory sex organs of

Figure 9.9 Klinefelter syndrome. Note the superficial ly normal male genitalia, gynaecomastia and feminine distribution of the pubic hair.

Mullerian origin are also feminine. The external genitalia, however, resemble the male.

CUNJCAL FEATURES The body conformit) is largel) male wim good tmLSCular development and broad shoulders. The voice is deep and the Lll)TOid cartilage is prominent. Hirsutism is present tO a remarkable degree, wit11 a male distl'ibul.ion of hair. The psychological sex is often but not invariably male. The external gen ita lia show hypertrophy of t11e clitotis and fusion of the labia m~ora due to failure of the cloacal membrane LO divide in congenital \'arieL)'· The vagina is often absent if t11 e cause is congenital (Figs9. 10 and 9.11). T he brea~LS are un derdeveloped. O t11er s igns are frontal, temporal and vertex baldness, hoarseness of voice, diminished size of breasts, hirsutism, cli tora l enlargement, acne a nd ame no rrhoea. Ad re na l wm o ur and male hormo ne secreting ova rian wmor are respons ib le for viril ism.

CUNJCAL VARIETIES ADRENOGENITAL SYNDROME Adrenogenital syndrome occut'S due to hyperplasia of the adrenal cortex and is of two types. This condition is also known as congenital adrenal hypet·plasia (CAH). Congenital or Intrauterine Adrenogenital Syndrome

Congenital or intrauterine adrenogenital S)ndrome (CAS) is the condition in which the p.-imary defect is a block in L11e conversion of progesterone to deoxycorticosterone due to ent.yme failure of21-h)drox)lase. The nonnal adrenal conex produces three C21 compounds: hydrocortisone,

CH APTER 9 - SEXUAL DEVELOPMEN T AND DISORDERS OF SEXUAL DEVELOPMENT

Figure 9.10 Female hermaphrodite showing hypertrophy of the phallus, masculine appearance of the glans and rudimentary scrotal sac.

Figure 9.11

Patient with a catheter In the Immature vagina.

11 5

of androgens, notably 17-hydrOx)'])I'Ogesterone. The main androgenic activity of 17-hydroxyprogesterone is clue to itS conversion imo 04-androstenedione and hence to other onJ1oclox androgens. These androgens are responsible for phallus of the female pseudohennaphrodite showing hyperu·oph). the masculine appearance of the glans, and the persistence fusion of the labia majora to resemble a scronun (Fig. 9.10). The miniature vagina opens into the w·ogenital sinus and the external appearance is that of a male \\~th h) pospadias (Fig. 9.11 ). The diagnostic feature is the very high value of 17-ketosteroids and I7-hyclroxyprogesterone (>8 mg/ mL) exCI'eted. As expected, the chromosomal pattern in these girls is XX. Ultrasound should be done to look for ov;u·ian and ad•·enal tumours. Electrol)•tes should be monitored, as there is a possibility of hyperkalaemia and hyponatraemia. The treaunent of this condition consistS in the administrati on of cortisone or hydrocortiso ne or the newer synthe ti c corticosteroids s ud1 as p red nisone o r p red nisolone (2.5 mg twice da ily is an adeq uate mainte nance dose for adu lt and will resto re tJ1e outp ut of 17-kewstero ids to normal). T he con tinued use of tJ1ese d rugs carries ce11.ain dan gers of adrenal defic iency d ue to s upp ressio n of ACT H, and this especially operates at times of su·es.~ such as whe n a patient needs an anesthetic. At tJ1ese Li mes, cortisone coverage should be given to tide over the period of stress (i.e. 1 clay before, on tJ1e day of operation and for 3 days aftenvarcls). Dose of co•tisone is 0.15 mg/ kg in fo ur divided doses for child. In a child with salt-losing condition, fludrocortisone 50-100 meg dail) witJ1 intravenous (i.v.) saline is recommended. The vulval abnormalit) is corrected by a small plastic operation, and as a rule, it is wise tO amputate the hype•·trophied eli to .-is between 5 and I 0 )ears of age. Cliwroplasty with conservation of glans is preferred to amputation. Fusion of labial folds should be con·ected at puberty. Mena•·che is often dela)ed and fe•·tility is reduced in these girls. Cases of virilitation of the fetus in utero have been •·eported following tJ1e use of progesterone in the pregnant mother. Ln fuct. all synthetic progestogens except 17hyclroxyprogesterone have some degree of androgen ic effect. Lf progestogen is to be used in p regnant woman it should be devoid of any androgenic effec t. T he effect on tJ1e fews depends largely o n the d uratio n of th e pregna ncy a t tJ1e tim e of ad ministratio n and th e dosage emp loyed . Lf p rogestogens are give n before the 12th 1.0 14 th weeks of gestation, tJ1 e neo natal picture may be similar to that of the inu"ii utcrine ad renogeni tal syndrome, i.e. enlarged p hallus and imperforate pe rin eal membrane. T he viri lism is, howeve 1~ nonprogressive. Postnatal Adrenogenital Syndrome

corticosterone and aldosterone and in addition certain androgen Cl9 compounds. The production of 17-hydroxyprogesterone, which is mildl) androgenic in action, is conu·olled b) adrenocorticotropic honnone (ACTH), and this, in turn. is controlled b) the reciprocal action of hydrocortisone. If, therefore, the hydroconisone-ACTH interaction is upset b)• a deficienq• of h)clrocortisone, the pituitary gland produces an excess of ACTH, whid1 in turn leads to adrenal co•·tical h) perplasia and excess output

This can be due to excessive output of ACTH from a basophil adenoma of the anterior pituitary gland (Cushing syndrome) which gives rise to adrenal cortical hyperplasia. An adrenal tumour that can be benign or malignam has the same effect. An adrenal tumour is not depenclem on influence of piwitaq gland. In an undiagnosed case, initial accelerated skeletal maw ration is followed b)' early epiphyseal fusion and swnted height. Precocious puberty and increased libido witJ1 aggressi'e beha,·iour is reponed in a

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few cases. Sterili ty is common. Cortisol th erapy can avo id t11ese undesirable effects. Males witl1 this syndro me also present with tl1ese feawres.

VIRILIZING TUMOURS AND OTHER CONDITIONS OF THE OVARY The virilit.ing nunours and other conditions of me ovary, such as arrhenoblastoma, hilus cell ttunour, polycysLic ovary and h) perthecosis, are cattSeS of ,-ir·ilism and produce a clinical picture somewhat similar to the posmatal adrenogenital syndrome and are due to excess of testosterone secreted by me O\'ft.

-....

- ---Rgure 9.12

CAUSES OF HIRSUTISM Genet.ic and e tJ1ni c. Excess androgen o r increased sensitivity of the pilosebaceous unit to testostero ne o Uver disease whe n th e SHBG level drops. o Ovarian. Polycystic ovarian disease ( PCOD), hype rthecosis, masculini:t.ing ova tian LLtmo urs, e.g. arrh enoblastoma, hilus cellwmour. • Adrenal. Congenital adrenal hyperplasia, Cushing syndrome, adrenal wmour ( I %-2% cases). • Dntlj,). Androge ns, progestogens witJ1 androgenic effect, e.g. I 9-norsteroids, and levonorgestrel a nabol ic steroids, phen)toin, da nuo l and minoxid il. • 011ten. 0 besi L), h) po tJ1) roid ism, a novula LOry hypooesu·ogenism, idiopathic- 15%, h) pe tprolact.inaemia. o H imllism occun rarl)• in collgtmitfll ttdwwl h)perplasia, arou11d puberl)• i11 PCOD a11d in eldl'rly womm aJ. 77Umopause. o

--

The spectrum of sex: possible sexual aberrations in diagrammatic and tabular forms.

released into the blood circulation as free testosterone, which can cause hirsutism. Similarly, obesity causes fall in SHBG as well as more peripheral conversion of a ndrostenedione to testoster·one. Ferriman and Gallwey desctibed a scoring system for hi rsutism in nine body areas on a scale of 0-4 and quamified h air growth. A score > 8 is labelled as hirsutism.

o

.. ..

o

Idiopathic increased sensitivity of end organ to 5 alpha reductase.

CUNICAL FEATURES • PCOD accounts for 80% cases of hirsutism and is characterized by oligomen orrhoea, obesity, hirsutism and often infertility. Bo th ova ri es are enla rged and covered with a thi ck, s moo th, fibrotic, pea rly wh ite capsule. Mu lt.i p le sma ll cysts, 2-9 mm in size, are present at the periphery of the ova ry, and tJ1 e ovarian s u·oma is increased due to theca cell hype rp lasia. Ultrasound reveals tJ1 e ovari a n mo rpho logy clea rl)', and diagnosis can be acc urate I)' estab lished. LH level is raised even in the preovulato ry phase of the menstrual cycle, ca using a high Ll-1/ FSI-I ra tio (mo re tJ1 an 1). This resulrs in anovulat.ion a nd high oestrogen level, b ut abse nce of progesterone. About 50% of wome n with PCOD will show raised leve ls of androgens (testostero ne, a ndrostenedione and DH E.A ). Testostero ne level al th o ugh raised. remains below 200 ng/d L, unlike t11at in ovarian tumolu· (see also Chapter 24). • Masculinizing ovarian tu mours callSe defem inization such as breast au·oph) and amenot-rhoea besides hirsutism, hoarseness of voice and muscular clevelopmenL Clinical examination may noL always detect small tumour.

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Laparoscopy. ultraso und and MRI may be required to locate the tumour. Testoste rone level is raised above 200 ng/ dL Removal of the uamo all' restores u1e menstrual cycle, but hoarseness of voice and existing hirsutism ma) require appropriate managemenL • Congenital adrenal hyperplasia is diagnosed a nd u·eated before pubett). It is due tO deficiency of e nzpne 21hydrox) lase. 17-H)drOX) progesterone plasma level is raised more u1an 8 ng/ mL Coa·tisol deficiency occurs at times of stress. To diagnose, dexamethasone suppression test is done by giving I mg of dexameu1asone at nigluand studying a single plasma conisol level in u1e morning. The level should be less than 130 nmoi/ L (100 meg)u1is test has low fa lse-positive finding. Computed tOmograph)' (CT) scan of abdomen and pituita•)' fossa may be required. • Cushing syndrome occurs d ue to overprod uction of ACTH by pituitary gla nd o r ad renal tum o ur. T he diagnosis is estab lished b)' dcxa me u1 aso ne suppresio n test, ACTH level estim ati on and CT sca n of u1e p ituitary and adrenal gla nds. DHI.!:A and androste ned io ne levels are raised in this S)•ndro me. • Hyperprolactinaemia may be due to e nlargement of the pituitar)' gland or d ue to a pituitjmssion of mulrogen~ wiiJ1 co mbined OCPs not co ntaining androgen ic progestogen such as noreiJ1isterone and levonorgesu·el will suppress ovarian androgens. Oestrogen is not only antiandrogenic b ut by stimulating production of SHBG will bind circulating free testosterone to SHBG. Ullls suppressing its peaipheral ac tion on u1e hair follicles. Antiandrogens used are ( I) spirono lactone and (2) C)'Pl"Oterone acetate. • Spironolactone in a dose of 100-200 mg daily blocks u1e androgen receptors, reduces its production and increases its metabolism, and thus prevents hirsutism in a furmer 60% of cases. It is best given wim combined oral pills to a,·oid irregular menstruation, and prevents conception, mlLS preventing possible feminiL.ation of a male fetus, lest the woman concieves. The side effects include transient diuresis, menstrual itTegula•·ity (polymenonilagia I 0%) and breast enl argement. Occasionall y, hyperkalaemia and hyponatraemia may ocelli: Maintenance dose after 6-12 months is 50-mg spironolactone wi u1 OCPs (sec also chapter o n Ho nn on al T herapy in Gynaecology). Drospireno ne 3 mg wiu1 30-mcg oesu·ad iol (Yasmin, Janya, and Tarana) used cyclically for 3 weeks is found very effective in h irsutism in PCOD. • Cyproterone acetate is a pote nt progestOgen wiu1 antiandrogenic ac tivity, a syn iJ1etic detiva tive of 17alpha-h)'droX)'pl"Ogesterone; it inhibits DHT binding to its receptors at the periphe ry and has a weak corticosteroid effec t. It is given co mbined with oestrogen as 50-100-mg cyproterone da ily for u1e first 10 days of the menstrual cycle wiu1 30-50 meg of e u1in yl oestradiol (EE) for 21 days. After 6- 12 mont11s, a maimenance dose of 5- 10-mg C)proterone acetate wiu1 EE will be effective in preventing recurrence of hirsutism. The effect becomes apparent after 4 months of treatmenL Oral co nu-aceptives regulariLe u1e cycle and prevent pregnanq'. Oesu·ogen presem in me pills avoids menopausal S)tnptoms and also raises me serum hormone-binding capacity, which bincls me ft·ee

CHAPTER 9 - SEXUAL DEVELOPMEN T AND DISORDERS OF SEXUAL DEVELOPMENT

androge ns a nd red uces ins ulin -li ke growth factor. Side e ffects are we ight gain , nausea a nd headache, rarely liver da mage. 3. Weight reduction will increase SHBG levels and bind free testoste rone, thus red ucing its peri pheral actio n o n hair fo llicles. cin I%, erythromycin 2% and retinoid~ also help. Vaniqa cream is applied twice daily for 24 weeks - some develop allergic dermaLilis and mild burning sensation. • lsou·e tinoin suppresses sebaceous gland secretion. • Dutasteride (Avoda tt) is 5-alpha-red uctase inhibitor is under u·ial. It inhibiLS DHT production in 99% cases. It is con u·aindicated in pregnanC)'·

• Detailed kllO\,iedge on genetic sex, honnonal innuences coupled \,itJl imestigations are required to make the accurate diagnosis and conduct the appropt·iate managemenL • Hirsutism is now increasing!)' encownered in )Oung women as tl1e incidence of PCOD has increased. Otl1er causes are idiopatl1ic, adrenal, ch-ug adminisu-ation, hrpoth) roidism and h) petprolaclinaemia. • Ultrasound and hormonal profile stud) are necessary. • Vatious dntgs used in hirsutism are C) proterone acetate, spironolactOne, finastetide and combined hotmonal pills. • Acne is a cosmetic problem and demands treaunem. • VarieLies of intersex now can be diagnosed based on chromosomal Sllld). Surgical management allows an individual to li\e neaNlOnnal life as possible. • Vitilism requires immediate management; otl1erwise, certain masc ulini~ing features wi ll persist despite treat· ing the cause. These persistent fealtlres are deepening of voice and baldness.

TRUE HERMAPHRODITE True hermap hrod ite is an individua l with ovotestes or ovary on one side and testes on tl1e o tl1er. The uterus and vagina develop and tl1 e person menstruates. In add ition, tl1e external genitalia is of male phenotype. The individual is brought up as a ma le until puberty, so it may be prudent to retain the ma le gender and do mastectomy and hysterectomy. TestOsterone therapy helps to develop secondary sexual characters of the male phenot)'pe. Plastic surgery on the phallus may be required, and sexual function is possible. Fertility, however, may remain low.

PSYCHOLOGICAL SEX Homosex ualit), transvestism and transsexuality are abnot·mal sexual behaviour. Transsexuality is defined as a disturbance of gender identit) in which a person anatOmically of one gender has an intense and persistent desire for medical, surgical and legal change of sex and lives as a member of the opposite gender. These are psychosexual patienLS and need careful handling and a lot of co unse lli ng before taking and accepting the individual's decis ion. lni tia ll)'• hormone therapy fo llowed b)' surgery will be needed to reconsu·uct the bod)' phenot)•pe of the desired gende r. Oestrogen for a male and progestogen for a fema le will red uce th e seco ndary sexual characters ove r a pe ri od of 1-2 )'Ca rs. Th is makes reconstructive surge ry easie r, apan fro m th e fac t th a t it g ives the individua l LO assert her/ his decision over the change of sex.

KEY POINTS • Intersexuali ty is a difficult gynaecological problem to tackle because the condition is extremely rare and the experience of a g,naecologist is limited.

SELF-ASSESSMENT I. Describe the phenotypic appearances of individuals with

sex chromosomal abnonnalities. 2. Enumerate tl1e components conuibuting to determination of sex. 3. What are the common causes of hirsutism? Describe their managemenL 4. Describe the features of Sw)er S)ndrome, Turner syndrome and Klinefeltct· S)ndrome. 5. Define Vit·ilism. Describe iLS clinical feawres, trpes and managemem of this disorder.

SUGGESTED READING Ehnnann DA. Pol)'C}">tic o"''"Y syndrome. N Eng J Mc-d 2005;352: 1223-36. lliorl 0, Birnbaum W, Marshall L. Wtlll>Ch L, Wcrn~:r R, SchrOder T, Cl al. ~1anagcment of disordct> of sex dc,clopm~:•H. 1at R~:v Endon A. 1ntrautcrin~: diagnosis of sex chromosome aneuploidy. Obstct Cynccol 1996;87:468-75. Norman ~J. ~1ctformin- comparison with other chcrapit:s in ovulation induction in polycystic ovary syn drom~:. J Clin End()(:rinol Metab 2004;89:4 797. Ostrer II. Disorders of sex development (DSDs): an update.] Oin Endocrinol Me tab. 2014;99(5): 1503-9. Spero!TL, Fritz MA. Oinical Gynecologic Endocrinology and Infertility. 8th ed. Philadelphia: Lippincott Williams & Wilkins, 2011;331-389. Speroff L, Frit1. MA. ll ir.mtism in Clinical Gynecologic Endocrinology and In fertility. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2004;46~98.

Studdj. PrOj,'T"SS in ObMetric;,and GynaccoiO)O'· 3:197.

DISORDERS OF MENSTRUATION

1 0 Common Disorders of Menstruations 11 Abnormal Uterine Bleeding (AUB) 12 Primary and Secondary Amenorrhoea

13 Fibroid Uterus 14 Endometriosis and Adenomyosis 15 Hormonal Therapy in Gynaecology

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Common Disorders of Menstruation

Menstrual Cycle Irregularities 122 Heavy Menstrual Bleeding (HMB) 122 Oligomenorrhoeo and Hypomenorrhoeo 123 Polymenorrhoea or Epimenorrhoeo 123 Metrorrhagia 123

Dysmenorrhoea 124 Premenstru al Syndrome 126 Key Points 127 Self-Assessment 127

MENSTRUAL CYCLE IRREGULARITIES Mensu·uation is the e nd po int in a series of evenrs wh ich begins in the cerebral co n ex and hypothalamus and ends at t11e uterus in t11 e h)'j)Otha lamic-pituitary-ovarian-merine axis. An y break in this axis creates me nsm..al problems. Excessive o r inappropriate ly timed mensLruauon and amenoni1oea are the most commo n co mplainLS for whid1 women seek advice from medical healtll ca re providers. As described in Chapter 4, no tmal mensu·uauon requires imegratio n of the h) pothalamic-piLUitary-ov:uian (H-P-0) axis with a functional uterus, a patent lower genital outflow u-act and a nonn al genetic kat')Ot)pe of46XX. Abnormal mensu·uation can be a harbinger of a sinister pelvic pathology or denote a relatively minor problem; therefore, a thOt"'ugh investigation into the problem is called for in eve•')' patient presenting with this complaint. ln nonnal healt11y women, menard1e occurs between t11e age of 10 and 16 yea rs, mea n age of menarche being around 12.5 years. Cyclic menSU'U(Itio n persists tJuu ughout the repi"'ductive era oflife with an average rll)1.hm of28:!: 7 da~, inclusive of 1-6 da)s of bleecUng (except pregna ncy and lactati on) . It is not uncommon for minor valiations to occ ur fi'Om time to time.

VARIOUS TYPES OF MENSTRUAL CYCLE IRREGULARITIES Except amenorrhea rest are th e disca rded termino logy not used now a days. • Amenorrhoea indicates th e abse nce of menstruation. It is a sympto m and not a disease entity. • Oligomenorrh oea denotes infreq uem and irregularly timed episodes of bleeding usually occ urring at intervals of more than 35 da)S. • Polymenorrhoea denotes frequent episodes of mensuuation. usuall) occun·ing at ime r·va ls of 21 days or less. • Menorrhagia denotes •·egularl)' timed episodes of bleeding thata•·e excessh·e in amou nt (> 80 mL) and/ or duralion of flow (> 5 days).

122

• Metrorrhagia refers to irregularly tim ed episodes of b leeding superim posed on norma l C)'Ciical bleeding. • Menometrorrhagia means excessive and prolonged b leeding thatocctu·s at irregularly timed and frequent intervals. • Hypomenorrhoea refe rs to regularly timed but scanty episodes of bleeding. • Intermenstrual bleeding refers to bleeding (tLSttally not excessive) that occurs between otherwise no nnal mens Lrual cycles. • Precocious menstruation denotes the occurrence of menstruatio n before the age of I0 >ears. • P ostcoital bleeding denotes ' oagina l bleeding after sexual imercourse.

HEAVY MENSTRUAL BLEEDING (HMB) The term ' heavy mensLrual bleeding' defined as excessive blood loss intet·fe.-ing with physical, socia l, emotional and or material quali ty of life. It is ge nerally ca used by conditions affec ting the uterus o r its vascula tity, rather than any di swrbance of functi o n of th e H- P- 0 axis. Whenever the uterine e ndo me u·ial s urface is e nlarged, the b leeding surface is increased, conu·ibuting tO excessive b leeding. Such co nditi o ns preva il in uterine fibroids, adenomyosis, uterine pol)'pS, myo hype rplasia and e ndometria l h )'perplasia. HMB is also see n in wome n wi l11 increased uterine vascularity such as in chronic pelvic innammatO t')' disease (PIO) and pelvic e ndom euiosis. The uterus is often reu·overted in position with restricted mo bilicy. Such a utenLS tends to be bulky and co ngested. The presence of an intrautedne conLraceptive device (IUCO) ofte n leads to hea~y and prolonged bleeding. Lastl), menorrl1agia may be the result of bleeding diso rders like Von Wille brand disease or an arteriovenous aneUI')Sill. A normal mensuual blood loss is 5~80 mL and does not exceed 100 m L. ln menot-rhagia, the me nstrual C)cle is unaltered, but the duration and quantity of the mensuual

CHAPTER I 0 - COMMON DISORDERS OF MENSTRUATION

loss are increased. Menorrhagia is essentially a symptOm and not in itself a disease. It affects 20%-30% of women at sometime or other with significant adverse effects on the quality of life in terms of anaemia, cost of sanitary pads and interference witJ1 da)·to-da) activities. Several causes may prevail in a few cases and attribute to excess bleeding. ln a few cases. the underl) ing cause may be difficult to detecL

OLIGOMENORRHOEA AND HYPOMENORRHOEA

OUGOMENORRHOEA ln some women, the pauem of menstruation extends to cycle lengths exceeding 35 days without any impairment of th eir fertility. This is compatible with normal reproductive capacity within the limits of its own infreq uent ovulation, so it requires no trea tm ent. lloweve r, if the cycles are very erratic and infreq ue nt, medical auemion is called for. T he causes and findings of cli n ica l inves ti gati ons are similar to those of amenorrhoea. Many of these women are obese, hirsute with poorly deve loped secondary sex ual characteristi cs, gen ital hypop lasia and ova rian s ubfunction. Amenorrhoea is often tJ1 e contin uu m of o ligomenorrhoea. T his condition is often enco untered in women at the extremes of reproductive life and in some lactating women . Other causes are genital tuberculosis and poly· cystic ovarian disease.

HYPOMENORRHOEA ln some women, mensu·uation lastS for only 1-2 days, and ilie blood loss is so scanty tJ1atshe ma)' need a change ofjust one to two sanita•y pads. Scanty menses, which is otherwise regular, may not be pathological because its regularity presupposes a normal H-P-0 relationship. ln these women, ilie ute•·ine end organ may be at fuult. A small hypoplastic uterus, genitaltube•·culosis and panial Ashennan syndrome also cause hypomenorrhoea and need investigation and treatment. Oml rombin~l fJills t1lso cause hypomenoniwea. Scanty periods may precede menopause.

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pituitary gland initiated d uring pregnancy into the postnatal phase. The excessive stimulation by the gonadotro· pins causes frequent ovulation and menstruation. ln a substantial number of women, associated pelvic pathology, such as PI 0, endometriosis and fibroids, is also encoLuuered. Treaunent should then be directed LO the caLlSe. When no definite caLlSe is identified, u·eaunent with C)•clic honnone therap) restOres the nonnal menstrual pattem.

METRORRHAGIA The preferred tenn 'intennensu·ual bleeding' is used LOdefine any acyclic bleeding from tJ1e genital tract. ln su·ict terms, the term should be rcsu·icted LO bleeding atising from the uterus only. The bleeding may be imennittem or continuot.lS. It is superimposed o n a norm al mensu·ual cycle. lnterme nsu·ua l bleeding may be physiological, occ urring at the ti me of ovula ti on when horm o na l changes u·iggering ovulati on take p lace. T hese women complain of midmenstrual bleeding (Miue lsc hm erz) l a~ti ng from a few ho urs to l da)', a profuse sticky discharge and ime nn ittent cramping pain of short duration. These episodes coinc ide wiili ovulation, and this fact can be confi rmed by ba.'\al bod)' temperature (BBT) charts/ sonograp hy. All that is req ui red is to provide an explanation to tJ1e patientofthe underlying cat.lSe and alleviate her anxiet)'· 1\ fnv 1rumths of combined oral jJills will cure ovulfllion bleed. Particular!) in elder!) women, postcoital bleeding should not be bt"LlShed aside lightl). It ma) be the earliest sympwm of a neoplasm; a meticulous search should be instituted LO exclude such a possibilit). Besides a tJwrough clinical examination of tJ1e lower genital u-act, speculum examination of ilie cen·ix in good light for a pol)p, vascular erosion, endocervicitis, cancer of the cen ix and ilie presence of an l UCD should be looked for, along with lower genital tract ulcers and growths. A Pap l711f'(lr l'xamintJiiQn should be ol>tained. A diagnostic h)Steroscopy and an endomeu·ial curettage for histological study of tJ1e endometrial tissue a•·e importanL A pelvic sonog•-aphy to evaluate the pelvic organs is recommended. Refer to Table I 0. 1 for a brief summ ary of the types of uterine bleeding.

POLYMENORRHOEA OR EPIMENORRHOEA Women with polyme no rrhoea (epime no n·hoea) suffer from shorte ned C)'Cies. Meno rrhagia often goes hand in hand witJ1 this comp laint. It is more freq ue nt in ado lescent girls and in perimenopausal women. The exact aetio logy of this problem is not known. In most of these women, the fo llicular phase of the cycle is acce lerated, resul ting in shorter cycles. The ovaries often appear hyperaemic and may contain haemorrhagic follicles. Myohyperplasia of the uterus is a common accompaniment. The lining endomeu·ium is generally of nonnal tJ1ickness; however, in women suffering from pol) menorrhagia, the lining endomeuium may appear thickened. The caLtSe of ovarian overacti,~ty seems to be the result of a disturbed endocrine axis. Pol)lnenorrhagia is frequent!)' observed when women resume menstrual acti,·ity after a delivery. lt is aw·ibuted to the persistence of the activity of ilie anterior lobe of the

Table 10.1

Types of Abnormal Uterine Bleeding

Te rms In Clinical Usage

Menstrual Patte rn

Oligomenorrhoea

Cycle length

>

38 days

Polymenorrhoea

Cycle length


ariety.

DYSMENORRHOEA

DEFINITION Dysmenon·hoea means cramping pain accompanying mensu·ualion.

AETIOLOOY Patients can be classified imo groups for understanding t.he palhogenesis of this distressing condition.

AETIOLOGY OF PAIN (Fig. 10.1) TYPES I.

Spasmodic pain is atuibuted to myom euial conu-act.ions due to ina-eased PGF2a secreted under progesterone elfecL Increased peristaltic action is seen in the subendomeu·ial zone on ulu-asound scan and this ca uses myometrial activity. The pehic venous congestion as recognized o n Doppler ultrasound explains congestive ctysme nord1oea. Reli ef from dysmenorrhoea foll owing cervical di latatio n and vaginal deli vet)' is attributed to da mage to sympa the tic ne tves around the cervix. Vasopressin by increasin g PGF~a sec re Lion in prima t) ' d ysmenorrhoea is a lso he ld responsible. Similarly, endotheli n b)• increas in g PGF~.a conLribuLes to d)•smeno rrhoea.

Priiii{J')' dy~11U!1Wrrlwro n~fers LO

the one that is not associated "1th any iclent.ifiable pelvic patholog)~ It is now clear that lhe pathogenesis of pain is aw·ibuted LO a biochemical det·angement. It affects more than 50% postpubescem women in the age group of 18-25 )'Cars with ovul a to ry cycles. 2. SecondriYy dy~meuorrlwea refers LO the one assoc iated with the presence of o rga ni c pelvic pathology, i.e. fibroids, ade nom )•Osis, PID and endome u·ios is. Un ilateral d ysmenorrhoea occ w'S in a rudimentary ho rn of a bicorn ua te uterus. It is also seen in some women wearing IUC D and in cases of cervical stenosis.

CUNICAL FEATURES (Table 10.2) VARIETIES

Primary dysmenorrhoea is widely prevalent; more than 50% of teenagers and 30%--50% of mens u·uating women suffer from varying degrees of discomforL The severe incapacitating type, which imetferes with a woman's daily activities, affectS only about 5%-15% of Lhe population. Its pre,'•·iad and not associated with organic lesion in the pelvis. T he classic desc•·iption includes increasing breast tenderness, abdomina l bloating, headache, sleeplessness, fatigue, emotional lability, mood swings and depression, it-ritability, fluid retention and weight gain beginning 7-14 days plior to menses. As menstruation approaches, psychological abnorm ali ti es such as irri tability and h ostility increase. T he dom inant symptom in different gro ups varies from anx iety, to depression, 1.0 fluid retention, bloa ting, headache and breast pain, to increased appetite a nd craving for sweet foods. About 5% suffer from seve re sympwms whi ch influence da il y activity. T he body we ight increases b)' I kg and breast vo lum e by 20% d ue to oedema and increased vascu la rity. PMT does not occ ur before pubert)', during pregnanC)' o r afte r me nopause. It may, however, occur if the postmenopausal woman goes on ho•~ mone replacement therapy (1-1 RT).

AETIOLOGY The exact cause of PMS is not known. It has been poswlated that it represents aS) ndrome which is the result of multiple biochemical abnormalities. Amongst these, the following have been implicated: (i) oesu·ogen excess or progesterone deficienc> in the luteal phase; (ii) increased carbohydrate imolerance in the luteal phase; (iii) p)lidoxine deficiencythis vitamin plays a role in oestrogen S)nthesis and also in dopamine and serotonin production; (iv) increased production of vasop•·essin, a ldosterone, prolactin and systemic prostaglandins which adversely affect renal fw1ction and comribute to fluid •·eten lion and bloating; and (v) fluctuations in opiate peptide concentrations affecti ng endorphin levels. Howeve•; biochemical estimati ons do not bear these out. He nce, at present it is not yet clear whether P.MS is an abnormal response to nom1al ho rmonal fluctuation o r a result of hormonal abnormali ties. A w011tan with hysterectom)'

DIAGNOSIS Diagnosis depends on his tO f) and careful questio ning. Temporal con·elation ofs)lnptoms with the premenstrual phase of the cycle as documented in a menstrual diary helps LO arrive at a rational diagnosis. o organic pelvic lesion is detected, and no definite test is available to confinn the diagnosis.

TREATMENT (Table 10.4) • For ps)•chological symptoms (psrchotherapy), counselling and reassw-ance alone suffice for the milder cases. Vitamin B12 5-50 meg, vitamin Br. 100 mg and vitam in E 200 mg daily help PMS cases. • For breast symptoms alone, be ne ficial th erapies include (i) Danazol 100-200 mg in divided doses during the luteal phase. However, adverse mascu li ni zing effect following long-term usage is a d rawback. (ii) GnRH analogues

Table 10.3 Various Symptoms of Premenstrual Tension 1. Pain

Headache, breast pain, abdominal cramps, muscle stiffness, backache, generalized body ache

2. Water retention

Breast pain, bloating, weight gain

3. Behavioural changes

Low per1ormance, difficulty In concentra· tion, Irritability, depression, forgetful· ness, low judgement, anxiety, loneli· ness, feeling like crying

4. Autonomic changes

Dizziness, faintness, nausea, vomiting, hot flushes

Table 1 0.4

Management of Premenstrual Syndrome

Psychosomatic

Vitamins 8 1 , ~. E Selective serotonin reuptake Inhibitor, sertraline, citalopram anxiolytics

Breast pain

Oanazol, bromocriptine GnRH

Pelvic pain and bloated ness

Yasmin, primrose Prostaglandin Inhibitors OC, progestogen Mirena IUCD

CHAPTER I 0 - COMMON DISORDERS OF MENSTRUATION

•

•

•

•

•

•

• • •

provide relief, but long use causes menopausal (antioestrogenic effecLS) S)~npLOms and osteoporosis. Besides, the dntgs are expensive. The following drugs are used: • Goserelin (Zoladex) 3.6 mg subcutaneously, 4 weekly • Leuprore lin acetate (Prostap) 3.75 mg i.m., 4 weekly • ·r.·ipLOre lin (Decapept) l) 3.75 mg i.m., 4 weekly • Busere lin (Suprefact) 20(}-500 meg daily subcutaneous!) three times a da) for 6 months. O estrogen and progestogen as add-back therapy to GnRH prevenlS side effecLS of oesu·ogen deficienq•. • Bromoc.-iptine 0.25-2.5 mg relieves breast tendemess but has side e ffeclS s uch as nausea, diLLiness, weight gain a nd swe lling. For bloateclness, weight gain, fluid retention and headaches (i) salt a nd fluid resui ction and (ii) spi1·onolactones 100 mg and diuretics may help. Buspirin one 7.5-15 mg daily or drospire none may be used. Yasm in con taining 3 mg of spironolactone and 30 meg of EE2, is used cycli· call y as combined oral p ills. Eve nin g p rimrose oil (Pri· mosa) 500 mg t. i.d.; it is no nho rmo nal a nd co n tains po lyunsawra ted esse ntia l fatty ac ids. It dive rts ha rmful PGE2 to PG£ 1 and rep le n ishes CNS PGE1. By this, it s up· presses i11·itab ili t)' and dep ression as well as re duces fl uid re ten tion and mastalgia. Go ld pli m contains Primosa with vitam in and mine rals (six capsules a day). Plmtagl.mulin inhibitor,~ Me fe nam ic ac id and naproxen improve mood and physical symptOms. These drugs cause gastrointestinal (G I) upseLS and rashes. Cyclooxygenase inhibitor (cox-2) has fewe r side effecLS than NSAlD. fbu· pro fen 400 mg 6-8 ho uri) is a lso useful. Anxiol)tics (alpra£olam ) 0.25 mg and antidepressanLS ( L.-i· cycl ics) do pro, ide some re lie ffro m PMS, but the benefilS of the raP> must be weighed against the side effeclS. ')'-Aminobut)I'ic acid (GABA ) suppresses anxiety level in the brain. Therefore, GABA agonislS are effective. Selective sei·otonin re-uptake inhibitOrs (SSRl) such as fluoxetine 20 mg d a ily a nd senraline 50 mg have been beneficial in treating ph)sical as well as behavioural S)1nptoins (60% curative). Th e side e ffecLS include headache, drowsiness, insomni a, sexual dysfunction and G I disturbances. Sertraline 50-150 mg and citalop.-am 20-40 mg dai ly are also use d in the premenstrual phase. Vitamin B6 (60-100 mg) and magnesium (200 mg) are cofactors in tl1e synthesis of neurou·ansmi ue rs serotOnin and dopa· mi ne. One gram calc ium da ily also he lps to re lieve neu ro logica l symp to ms. Ven lafax ine is a co mb inatio n of sertraline a nd norad rena line re u pta ke inh ib itor. Micron ized p rogesterone pessa ry 200-400 mg d aily in the premensu·ua l p hase. M irena IUC D is now used instead of oral progestoge ns. OCs render the cyc les anovu la tory and provide relief. Oesu·ogen skin patc h re leasi ng 100 meg daily or 50 mg oesu-ogen implant witJ1 100-mg testoSterone is also employed. General measures suc h as e xe rcise , relaxation and hob· bies, meditation a nd >oga are likely LO be beneficial.

127

• Hysterectomy witJ1 removal of ova lies is a last resort. ln a younger woman, oophorectomy will need in vitro fertilization (LVF ) programme with donor eggs. • ReassLtrance, counselling, psyc ho therapy and selective use of drugs help to co ntro l t11e S)lnpLOms.

KEY POINTS •

•

•

•

•

•

onnal mensu·uation occurs as a resull of fine coordination between h) pot11alamus, inte1·ior piwitary gland and O\'osis. Premenstrual S) ndmm e is a fun c tional disorder found in eclucated and economicall) well-to·!.'Y· 2003; 15: 169. SpcrofTL, Fritz MA. Clinical Gynecologic EndocrinoiO!,'Y and Infertility. 8th cd. Philadelphia: Lippincou William$ & Wilkin$, 2011: 567.589. Studdj. Progrc.,., in Obstetrics m1d Cymoc,-oiO!,'YVolume 3, 11:189. Usshcr JM, Pcrzj. PMS a. a procc"S:I ofnegoiiat.i on: women '$ experience and management of prcm etutrual distrt"S:~. P.ychol llealth. 20 13; 28(8):900-27. Vigod SN, R LE, Steiner M. Under.uu1dingand treatingprernenstmal dy>phoric di>order: an update for the women"s he-.lith prdtritioner. Ob>tct Cync'Col Oin !\'orth Am. 2009;36(4):907-924, xii.

Abnormal Uterine Bleeding (AUB)

Introduction 128

of Menstrual Bleeding

128

of Abnormal Uterine Bleeding

128

Normal Conlrol

Abnormal Uterine Bleeding in Reproducfive Age and Premenopausal Women 133

lnvesfigations 131

Abnormal Uterine Bleeding in Adolescents 139

Management 131

Key Points 140

Palm-Coein Classi~cation 132

Self-Assessment 140

Causes

INTRODUCTION Mensu·ual irregularities and abnormal heavy mensm1ation accoum for up to 25%-33% of women attending gynaecological outpatient deparunem. Although woman of any age group can be affected with abnormal merine bleeding (AUB). it is more common I) experienced b)' women of 35-'15 >ears of age. It is also commonly seen among young girls soon after attaining menarche. There have been a number of classification systems to classiry causes of AU B but recently lmernauonal federation of g) naecologisLS and obsteuicians has suggested newer classification popula!·ly known as 'PALM-COEI ' classification to define cause of AUB. Further, AUB is divided imo acute and chronic AUB, depending on the duration of the problem persisting in the woman. Chronic AUB is defined as bleeding that isabnonnal in volume, 1·eguladty and/or timing for the past 6 months. It does not usuall y require immediate intervention. Acute AUB is an episode of heavy me nstrual bleeding of sufficient quantity to 1·equire immediate in ten•entio n tO prevent fun.her loss. It ca n be seen \\1th existing chro nic AUB. About 10%-25% of women experience episodes of AUB at so me tim e chu·ing tJ1e reproductive yea rs of tJt eirlives. lt is common during tJ1 e ex u·emes of rep rod uctive life, following pregnancy and d uring lactation. It has been shown that 55.7% ofadolescenLS experie nce abno nnal menstrual bleed· ing in the first year or so after tJ1e onset of menarc he because of the immaturity of tJ1e hypotJlalamic-pitui tary-ovarian {H-P-0) axis leading to anovulatory cycles. It generally takes 18 montl1s to 2 years for regular cydes to be established. It is not uncommon for a premenopausal woman to develop menorrhagia, and tl1 is is often due to anovulatOry cycles in 80% of cases. However, endometrial malignancy should be ruled out before deciding the type of u·eaunenL The term 'd)sfunctional uterine haemoni1age' was specificall) used when meno1-rhagia was not associated ~

with an)' genital u·act abnorma li ties, general or endocrinological diseases. In this case, a ho rmona l imbalance is considered the root cause of hyperp la~ia of the endometrium that causes menorrhagia; this often happens in anovulatory cycles wiLI1 excessive or unopposed influence of oestrogen on the endometrium. This term is now replaced by Abnonnal utel'ine bleeding. ln some cases. abnormal endometrial haemostasis is tl1e cause ofabnonnal excessive bleeding.

NORMAL CONTROL OF MENSTRUAL BLEEDING Once the mensuual bleeding starts, the platelet aggregation fo1·ms dots in the opened vessels. Prostaglandin F2a ( PGF2a) causes myometrial conu-actions and constricts the endometrial vessels. The repair and epithelial regeneration begin on the tl1ird and fourth day of period, by tlte growtl1 of epiL11elial cells from the open e ndomeuial glands aided by tlt e vascular e ndotJ1elial, epidermal and fibroblast growtll factors. In excessive b leedin g with regul ar mensu·ual cycles, the H- P-0 axis is intac t, b ut e ndometrial changes get altered. It is observed tJ1 at, in these cases, PC ~ (p rostacyclin), which is a local vasod ilato t; is increased compared to PGF2a in the endometrial tissue.

CAUSES OF ABNORMAL UTERINE BLEEDING

(TABLE l 1.1) The causes can be di' ided into following: (i) tl1ose due tO general diseases. (ii) those which are local in t11e pelvis, (iii) tJhose caused b) endocrine disorders, (iv) conu-aceptives and('') iatrogenic. The new classification of causes of AUB is shown in Fig' 11.1- 11.1.

To \iew the k-cturc note> :.can the >pnbol or log in to rour account on """·~lcdEnat"t.mm

128

CHAPTER II - ABNORMAL UTERINE BLEEDING {AUBI

Table 11.1

129

Aetiology of Menorrhagia

General Causes

Contraceptive Use

Pelvic Causes

HormonaVAUB

Blood dyscrasia

PID, pelvic adhesions

IUCD

Ovulatory: Irregular ripening or Irregular shedding

Coagulopathy

Uterine fibroids, endometrial hyperplasia Adenomyosis

Posttubal sterilization

Anovulatory: resting endometrium - 80% Metropathia haemorrhagica

Thyroid dysfunction

Feminizing tumour or the ov;ry

Progestogen-only pills

Genital TB

Endometriosis Pelvic congestion, va-icose veins in the pelvis

Coagulopathy

Po lyp

.I Submucosal I 'I Other I

Adenomyosis L eiomyoma Mali gnancy & hyperplasia

Ov ulatory dysfunction Endometrial Iatrogenic

Figure 11.1 Basic FIGO classification system for causes of AUB in th e reproductive years. Th e system Includes four categories that are defined by visu ally obj ective structu ral cri teria (PALM : polyp, adenomyosis, leiomyoma, malignancy or h yperp lasia); four unrelated to structural anomalies (COEI: coag u · lopathy, ovulatory dysfunction , endometrial, Iatrogenic); and one (N) that Includes entitles not yet classified . (Source: From Figure 1. Malcolm G Munro: Obstetrics and Gynecology Oinics. Vol 38(4): 703- 731, 20 11 .)

N ot yet classified

Coagulopathy

Polyp

Ade nomyosis Leiomyoma

Maliglancy & hyperplasia

"\.I v1

0 111Jiaklry dysfunction St.brrucosal

Endome1rial

Other

Iatrogenic Not yet dassified

Leiomyoma subclassification system

3

4

(j\

( 1

2- 5

6

I

5

2

---

SM · Submucosal

0 · Other

--::::;l

0

Pedmc.Aated i ntracaV11ary

1

< 50% Intramural

2 3 4 5 6 7 8

7

Hybrid

leiO"'IOmaS (impact both endometrium and serosa)

~ 50 %

Intramural

Contacts e ndome trium; 100% Intra mural

Intramural Subserosai :.SO% Intramural Subserosa! < 50% Intramural Subserosa! pedunculated Other (specify e.g. cervical, parashlc)

l'Wol'ltll'ltl&f's areletedeepat'atedby 11 t\'lflotn. Bycaweni Ot\ ,,.. hffll M rs IG it'e re&atoneNp\MI\ IN ~'l.fllte floeaeeord rei&rt iO he retlt.onet'lipiO tw.e&roea . ON e.~e~tlliMirl bNow

2-5

SUbmucosalandsuboeiOsal, eachwllh loss than half the diameter In I he endometrial and perhoneal cavhies, "'spectlvely.

Figure 11.2 FIGO classification system Including the leiomyoma subclassification. The classification of leiomyomas categorizes the submucosal (SM) group according to the Wamsteker system 12 and adds categorizations for intramural, sub serosal and transmural lesions. lntracavita-y lesions are attached to the endometrium by a narrow stalk and a-e classified as type 0, whereas types 1 and 2 require that a portion of the lesion is intramural, with type 1 being 50% or less and type 2 more than 50%. Type 3 lesions a-e totally extracavlta-y but albut the endometrium. Type 4 lesions a-e intramuralleiomyomas that a-e entirely within the myometrium with no extension to the endometrial surface or to the serosa. St.bserosal (types 5-7) myomas include type 5, which are more than 50% intramural; type 6, which are 50% or less intramural, and type 7 being attached to the serosa by a stalk. Lesions that a-e transmural a-e categorized by their relationships to both endometrial and serosal surfaces. The endometrial rela· tionship is noted fist, whereas the serosal relationship is second (e.g. type 2-5). An additional category, type 8, Is reserved for myomas that do not relate to the myometrium at all and indude cervical lesions, those that eXist in the round or broad ligaments without a direct attachment to the uterus, and other so-called pa-asitic lesions. (Soutte: From Figue 2. Mak::olm G Munro: Obstetrics cases. The endomeu·ium is destro)ed upto the basal la)er. Fertility is tWI possible Jollmuing abkltit~e themp)'- Therefore, these procedures are mainly suitable for women who wish to preserve the uterus, a'•oid hysterectomy, but are not interested in pregnancy. The method should desu·oy 2-3 mm of myomeuium, if recurrence of menonhagia h as to be avoided. Vatious procedw-es have been dC\•eloped. These are as follows: • First generation- Hysteroscopic endometrial abla tion by resectoscope, loop, rollerball coagulatio n a nd lase r (transcervical endo me u·ial resectio n [TCRE )) • Second genera ti on - Racl iofreq uency-ind uced the rmal ablation, Cavate rm balloo n tJ1e rapy, microwave endometrial ablati on (MEA), lase r the rapy

E E

~

Ta ble 11.3

Figure 11.1 1

Mirena IUCO.

Minimal Surgical Methods of Treating Menorrhagia

Ablative technique First generation Hysteroscopic ablation endometrium resectoscope, roller ball laser (TCRE) Second generation RITEA, balloon therapy, microwave ablation Uterine tamponade In acute bleeding Bilateral uterine artery embolization

CHAPTER 11 - ABNORMAL UTERINE BLEEDING (AUB)

• Utet·ine tamponade • Bilatera l uterine arter-y embolitation Hysteroscopic Endometrial Ablation. These procedures should be performed soon after the mensu·ual pe•·iod or the endometrium is thinned out by giving progestOgens, danaLol or GnRH for 1-6 weeks before the procedure. The patient needs to be selected and contraindications are as noted below: • • • • • • •

Uterine siLe > I2 weeks ( 12 em) (voiLUne > 30 mL) Uterine fibroid Sca•Tecl uterus (previous surgery) Young woman desirous of pregnancy Adenomyosis- TCR£ can cause dysmenorrhoea Geni La l infection Uterine ca ncer or preinvasive cance•~ at)•p ical h)•pe•plas ia

TC RE un der ge ne ra l anaesthesia using hysteroscope desu·oys 4-5 mm e nclomeuium and forms uterine synec hiae. T he ea rli er monopolar e lec trode is rep laced b)' a bipolar eleCLrode (VE RSAPO I NTTM). Complications arc as follows: • Anaesthetic complications. • Fluid imbalance with Auid overload (glycine 1.5%), pulmona•-y oedema, hypertension, hyponatremia, anaphylactic reaction with dexu-an, haemolysis and at times death. • Uterine, bowel and bladder i•'\iury with burns and vaginal fiswla. • Embolism, infection and haemorrhage. • Menorrhagia •·ecurs in 25% cases b)>the end of 3 years and needs repeat TCRE or h)sterectomy. • Dysmenorrhoea in a few women. and haematOmeu-a due to cervical stenosis. Radio frequency-Induced Thermal Endometrial Ablation. lt is a blind procedure using radiofrequency electromagnetic thermal energy which destroys tl1e endometriLUn at 66°C. A 0.6-mm metallic probe is inserted u-anscervically tmder

137

geneml anaesthesia and •·otated over 360° fo•· 20 minutes. About85% get cured and 30% develop amenonhoea by the end of I year. It is cheaper compared to TCRE, does not require hysteroscope and complications of distending media are a'oicled. Conu-aindications and complications are similar to those ofl'CRE. Advantages of RITEA

• Less skill required to perfonn tl1e procedLu·e. Hysteroscopy not required. • Less risk with tl1 is procedure. An occasional uterine perfor-ation, vaginal heat leading to vesicovaginal fiswla has been reported. Cava term Balloon Therapy (Fig. 11.1 2). First invented b)' Ne uwin.h in 1994, this insu·ument comprises a central comp ULer S)'Stem, battery and a disposable silicon rubber balloon cathe te r 5 m m in d ia me ter. Under local anaesthesia, th e catheter is inserted transcervicall y in tO the uterine cavity, and t11e ba ll oon is d is te nded witl1 15-30 mL sterile solution such as 5% glucose o r 1.5% gl)•cine. T he hea ting element in the balloo n raises the temperature to 87°C ( 187°F) and this tempcrawre is maintained for 8 minutes over a pressure of 160-180 mm Hg to exert a tamponade effect. The catheter h as an inherent safety design related to time, pressure and temper-attu·e, and it gets automatically deactivated to avoid complications. About6 mm of endomeu·ium gets clestrO)ed, so preoperative endometrium thinning is not required. Approximately, 70%-90% resume nonnal C)cles ancll5% become amenorrhoeic by the end of I >ear. Hysteroscopy is not required. Failure in retroverted utenLS is due LO unequal distribution of heat over the endometrium. Cramping felt in tl1e first few hour-s is treated with SAIDs and antibiotics are ghen. Conu-aindications are endometrium tl1icker tl1an II mm and others similar LO TCRE. This technique is eas) Lo learn. Microwave Endometrial Ablation. It utilizes magnetic energy and works atLhe frequency of 9.2 GHz. It is an OPD procedure, clone under local anaesthesia. It LLSes an 8 mm

Endometrial lining

A Figure 11.12

B Gavaterm balloon. (A) Balloon inside the uterus. (B) Using the syringe, fluid is Injected through the catheter-inflating balloon.

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SHAW'S TEXTBOOK OF GYNAECOLOGY

app licaLOr witJ1 no need of preoperative endomeu·ial tl1inning. Temperature ofSO•C is maintained for 3 minutes. About 50% become oligomenorrhoeic and 40% amenorrhoeic. Up to 6 mm endometrium gets ablated. No eanl1ing is required unlike TCRE. "Iota! operming time is 12 minutes. Hysteroscop) is also not required. ll1e comraindications and complications are similar LO otJ1er ablative procedures. Vesta System. This system uses a single-use multielecu-ode intraute•·ine balloon to ablate the enclomeu·ium. The silicon inflatable electrode carrier has a triangular shape, which unfolds when its insertion sh ea tJ1 is wimclrawn. The controller unit is connected to a standard electro sm·gical gener-ator. It regulates energy to each balloon elecu·ode plate. The temperature is set at 75•c. The balloon is inflated with air following cervi cal dilatation up tO No 9. T he procedure takes 5 minutes under local anaesthesia. About90%-94% a re cured of menorrhagia. T he instrument is very expensive and suffic ie nt cia ta are no t ava ilable to assess its o utcome. Uterine Tamponade. Go ld rath advocated ute •ine tamponade in ac ute episodes of bleeding b)' inserting a Foley catheter, distending witJ1 30 mL fl uid and leaving Lhe catheter for 24 hours. NovaSure (impedance-conu-ollecl e nclomeu·ial ablation) is t11e latest and most safe procedure, ta!Ungj LISt 90 seconds. It t.ases bipolar radiofrequency and vaporizes endomeuium up to myometrium. Endometrial laser in trauterine 1J1ermotherapy (EUTT) is a new laser tl1e1-ap) that desu·oys t11e en tire e ndome u;um as well as 1-3.5 mm of m)Omeu·ium. It is clone as an OPD p•-ocedure, and mkes 7 minutes. The mad1ine is known by tJ1e name 'G>neLase'. Both touch and non-touch technique can be emplo)ed. The second-genemtion ablative techniques are simpler man TCR£; tl1ey are more effective, safe OPD p•-ocedures; mey are cost-effective and sa'·e h)SterecLOmy in several women. They do not requi•-e p•-e-opemtive p•·eparations, easy to learn and pe1·form quickly without tl1e risk of fluid imbalance. Bilateral Uterine Artery Embolization. P1imarily used in uterine flbroids, tJ1is tec hnique is exte nded in intractable AUB in a yo ung woman to preserve he r reproductive function. It is also useful in AUB co mp licated by varicose uterine vessels.

HYSTERECTOMY Hysterectomy for AUB is req ui•-ed: • If medical/ MIS fails or menorrhagia rec urs. • In older women more than 40 years not desiroLIS of childbearing, and who opt for hyste•-ectOm)' as a primary u·eaunem or ab latio n fails.

Initial!) perfonned b) abdom ina l route, it was replaced b)• laparoscopic h)Ste•·ectomy or laparoscopic-assisted vaginal hyste•-ectomy (LAV H) for its quick recovery, less pain, less abdominal adhesions and avoidance of abdominal scar. Lately, many gynaecologists have shifted LO vaginal

hysterectOmy for undesce nded uterus which may even be enlarged. This trend is adopted because o f lesser morbidity, and lesser postoperalive complications of adhesions, scar hernia and pulmonal') complications. Vaginal h)sterectOm) is co nu-aindicated if: I. Ute nas is gross I) enlarged. 2. PreviOltS surge•') with possible ad hesio ns, fixity and limitation of uterine mobility. 3. Presence of endometriosis or adnexal mass.

Nullipa•-ous women or women wim a very na n·ow vagina. In a woman less than 50 )Cars of age, ovaries should be conserved unl ess tl1 ey a1-e diseased. Sequelae or Delayed Complications of Hysterec:tomy

Altho ugh hysterecwmy is a o ne-tim e procedure, safe and cures AUB, delayed complica tions are kn own to occ ur. T hese are as follows: • Ovari an atrop hy due tO devasculariza tion; the woman develops menopa usal S)•mpto •ns and its co mplications. • Adhesions of the ova ri es to th e vaginal va ult causing a n ovarian res idua l syndrom e, dyspareunia and chronic pelvic pain. • Vault prolapse. • Sext.tal clysfw1ctio n - dyspareunia cl ue to a short ~-agina. • Chronic abdominal pain due to postoperative pelvic adhesions. • Urinary and bowel S)lnptoms clue to denervation. • Psychological disturbances.

NEW SYSTEMS VERSAPO JNTfM bipolar elecu·osurgical S)'Stem works in normal saline, is cheap, has excellent haemostasis and causes instantaneous tissue \'llpo•·i~:ation. Advanmges of Mirena l lJCD over ablative techniques :u·e as follows:

• Low cost • OPD procedu•·e - no h ospitali zation • Prese•'\-ation of ferti li ty after its removal Pregnancy occ urs wi tJ1in a year. The o nl y disadvantage is occasional systemi c side effects of progeswgen.

SUMMARY I. Medical treatm ent sho uld be the first li ne of treatment,

unless con traindicated. The drawbacks are the side effects of hormones a nd Lhe fac t tha t S)•mpwms so metimes return once the hormone the rapy is stopped. A prolonged t11 erapy may not be desirab le. 2. If medical t11erapy fails or is co ntra indicated, consider tvlirena IUCD. 3. If Mirena fails or side effects develop, go for ablative techniques. The second-genemtio n ablative techniques are safer. quick to perform and are eq ually effective. 4. When me abo'e methods fail, consider hysterectomy.

IRREGULAR RIPENING It is an ovulatory bleeding due to deficient co•·pus luteal function. The breakthrough bleeding occurs before the

CHAPTER II - ABNORMAL UTERINE BLEEDING {AUBI

actual menstruation in the form of a spo ttin g or brownish discharge. Progestogen given d urin g the late luteal phase cures the spotting.

IRREGULAR SHEDDING (HALBAN DISEASE) It is rare and self-limited. Irregular shedding is due to persistent corpus luteum. The menstruation comes on Lime, is prolonged but not hea'T· Progeswgen can suppress the bleeding, but needs to be ta ken on a tapering dose for 20 days to complete the cycle.

ADENOMATOUS ENDOMETRIAL POLYP This fonn of polyp is really a locali zed area of endometrial hyperplasia when area or areas of thickened endomeu·ium project into th e cavity of the endometrium to look li ke polyp. T he polyp may be single or multiple, small or large enough to protrude thro ugh the cervical ca nal. Mostly, t11ey are sessile and small. Th is type of poi)'P occurs in fo llowing: • • • •

Endometri al h)•perplasia (a novulawq • C)•cles) Metropathia haemorrhagica (diffuse pol)•posis) A woman on tamoxifen Some cases of fibroid

PATHOLOGY A pol)p is covered b) cubical epitheli um and contains e ndometrial glands that do not respond 10 hormo nes.

CUNICAL FEATURES These pol) pi cause menorrhagia, metront1agia or postmenopausal bleeding. The uterus is nonnal in size or slighlly enlarged un ifonnly. Ultrasound, sonosalpingography and h)'Sterosalpingography detect these pol)pi, but may miss them, if they are very small. Hysteroscopic visualization and •·esection is the best treatment, and h)Sterecwmy can be avoided. Histopathology is mandatory to rule out a tnalignant change. Adenomromatous polyp resembles aden omatot.tS polyp, but it contains muscle tissue in the stroma. The symptoms and management are similar in both conditio ns.

139

however, has th e tendency to deve lop into carcino ma in as much as 60%-70% cases. While 80% cases of simple h)'perplasia wi thout atypia respond to progestogens, response of atypical hyperplasia is only 50%. but with the risk of malignancy. For this reaso n, atypical endometrial h) perplasia should be treated by h)'SlereCLomy and not merel) b) an ablative tedlnique. A small portion of endometrium left behind and undergoing malignancy may not be easily detected follo\\ing ablative u·eaunenL Surprningly, Mirena i~ not iff1'clitlt' against e1ulometrial hyperplalia wused b)' tamoxif('ll.

ABNORMAL UTERINE BLEEDING IN ADOLESCENTS The comm onest cause lies in the H- P-0 dysfunction (50%) . Immatu re develop ment of these orga ns resultS in anovulation in t11e 1-5 years following menarche, unopposed estrogen causing endo metria l h)•perplasia. As t11e girl matures, the normal mens u·ual C)•Cies a re estab lished. • Blood d)•scrasia- Coagu laLion disorders, thrombocytOpenia pt.u·pura, Von Wi lleb rand disease, leukaemia acco unt for 20% of cases. • Hypothyroidism- 4% of cases. • PCOO - 10%-12% of cases. • Genital tuberculosis- 4% of cases. • Liver disorders. • Feminizing ovarian tumours - granulosa cell a nd t11eca cell tumours. • Adrenal h) perplasia.

CUNICAL FEATURES Menontlagia may be noticed from t11e start of menarche, but often the initial C)cles may be nonnal. It takes t11e fonn of heavy regular C)cles, or normal bleeding lasti ng for several days, but d)smenorrhoea is invariably absent in a novulal.OI')' crcles. Anaemia may supervene. T he pelvic findings by ulu-asound scanning are normal except in ovati an tumolll: It is important to rule out other causes of menorrhagia before instituting hormonal therapy.

ENDOMETRIAL HYPERPLASIA

INVESTIGATIONS

This occurs in following cases:

• Blood profile- li b%, bleeding and clotti ng ti me, coagulation fac to rs; b lood fi lm. • X-ray chest fo r tube rculosis. • Thyroid function testS. • Pe lvic ultrasound to n de ouL PCOO, early fibroid. • If medical u·eaU11ent fails, O&C sho uld be done to ru le o ut endometrial tuberc ulosis by PCR tes t

• Anovu latOt)' C)'Cies with un opposed oesu·ogen acting on th e endome u·ium • Metropathia haemorrhagica • Obese women • PCOO • A woman on tamoxifen • A menopausal woman on hormo ne replacement Ll1erap) without progestogen • Feminit.ing ovarian tumours H)petplasia ma) be simple h)perplasia, glandular or atypical. Two per cent women with simple h)pe•·plasia are at a risk of endometrial cancer, and lo/o- 10% women will1 glandular h) pe•plasia de,elop the cance•: Atypical hyperplasia,

MANAGEMENT Aim is to:

• • • •

Conu·ol menon·hagia. Prevent or treat anaemia. Prevent recu•·rence. Treat the cause.

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• Anovulatory cycles • In an acute episode of bleeding, i.v. Premarin 25 mg 6-8 h ourly will control bleeding in 24-48 hours. Thereafter, oestrogen for 21 days with progestogen added for 10 da)S for H C) des "ill •·egulari.t:e the C)cles. • In chro ni c menorrhagia, oral combined pills or cyclical progestogen is the first line of treaunenL About 70%-80% responds well. Medical u·eaunem is detailed below. • SA1Ds: Mefenam ic acid 250-500 mg t.i.d during periocl~. Naproxen, ibuprofe n. • Androgens (dana:t.ol) are not recommended, though effective, because o f androgenic effects in yo t.mg girls. • Gn RJ-1 the rap)' ta kes 4 weeks to act, so not useft.tl in acute episode. The drug is expe nsive and a prolonged treatmem more than 4-6 months can cause osteoporosis. • If progestogens cause side effects, Mirena l UCD for a few momhs ca n co ntrol menorrhagia. • Ane ria l e mbo li:t.a ti on is requi red in case of varicosity of ute rin e vessels. • Whe n th e above u·eaun e nts fail, ute rine tamponade using Foley cath eter fo r 24 ho urs can con u·ol bleeding in th e acute episode. • Anti-TB trea tme nt in endometrial tuberc ul osis. Blood u-ansfusion may be required to correct anaemia. Lately, the trend is to give intravenous tranexam ic acid I g with 25 mg of oesu·ogen , and then continue with oestrogen and progesterone as mentioned above. Desmopressin analogue of a•·ginine vasop•·essin is given intravenously or by a nasal sp•-ay ( 1.5 mg/ mL- total l 50-300mcg diluted in 30mL saline) in \'lin Willebrand S) ndrome. Tranexamic acid inhibits tissue plas minogen activator which is a fibrinol) tic enL) me, whose level increases in AUB.

KEY POINTS • AUB ma) be due to general systemic causes, local pelvic patholog) such as fibroid, adenomyosis, endometrial pOI)p, PI D, fe miniL.ing ovalian tumot.u·s and pelvic e ndo me uiosis. • T he manageme nt of AUB is based on th e age of the woman and her parit)', and th e cause. • Medical the rapy co mprising va ti o us hormo nes and drugs sho uld be e mp loyed in youn g wo men as the first line of treatment. Whe n this fai ls, Mire na, conservative minimal surge•)' or hysterectomy should be co nsidered. • Medical th erapy is effective and is the first-line treatment. Some, howeve1; develop side effects with a prolonged the•-apy; Mirena IUD is the next choice. • Mirena is a nonslll-gical effective method to comrol menorrhagia, and may h elp avoid h)Sterectomy in many women. Abla li\ e therapy was popular in the pasL H)Sterectomy is the last choice in AUB. • In perimenopausal women, D&C is mandatory to rule out malignanc). lfhistOIOg) is benign, either honnonal the•-ap), t.lirena o•· hrste rectom) wi ll be required. • HySLerectOm) can be don e b) alxlominal, vagi nal route or laparoscopic h)Sterectom). f.ndomeuial hyperplasia ma) be simple or glandular without atypia

whose malignant potential is low. It can be treated conservatively with honnones or minimal invasive procedures. • At)pical endometrial h)perplasia has 28%-30% 1isk of malignancy and should be managed by hysterectom)~

SElf-ASSESSMENT l. Enumerate the catL.Ses of AUB. 2. How wo uld you investigate and manage a case of AUB. Define AUB. How would yo u manage an adolescem witl1 AUB? 3. Desc tibe t11 e alte rnatives of minimally invasive surgery in the manage me nt of AUB. 4. Disc us.~ the med ical manageme nt of AUBin a 35-)•ear-old woman. 5. Desc ribe puben y menorrh agia and its management. 6. A 38-year-old wom an presents witJ1 polymenorrhagia. T he uterus is 12 wee ks size. Disc uss tl1 e management. 7. Write shon no tes o n tJ1 e following: • Me u·opatJ1ia hae morrhagia • Endomeu·ial hyperplasia

SUGGESTED READING Aberd een Endome1rial Ablation Trial> Group. A r-mdom.ized trial of endomelrial ablaJ.ion \CI'>U~ h)Mcr~-cJomy for 1he Jreatmem of dysfunctional uJerine bleeding: ouJcomc of four )ia in premcnopau>dl women with abnormal ulrine bleeding. Am J Ob>rcr c,.,~-col 1999:181 (S) :585. Rhrouf ~1 . Terr.L> R. Dial-,'llO>i> and .\l.tnagcmcnt of Fonnerly Called "Dysfunctional L'tcrinc Bk-cding· According LO PAL.\1-COEJ!'\ FICO Classifiettion and 1hc 1\cw Guidclintct Ctnaccol India. 20 14 ;64 (6) :388-93. Rouide$ PA , Phatak PO , Burkart P. ct al. Gynecological and obstetrical morbidity in women with typc~l •on Willcbrand di>ea,.,c: Resui LS of patiem sun·cy. tl cmophilia 2000:6(6) :643. Laberge P, Leyland N, Mwji A, F'onin C, Martyn P, Vilo> C, ct al. Endomclrial ablation in ehc management of abnonnal u1crinc bleeding. J ObsiCI Cyn ac in Abnonnal L'rerine Bleeding and ~ledical ~lanagemenr. 2000:14. S1uddj , Seang Lin Tan, Fr.mk A Chencnak. Progress in Obsreuicsand C, naecology. ~n RE~A 2005;16:!189. Studdj, Se-'.tng Lin T.m, Frank A Chenenak. Progress in Obsteuicsand Cynaecolog). ~linim:~ lm·"->i•c Surge!') 2006:1i:259. \ '!los CA, Ture-'mu V, Garcia ~I . Abu·Rafea B. The k·\Onorgt:strd inlf".tuterine ~)-stetn ~ an cfTt-"Cti\C t~atmcnt in women v.ith abnonnal uterine bleeding:md anticoal-,'\tlamther.tp).j Minim lmasin: C)necol. 2009; 16(4):48().4.

Primary and Secondary Amenorrho ea

Amenorrhoea 141

Primary Amenorrhoea 141 Secondory Amenorrhoea 146

Key Points 153 Self-Assessment 154

AMENORRHOEA The initiation of mensu-uation is an imponant milestOne in the reproductive lives of women. Ameno•·rhoea denotes the absence of menstruation. It ma) be ph)'siolbgical or patholbgictll. Its onset may be pri"wry or seco11dar)'. Plr;•swlogical tmterUJrr/UJe(l nawrall) prevails before the onset of puberty, dt.tring pregnancy and lactation and after menopause. Pathological tlmeJwrrhtie(l is th e result of gene tic factors, systemi c diseases, endoc rin opathies, diswrbance of the h)'PO tha la mic-pituitary-ova rian-t tterine ax is, gynatresia, nuu·itional factors, drug usage, psychological factOrs and other •·arer causes. Primary tmwwrrhoea refers to the failure of the onset of menstmation be)ond the age of 16 )ears, regardless of de,-eJopment of secondary sexual charactet'S. Seco11tlary amnwrrhow1 refers to the faillU·e of occurrence of menstruation for 6 momhs or longer in women who have previously menstruated. Normally, menarche occurs between 10-16 years of age, with a mean age of 12.5 years.

PRIMARY AMENORRHOEA Prima•-y amenorrhoea at the age of 11 years behoves the clinician to unden.ake investigations for the cause of failur~ of occurrence, and institute a timely therapy. Howeve•·, 111 the presence of well- 40 mlU/mL), e ugonadou·opic or hypogonadotropic (Tahl e 12. 1).

HYPERGONADOTROPIC PRIMARY AMENORRHOEA • Gonadal dysgenesis: 450X (Tumer S)ndrome) mosaics, abnormal X. • 46XX pure gonadal dysgenesis. • 46XY gonadal dysgenesis - Swyer S)ndrome, testicular femini:ting S)'lldrome. Savage • Gonadou·opin-resistant ova•-y syndrome sy ndrome. EUGONADOTROPIC PRIMARY AMENORRHOEA A. Absence of Mt~tl l erian development: • Androgen insensitivity syndrome (testicular feminization).

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Table 12.1

Classification of Primary Amenorrhoea

Secondary sexual characteristics normal Imperforate hymen • Transverse vaginal septum • Absent vagina and functioning uterus • Absent vagina and nonfunctioning uterus (Mayer- Rokitansky- KUster- Hauser syndrome [MRKH]) • XY female - androgen insensit ivity • Resistant ovary syndrome • Constitutional delay Secondary sexual characteristics absent Normal stature Hypogonadotrophic hypogonadism Congenital Isolated gonadotrophin-releasing hormone defiCiency Olfacto-genital syndrome Aoquired Weight loss/anorexia Excessive exercise Hyperprolactinaemia Hypergonadotrophic hypogonadism Gonadal agenesis Chromosomal aberrations resulting from XX· agenesis Gonadal dysgenesis Turner mosaic Other X deletions or mosaics XY enzymatic failure Ov a"ian failure Galactosaemia Short stature Hypogonadotrophic hypogonadism Congenital Hydrocephalus Acquired Trauma Empty sella syndrome • Tumours Hypergonadotrophic hypogonadism Turner syndrome Other X deletions or mosaics Heterosexual development Congenital adrenal hyperplasia Androgen-secreting tumour Sa-reductase deficiency Pa'tial androgen receptor deficiency • True hermaphrodite • Absent M Ollerian inhi bit or

B.

C. D. £.

• M Clile rian agenesis- th e abse nce o f ute rus/vagina. Ro kita nsky-KCISter-Hauser synd ro me. ormal Mf1lle rian development: • Female o r true intersex. • Po l)C)'Sti c ovar y sp 1dro me. • Adrenal or thyroid diseases. C.)'ptomenoni1oea - imperforate hymen, vaginal septum, cervica l atresia. Tube rcular e ndometritis. Constitlllional delay- nuu·ition.

HYPOGONADOTROPIC PRIMARY AMENORRHOEA A. Hypothalam ic causes: • De layed menarche and puberty.

• l-l) pOth alamic hypogonadism (Kallma nn S) ndrome); gonadou·opin-releasing hormone (GnRII ) d eficie ncy S) ndrome. • Ps)ch ogeni c causes, weight loss, stress, anore xi a nervosa and maln utrition. B. Pituita•)' ca uses: • t>i tuitarism causes short statw·e, obesity, genital dr->uuph)\ menta l reta rdation, pol)•dactyly and retini tis pigmemosa. • Neoplasms - prolac tinomas, cra niopharyngiomas, ade no mas and empty sella tu rcica. • Hypopituita •)' StateS- Simmond disease, Chiari-Fromme l S) ndrome, Forbes-Albright syndrome and pineal gland tumour. C. Severe S)'Stemic diseases sud1 as tuberculosis, S) ph ilis. D. Other e ndoc•·inal disorders - th)l·oid o r adre na l gland.

AETIOLOGY According to the location of cause of ame no rrl1oea aetiology is as follows: • De layed pubert)'· • Pregnancy before menarche is exu·emel)' rare, b ut not impossible. • Ce re bral co n e x - stress, emo tional disturbances, infection . tra uma, tumo ur. • H) pothalamus- Kallmann syndro me.' igo rotiS exe rcise , weight loss. • Piwitary gla nd - empty sella turcica, Frohlich S) ndrome, Laurence-Moon-Biedl syndrome, Cushing disease, pineal tum our, prolactinaemia, galactosaemi a. • Oval)' - Turner syndrome, primat)' ova ri an failu re (Savage syndrome), polycysti c ovarian disease (PCOD), 17-hyd rox)•lase defic iency. • Gen ital u·act- abse m uterus, (Ma)•ei'-Rokitansky-Kusterl-la\ISe r [MRKH] syndrome. Testicular fe minizing syndrome), refractOry endometriLtm, obstructio n in the lower ge nital tract, ge nital tuberculosis, Ashe rman syndrome (uterine adhesion) . • Chro moso mal - ime rsex, Turner S) ndro me, testicular femini1.ing S) ndrome, Swyer S) nd•·ome. • Other endoc•ine glands - juvenile di abetes, thyroid, adre nal glands. • Drugs- u-a nquillizer·s, antihypertensives, antidepressantS, metoclopramide, oesu·ogen. • Nuuition- overweight, weight loss, tuberculosis, malnuuition.

ANOREXIA NERVOSA Anorexia nerv0.5ergonOllotropic jJrinwry ammorrh()('a patim!S have gonadal

failtt1'11. Various fonllS of gonadal dysgenesis account for t11ese cases. These women h ave streak ovati es with the absence of ovarian follicles, there is no oestrogen production and they have eleva ted levels of FSH (>40 m iU/mL) and low oesu·ad io l levels (< 25 pg/ mL ). T he sexual developme nt is prep ube rtal with no endometrial proliferation; lumce, the fJroge:.teroue clwllfnf,re II'St is 11egative. Chromosome studies reveal 45XO chro mosomes (Turner sy ndrome) . Some pa ti e nts wi tJ1 mosaicism or minor su·ucLUral abnorma li ties of the X chrom oso me ma)' have a few functional fo llicles capable of inducing menstn.tation, stray ov ulation and pregnancy. Cluvmruome ~tudy is rPlruant. Gonadectomy is indicated in patientS with testicular femini.ling syndrome, as these male go nads are prone to malignancy. Intersex is discussed in Chapter 9. Women with streak ovaries are infertile, but tl1ey can bear children with OOC) te donation. All women in tl1is group must be treated with C)clic oesu·ogen and progestogen to promote feminialtion and secondat) sexual characterisLics and prevent osteoporosis. Women with resistant ov:uian srndrome have nonnal ov:uies on histology, tlley show the presence of pt·imordial follicles, but there is probably a deficiency of receptors for FSH. They are not amenable to u·eaunenL

Savage syndrome is due to a receptor defect of gonadotropic hormones in ovaries, and resembles autoimm une disease and resistant ovary S) ndrome. The height is normal, ovaries com:Lin follicles but serum FSH is raised.

EUGONADOTROPIC PRIMARY AMENORRHOEA l ftlle FSH levels are within a normal range, t11e women have nonnal breast development; but due to abnonnal Mullet;:m development, tlle ULentS may be ntdimemat)' or absem because of insetlSiti,'ity to androge tlS. ln women witll testicular feminia~Lion syndrome, the phenotype is a female with a kat)Otype of 46XY chromosomes. The gonads are testes often present in the inguinal canal and produce testosterone and Mullerian-inhibiting factor, but because of androgen insensitivity at tat·get ot·gans (due to deficiem andt·ogen receptors or lack of enzymes to convert testostero ne to th e mo re active dihydrotesLOstero ne) tl1ese patients present witJ1 lack of axillary h air and pubic hair, absent ute ms and upper vagina. T hey h ave a blind pouch of the lower vagina. Breast develop ment appears normal because of peripheral co nve rsion of a ndroge n to oestrogen. T hese gonads a re prone to maligna ncy; therefore, as soon as full sex ual deve lopmen t is ac hieved b)' the age of 18-20 years, a prop hylactic gonadec tomy sho uld be advised, followed by oesu·ogen tJ1 erapy to maintain feminization. A vaginoplasty may be contemp lated at an appropriate Lime in the future. On t11e contrruy, women witJ1 simple MCtllerian agenesis and a kaf)'Otype of 46XX present witJ1 normal secondary sexual cl1aracters and functional O\-aries (RokitaJlSky syndrome). Tl'le) reveal a normal hormone profile. l11issp1drome is associated with renal and skeletal abnonnal ity in 30% of tlle cases. l11ese women do ovulate, and appropriate managemem requires a-eation of a functional vagina for coital putposes. If tlley plan to have children, it may be through sw-rogacy. ln women with Ct)ptomenot·rhoea presenting as pt·imaJ)' ;unenorrhoea, tlle common cattSe is an intact hymen or vagina l septum. A histOt)' of cyclic abdominal colicky pain, retention of urine, tl1e presence of a palpable abdominal lump a11d t11e visualia~Lion of a tense bluish bulging membrane on separation of tl1e labia enables the diagnosis. Ultrasotmd scan ofthe pelvis confirms it. A simple cntciate incision ofthe hymen permits free drainage of t11e collected mensm.tal blood and leads to a normal reproductive functi on. Septate vagina or a u·esia vagina req uires excisio n and vaginoplas ty. T he vagina l septum is recognized from the im perforate hymen by a pinkish concave cove ring in co mrast to the b lu is h convex bulge in the Iauer. The vaginal sep u.un , i.e. atres ia, requires more ex tensive dissection and vaginop lasty. T he atresia in tl1 e upper vagina and cervix often restenosis after surgery a11d eventually requ ires hyste rectOmy. • Polycystic disease is desctibecl in the chapter on Ovarian Ttunours. • 17-hydroxrlase deficienC) cattSes deficiem cortisol secreLion and raised levels of adrenocorticotropic honnone. This cattSes h) pertellSion, h) pernatraemia, hypokalaemia and ;unenot·rhoea. • Endomeu·ial nonresponsiveness and amenorrhoea are due to absent hormonal t·eceptors. Honnonal profile remains normal. • Tubercular endometritis requires anti-T B treaunenL

CHAPTER 12 - PRIMARY AND SECONDARY AMENORRHOEA

NUTRITION Excessive we ight, anorexia ne rvosa a nd maln utrition with loss of we ight are also respo nsible fo r ame no n·hoea in yo ung gi rls. The most common ca use o f h) po thalamic dysfunclion is re lated to ps) choge nic effects, a nore xia ne rvosa, we iglu loss and inapprop riate secretio n of neurotransmine rs leading LO Jack o fCnRH S) nthesis (Kallmann S) ndro me) . Wo men with Kalbnann S) ndrome manifest isolated d eficiency of CnRH associated witll olfactory dysfunction and a nosmia . Pituita ry fa ilure generally follows hypopituitarism, neoplasms or empty sella turcica. Skull radiogra phy or preferabl y MRI, estima ti on of prolactin levels and ophtl1almic evaluation of the fields of vision help to arrive at a diagnosis. Fn:ihlich syndrome consists of short stature, Jet11argy, obesity, genital dystroph y a nd amenoni1oea. In La urenceMoon-Biedl syndro me, polydactyly, retinitis pigmen tosa and mental defici e ncy are the additi o nal featur-es. In all such wo men , C)'Ciic ad ministra ti o n of oestrogen and p rogestogen to mainta in fe mininity and preve nt osteoporosis is essenti al. In case tlle woman desires LO conceive, induCLio n of ovul ati o n with gonadotropins is warranted. In wome n with neoplas ms, app rop ria te ne urological consul ta tion fo llowed by treaun e nt with b romoc rip tine for prolacti nomas or surge r)' sho uld be pla nned.

HYPOGONADOTROPtC PRIMARY AMENORRHOEA l11ese women have FSH level less than 40 mlU/ mL Hypogonadotropinaemia leading LO h}p ogonadism is usually t11e result of h)-pothalamic d) function, pitui tary failure o r systemic illnesses. Administration of GnRH helps to differentiate hypotllalamic dysftulction from pi LUi tal) failu re. In t11e latte•·, GnRH stimulation will not raise LuteiniLing Honno ne (LH ) level. Empty sella turcica is characte JiLed by he.-njalion of subarachnoid membrane into t11e pituita•) ' sella wrcica and may exist with pineal gland tumour as prolactin adenoma. The absence of pituitary gland causes absence or low level of FSH and LH. Gonadotro pin honnone t11erapy is required. OTHER HORMONAL DYSFUNCTIONS Both hypot11y•u idism (c•-etinism) and hype•·tl1y•u idism can cause amenon·hoea. Congeni ta l ach-enal hype•·plasia an d tumour are also respo nsible fo r pri mary ame norrhoea, so also j uven ile diabe tes. Prematw-e ovari an fa ilure seen in I% of the cases is clue to poor germ cell migrati on fro m t11 e yolk sac dUJing fetal development or d ue to an acce lerated rate of depletion (apop tosis) of unkn own reaso n. In t11i s co nditio n, FSH leve l is more t11an tiO miU/ mL, and E2 level is below 20 pg/ mL KaryoL)'ping is req ui red. T he woman prese ntS me nopausal S)'mp toms. She needs hormo ne r-e placemem tll erapy (HRT) .

(

Primary A menorrhoea

)

Absence of menses by 14yr with normal pubertal changes

~ Examination of girl height, weight, breast, pubic & axillary hair

~

~ Short height Poor breast development

Normal height Normal weight Normal breast

• Tall/Normal height • Features of hirsutism

~

~

~

Look for presence of vagina

O varian Dysgenesis (Turner's syndrome) 45XO/Mosaic

Investigate for : • Androgen Insensitivity syndrome • Polycystic ova ries

• Absent uterus • Non canalised vagin a

Mullerian Agenes is

145

Uterus presen 1 Vaginal patent

Asherman Syndrome (Normal FSHILH) Or Ovarian Dysgenesis (Raised FSHILH)

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SHAW'S TEXTBOOK OF GYNAECOLOGY

SUMMARY

AETIOLOGY (Fig. 12.3)

MCtllerian agenesis: Absenl/blincl vagina, normal breastS, normal FSH/ U I. Ashennan S) ndrome: ormal uterus, nonnal vagina, nonnal FSI-I/ Ll-1 but fail to have withdrawal bleeding wil.h oesu-ogen + progesterone. Ovarian d)sgenesis: o rmal/s hon heiglu, poor breast d evelopmem , raised FSI I/ LH, ka•)Otype abnonnality. Androgen insensith·ity S) ndrome: Tall, nonnal breastS, blind vagina, absent Ulems, 26XY pattem. PCOD: Obese, hi rsutism, n ormal FSH/ LH, increased LH.

Many causes are similar to those of p•imary amenorrhoea. However. the emphasis is so mewhat different. Dysfunction of the h)pothalamic-pilllital") - Ova ria n-uterine axis accotuus for the majorit) of cases of pathological secondary a me no n"hoea. The catLSes can be classified as follows: • Physiological

I. Pregnancy 2. Lactation • Pathological

SECONDARY AMENORRHOEA

I. Genital u-act

Secondary ameno rrhoea is clefinecl as amenorrhoea of 6 months or more in a woman with previous normal menstrual paue rns in the absence of p regna ncy a nd lactation (2%-3% women). However, in cli nical practice, pa ti e nts seek advice earlier and it is prudent to begin with s im pler investigations and reassurance and awa it the outcome.

(

• Acquired obsu·ucti on (gynatresia) of cervical canal causing severe stenosis or atresia follows elecu·ocauterization, che mi cal burns, ce rvi cal amputation in a Fothergi ll repair opc•·atio n, co ni zation for cervical dysplasia or ce rvi cal inu·aep ith elial neoplasia (CIN) and genitalwbercul osis. • Vaginal au-esia due to scam ng following a u-aum atic delivery.

Causes of amenorrhoea

i

)

Critical and external stimulus

( Chromosome )1------•t~•l

Hypothalamus (GnRH deficiency)

Portal vessls

Anterior pituitary gland

Endocrine gland

• Environmental factions • Nutrition

Adrenal diabetes thyroid

Ovary • Turner's syndrome • Swyer syndrome • PCOD • Primary CNarian failure

Absent uterus • Mayer-Rokitansky-Kuster syndrome

Normal uterus (Refractory endometrium tuberculosis) Figure 12.3 causes of amenorrhoea.

Obstruct • Imperforate hymen • Absent vagina • Atresia cervix

CHAPTER i 2 - PRIMARY AND SECONDARY AMENORRHOEA

• Ashe rman sy ndrome followin g excessive curettage, uterine infec tion o r endomeu·ial tuberc ulosis, transcervical resectio n o f endo metri tun for abnormal ute line bleeding (see Ch apter 21 ) and uterine packing in postpa rtum hae mo rrhage. • Vesicovaginal flswla - ca1l.Se unknown. 2. Ova rian causes • Surgical extirpation. • Radi othem py. • Autoimmune d isease (th) roid, diabetes). • Inducti on of mul tiple ovulation in infertility leading to premawre menopause. • PCOD. • Resistant ovalian syndrome - due to absent FSH receptors. • Infecti o ns- mumps, wberculosis, and in rare cases, pyogeni c infections. • Masc uli nizing ovarian w mour'S. • Pre ma ture menopa use p rematu re ovarian fa ilure . 3. NutriLi onal ca uses • Ano rexia ne rvosa, bulimia (Fig. 12. 1) . • Ex u·eme obesity. • Excessive weiglll loss in athletes and ballet dan cers. 4. Pituitary causes (Figs 12. 1- 12. 9) • Insuffi cie ncy as in Simmo nd disease, Shee han sy ndrome .

Figure 12.6 X-ray of pitui tary fossa showing extreme bone expansion due to pituitary tum our.

Rgure 12.4 Acromegaly. Note the broad enlargement of t he nose and coarse facies. (Source: Wlklmedla commons.)

Rgure 12.5 Gigantism. Child aged 1 yeac, measuring more than 3 feet in height.

147

Figure 12.7 FrOhlich syndrome.

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SHAW'S TEXTBOOK OF GYNAECOLOGY

Figure 12.9 Cushing syndrome. Note hirsutism of face, obesity and striae.

Figure 12.8 Pituitary infantilism, patient aged 17 years. Note obesity, aplasia of breasts, absence of pubic hair and short stature.

• Re na l disease - d ue LO red uced exc re ti on of LH and prolac ti n. • Severe anaem ia, maln utrilion. • ldiopatl1ic, genetic.

RESISTANT OVARIAN SYNDROME

5.

6.

7.

8.

• 1-l)perprolaclinaemia. • Tumours such as prolactinomas and chromophobe adenomas and Cushing disease. • Empty sella syndrome. • Drugs - tranquillizers, oral co ntraceptive (OC) pills, metoclopramide, dopamine blockers, antihype nensives, antidepres.\>ants, cimelidine and p henothi azine. Hypothalamus. • Gn RH deficiency. • Vigorous exercise -stress, obesity. • Pseudocresis. • Brain tumours. • Ano•·exia nerYosa. u prare nal causes • Addison disease. • Adrenogenital syndrome. • Suprarenal tumour. Thyroid • 1-1 )'pothyroidism, chest wa ll lesions. • Graves d isease. O ther ca uses • Diabetes. • Tuberculosis- li ver disease.

In resistant O\' in gonadoblastoma induction in 46. XV indi,iduals. The Lemen experience in 46, >.'Y pure gonadal d)~gcnc.i> and testia•lar fcminit~uion >)1>dromes. Genet Couns 1991; 2:9. Martin KA, llaii.JE, Adams J~f. Cro"·lcy WF Jr. Comparison of exogenow. gonadotropins and pulsatile gonadot ropin-rde-~sing hormon e for induction of ovulation in hypogonadotropic amcnorrl1e-a.j Clin Enderinol Metab 1993; 77:125. Pr.tctice Com mittee of the American Society for Reproductive Medicine. Current evaluation of amenorrhea. Fcrtil Steoil 2006; 86:S 148. Rein dollar Rl I, Byrd .JR, McDonough PC. Delayed sexual d evelopment.: a study of252 patien ts. Amj ObstetGynL-col l 98 1; 140:371. Samoro N, Filicori ~r. Crowley WF Jr. llypogonadotropic disorders in men and women: diagnosis and therapy "ith pubatilc gonadotropinrclca.ing hormone. J!:ndocr Rev 1986: 7: I I. Treloar AE, Bo)nton R£, Benn BG, et al. Variation of the human menstnoalc)clc through reproducri,·e life. lntJ Fertill967;12(1):77-126. Tnoncll EP. Tumer CW, Ka)e WR. A comparison of the ps)chological and hom10nal factOrs in women "it.h and without premenstmal syndromc.J Abnonn P~)'Choll988;97:429-36. Warren MP. The effeet of e xercise on pubertal progre>sion and reproductive function in girls.] Clin J!:ndocrinol Me tab 1980;51: 1150-57. Weiss Mil , Teal I, Con P, et al. Natuml history of microprolactinornas: Six year follow-up. 1c urosurgery 1983; 12: 180-83.

Fibroid Uterus

Fibromyomas 155 Endometria l Polyps 172

Key Points 173 Sell-Assessment 173

FIBROMYOMAS Fibrom)'Omas (leiomyoma, fibroma, fi bro ids) are th e co mmonest benign neop lasm arising from uterus. T hey are common!)' seen in women of rep rod uctive age, incidence varies from 5%-20% of women depend ing upon age group. They tend to be mul t.ip le in numbers. Size may vary from peanut size to often as big as size of a head of a newborn. Small fibroids may be palpable only on vaginal examination. but once uterus is enlarged, they may become palpable per abdomen. All fibroids begin in myometrium but some ma) grow more towards endomeLrial ca,~ty (submucous type). or others ma) grow tOwards Lhe serosal surface of uLen.tS (subserotLS t)pe). However, most. Lend 1.0 remain in m)omet.-iwn (interst.itialt)pe). Fibrom)omas (leiomyomas, fibroids or simply myomas) are the commonest benign uterine neoplasms, commonly encountered in gynaecological pract.ice (5%-20% of women in the reproductive age group). They are slow-growing tumours and Lake 3-5 yea•-s 1.0 be clinically palpable unlike ovarian wmour-s. They tend to be mult.iple in numbers, but some may grow large in size.

AETIOLOGY A m) 0 ma is derived fro m smooth muscle cell rests, e ithe r from vesse l wa lls or ute rin e musc ulawre. Al th o ugh oestrogen, progestero ne growLh hormo ne and hwnan p lacen tal lactogen have bee n im p licated in the growtJ1 of myomas, the evidence in support of oestrogen a nd progesterone dependence for their growtJt is impressive: 1

• Myomas are rarely found before puberty, and they generally cease to grow after menopause. • New myomas rarel) appear aft.er menopause. • The associat.ion of fibroids in women witJt hyperoestrogenism is evidenced b) endometrial hyperplasia, abnormalut.erine bleeding and endometrial carcinoma. • M)omas are kt10\\1l 1.0 increase in siL.C dw·ing pregnancy and witJ1 oral conu-acept.ives trsage and shtink aft.er delive ty.

• Trea un ent witJ1 mi fep ristone to shtink Lhe fib roid proves that progestero ne, like oestroge n, is respo ns ib le fo r th e growtJ1 of the fibro id. Gn RII also shrinks Lhe fibro ma. • Risk fac tors are early menarc he, nu llipara or low pa ri ty. Un usual fo 11ns of le iomyomas inc lude inu·aveno us leiomyomatosis, which is characterized by polypoid projections of smooth muscle wmours into the veins of the parametritun and broad ligaments. During surgery these appear as wonn-like cords of benign fibrous tissue when pulled out of tJ1e veins. Fragments of tumour emboli can catLSe obstruct.ion of blood now from tJte atrium and sudden deatJ1. Similar!). a rare form of disseminat.ed intrape tiLOneal leiom)omatosis imoh ing large areas of subpe•·it.oneal surfaces is seen du.-ing pregnancy and while on oral conu-aceptives. The fibroids are often associaLed with adenomyosis, pelvic endomeuiosis and pelvic inOammaLory disease.

PATHOLOGY Grossly myoma is a well-circumscribed tumour with a whorled appeat·ance and a pseudocapsule. It is firm in consistency. T he cut surface is pinkish white and has a whorled appearance. T he capsule consists of connec t.i ve t.issue ,,11ich surro unds the wm our in the m)'Omeu·ium . T he vessels that suppl y blood to the fibro id li e in the capsule and se nd radial b mnches inLo tJ1e lllm Ot ll~ Beca use of tltis arrangeme nt of b lood supp ly, the cenu·al po rt io n of tJ1e fi broid receives the least blood suppl)', a nd degeneratio n is no t.iceable early and most often in tJ1is part of Lhe fibroid. O n t.he other hand, calcification begins at tlte pe tip hery and spreads inwards along tlte vessels. T he vessels are best seen over the subserous myoma whereas in tJ1e case of large in tram ural growth, they can be seen beneatJl Ule periLOneal covering of the uterus tJtis serves to distinguish tlte enlargemem of t.he uterus due 1.0 a myoma from a normal intmuterine pregnancy. Microscopicall). the tumour consistS of bundles of plain smooth mtLScle cells, separated b) var) ing amoum of fib roLLS strands. Areas of embt)Onic mtLSde Lissue may be presem in a m)Otna.

IE To \iew the lecture nole> .can 1he >pnbol or log in to your account on """·~fedEn.u1.mm 155

156

SHAW'S TEXTBOOK OF GYNAECOLOGY

The tumour may grow symmeuically, remain ing with in t11e myo metrial wall, when it is called 'inu·amural' or 'interstitial'. Lf the tumour grows outwarcl5 LOwarcls tlle peritoneal surface. it shows itse lf as a bossy growtll and is tenned as 'subserous'. Further extrusion o utwards witll tlle development of a pedicle makes it a ped unculated fibroid. Ln rare cases, sucll a mmour gets attached to a vascular organ and is cut off from its ute•·ine origin (parasitic fibroid). Ute•;ne conu-actions may fo rce the m)oma towarcl~ the ca\ity where it is covered only by a min endometrium, it is then called 'submucous' m)oma. This myoma may force itself downwards LOwaJds t11e vagina by a pedicle, and become a 'submucous myomatous pol yp'. The distribution of m)Oma in me body of tl1e uterus is broacU y classified as follows (Fig. 13.1A) :

The majority of myom as arise in the uterus b ut t11ey may also arise from the round ligame nt, the uteroma has been desclibecl in Lhe chapleron Displacements of t.he Uterus.

CHAPTER 13 - FIBROID UTERUS

Rgure 13.13 Red degeneration of a myoma. Note that the encap sulated tumour shows uniform dark dlscolouratlon.

161

Figure 13.15 Myomas with concomitant carcinoma of endometrium. (Source: Nirmala Duhan, Daya Srohiwal. European Journal of O:>stetrics and Gynecology. Uterine myomas revisited. Elsevier, 2010 .)

Table 13.2 Clinical Symptomatology and Complic ations Associated with Uterine Fibromyom as Menstrual disturbances - menorrhagia, polymenorrhagia, Intermenstrual bleeding, continuous bleeding, postmenopausal bleeding Infertility Pain - spasmodic dysmenorrhoea, backache, abdominal pain • Lump In the abdomen or mass protruding at the Introitus • Pressure symptoms on adjacent viscera - bladder, ureters and rectum o Pregnancy losses, postpartum haemorrhage, uterine inversion o Vag inal d ischarge

Rgure 13.14 Sarcomatous change In a uterine myoma. The dark Irregular areas in the substance of the myoma, which lie in the middle of the specimen, represent areas of sarcomatous change.

Capsular Haemorrhage

If one of the large veins on 1he surface of a subserous m)Oma ruptures, profuse inLrnperitoneal haemonnage can cause acute haemorrhagic shock. Infection

Infec tion is common in s ubm ucous and m)'Omato t.LS polyps if Ll1e)' project imo Ll1e ce rvica l canal or the vagina. An infected polyp can ca tL5e blood-sta ined p u rulent discharge. Infec ti on is more like!)' in the postpartum and postabonal state. lf the tumour causes delayed postpartum haemon·hage (PPH ) or sepsis, it m ay have to be removed.

Associated Endometrial Carcinoma Endometrial carcinoma is associated with fibromyoma in women o lder than 40 years in 3% cases. H) peroesu"Ogenism expla ins the coexistence of th ese two cond itions (Fig. L3.l5 a nd Table l3.1 ) .

SYMPTOMS (Table 13.2) o

o

Me norrhagia, pol)1m e norrh oea, me trorrhagia, con ti n uo us o r postmenopausal bleed ing Inferti lity, recurrent abortio ns

o o

o o

Pain PressureS) mptoms Abdominal lump Vaginal discharge Not a ll fibroids cat.LSe symptom.~.

1\~ 11W11)' tl.l 50% women (Ire m)•mpwmatic. These fibroids are d e tec ted during gynaeco logica l c heck- up or ulu·aso u nd done for u nrela ted sym ptoms. T he woman may have a va li ety of sy mptoms depending upon Ll1e number, size and location of the fibroids. Fibroids are seen in women of chi ldbeal'ing age, and rarely may be seen in younger women. Wom an ma>' be nullipai'Ous or of low parity (only 20%-30% women are multiparous). Oela)eomectOm) co nfirmed. • An incision ove r tJ1e anterio r uterine wall is prefe1Ted whenever possible and as man> fibroids removed through minimal tw1nelling incisions. • Haemonilage should be conu·o lled with the myomectomy clamp. The cla mp should be applied fro m the pubic end of the abdominal wound and tl1e round ligamentS whi ch will include the ute•ine vessels should be g•·ipped. The ovari an vessels may be tempora•·ily occluded wim a sponge fo•·ceps. If the myomectomy clamp cannot be applied as in ce1v ical fibroids, a rubber tourniquet wi ll serve the pL11pose. Local i •~j ection of dil ute vasopressin also h elps to reduce blood loss.

• The capsule should be incised and the fibro id en ucleated. This will minirni:t.e bleed ing and avoid u·auma to the bladder and ure te r. M>o mec to my sc rews help during e nuclea tio n (Figs U.20-l :3.22). • Fo llowing enucleation, the hae mostasis is sec ured and the cavityoblite mted witl1 se-.eral catgutsuwres. This will avo id scar rupture during subsequen t pregnancy and labour. • The clamp should be released and haemostasis confinned. • The raw visceml area should be well pe•·ito niLed to preve m postoperative adhesions. H) droflotation also

Figure 13.20 Bonney's myomectomy clamp.

Figure 13.21 Multiple fibroid removed by open myomectomy.

Flgure 13.19

Myomectomy operation.

Figure 13.22 Myoma screw.

CHAPTER 13 - FIBROID UTERUS

167

reduces adhesions. The uterus remains bulky foll owing myomectomy and r·equir·es to be anteverted by plicating the round ligam e nts with nonabsorbable sutures. Results. Pregnancy rate of 40%--50% has been reported following m)omectomy, and pregnancy loss reduced. However, IOo/o- 15% continue to suffer from menorThagia. Recur-ren ce offlbr-oids in 5o/o-l 0% cases is due to overlooking seedling flbmicls at the time of surgery. Complications. The complications that may result fmm myomectomy are as follows: • • • • •

Primary, reactionary and secondary haemorrhage Tra u ma to the bladder, u reter and bowe l dLUing su rgery lnfeCLio n Ad hesio ns and intestinal obstruc tion Rec ur re nce of flbro ids and persis tence of me norrhagia

Vflginrtl ln)'OIIIfttomy (Fig. 13.23): lt is indicated in s ubmucous flb ro id po l)'ps. Vagina l myomec to my is possible in cervica l fibro ids a nd ped unc ula ted fibro id polypus and if mo re tha n 50% submucous fib r-oids projec t in to the cavity. H ystemscojJic III)'OIIUittom.;( Hysteroscopic m yomectom y has become possible for submucous fibroids not rem ovable easil y by the vaginal route. T he fibroid is excised eitl1e1· by cautery, laser or resectoscope. It is best done under laparoscopic guidance to avoid uterine perforation. Complications of h)Steroscopi c m>om ectomy are as follows:

• Cervical trauma, ute.-ine perforation • Thennal injury • Bleeding- Fo ley cathe te r can be used as tamponade to stop bleeding • Infection • Failure • Uterine adhesions • Complications of distending media : Water overload or pulmonary oedema

Figure 13.24

(A) Subserous fibroid seen on laparoscopy. (B) Central

cervical fibroid (lantern on the dome of St. Paul's CathedraO seen on lap..-otomy. (Ccu'tesy (A): Dr \Iivek Mawah, New Deihl)

Laparoscopic myomectomy: Laparoscopic view of vario us fibm ids is shown in Figs 1:3.2 1 and 1:3.25. Laparoscopic myornectOm)' (Fig. 1:3.26A-1) is feasible in: • A pedun c ula ted flbro id

Figure 13.25 New Delhi.)

RgLre 13.23

Hysteroscopy reveals multiple endometrial polyps.

(Source: From FIQUre 2A Chumda Cheng, Tirg Zhao, Mil Xue, et al In: Use of suction ctrettage in operative hysteroscopy. Journal of Mirimaly

Invasive Gyneoology. VC>lJrne 16{6): 739-742, 2009.)

Mu~i ple

uterine fibroids. (Courtesy. Dr Vivek Marwah,

• Subsemus fib•-oid not exceeding 10 em in sit.e and noun ore than foLU· in number. Multipl e flbroids ofanysit.e should be approached b)' lapa•-otomy. t.Jnipol;u·, bipolar cautery and laser have been e mpiO)ed to re move Lhe fibroma and obtain haemostasis. Th e flb•-o ma is reuieved through posterior colpotomy, minilapa•-otOm) or b) morcellation. Mrolysis, a

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SHAW'S TEXTBOOK OF GYNAECOLOGY

Rgure 13.26 Laparosoopic myomectomy- steps of operation. (A) Rbromyoma uterus. (B)Incision taken on the fibromyoma. (C) Fibromyoma exposed. (D) Myoma screw Inserted to steady the myoma (E) Myoma dissected from its bed. (F) Edges of myoma bed approximated with interrupted Vicryl sutures. Removed myoma seen in POD. (G) Myoma being morcellated. (H) Tunnel in myoma after removal of cylincrical mass. (I) Laparoscopic myomectomy. (Courlesy: Dr VP.Iek Marwah, New Deln.)

technique of desu·uction ofm)Qma tissue b)' laser or cautel)\ is a sophisticated ted1nology practised by endoscopistS. • Laparoscopic-assisted vaginal hysterectOmy (LAVH) enables vaginal hysterectomy to be completed from below in the prese nce of pelvic pa thology.

wow1d. LajxJ.ro~copic 111)'011/eclom)• nury tilrrifow not be safo in an infertile wonum, except for small fibroids. The recw-rence rate is reponed higher than that in laparotomy. Newer minimal invasive procedures successfully introd uced in recen L years are:

Laparoscopic m)•O mectO m)' is made easier and faster by newer insuum e ntS, morcellator, newe r e ne rgy sources and newer suture mate rials. T he b leeding is controlled by infi lu·ation of ITI)'Oma witJ1 vasoconstricto rs and b ilateral uterine artery ligation before mromec tomy.

• UA£

Disadvantages of Laparoscopic Myomectomy

Although a minimal invasive surge ry, and without an abdominal scar, laparoscopic mro mectomy can cause more bleeding because of no napplicabilit) of a haemostatic clamp, and being an adhesiogenic procedu re, it lakes longer to perfonn. Postoperative acU1esions can increase tJ1e infertility rate. Scar 11.1pture is also rep01ted in late pregnancy and dLIIing labour. Some use imercede (oxidit.ed regenerated cellulose) to prevem or reduce adhesio ns. The major complication is •upture of me Ill) omectomy scar dLIIing pregnancy or labour due to imperfect or inadequate suturing ofthe m)omecwmy

• MRI-gui ded laser ab la ti on • Laparoscop ic m)•OI)'sis Uterine Artery Emboli:z:ation

In 199 1, J acques Ravina, a Fre nch gynaecologist, first perfonned UA£ preope rative !)' to reduce vascularit)' and the size of fibroid. Improveme nt in symptoms cancelled definitive surgery is some cases. Me norrhagia was relieved in 80%-90%. pressw·e S)'lnptoms in 40%-70%; the volume decreased by 50% at tJ1e e nd of 3 months, by 60% at 6 montJ1s and b) 75% at the e nd of I year. Thus, mis technique is now emplo)ed successfull) in selective cases. Contraindications

• Subserous Mul jlmtou:uwted fibroid:.. ecrosis and fall of the LUmour imo me pel'iloneal cavily ca n OCClll: Big fibroids are not sui led for UA£.

CHAPTER 13 - FIBROID UTERUS

169

I

\l

Catheter

I

I

\

Femoral --J~----411 artery /

~:fY I

A Rgure 13.27

\

\ y

\\

\

Uterine artery (A) Trans femoral catheteri zation of uterine arteries. (B) Injection of polyvinyl aloohol particles. (Sovce: Rao, K. A Textbook of

Gynaeoology, India: Bsevler, 2008.)

• Submucous Fibroid is not cured. • Inferti li ty rate m'• the removal of the uterus, is indicated in a woman older than 40 years, a multiparous woman or when associated with malignancy. Uncontrolled haemorrhage and unforeseen SLtrgical difficulties during myomectomy may also necessitate hysterectOmy. Hysterectomy guarantees removal of a ll fibroids and relieffrom symp toms. Norma lly, the aim is total hysterectomy. However, subtotal hysterecLOm)' may be performed in the presence of PLD, endomeu·iosis and any technical problem when the cervix is left behind. Prior cervical cytology is desirable. Types of Hysterectomy

• Abdominal hysterectomy • Vaginal hysterectomy • L..aparoscopic hysterectomy Abdominal Hysterectomy

Abdominal h)•Sterecto my incl udes: • Total hysterectomy • Subtotal hysterectomy when th e cervix is retained • Pan hysterectomy (TAl-l with B/L Salpingo Oopherectomy) when ovaries are also removed

• Extended and Wertheim h)Sterecwmy in cancer of the cervix and utet·ine cancer Most perfonn a total hysterectomy, as it prevents chronic cervicitis and cancer occ t.min g at a later stage. However, occasionall)', subtotal h)•Stereetomy ma)' have to be resoned. Advan tages of subtotal hysterectomy arc as follows: • Cervix retained for sexual function. T he normal cervical clischa Pge is beneficial. • Vault prolapse is less common. Less bleeding and less tisk of bladder and ureter trauma. • In a difficult surgery, total hysterecLOm)' may increase the surgical mOt·bidity due to trauma tO the bladder and denervation, causing difficult micturition and incontinence. Pap smear before St.trgery ensures that the cetvi.x is normal. What about the ovaries? In benign conditions, the ovaries sho uld be retained to avoid menopa usal symptoms in a premenopausal woman, p rovided they look normal. Disadvantage of conserving the ovaries: • Benign or malignant O\>at·ian tumour may develop in 1% cases. • Residual ovarian syndrome is known to occur in some cases and cause d)sparewlia. • Au·oph) of the ov;uies has been repotted due to kinking of the ovarian vessels within 3-4 years of hysterectomy; they become nonft.mct.ional and cause earl) menopause. Total Abdominal Hysterectomy

Hyste rectOm)' is straightforward in most cases of fibro ids. However, in case of a cetv ical, low a melior walJ and a posterior fibroid, and one encroaching imo the broad li gamem where bladder, ureter and rectum are displaced from their normal anatomical position, they :u·e at risk ofi tjury. In a cervical and large antetior wall fibroid which is close to the bladder, it is prudent to perfonn m> omectomy first. This allows a clear view of,omectomy or hysterectomy, is associated with a greater risk of i1'!jury to bladder and u1·eters besides increased blood loss during surgery. To decrease risk of injul)' to bladder or ureters, it may be desirable to first enucleate fibroid and then proceed with rest of the surgery. FIBROIDS COMPUCATING PREGNANCY Pregna ncy associated with fib roids is associated with th e increased chances of complica ti ons. Pregna ncy ge ne rally ca uses an increase in th e si:Ge of fib ro icls (Fig. 13.28); th e re is a n inc rease in their vasc ula rity a nd a highe r te nde ncy LO unde rgo clegene ra tive changes s uch as hyaline c ha nge a nd cysti c dege ne ratio n. Red dege ne ra tio n is a res ult of soften ing of the sur ro un d ing s upportive connec tive tiss ue. Th e cap illa ries tend to ru pture a nd b lood effuses ou t into the myoma, ca using a d iffuse reddish disco lo u ration of the same. Such a pa ti ent complai ns of severe pain in tlle abdomen and may present as an emergency for acute abdominal pain; examination reveals the pain to be restricted to the utenl.S around tlle site of tlle fibroid. and all other parameters remain stable. Such a patient is treated consen>ativel) with bed rest and analgesics, until the pain subsides. On rare occasions, when laparoLOm)' is carded out, the m>oma is seen to be dusky in appearance; its cut section has an appearance of cooked meat and is known to emit a fishy odou1: Fibroids by their sheer siLe may catl.Se respiratory emban-assment, retention of urine or obstructed labour. They are sometimes known to adver-sely affect the outcome of pregnancy and the1·e is an increased risk of abortion, prete1·m labour, abnormal presentation, accidental h aemoni1age, dystocia in labour; PPH , puerperal sepsis an d uterine in version.

(A) Subserous fibroid associated with uterine pregnancy. (B) Uterus studded with multiple fibrolds and pregnancy.

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SHAW'S TEXTBOOK OF GYNAECOLOGY

through the os with a long pedicle. It is pale looking, firm with infection and necrosis at l11e ba.se if it protrudes through the cervix. It can be sessile or a pedunculated cervical fibroid.

ENDOMETRIAL POLYPS UTERINE POLYPS Uterine pol)ps are usuall) benign comprising endomeuial, fibroid. adenom>omatous and placental polyps. Cervical polyps are mucous and fibroadenomatOtiS poi)'PS aJ;se from the endocervix.

ENDOMETRIAL POLYPS Endomeu·ial polyps mostly arise from hyperplasia of the endomeu·ium, some pan of the endomeu·ial lining protruding into the uterine cavity as poi)'PS. They may be single or multiple; they appear as pink swellings, 1-2 em in diameter, with a pedicle. The polyp is composed of endometrial glands and su·oma covered with a single layer of colum nar epitheli um. Seconda ry malignant change may occ ur in a benign polyp; l11us, it is mandaLOI)' LO study its histOlogy. In a ma lignant poi>'P ari sing ab initio, th e e ntire polyp shows ma lignanC)', inc lud ing its base whe reas secondary malignanC)' is seen at the apex of th e polyp- th e base or th e pedicle shows no suc h change. Adenomyomatous pol)•p has s mooth musc le as well as endometria l e lements. Tamoxifen can cause endometrial hyperplasia and polyps. A fibroid pofyp is a submucous fibroid developing a pedicle and protruding into the uterine cavity or projecting

PLACENTAL POLYPS Placental pol)ps are fonned from retained placental tissue, thus causing secondai)' PPII 0 1· intenniuem vaginal bleeding following an abonion or a nonnal delivery.

CUNICAL FEATURES Uterine pol)•ps can cause menOIThagia, metroni1agia or postmenopausal bleeding. If l11ese protrude through l11e os, may cause postcoital bleeding or continuous bleeding in a young woman after they arc asymptomatic. Cli nicall y, the ute rin e polyp may not be evident as the uten.IS may or may not be enlarged; it is easy to diagnose when tl1e polyp protrudes l11ro ugh the cervical canal. Ulu·aso und can detec t uterine polyp, so also sali ne sonosalpingogram or hys te rosa lpingogram (H SG). Hysteroscopy is bo tl1 d iagnostic and l11erape utic. MANAGEMENT D&C can scrape the pOl)•p. H)•Steroscopic removal of multiple pol)•ps may be desirab le to ensure tl1 eir complete removal. Endocervical pOI)'PS have been dealt with in tl1e chapter on inflammation of tl1e uterus and the cervix.

Fibroid Uterus

History Examination U/s, AbdomenfTVS

Treat if: • Size>12wks • Pressure symptoms • Infertility

• Hemostatic agents • Young patients -Hormones - MIRENA - Uterine artery embolization - Myomectomy • Older women(>45y) consider surgery (TAH) Management of Fibroid uterus

CHAPTER 13 - FIBROID UTERUS

KEY POINTS • Fibrom)omas are benign neoplasms of the uterus affecting 5%-20% of women in Lhe reproductive age gt·oup. • Fibrom>omas ma) be prese m without S) mpwms. Howe-.er. depe nding o n Lheir siLe and location, the)' ma) comribute to menstrual in·egularities, dysmenorrhoea, infertilit), pain in the abdomen, alxlominal fullness, pressure symptoms and complications during pregnancy. • Ultrasonogra phy, CT/MRI, laparoscopy and hysteroscopy help in establishing the diagnosis of uteri ne fibrom)om as. They are also useful tO determine the number, location and si.Ge of tumours. This h elps in planning the u·eau11 cnt. • Asymptomatic tumours ofLen do not req ui re treatmenL b ul follow-up is reco mmended. • Symptoma ti c fibro icls req uire u·ea une m. Myomecto my is inclica tccl in )'Ounger wo me n desiro us of retaining the chil dbea rin g func1.io n whereas in elde r I)' wo men, h)'Sterec to my is the proced ure of cho ice. • Medical u·eatmc m he lps LO re lieve me norrhagia. Gn RH a and SI::RM arc ac~j uva ms LO surge ry when a huge fibro id or mul tiple fibro ids are enco umered. They shrink Lhe fibroids and red uce Lhe b lood loss during surgery. • Endoscopic procedures e nable the removal of moderate-site m)Omas. • H)SLerectom> is ad' ised in elderly and multiparous women. • Laparoscop), hysteroscop) and ane•·ial embolitat.ion pro' ide minimal in\'asi'e surger) and have reduced the number of a bdominal h)sterectom>• in women with utel"ine fii)J'()ids. ~I R I-guided high-frequency ulu-asound is now possible. • UA£ is not recommended in women with infertility because of pelvic adhesions and risk of scar rupture dlll·ing pregnan C)' or in labour. • Location, site and number of fibroids decide the route of ope•-alion.

SELF-ASSESSMENT 1. Disc uss the cli nical fea w res of uteri ne fibro ids. 2. How wi ll )'O u manage a case of uteri ne fibro ids in a 32-)•ear-old, para I woman?

173

3. Disc uss the manage me nt o f uterine myo ma in a n ulliparous woman. 4. A woman, 38-year-old, presents with me norrhagia. She shows three fib ro ids on ui Lraso und. How will yo u manage the case?

SUGGESTED READING Amlkumaro~n

S. Acute complication> of fibromyoma. Clin Obstet Gynaecol 2009:5:23. Baird DO. Gam!tt TA. uughlin K, et al. Shun-term change in growt.h of uterine ldom)oma: tumor j.,'TOWth spuns. Fertil Steril 2011; 95:242. Baird DO, Ilannon QE, L:p;.on K, et al. A Prospective, UhrasoundBase estimat ed annual cost. of uterine leiom yomata in tl1e Unilcd States. Am .J Obst ct Gyncco12012; 206:211.el. Cornrnittc-c on Practice Bullelins-Cyncc'Oioj.,')'. Practice bulletin no. 128: diagno>i> of abnormal ut erine bk-eding in rcpmducth·c-agcd women. Obstct Gync-col2012;120:197. Reaffirmed 2016. Donnczj , Donnc1. 0, Malltlc 0, ct al. L.ong,..cnn medical rnanab~ment of uterine fibroid> 1\iLh uliprisLal acct>dC. Fcrtil Srcril2016;105:160. OunC). Yc C, Mur.tli R, Park Jg. s.,,'OndarJ lm ohernent of the Adnexa and Uterine CorptL> by Carcinoma> of the Uterine Cen·ix: A Detailed Morphologic De.cription. lntj Gjnccol P>lihol2015;!l4:501. Sengupta. Chattopadh)o SK. Epide mioloj.,')' of Uterine Fibroids: From ~knarche to Menopause. Clin Ol:>$tet Gynecol 2016;59:2.

Endometriosis and Adenomyosis

Endometriosis 174 Adenomyosis 185

Key Points 187 Self-Assessment 187

ENDOMETRIOSIS Endometriosis is the prese nce of endo metrium a t a site outside endo me u·ial lining. This co nd itio n was first desc ribed b)' Carl Von Roki nst.'\S)' in 1860. Since its original desc ription, th is condition is being increasingly recognized in women with infertili ty, chro nic pelvic pain (CPP) and menstrual irregularity. These islands of endomeu·iosis are composed of endomeu·ial glands surrounded by endometrial stroma. and are capable of responding to a varying degree to cyclical honnonal sumulauon. The disease alt.hough a benign proliferau'e growth process yet having some of the featttres of cancer like the propensity to invade the nonnal sttrrounding tissues, causing extreme pain and tendency for reclll·rences. Whereas cancer can kill the women, endomeu·iosis cripples her life. The reponed incidence is about 10%, but inc idence is increasing on account of greater use of diagn ostic laparoscop)'· Amongst infertile women, incidence is 20%, an d it is 15% in women with CPP. Th e incidence is very high amongst j apanese women. Charactelistics of endometl'iosis • T he ectopic endometrial tissue responds to ova ri an ho rm o nes. • Although prolifem uve e ndorn e u·ium is always seen, sec re to ry endome u·iurn depe nds upon the presence of p rogesterone recepto rs in th e tissues. • Blood oozing d uri ng menstruation in ec topic endometrium ca uses local ad hesions in t11e pelvis. • Malignancy is extreme!)' rare, though e ndome tl"ial tissue is highl)' proliferative.

AETIOLOGY Endomeu·iosis is a proliferative hormone-dependent disease of the childbearing period. It is extremely rare before menarche and disappears after menopattSe. Its incidence appears to be on the increase panly due LO improvement in diagnostic techniques and panly clue LO changing social patterns such as late ma r-riage and limitation of family si.t:e. It tends to occur more amongst t11e

174

afflue nt c lass, a nd is freq ue nLI )' assoc ia ted with infe rtili ty. Ge ne tic suscepLibiliL)' a nd fa mi lial te nde ncy a re see n in 15% cases. Several theories have bee n propo unded to explain e ndo me uiosis; chief among t11ese are t11e fo llowing.

IMPLANTATION THEORY Sampson's pioneering work in 1922 attrib uted endometriosis to reflux of menstrual endomeu·i um Ll1rough the fallopian tubes and its subsequent implantation and growth on the pelvic per-itonewn and the surrounding structures. Sampson observed that in cases of uncompl icated endometriosis, the fallopian LUbes were ttSually patent Several workers then questioned the ,-iabilit) of desquamated endometrium and its capacity to implant and grow. Convincing support to ampson 's theory of reu·ograde menstruation, implantat.ion and spread has been provided by the experimental work of Scolt, Te Linde and Whanon. The occurrence of scar endomeuiosis following classical caesarean sect.ion, hyster-otomy, myomectomy and episiotomy further suppons this view. Lately, it h as been suggested that h ypowni a of th e uterotubal j unct.io n influences th e qua ntity of retrograde spill a nd occ urrence of pelvic e ndo metliosis. T he occw-rence of e ndo me ui osis in youn g girls with crypwme no rrhoea, and re u·ograde collec ti o n of me nstrual fluid, is also a p roof of Sampso n's implantation theOI')'·

COELOMIC METAPLASIA THEORY Me)•er and Ivanoff ( 19 19) propoun ded that endometriosis a rises as a resul t of me tap lastic changes in embryonic cell rests of embryonic mesothe liu m, which are capable of respond ing to hormonal stimulation. Embryologically, MCtllerian ducts arise from these same ussues; hence, such a tranSfonnaLion in later life seems plausible.

METASTATIC THEORY Although the above tl1eories can explain t11e occtm·ence of endomeu·iosis at the usual sites, the) found it difficult to explain its occurrence at less accessible sites such as t11e umbilicus, pel\'ic l)lnph nodes, ureter, recto"aginal septum, bowel wall, and remote sites such as the lung, pleura, endocardium

CHAPTER 14 - ENDOMETRIOSIS AND ADENOMYOSIS

and th e ex u·em iLies. Hence, it was suggested by Halban et al. (1924) that ernboli.t.ation of mensu·ual fragmentS occ urs tJwough vascular or l)mphatic channels, and t11is leads to t11e launching of endometriosis at distal siteS. Endometrial tissue has been retrieved in pelvic l)mphatics in 20% women witJ1 endometriosis.

HORMONAL INFLUENCE Whatever be the initial genesis of endomeu·iosis, iLS further developmemdepends on the presence ofhonnones, mainly oesu·ogen. Pregnancy causes au·ophy of endomeu·iosis chiefly through high progesterone levels. Regression also follows oophorectomy and irradiation. Endometriosis is rarely seen before puberty and it regresses after menopause. Hormones witJ1 antioestrogenic activity also suppress endometdosis and arc used t11erapeutically. Cyclical hormo nes sti mulate its growth, but continuous hormone secreti on or the rapy suppresses iL Smoking reduces oestrogen level, the reby t11 e incidence of endometriosis prolifera ti o n.

Table 14.1

175

Sites of Endo metriosis

Pelvic endometriosis Pelvic peritoneum, pouch of Douglas, uterosacral ligament Rectovaginal endometriosis Ovarian endometriosis Chocolate cyst of ovary Other sites - appendix., pelvic lymph nodes; metastatic lungs, umbilicus and scar endometriosis

IMMUNOLOGICAL FAOOR The perito neal flu id in endo metriosis comains macrophages C)'tokines and natura l kille r (NK) cells wh ich clear blood spilled into t11 e peritoneal cavity. Impaired T cell and NK cell ac tivity and altered immunology in a woman may ina·ease t11 e susceptibility to proliferation and growrll. OTHER FAOORS Other faCLors implicated in t11e occurrence of endometriosis are genet.ic, multifactorial, vaginal or cervical atresia encouraging retrograde spill. The more frequem the cycles, and tlle more the bleeding, greater is t11e risk of endometriosis. Prostaglandins secreted by endometriotic tissue may exacerbate chronic pain and clysmenon·hoea. Risk factors are polpnenorrhagia, retroverted uterus, which increases t11e risk of retrograde spill. A woman who has undergone wbectomy rarely develops endom etriosis. History of familial tendency is reponed in 15% cases. Genetic basis accountS for 10% of enclomeu·iosis; and incidence in first-degree relative is sevenfold. It may be t11at several factot'S are involved in t11e aetiology of endometriosis at different sites and none of t11 e above t11 eo ries fitS into the develop men t of e nclome u·iosis in a particular category. The incidence is lowe r in multi paras and t11 ose on oral contraceptives.

A

SITES OF ENDOMETRIOSIS (Table 14. 1) Endomeu·iosis is found widely dispersed throughout the lower pelvis, and below t11e level of umbilicus. The common sites are t11e ovaries, t11e pouch of Douglas, including rl1e uterosaa·al ligaments, pelitoneum overlying t11e bladdet~ sigmoid colon, back oftJ1e uterus, ovatian fossa, imestinal coils and appendix. Endometriosis is seen in the umbilicus following an operation, in laparoLOm) scars, in wbal stumps following Sterili..ation operation. in t11e amputated stump of t11e cervix and in t11e scars oftJ1e ntlva and perineum (Fig. II. I). Scarendomeuiosis following lower segmenL caesarean section is seen in only 0.2%, buL is high following classical caesarean section. RectO\' 3cm

2

4

Superlicial

Right side- superficial Deep

4

- - - - 16

> 3cm

20 4

Left side - superficial

2

Deep

4

16

Posterior cul·de-sac obliteration

Partial

Com plate

4

40

20

1/3-2/3 Enclosure

> 2/3 Enclosure

2

4

4

8

16

2

4

Dense

4

8

16

Tubal adhesions•

< 1/3 Enclosure

1/3-2/3 Enclosure

> 213 Enclosure

2

4

8

16

2

4

8

16

Ovarian adhesions

< 1/3 Enclosure

Right side- flimsy Dense Left side - flimsy

Right side- fUmsy Dense

4

Left side- flimsy Dense

177

4

---------------------

•11the fmbriated end of the r.-lopian tube is completely dosed, ch becomes ver> severe, presenting as an acute alxlomen necessitating immediate surgery. At laparotomy, a nrpLUred chocolate cyst is observed. DYSPAREUNIA Endometriotic involvement of the cul- 35 UlmL Ultrasound - mass, echogenic areas MRI: Colour Doppler - increased blood flow Cystoscopy - Urinary cause Sigmoidoscopy -rectal cause Antiendometrial antibodies

INVESTIGATIONS (Table 14.3) LAPAROSCOPIC FINDINGS These have already been described earlier. Laparoscopy sho uld be emplo)•ect not merely for diagnosti c p urposes; the endoscopist s hotJd be able to proceed with minimal invasive surgery (see be low) in th e presence of this pa thology. Laparoscopy is the gold standard in the d iagnosis of e ndome u·iosis. T he d iagnosis sho uld be va lidated by pe ri to neal and tissue b iopsy (Fig. l tl.()) beca use corp us luteal hae matoma can resemble a chocolate cyst. Role of laparoscopy • • • •

To detect and diagnose pelvic endome u·iosis. Locate the site of e ndo me u·iosis and staging. To take biopsy. To surgical I) treat endo metriosis by ablation and removaL CA-125. gi)COprotein a nd cell surface antigen, is raised

more than 35 U/ mL in 80% cases of endomelriosis and the level is directly proportional to the extem of the disease. The Je,el is not specific, because it is also raised in abdominal lll berculosis, PI D, malignant epithelial ovarian tumour, chronic liver disease and in 2% normal women, especiall)• during menstruation. Although CA125 estimation may n ot be h elpful in the initial diagnosis, once the diagnosis is established, raised level of CA-125 indicates either pet-sistence or recu t-renee of the disease in the follow-up. LO

ULTRASOUND AND MRI Tra nsvagina l ultmsound reveals an ec ho-free cyst, low-level ec hoes or clum ps of hi gh-density level echoes represe nting clots. T he cyst wa ll is tl1ick and irregul at; and multiple cysts in different phases of evolution ma)' be observed. Ultrasound is 83% sensitive and 98% specific, as small nod t.Jes may not be picked up by ulu·asound. CT and MRl give identica l picture as in ul u·aso und, and are not more useful in the diagnosis of endomeu·iosis (Figs 1 I. 7 and I 1.8). • Colour Doppler flow shows increased vascularity but does not confi1m the diagnosis - vascularity is diffuse; in a fibroid. blood ' essels are seen in the periphery. • Cystoscop) will idemif) involve mem of the bladder. • Sigmoidoscop) is •·equired if t11e woman develops bowel S)lnptoms. A biopS)' is req uired if malignancy is suspected.

• Antiendomeuial antibodies are identified in tl1e serum, peritoneal fluid and endometriotic fluid as we ll as in nom1al endometrial tissue. However, as yet, these are not measmed to be of screening value and tl.Sed as a tissue marker. ll1ese ma> also not be sensitive and specific. • Tlllnour necrosis factor is raised propo rtionately to the severity of the disease. • MRl reveals thickening of ligaments and nodules.

PROPHYLAXIS • Low-dose oral contraceptive pills reduce t11e menstrual flow and pt·otect against endometriosis. Three montl1ly ot-al pills are convenient to take and are effective. • Tubal patenC)' tests should be avoided in the immediate premenstrual phase to avoid spill. • Operations on the genital tra ct should be scheduled in the postmensu·ual period. • Classical caesarean section and hystero tomy operatio n which cause scar endometriosis are now rarely perfo rmed.

MANAGEMENT Mi n imal as)•mp to rn atic cases s ho uld be obse rved over ~8 months. Inferti li ty should be investigated and treated as necessary (Fig. 1 1.5 ). Al l symptomatic women need treatment. T he treatment (Fig. 11.9) depends upon t11e age of the patient, need for preserving reproductive functions, severity of the symptoms, extent of the disease, response to medical treaunem, relief obtained with an> previOtl.S conse rvative surgery and the attitude of the patient towards her problem. The oqject.ive of the treatment should be to e •-adicate the lesion and avoid recurrence of the dis ease process, alle,·iate S) mptoms, facilitate childbealing and enable tl1e patient to lead a comfortable life. Therefore, t11e u·eaunent should be indi,~clual­ ized. The treaunent comptises medical and surgical and a combination of botl1.

DRUG TREATMENT Drug treaunent should aim at causing atrophy of tl1e ectopic endometrium witl1 minimal side effects, improving symptoms, ferti lity rate and avoiding or delaying rec urrence. Endome u·iosis is oesu·ogen depe nde nt. Horm ones act o n recep to t-s in the e nclo metrio ti c tissue and cause the ir a troph y and shrinkage. T he purpose of ad minis u·atio n of vario us hormones is to act as antioestrogens; the d rugs p roduce a hypo-oes u·ogenic effecL Supe rfic ia l lesio ns respond better than th e deepe r ones. llowever, one must no te th at hormonal therap)' suppresses endometriosis for the d uration of tl1erapy; it does not prevent rec un·ence once the therapy is stopped. Moreove•; the hormones delay pregnancy by tl1eir contraceptive e ffect and cause side effects on prolonged tl1erapy, besides t11 e drugs being expensive. The drugs are best suited for multiparous women. I. Combined oral contraceptives (OCP). It is tl.Sed as a p•i-

mary treatment o r preope•-ativel) to shrink endomeuiosis. Administered intermitte ntly or continuously, oral conuaceptives may aiiC\·iate the disease. However, high incidence of side effects and risk of thromboembolism

CHAPTER 14 - ENDOMETRIOSIS AND ADENOMYOSIS

181

Rgure 14.6 (A- D) Appearance of o ld endometriosis w it h 'tattooing' {blue-grey lesions), and red, brown and black raised lesions of active endometriosis at the t ime of laparoscopy. (E) Pel vic endometriosis showing red lesions on laparoscopy. (F) Complete obliteration of t he pouch of Doug las (white arrowhead) was noted during diagnostic laparoscopy. (G) Laparoscopic view of bilateral endometriosis. (Source (A-D): Hacker NF, Gambone JC, Hobel CJ. Hacker and Moore's Essentials of Obstetrics and Gynecology, 5th ed. Phiadelphla: BseiAer, 2010.) (Courtesy (G): Dr Vivek Marwah, New Delhi.)

li mit tl1eir prolonged use. About 30% p regnancy rate is reported fo llowing th is treaLmenL OCP de lay pregnanC)'· Seasonale OCP for 84 days, with 6 days tab let-free, reduces the mensu·ua l periods to j ust four cycles in a year and may be suited in endome u·iosis. 2. Oral progestogens. These drugs exert an antioestrogenic effect and tl1eir continuous adminisLratio n causes decidu· alizaLion and endometrial atrophy. The treaunem over a period of ~9 months produces a state of pseuclopregnruK). whicl1 ultimate!) causes regression of the disease. The drugs in common Ltse are noret11isterone, 5.0-20.0 mg daily, or d)drogeste•·one 10-30 mg daily. Oydrogesterone I~ mg daily in the luteal phase relieves spnpwms. This lwmume tire. 1101 prromt mmlaJion and is suitable for a

wu11um tr)'i1tg to conceive. IL also has less toxic side effects. Instead of restricted 1\lleal phase adm inistration, it can be given 10 mgb.d. from clay 5-25 for three cycles. Tibolone is also Ltseful in e ndome u·iosis. Medroxyprogesterone acetate may be adm inistered as a long-acting depot preparation, 50 mg i.m. weekly, 100 mg i.m. every 2 weeks for 3 montllS, followed by 200 mg montl1ly for 3-6 montl1s or oral 30 mg daily. About 50%-70% symptomatic relief and pregnanC) rate of 40%-50% have been reponed. Weight gain and irregular bleeding ru·e the side effects of progestogens. Other side effects include reduced libido, mental depression, breast tenderness and decreased high-density lipoprotein (HO L). Moreover, fe•·tility is impaired for 2 )Cars after prolonged

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SHAW'S TEXTBOOK OF GYNAECOLOGY

Figure 14.8 MRI showing endometri oma.

Figure 14.7 Ultrasound showing endometrioma.

Management of endometriosis

Observe for 6-$ months, investigate for infertility

Minimal invasive surgery

+

Laparoscopy Drug treatment I . Destruction 1. OCP by cautery, laser 2. M irena IUCD vapourization 3. Progestogens 2. Excision of cyst 4 . Androgens 5. GnRH analogues 3. Adhesiolysis 4 . Presacral neurectomy 6. Letrozole 5. LUNA (laparoscopic 7. RU-486 ut erosacral nerve ablation)

Surgery

1

Laparotomy I . Incision o f chocolate cyst, and removal of lining 2. Salpingo-oophorectomy 3. Hysterectomy and unilateral or bilateral salpingo-oophorectomy 4. Excision of scar endometriosis

Figure 14.9 Management of endometriosis.

hormone Ule rap)'· T he side effectS are dose and duration re lated. Mimw!UCD red1tces •ears with minima l systemic side effectS. Danacrine, an anabolic drug, does not cause menopausal symptoms, as~ level does not drop below 50 pg!mL. The progesterone level rises in 15 minutes, peak5 in a few hours and stabilizes tl1ereafter. It causes endomeuial gla nd atrophy, and decidualia~Lion of stromal cells. I L is ideal LO relieve pain and menon·hagia in premenopausal women who have completed tl1eir families. 3. Dydrogesterone I~ mg clail)' in the lllleal phase or 10 mg daily from 5tll-25th cia)' improves S)lnpLOms and the ferLility rate.

4. Danazol, a S)'ntheLic derivaLive of e tllin)•l testosterone, inhibitS p ituitary gonadotropins. It is mi ld ly anabolic, amioesuugenic and an LiprogestaLional. It reduces sex hormone-binding globuli n SHBG and re leases free testosterone. It is a very effective, t11ough an expensive drug, and is administered in closes of200-800 mg daily for 3-6 months starting on t11e first day of menses. It causes S)'lnptoms simulaLing menopause if lL5ed in higher doses over 6-8 months. The lesions regress remarkably, but many paLienLS suffer from side effeCtS such as weiglu gain, hirsuLism, excesshe sweaLing, mtLScle cramps, depression, auuphy of breasts and vaginal epithelimn, lowering of HDL, and liver and renal damage. The resulLing amenorrhoea p•umplly con-eelS itself on withdrawal of tl1e dJUg.

CHAPTER 14 - ENDOMETRIOSIS AND ADENOMYOSIS

The chances of successful pregnancy follo"~ng this therapy range fro m 30% to 50%. It is reported that 80% of endometrial implants resolve with danazol. Recurrence, however, is like I) after stoppage of the dn•g (30%) . It is conu-aindicated in liver dysfunction, and pregnancy should be avo ided as it is teratogenic. Recently, danazol is implicated in the development of ovarian cancet·, and man> ro naecologists are now reluctamto use this drug. Gestrinone is a 19-nonestosterone det·ivative similar w da n;uol in action, but it has fewe r side effects and is longacting. It reduces the LH surge and SHBG. Dose is 2.5-5 mg twice weekly. About 85%-90% patients experience amenorrh oea. Anti-inflammatory drugs, such as mefenami c acid 500 mg three tim es a day dm·ing menstruation, relieve dysmenon·h oea in 70%-80% patientS. Other amiprostaglandin and anti-inflamm atOry (not1Steroidal) drugs such as naproxen are also useful. 5. Gonadotropin-releasing hormone (GnRH). This hormone is ad ministe red continuo usly to downregulate and s uppress pituitary gonadotropins; it ca uses atrophy of the endometriotic tissue in 90% cases. T he synthetic analogue of GnRII is given in doses of 10-20 mg i.v., twice da il>'• or 200-tiOO mg in tranasa ll)' dail)' for 6 months. Monthly depot iqjec tion (Zoladex) of3.6 mg is also avai lable. Discontinuation of Gn RH and danazol causes recurre nce of e ndome u·iosis within a year in 50% cases. GnRl-1 is better to lerated than danazol. 1-lowevet~ prolonged Gn Rl-1 therapy ove r 6 months causes hypooestrogen ism a nd menopausal symptoms such as hot flushes, dt] vagina, urethral syndro me and osteoporosis. To avoid this, add-back therapy with progesLOget1S and l.ibolone or etidro nate is recommended. This also allows prolonged Lherap) with GnRH for 2 >ears. Other dt·ugs available are as follows: Buserelin and leu protide (nonapeptides) . afarelin and goserelin (decapeptide). The superficial lesio11S respond beuer than the d eep-seated lesions. Ceu"'relix (GnRJ I antagonist) -3 mg weekly x 8 weeks. Goserelin 3.6 mg momhl y subcutaneously. Leupt"'lide 3.75 mg i.m. monthly or 11.25 mg 3momhJy. 6. Aromatase inhibitors. Aromatase inhibitors available are letro:wle (2.5 mg), an asu·ozole ( 1-2 mg) and rofecoxib ( 12.5 mg) daily fo r 6 mo nths. These are amioesu"Ogen and should be give n with vitamin D ( 400 g IU) and calcium (I g) to preve nt osteoporosis. Nausea, vomiting and di arrhoea are tlte other side effec ts. Anastrozole is less osteoporotic tl tan others. They b loc k aromatase activity by preve nting tlt e conversion of androgen to oestrogen. T he)' may be combined with 2.5 mg nore tJtisterone. 7. RU486 (an tiprogestogen) is also u·ied in a dose of 10-25 mg dail)' for 3 montJ1S. It red uces pain and delays recun-ence. T he failure and rec urre nce following medical therapy is due to tJ1 e following: The drug cannot penetrate t11 e fibrotic capsule. Ectopic e ndo metrium respo nds less to hormones as compared to normal endometrium. Side effect; - Hormones prevem conception besides other co t1Sequences. MINIMAL INVASIVE SURGERY Honn on es delay pregnancy, so p•·imary surge•·y is preferred in infet·tile women. Re cent advances in ro naecology have

183

imrod ucedlapat"'scopy in tJ1e manage ment of pelvic endometriosis in young women. This o ffe rs the advantages of conserving the ovaries a nd tJ1 e fallopian tubes, and improving ferl.iJit). The method.1 emplu;·ed aTI! a.; folkJws: • Aspiration of pe.-itoneal fluid in cul-de-sac: It removes PG£2 and relie,es d)Smenorrhoea, pelvic pain and improves pregnanC)' rate. • Destruction of endomeu·iotic impla nts less than 3 em by diathenny caULel'it.ation, or ' -apo•·it.ation by C0 2 or Nd:YAG laser. Superficial lesions are easier to d estroy and yield beuer fertility results than the deep implants. Laser has the adva ntage of con trolling the deptJt of desu·uction by adjusting tJ1 e power density. It does not cause adh esiot1S and fibrosis. IL can be applied to the bowel and bladder. • Larger lesions and chocolate cyst ca n be excised. The residual lesion ca n be dealt witJ1 by ho nnonal therapy. Cauterizati on of the C)'SL wa ll is preferred in young women. It avoids ova ri an destructi o n with peeli ng off of the cyst wall but rec urrence is slightly high. • Role of s urgery • Failed medical tJ1e rapy • lnfertilit)' • Rec urrence • Chocolate cyst o f ovary • The consensus of opinio n is that cystec to my is more beneficial in extent of pa in relief, longe r recurrence time and longer pain-free in terva ls. However, tJt e excision of the cyst wall deprives tll e patiem of potential ova and t11ereb> reduces her fertilit) potential. In o lder women, excisio n of the C)SL wall is recommended. • Laparoscopic lysis of acl hesiot1S in the pelvis relieves dys menorrhoea and peh·ic pain. It also restores patency of the fallopian Lubes a nd O\ulation. Presacral neurectomy can be perfonned simultaneously. Bleeding and haematoma are its complications. Pregnancy rate following minimal invasive surgery is at"'tmd 30%-50%. • Laser ULerine n erve ablation ( LUNA) for midline pain in endometriosis is eff-ective in some cases. • Pregnancy rate following conservative surgery is 40%, 50% and 70% in severe, modera te a nd mi ld endometriosis, respectively. • Prolapse of genital tract a nd bladder dysfunction are noted witJ1 LUNA. It is advisable LO postpone laparoscopic tec hnique for 3 mo nths if hormon e therap)' has already been given to avo id unde r d iagnosis. OTHER MODAUTIES OF TREATMENT IN AN INFERTILE WOMAN ASSOCIATED WITH PELVIC ENDOMETRIOSIS (Fig. 14.10)

Ultrasonic-guided chocolate cyst asp iration followed by mifepristo ne for 6 montJ1s is also tried. • Mild endometriruis. Surgeq followed by superovulation

and IUl/fVF (aspiration of e ndometriosis cyst). • Advanced endometl'iosis in,olving t11 e fallopian tube. The choice is between wboplast) a nd IVF. Altematively, 3 montl1S of medical therapy followed by IVF. • Postopemti,·e medical therapy to deal with the residual tissue and pt-e\enL recu•·•-e nce.

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technically difficu iL Therefore, some prefer laparotomy over laparoscopy when repeat surgery is required. Indications for open surgery are as follows: • • • • •

Advanced stage of disease detected Large lesion -can be dealt with Medical therap) fails or is intolerable Recurrence occurs In elderly parous women

LAPAROTOMY Laparotomy is also required in advanced stages a nd for larger lesions if medical therapy fails or honnones cannot be toler-ated and for •·ectm·ence. • Dissection and excisio n of a chocolate C)'SL • Salpingo-oophorectomy. • Abdominal hysterecto my and bilate ral salpingooop horectomy. Surge•)' ca n be d ifficult due tO adh esio ns in pelvis. Mirena LUCO is an alte rnative to a repeat surgery. A premenopausal woman may need HRT afte r the rad ical surgery; ti bolone is safer than E2 P Lherapy. Scar endomeuiosis req uires excisio n or danazo l. HRT following bilateral ovluian remova l in youn g women may be prescribed under suict monitoring, as the 1isk of recurrence remruns. Calci um and vitamin 0 are added w HRT. lt may be better to dela) HRT by l-3 months tO reduce risk of recun·ence. As mentioned before, tibolone 2.5 mg daily is better than E2 and progestogen.

COMBINED THERAPY Combined therapy is indicated in the folio" ing conditions. • Preoperative GnRH monthly for 3 months reduces the sue and extent of the lesions, softens the adhesions and makes the subsequent surge•)' easier and more complete. • Postoperative honnonal ther·apy may be required if the surge•] ' has been incomplete, and some residual lesion is left behind clue to techni cal difficulty. It also reduces the rec urrence rate.

ENDOMETRIOSIS OF THE RECTOVAGINAL SEPTUM Rgure 14.10 (A) Endometrlotlc cyst (chocolate cyst). (B) Same as (A), except that the cyst has burst. (C) Cut section of endometriotic cyst . (Courtesy (A) and (B): Dr Vlvek Marwah, New Delhi.)

• Oydrogesterone 40 mg in the luteal phase re lieves pain without compromising inferti li ty, as it does not prevent ovt~ation .

• Pre- and postoperative hormonal therapy may alleviate S)'lnptoms but dela) pregnancy.

SURGERY Recun·ence following conse•vative surgery may be see n in 10% at the end of I >ea•· and 25% at the end of 3 years. Adhesions fonn in 10%, more \\ith cauteriLation than laser. These women may require second surge•·y, which may be

Recwvaginal endo me u·iosis "~th oblite •-a tio n ofLhe po uch of Douglas in volves the uterosacral Iigame ms, posterior fornix and anterior wall of the rec wm and sigmoid colo n. T he aetiology of this conclition d iffers from Lhat of pelvic endomeu·iosis. lt is not caused by deep in filu-ation of pelvic endomeu·iosis and reu·ograde mensu·uation b ut accord ing tO Nicolle et al., it is derived from emb•ro logically de•ived MCtllerian tissue and the theo•]' of Milllerian metaplasia applies here. Recwvaginal endometriosis contains more fibrous tissue than glandular tissue with flame-like appearance. Laparoscopicall). it is seen as a )ellowish-white appearance with small haemorrhagic areas and dense fibrotic adhesions.

CUNICAL FEATURES The woman is often of rep•·oducti\e age. She complains of dysmenorrhoea, d)spareunia abdominal pain, backache

CHAPTER 14 - ENDOMETRIOSIS AND ADENOMYOSIS

185

and menorrhagia. If the recLUm is invo lved, rect:a l pain, constipation and occasional diarrhoea may occu t: Cyclical rect:al bleeding is also reported. Ureteric compression with merosacral ligament involvemem causes renal damage. Speculum examination is painful. Red spoLS are seen in the posterior fomix. Bimanual examination reveals Lhickening of Lhe poste.-ior fornix and uLerosacralligamenLS. Rect:al examination should be perfonned to assess the rect:al involvement.

DIFFERENTIAL DIAGNOSIS The clinical featur·es mimic PID, diven.iculitis, colonic cancer and inflammatory bowel syndrome. INVESTIGATIONS Investigations include ultrasound using rectal probe, CA- 125 ( may be raised), MRI , but are nonspecific and unrewarding. Proc toscopy and sigmo idoscopy rule out malignancy. IVP needs to be don e if ureter appears involved. LaparoscO p)' is both diagnosti c and therape utic, and biopsy shoul d confirm the d iagnos is. MANAGEMENT Poor hormonal response makes lapa roscopic s urgery the u·eaunem of cho ice. Bowel preparatio n preoperatively is necessary in case bowel is invo lved and needs resection. Ablative and excisional techniques are employed depending upon the degree of involvement. Normally, bowel mucosa is spared, but in case su·icwre has fonned, resection of bowel mandates the involvement of anoreCLal SLu·geon. l\itirena lUCD is \et') effective in relieving S)lnptoms. PROGNOSIS Mot·bidity and quality oflife are influenced by CPV, dysmenorrhoea, cl)spareunia and renal damage. Malignam change is rare (1:150) and manifesLS as endometrioid cancer.

Fig...-e 14.11 (A) Adenomyosis of the uterus. (B) Adenomyosis of the uterus showing cystic spaces and myohyperplasia.

ADENOMYOSIS Adenom)•osis, also labelled as uterine endometriosis, is a relatively comm on co nditi o n in which islands of endomel!'ium are foun d in the wall of the uterus. It is observed freque ntl y in e lder!)' women. More tl1an one-third of the hysterec tomy specime ns from wome n aged 40 yea rs and above reveal the presence of adenomyosis, irrespective of tl1e indica ti o ns fo r hysterectomy. T he d isease often coexisLS with uterine fibromyomas, pelvic endome u·iosis ( 15%) and endometria l carcinoma. Grossly, tl1 e uterus appears symme u·ically en larged to not more than I )>tcmatic n:•icw. BJOC 20 II: 118:285. Donnezj, eta!. Fenil Stcril 1999:62:63. Duncan J, Shulman (Etb). Yearbook of Ob>tctric. and C~necology. 2010;347. Dunselrnan CA, Vennculcn N, Becker C, ct al. ESIIR£ guideline: man· agernent of women with cndomctrio>b. llum Rcprod 20 14; 29:400. Elt.abbakh Cn, eta!. Min en·,, Cin~- Dcrmat.ol 2013; 88:12 I. Kennedy Sn , ct al. Greentop Cuidclint:s 2006; 24. Mechsncr S, Kaiser A, rtctric; .md Gynecology 2009;9:226. Vercellini P, Fedele L, Aimi C, c1 al. lbsociation bemeen endomeuio· sis stage, le>ion t)'J)C, paticm char.tcteristics and se,erity of pehic pain spnptom.: a muhhtct Cp>i> and drug ther.tpy ofprolacrinomas. Drugs 1996:51(6):954. Cr.tndall CJ, llovey KM, Andrews CA, e1 al. Breast cancer, endometrial canct::r, and cardiov·..beular cvl'nls in participants who used vaginal L'Sirog~n in the Women's ll ealt h Initiative Obscrv.tlional Study. Menopause 20 18; 2.~: II. Duncan J & Shulman P. Yearbook of O~letrics, Gynaecolo~,'Y and Women's l lcalth , 2010;207. ECAB (Gn Rll ). Clinical Utxlatc in Obstetrics Gynaccok>!.'Y· 2010. Fdson DT, Zhang Y, l Iannen MT, el al. The eff," II , et al. Long,.enn honnone therapy for pcrimenopau;,.tl.tnd po>tmenopausal women. COchrane Database S)'>l Rt:v20 17: I:CD004143. Obs1e1 Gyneool Oin N Am Petiri DB. COmbination :utsc 2017; 24:728. Won>lcy R, Davis SR, Cavrilidis E, cl al. llormonal therapies for new onset and relapsed depression during perimcnopat.1$t:. Ma1uri1as 2012; 73:127.

COMMON CONDITIONS IN GYNAECOLOGY

17 Ectopic Gestation

19 Temporary and Permanent Methods of Contraception

18 Acute and Chronic Pelvic Pain

20 Medical Termination of Pregnancy

16 Infertility- Male and Female

201

Infertility - Male and Female

Physiology of Fertilization 202

Assisted Reproductive Technology:

Infertility 203

An Overview 225

Mole Infertility 203 Vaginismus 2 12

Key Points 226 Self-Assessment 226

Dysporeunio 2 13

Procreati on or desire to have one's own offsp ting is the great· est desire among human beings. Since inception of civilization, failtu·e to have one's own 1:>.'\by or infe n.ility has affected count· less couples both rich and poor alike. Infertility besides being a health issue is more of a social problem whid1 affectS per· sonal. social and mental health of affected person. lt is estimated that 1Oo/o-15% of married couples suffer from infen.ility. Due to changing social S)stem, professional life and academic ad1ievemem more and more couples face this problem. In India common I> held notion about infertility is that it is due to female paru1e1~ however, in actual life both pan.ners contribute equally to infertilit)t Following section discusses physiology of reproduction, common causes ofinfenility, modes of investigation and therapeutic approaches for infertility.

PHYSIOLOGY Of FERTIUZATION Conception results from the ferti li zation of the ovum by a spermatozoon. Much information is now ava ilable about the biological process whereby the spermatOzoon enters the ovum as ferti liza ti o n ca n be swdied in, in vitro fertilizati on (LVF) progn11nme. T he mec hanism whereb)' spe nnawzoa pass along the uterus is not proper!)' explained. A5 ciliary movement of the cervical and endometrial cpitJ1elia is downwards, the spermaLOzoa must migrate against t11e ciliar)' current. ltcan on !)' be assumed tJ1at spermato:t.oa, which live in an attractive alkaline medium of tJ1e sem inal nuid (pH 8), find the ac id environmem of tJ1e vagina l secretion (pH 4.5) lethal in a matter of 2-4 hours. The cervix has the same p H as the seminal nuid and is undoubtedly and demonsu-ably atu-active to the spermato£oa. SpermatOzoa are powerful, fast swimmers. and from tJ1e time of ejaculation to the t.ime of arrival in the ampulla of the tube, it takes about60 minutes for the spermato£oa to cover tJ1e intervening 20 em. This distance compared to the si£e of a spennatoLoon represents a t-apid and plll·poseful u-avel. The subendothelial layer of the endometriwn exhibits increased upward peristalsis

202

during th e fo llicular phase near ovulation ti me, and this ma)' hasten the migration of sperms into tJ1e fallopian tube. lt is now generally accepted that though a spermatozoon after ejaCL~ation may remain moti le for a long period, itS usefL~ life span is limited to 24 hours, and after tJ1is short interval, it is less capable of performing its biological duty. The period of survival of a mawre ovum is probably even shorter than that of aspermato£oon, and the time which elapses after its escape from a ripe Graafian follicle and its entry imo the fallopian tube during which it is potentially fertiliLable is eslimated atl2 hours and rarely up to 21 hours. The significance of this statemem is that coiws, to be capable of fet·tiliLat.ion, must take place in tJ1e 24-hour period around 0\'ulat.ion. Ovulation most commonly occurs 14 da)S before the onset of the next period, t110ugh variations are known. The fimbriae of tJ1e fallopian tube by muscular con u-action spread out over the ovary at t11e time of ovulation, a movemem which simplifies tJ1e u-ansport of the discharged ovum into the lumen of tJ1e fallopian tube. FurtJ1ennore, the musc ulawre of th e fallopian wbe undergoes rhythm ical conu-actions, especially at tJ1 e time of ovulation. It is most li kely tJ1e peristalti c co ntractio n of the fallopian LUbe that determines th e transport of the ovum towards the cavity of the uterus. T he sperm UHil reac hes the ovum first penetrates the zona pell ucicla and norma ll y inhibits enll) ' b)' o tJ1 er sperms. By tJ1e tim e the fertilized egg emers t11e uterine cavil)', the endo me u·itun has grown under the effect of progesterone into secretory endome u·ium and is ready tO receive tl1e egg for implantation and provide itS n utrition. On general biological principles, tJ1e blame of infertili ty should be shared between tJ1e two partners. It is not tmcommon for patients to complain of difficulty during coims when they have little knowledge of the correct metJ1od to be employed DLLI·ing sexual intercourse, tJ1e erectile tissues aroLmd tl1e vaginal orifice become engorged and the vaginal o tifice becomes more pan~ous. There is a discharge of mucous from the ductS of Ba•·tl10lin 's glands, "hich acts as a lubricant. The female orgasm is induced by stimwation of tl1e clitoris pat·tJy of spenns. A normal sperm is motile, 50 microns in length, half the siLe of ovum and consistS of a head covered by an acrosomal cap, neck, body and tail. Hypospennia means low volume, less than 1.5 mL. This may be d ue to improper collection or retrograde ejac ula Lion. I lype rspe nnia with more than 5.5 mL means prolonged abst.inence or inflammation of seminal vesicle. The most important facwr is the density of tJ1e sperm, and countS below 15 million/ mL are usually associated with infenjJity. Oligospermia is mild when the coum is 10-20 million, moderate when 5-15 million and severe when less than 5 million/ mL spenns a•·e seen. If one repon shows abnormal findings, the patient should be instructed to produce another specimen after a momh or so. During this Lime, tJ1e patient should be advised LO take a good nuu·itional diet and restrict smoking and consumption of alcoho l. He should take cold or tepid bath and discard Light underwear. Only after two negat.ive or below average co unts, he shou ld be proclaimed azoospennic or o ligospermic. If so, chromosomal stud)' should be done

207

A few normal spenns and normal testosterone suggest reu·ograde ejaculation. Cenu·ifugecl specimen can be used for intrauterine insemination (l UI), IVF. Postcoital Test (Sims' or Huhner's Test, PCT)

The couple is advised imercourse close to ovulation Lime preferably in tJ1 e early hours of the morning. T he woman presents herse lf a t the clinic witJ1i n 2 ho urs after the interco u rsc. The muco us is aspirated from iJ1e ce rvical canal and spread ove r a glass slide. Another smear made from iJ1e posterior fornix serves as a control. Normally 10-50 motile sperms are seen per high-power field in cervical mucous. If there are less than I 0 sperms, proper semen anal) Sis should be undertaken. The sperms should show progressive, but not rotatory movementS. The presence of antispennal antibodies in the cervical mucous leads shaky or rotatory movementS to tJ1e sperms or may totally immobilize them. The cervical mucous is simultaneously exam ined for iLS quantity, viscosity and fern test. T he advantage of this test is iJ1atthe cervical mucous can be simul taneo us ly s tudied for oes u·ogenic effect and ov ulation, iLS capability to allow sperm penetration and th e presence of any an tisperm antibodies. The test is useless in the presence of cervical infection, which sho uld be treated before performing the postcoital test. Immunological facLOr is encountered in 5 % cases. This test is less emplo)ed lately, and many gynaecologistS consider this obsolete. This is because the)• resort to I Ul, if semen analysis is abnonnal. A test called the Miller-Kurzrvk test consistS of placing ovulation mucous on a glass slide alongside the specimen of the husband's semen and studying the penetration of sperms under iJ1e microscope. Normal cervical mucous permitS invasion by motile sperms. Penetrat.i o n less iJ1an 3 em at30 minutes is abnormal. Sperm Penetration Test

The physiological profile of the sperms can be studied in vitro b) using the zona-free hamster egg, which resembles the human ovum. A normal spenn is capable of penetrating the LOna-free hamster egg, showing iLS fertiliJ:ing capacity. The test is expensive and not reliable. Sper·m agglutination testS, immobilil8tion testS and immunoglobuli n specific assays are avai lable to detect immunological defectS in the semen. Semen-cervical Mucous Contact Test

Equal quantit)' of semen and mucous is mixed, so iJlat there is no interface. In the presence of antibod ies more than 25% sperms show jerky or shaky movements by 30 minutes. The cross-d1eck with the donor semen will indicate the source of antibodies, whether it is cervical or seminal antibodies. 'Ji!!.tiwlar biopsy. Testicular biopsy is indicated in aLOospermia to distinguish between testicular failure and obstruction in the vas deferens. It also re,•eals whether iJ1e seminiferous tubules are no•·mal but unstimulated by tJ1e anterior pituitary gland, or whetl1er tJ1 ey are incapable of function clue to p rim a •) ' gonadal fai lure. Tes t.i cul ar b iopsy wi ll estab lish whi ch of the facwr is at fau lt (Figs 16.3 and 16.'1). The biopsy can also diagnose genital tuberc ulosis. The tru-cut biopsy under local anaestJ1esia is simple tO

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SHAW'S TEXTBOOK OF GYNAECOLOGY

• Fragmentation of sperms suggests infec tion. Chlamydia! and other infections sho uld be investigated. • Sperm fertilization poten Lial. In !VF. tl1is test is useful in selecting the best spenn for fertilization. This is called h) psmolic swelling test (HOS). The spenns are u·eated witl1 h)psmotic saline. If the spenn membrane is intact, the sperms swell up and coiling occurs. These are the best spenns.

MANAGEMENT OF MALE lNFERTlUTY Management is based on t11e assessment of coital function, semen examination repon and the result of tl1e postcoital and immunological tests, as well as hormonal repo•·IS (Fig. 16.5). !. Ed ucation. This involves: (i) sexual counselli ng- coital Rgure 16.4 Testicul ar biopsy. Tubular atrophy showing the Sertoli cell s only (x250). (Courtesy: Dr Sandeep Mathur, AIIMS.)

2. perform. One to tJ1ree per ce nt ma les have e ndocrine dysfunction. In recent time~, tlw testit~tlttr biof>~)' has a very big role to f>l«)•. IIJmrt from chromosom(l[ and histolo[.,riWl st·tuly, the testicular ti~Hte provide~ cryof>re~ervrltion in assisted -ref>roduction. The sperma tozoa as we ll as spe rmatids exu·acted from tl1e testicular tissue ca n be used in imrac ytOp lasmic semen insemination (ICSI) in assisted reproduction. Sperm morphology is studied b) preparing a slide, air-drying, fixing it witl1 70% alcohol and staining with Pap stai n. FSH level. A high FSH level denotes primary gonadal failure. A normal level in uoospermia suggesiS obsu·uctive lesion in the vas or epidid) mis. A low FSH level indicates pituitar)' or h) potl1alamic fai lure and a need for FSH/ LH / Gn RH u·eaunenl. Prolactin level more than 30 ng/ mL indicates h) perprolactinaemia requiring u·eaunenL Low testoste•·one IC\el indicates low LH or Leydig cell dysfunction. No •·esponse to GnRJ I suggesiS pituita•)' failure. Chromo:.o11UJl 5/udy. Ka•')Otyping should be undenaken in azoospennic men, as 15%-20% of t11em have chromosomal disorde•:s. The most common disorder is Klinefelter syndrome witl1 47XXY ka •)'Otype. l mmwwlogiml d~ordm. A recent interest in immunological aspects of infe 11.ility has led to the detection of various sperm antibodies, both in the se minal plas ma and in the cervical mucous. Immuno logical factors may be important aetiologicall y in up to 5% of patients witl1 male infe rtili ty. An immuno logical test is req ui red in ca~e of an abno rmal postcoital test, abnorma l semen profile and unexp lained infertili l)'. ELLSA and RIA LeSts determ ine antibodies to sperm, seminal p lasma and ce rvical secretion. Ultrawwul ~auwing. The ul u·aso und scanning of the scrotum deteciS SCI'OLal volu me a nd varicocele and is useft.LI in ultrasound-guided biopsy. Colo ur flow Doppler and scrotal thermograph) detect varicocele. • Vasogram. It is required when normal FSH level is associated witl1 at.oospermia to rule out obstruction in the vas. • Urine examination. In suspected reu·ograde ejaculation, postejaculatOI') urine is made a lka line and centrifuged. The presence of spenns in the lll·ine proves retrograde ejaculation.

3.

4. 5.

6.

7.

frequency and timin g, (ii) coital position and (iii) masturbation leading tOsperm d ilution. Substance ab use. Advi ce on avo idance of tobacco (smoking, chewing), modera ti on in co nsump tio n of alco hol a nd avo idance of drug ab use. Antioxidants, vitamin E imp rove semen parameters. Pentoxifylli ne 400 mg Li.d. imp roves sperm mo ti li ty. Red uce heat around tl1 e scro uun. Avo id ho t baths, wear loose cotton 1mderwear (cotton clotJ1ing LO enco urage ventilation) , avoid stren uo us aCLivities and occupation in hot environment and control obesity. Correct endocrinopatl1ies. Prompt attention to diabetes and tl1yroid disorders. SLLrgical. Surgical correction of varicocele after t11e diagnosis has been confirmed on ultrasound scan ning helps tO improve spenn motilit). Though recently percumneous embolit.ation of va•·icocele is atLempted, damage tO the testicular artel')' and recun·ence of \ll\l·icocele make microsurge•')' the gold standard and the best option for \'llricocele. Lately, tl1e beneficial effect of \ll\l·icocele surgery is questioned by many who feel that the surge•')' for correction of valicocele has no rol e in improving male infertilit)'· Surgical con"ection of the undescended testes in childhood improves the semen quali ty in 60%-70% cases. The obstruction in the vas by mi cro surgical vasovasal or vaso-epididymal anastomosis wi ll restOre patency. Ephedrine 60 mg orall y four Limes a day for 2 weeks or a-adrenergic drug such as phenylep hrine (2.5 mg) is tried in retrograde ejacu la Lion. If tl1is fa ils •-econsu·uctio n of the b ladder nec k is reco mm ended. Va~ovasos to my in the reversal ofvasecLOI'n)' operation yie lds a poor res ult if an interval of more tlHin 5 years has e lapsed s ince vasecLOm)', because of the forma tion of sperm antibodies. Antibiotics. Infec tion ind icates the need for appropriate antibiotics to treat epididymo-orc hiti.~, prostatitis and sexually transmitted diseases. Doxycycline 100 mg b.i.d. for 6 weeks is beneficial for chlamyclial infectio n. Role of oxidating su·ess on sperm func1jon t11rough prooxidants liberated b) leuCOC)Les, and ab normal spenns is now reali£ed. Some have observed improved spenn coLUH b) prescribing I)COpene 2 mg daily and vimmin E. AntioxidaniS contain vitamin E 100 mg, \~tamin C 500!000 mg, -acet) lcysteine 200-500 mg Li.d., carniline 3 g daily, selenium 225 mg, pentoxif) lline 400 mg Li.d. L)copene 2 mg daily for 6 months is repo•·ted to

CHAPTER 16 - INFERTILITY- MALE AND FEMALE

I

I

Male Infertility

1

[

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Semen examination

I

l Normal findings

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]

l

!

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Abnormal findings

r

1 lUI 3-6 cycles

209

1

I Investigations

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1

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Hormonal. FSH, LH, E2, prolactin, testosterone

If sperm count> 10 million/ml • Without ovarian stimulation • With clomiphene or letrozole • WithhCG

Ultrasound

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1 Biopsy

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I

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Failed lUI

~

IVF. If count> 1 o6 progressive motile sperms

Figure 16.5

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ICSI. If count O.Sx 106, progressive sperms

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Correction

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! Failure

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Management of male infertility.

improve quality of the spenns and preo.·e m spenn 0 A damage, but data-based eo.•idence is lacking at presenL 8. Premature ejaculation. Selective serotonin reuptake inhibitors take 2 weeks to reach the therapeutic level, but dapoxetine works within I hour; 30-60 mg is taken I h our befo•·e imercolJI-se. 9. Hormon es. Testosteron e, piwitary honn ones and GnRH h ave all been u·ied to improve spenna10genesis with variable res ults. Bromoc riptin e is useful in hyperprolactinaemia.

HORMONAL THERAPIES FOR MALE INFERTIUTY I. 1-ltunan cho rionic go nadotrop in (hCG) 3000 IU i.m. thri ce wee ki)' for 12 weeks. Alte m ati ve ly, 5000 IU twice weeki)' may be given. l...'\tely 2500 IU dose has been recommended. The reafte r, 37.5-75 mg FSH subc utaneous !)' is added thrice a week. Follow-up wi Lh testosterone level and seme n analysis. It takes 6-9 months to prod uce normal seme n co un ts. Stop FSH, but continue \\~th hCG. About40% pregnancy •-ate is reported. 2. Testosterone- An oral daily dose of25-50 mg improves testicular function. A larger dose of 100-150 mg daily suppresses spermatogenesis. After a 3-momh course of treatment. rebound phenomena occur with improved spermatogenesis. 3. Clomiphene- A daily dose of 25 mg for 25 days followed by •·est for 5 days is gi,·en C)clically for 3-6 cycles. It is recommended in h) pogonadal infertility, but is not

4.

5.

6. 7.

8.

effective in h)pogonaclal h)popiwita•·ism. Instead of clomiphene, letrowle 2.5 mg may be e mplo)ed. Human menopalLSal gonadou·opin (hMG) 150 IU thrice a week for 6 months is recommended in pituita•)' inadequacy, but it may take as long as I year to induce spermatogen esis. GnRH- is indicated in hypoth ala mi c failure. GnRH 5-20 meg subcuta neously 2 h ourl y for 1-2 years. Nasal spm y is also available. Tamoxifen- A daily dose of I0 mg for 6 months has been found effective in so me cases. Dexa me th aso ne- A dail )' close of0. 5 mg o r 50 mg prednisone daily fo r 10 da)'S in eac h cycle for 3-6 months is recomm ended in the presence of spennal antibodies. About 25%-40% pregnancy rate is obse rved, Lhough avasc ular necrosis (AVN) of th e head of Lhe fem ur and osteopenia as side effecLs have to be borne in mind in a prolonged therapy. Cyclosporin A- A daily dose of 5-10 mg/ kg for 6 monLhs is better than corticosteroids in T-cell suppressio n. If corticosteroids are contraindicated, an anli-i nflammatO I)' age nt such as naproxe n 50 mg twice dail) ma) lower the antibody levels. Sildenafil (Viagra)- A dose of25-100 mg I ho ur before imercourse imprO\es erectile functio n but recem repons o n ischaemic heart disease is alarm ing, and should be presc1ibed with care. Colour ' 'isual disLu•·bances, headache, rhinitis and dyspepsia have also been reponed. It is contraindicated in men on antih)penensive

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drugs. Sildenafi l dye is used only in erectile dysfunction, and does not improve libido. With 25-100 mg orally 1 hour before imercourse, the effect lastS for 1-2 hours. The drug is effective in 50%-SO% cases. It is contraindicated in the following: • Retinitis pigmentosa. • Diabetic re ti no palll). • Patient on antih)penensive drugs, nitrates. • Cardiac disease, p•·~·ious m)ocardial infarct, stroke. Local self-it1iection of \'li.SOOCtive drugs for erection is taken 5-10 minutes before intercourse and is 50o/o70% effecthe. Side effects are penile fibrosis, infection and prolonged erection. Prostaglandin E1 causes penile vasodilatation. Urethral pellets are also available. Penile vasctdru· surgery and penile proSthesis im plantation rods are also available for erectile dysfunction. Pe nile implant AMS 700 is three-piece inflatable penile prosthesis whi ch is now available. 9. Artificial insemination. An artificial insemina ti on with husband's semen for four cycles ha~ yielded 30% overall success witl1 10% success pe r cycle. T he resultS are better if co mbined witl1 ovul ati on inducti on for multiple ov ulation, and this is tJ1c practice recommended today. lt is indica ted in the fo llowing: • Chronic medical disorder. • Oligospermia im potency- ejac ulatory failure. • Pre mature ejac ulatio n, re u·ograde ejac ulation. • Hypospadias. • Antispermal antibodies in tJ1e cervical mucous. • Unexplained infertilit). • It is also possible to free.te the semen if tl1e husband is a frequent traveller and not available at the time of ovulation for lUI. The semen can also be frozen and used later in case the husband needs to undergo radiotherapy or chemotherap)'· • HI V-posithe male or female. Techniques used for artificial insemination include (i) intrauterine insemination (lUI) (ii) intracervical, (iii) pericervical and vaginal and (iv) vaginal insemination. The semen is washed, concentrated and its quality improved by the 'swim-up' technique or by use of Percoll gradienL The semen \\i th notm al spe rms witJ1 good moti li ty Ull.tS obtained is then inseminated into tl1e female ge nital u·acL Obviously, artificial insemination is done aro und ovul ation. About 1/2 mL of co ncen ue•·culosis ma)' lead to infertility. Smoking is known to impair ova•·ian function and prevent embrro implantation in to tl1e endometrium.

WORK UP OF FEMALE PARTNER Approach to a female pa•·u1er of infertile couple comprises the following: • Hiswry. • Examinat.ion. • Special invest.igations.

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SHAW'S TEXTBOOK OF GYNAEC OLOOY

History

Age of the woman, past obsteu·ic history in case of secon dary infertility regarding puet·peral infection, coital difficulty and mensu·ual histO•)' gi1e clues to the possible cause. History of tuberculosis and p•·evious pelvic infeclion is importanL HistOry of diabetes and th) roid dysfunction may be evidenL The duration of infe11.ility and previous use and the type of conu-aceptive ma> be linked to infertility. Examination

This includes height and weight of the woman; blood pressure should be checked. llirsutism. palpation of thyroid and lymph nodes, palpation of tl1e breasts, tl1e presence of galactorrhoea suggest hormonal dysfunction. An abdom inal swelli ng may be d ue to uterine fibroid . Biman ual pelvic examination will reveal an obvious gy naecological cause for inferti lit)'· Tests for Tubal Patency

Hysterosalpingograp h)' (IISG) and di agnostic laparoscopy with chromo wbat.io n a re two comm on ly used tests for tubal pa te ncy. A mere pa tency of the tubal lum en is no t the only Ctiteri a to affect fertility. T he normal p hysiological fun ction of tl1e fallopia n tube is essen ti al for pregnan cy to occ ur. The endosalpin x is lined by ciliated epithelial cells and the secretOry cells. T he cilia help in propulsion of the fertili zed egg LOwarcl5 the uterine cavity. The secretory cells provide nutrition to the spenns as well as tl1e ovum during their passage across the LUbe. The pe•·istaltic movements of tl1e fallopian tube are under the influence of oesu·ogen, progesterone and prostaglandins, and S)nchronized movementS help in propulsion of spenns and the fertiliLed egg in either direction. The 01nt ovulation in /VI~ lUI all(/ in timing inlercourse.

This requires daily ul trason ic visualization of ovaries from the IOtJ1 tO 16th day of the mensu·ual cycle. It is noninvasive, acc ura te a nd safe. Apart from fo llicular study for ovulation, pelvic pathology if any can be picked up and endometrial tJ1i ckness measured. The foll icle grows at the rate of 1-2 mm daily to reach 20 mm or more when follicular

ruplllre and ovulation occur at miclcycle. The sudden disappeara nce of the follicle, presence of free flu id in tJ1e pouch of Do uglas and growth of corpus lute um are evident. Endometrial thickness of 8-10 mm is tJ1 e norma l response of endometrium to progesterone. A lesser thickness indicates corpus luteal phase deficiency (CLPD).

HORMONAL ASSAYS Plasma Progesterone

Plasma concenu-ation of progeste1·one rises after ovulaLion and reaches the peak of 15 ng/ mL aL mid-luteal phase (22-23t·d clay) and then declines as the corpus IULeum degenerates. A low level of the plasma progesterone below 5 ng/ mL at mid-luteal phase, suggests co rptL5 LPD and pro mpts hormona l therapy. Use of da il )' progesterone suppository in th e luteal phase or administratio n of hCG 5000-10,000 IU weekly wi ll help to improve the chances of conception. Oral micronized progesterone 100 mg b.i.d. or 300 mg vaginal pessary twice dail) is useful in corpLLS LPD. Weeki) proluton injection (500 mg) and oral dydrogesterone are also used. Cot·plLS luteal phase deficiency Aetiology: • • • • •

Hypopituitar·ism with low FSH, LH Poor follicular developmenL Hyperp rolactinaem ia. Clomiphene citrate (CC) ovulation inducti o n. Reui eval of egg in IVF. CLPD is see n in posunenarchal and premenopat.LSe period.

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SHAW' S TEXTBOOK OF GYNAECOLOGY

• Poor response of endometrium to endogenous progesterone. Diagnosis: • BB'[ • Mi d-lutea l progestero ne es1i maLion (normal 15 ng/ mL) . • l.!:ndome u·ia l biopsy.

Treatme nt: Administra tio n of progestogen or hCG adminisu-ation i.m. weekly. LH

LH surge from the ame•·ior piwita•1' gland occurs about 2 1 hours prior LO ovulation. Radioimmunoassay of the morning sample of urine and blood gives the LH resultS in 3 hours. ot only does the LH surge help in predicting ovulation, but t11e approximate Lime of on~ation can be gauged and co itus aroun d this Li me can improve t11e chances of concep ti on. Ga ug in g the time of ovula ti on has tllerape uLi c app licati o ns in IVF a nd in a rtific ia l inse min a tio n. LH kiLS are now ava ilable. Hyperprolactinaemia

It is seen in pituitary adenoma, hyperplasia, hypot11yroidism and witl1 tlle usage of drugs, i.e. metoclopramide, cimetidine, n~eth)ld?pa. Hyperprolactinaemia (more than 25 ng/ mL) w1ll reqlllre X-ray of p•tllltary fossa or CT scan, and a f·undus examination to exdude a neoplasm. Macroadenomas ma> require surgery. Microadenomas and hyperprolacLinaemia respond to Bromocriptine and allied drugs (see chapter on Hormonal T herapy).

FSH Ra ised FSI-l leve l is seen in ova li a n fa ilure. Low FSH le ve l in d ic.ates pitui tary dysfun cti o n a nd anovulation. Norm al FS H level in the preovulatory p hase is 1-8 m lU/ mL, a nd LH level at ovulation is 1-5 mJ U/ mL FS H level> 25 IU/ m l clomiphene on day 3 fu ils ovulation. Thyroid Tests

These should be done especiall) in case of h) perprolactinaemia. l-l)pot11yroidism witl1 raised TSI-l level is related to hyperprolactinaemia. Ovarian reserve o r premaLUre failu re incl udes bo tll q ua lita ti ve a nd q uantitative esti mation of FSl-1/ LH. MANAGEMENT OF ANOVUlATION Anovulation is a common problem encoumered in inferti lity. Several endocrin e disturbances contribute to itS occu•-rence; hence, d ifferent drug combinations are required to obtain optimal resultS. Following are the common!)' used drugs for ovwaLion induction: Clomiphene Citrate

Ovu lation should be ind uced with CC, with a dose of 50 mg/ da)' starting fro m da)' 2 to day 6 of the cycle fo r 5 clays. Ov ula ti o n is mo ni tored by seri a l 1~traso und mo nito rin g of the foll ic ula r size, a nd occ u•Te nce of ovula ti o n. If the response to 50 m g CC is no t s:uisfactOI)', the d ose o f CC should be increased to 100 mg/ day from da)' 2 to day 6.

Fun.her increase in dosage dose of CC, if •·equired, should be undertaken in an infertility set-up, where monitoling facilities b) sonography and honnone estimation are easily available. If clomiphene t11erapy fails following six cydes, other regimen of ovulation ind uc tion is recommended. T his regime requi res constant mon ito ring, so t11e u·eaunent s ho uld be initia te d in s pec ial inferti lity c li ni cs. T h e risk o f mu lti ple ovula ti o ns a nd mu lti p le pregnanc ies with this regim e is aroun d IO%. In hypo th a la mic d isorder, GnRH is g iven to stim ulate the pitui ta •)' FSH and Ll-1 and tll e foll iculogenesis monitored. T he pituita •)' and hypotl1alam ic stimulation is often emplo>·ed in in vitro and Gl}! techniques to avoid peripheral suppressive oesu-ogen action on cervical mucous and endometrium by clomiphene, and to improve the fertility mte. Letrozole

Leu-o:wle 2.5 mg (nonste1-o idal a•-omatase in hibitor) is fo Lmd s u perior LO c lomip he ne, whic h has no suc h adverse actio n. With lc u·ozole, ovu la tio n occ urs in 90% of cases a nd with a p regna ncy ra te of 40%-50%. Le trozo le is g ive n 2.5 mg da il y fo r 5 days starting on th e seco nd da)' of the cycle or 20 mg single dose o n day 3. Letrozole has no adverse pe•·ipheml action on endomeu·ium and cervical mucous as witl1 clomiphene (antioestrogen action). It, however, causes drowsiness (no women who fail to respond to CC + h MG treaunem as well as amenorrhoeic women wit11 low oesu·ogen levels need to be treated with hM G + hCG as deta iled be low. Combin a ti o n of hMG + hCG l. Pe rform

scanning.

baseli ne

oestradio l assay and

ulu·asound

CHAPTER 16 - INFERTILITY- MALE AND FEMALE

2. Administer hMC, two ampoules (75 IU each) per day for 3 days. 3. RepeaL oestradiol. If it is doubled, monitOr hMC dosage; if noL increase hMC dosage by 50% for 3 days. 12 em, weight gain > 5 kg

Grade V

Grade IV .,. hypovolaemia, hyponatraemla, hyperkalaem Ia, Increased blood viscosity, hypercoagulabllity, decreased renal perfusion, oliguria, hypotension, hypoprotelnaemia, thrombosis, coagulation failure, electrolyte Imbalance, leucocytes > 15,000/mml, hepatic, renal failure Haematocrit > 55% and se· rum aeatinine > 1.6 mg%

OVARIAN HYPERSTIMULATION SYNDROME OHSS (Ta ble 16.:l) is a compli cation of assisted reproductive technologies and an iau·ogenic complication occurring in t11e luteal phase or ea rl)' pregnancy. It is a poten ti all y lifethreatening condiLion, occu rring in I %-10%. It results fr om inductjon of ovulation in infertility cases. It is m ore co mm on in FSI I/ LII the rap)' than c lo miphe ne a nd pu lsatile GnRl-1 drugs. Its inc idence is hig he r in PCOS a nd a novulatory infenilit)' com pared to infertility ca used by amenon·hoea. Raised Ll-1 in PCOS is responsible for hypers timula tion, and hCC sho uld not be incl uded in the ilierapy in these cases. hCC adm inistration increases th e risk, so also the dose of drugs, size and number of ovarian follicles. It is also common in a conceptional cyde if m ulti ple ovulation OCClli'S. It is characteri:t.ed by ovarian e nlargement, pleural and peritoneal effusion, oliguria, liver damage and thromboembolism. Severe form of O H SS occ urs if Lhe woman conceives during tl1at C)cle.

PATHOGENESIS

COMPUCATIONS OF OVULATION INDUCTION • Multiple pregnancy • O HSS

The main reason for 0 1ISS is the increased vascular permeability leading to Ouid shift from inu-avascul:u· to exu-avascular space. This catLSCS decreased blood volume

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SHAW'S TEXTBOOK OF GYNAECOLOGY

and decreased a lbum in as we ll as decreased elecu·olyte levels. lt leads to accum ulation of fluid suc h as ascites and hydrotJ1orax. The increased vascular permeability is due to prostaglandin, C) tokines and growth factors secreted by multiple growing follicles. The •·isk factors for O HSS are as follows: • • • • • • •

Young age of the woman PCOS Previous OHSS Increased oestradiol level > 3000 pg/ mL 20 or more small follicles Increased renin and angiotensin Factors Vascular endothelial growth Factor (VEGF) causes neovascularization of g•-anulosa cells and increased E2 level • PCOS hi gh LH/ FSH •-atio, h CG and pregnancy in stimulated cycle • FSH/ LH causes higher incidence of O HSS (30%) than clomiphene ( 10%) a nd Gn RH ( I %) • O HSS can be predicted b)' hig h level of E 2 (>3000 pg/ mL), more Ulan 20 fo lli cles o n ulu·asound a nd in creased Doppler b lood flow. T he re is in c reased release of renn in and angio te nsin .

COMPLICATIONS

• Diuretics and NSA!Ds sho uld be avo ided beca t.LSe of hypovolaemia and poor renal perfusion except in pttlmonary oedema and to correct e lectro lytes. • H igh thigh venous support stocking preventS deep venotLS thrombosis. • l mmtuloglobulins i,,, ma) prove to be effective. • Glucocorticoids. • Anticoagulants- hepa•·in. • Dop:unine improves renal blood flow, o ligu•·ia :u1d prevents renal failure. • Correction of elecu·ol) tes.

INVESTIGATION AND MONITORING Investigation and monitor·ing are done by u1e following: • H b%, T LC, platelet count- T LC 15,000 and haematoc•·iL • Urea, electrolyte estimation, se rum protein level. • Repeat ultrasound to mo nitor size of ovarian cyst a nd ascites. • Weight recording. • Re nal function tests. • Liver function tests. • Coagula ti on profi le. • Central venous press ure reco rding. • X-ra)' chest for p le ural effusion.

Complications of OI-ISS are as follows: • Vascular - cerebrovasc ular accide ntS, t11romboembolic phenomenon, deep venous unombosis • Coagulopatll) • Liver dysftmction • Adult respiratOI') disu·ess catLSed by ascites/ hydrotllorax • Renal Failure due to h) povolaemia • Gasu·ointestinal - Re lated to E2 level • Torsion and haemon·hage in t11e ov:u·ian C)'St

PREVENTION hCG should be withheld in a cycle if more than 20 follicles are seen on ultraSound and E,.lievel rises tO 3000 pg/ mL In PCOS, it is pi'Udent to withhold hCG. Albumin 5% infusion in 500 mL la ctated Ringer's solution du•·ing and after oocyte retrieval prevents O HSS. Dopamine agonist Cabergolin e 0.5 mg daily for 8 days sta rting on day I of hCG avoids OHSS. O HSS occ urs wi u1 s mall e r u1 an la rger folli c ular size 5 to 8 days after hCG ad ministra tio n. It is a n ia troge nic conditi o n of in creased vasc ula r permeabili ty resulti ng in e xudation of fl uids from the in travascu la r LO t11 e ex tracellular comparun ent. Progesterone suppo n he lps.

TREATMENT OHSS requires hosp ita liz.'ltion. Med ical therapy includes following:

• l.v. fluid... for llypUIIQ/a~mitt. Colloids, plasma expanders or human albumin infusion 5 % in 500 m L Ringer's lactate. Half-life of albumin is 3--10 days. Fifty grams of albumin (25% albumin in 50 mL) 1-aises blood volume to 500 mL H uman albumin 20% with 2 L of dextrose may be needed. GeloftLSine fo•· h) povolaem ia ma)' be requiredcontinuous autotransftLSion of ascitic fluid (C\TAF) is performed for 5 hours each day.

Surgery is required if tJ1e ovarian cys t ruptures, un dergoes tOrsion or haemorrhages. Aspi•-ation of ovarian cyst, ascites, plettral and pericardia! effusion may be required.

PERITONEAL FACTORS Pe 1itoneal disorders include periwbal adhesio ns :u1d endomeuiosis, and are diagnosed on laparoscop)'· Therapy consists of ope•-ative laparoscop)' for adhesiolysis, ablation of endomeu·iosis, incising the c hocolate C)'St and removing its lining at laparoscopy. Dilatation of fimbria! phimosis, opening of the terminal e nd of a h)drosalpinx and microsurgery for restoring wbal patency :u·e also possible with laparoscopic methods.

ENDOMETRIOSIS Endomeuiosis, associated with inferti li ty, is treated m edicall y, s urgicall y or as a combinatio n of t.h e two.

LliTEINIZED UNRUPTURED FOLLICULAR SYNDROME LUF S)'ndrome is see n in 9% cases of infertility and is diagnosed on l)' on ulu·asow1cl scannin g. Micro nized progesterone or hCG is needed in these cases (Table 16.2 ).

UNEXPLAINED INFERTILITY Infertility is labe lled as unexplained when no obvio tLS facwr is found in male and female partner. Approximately 10% of infertilit) accounts for this subcatego•·y of infertility. H owever. the more we investigate in depth lesser becomes the proportion of unexplained infe,·tility. Common conditions which may account for unexplained infertility a•·e immunological factors, clinical or subclinical

CHAPTER 16 - INFERTILITY - MALE AND FEMALE

hypothyroid ism, hyperprolaCLinaem ia, functional disorders in the partner. Many a Lime, infertilit) is unexplained, but this could be attributed to inadequate or inefflcien t investigations and inabilit) to detect biological capability of the sperms tO fertiliLe an ovum. Spe•m dysfunction and its biological function are now detected on computer-assisted semen analysis (CASA). Abnormal acrosome reaction and spenn~ocyte fusion defects ha'e been identified by CASA and male infertility problems better understood. It has been observed that 20% of such unexplained infertile couples succeed in having a baby in clue cow-se of waiting. Perhaps newer and advanced technology in this field may yield a bener pregnancy rate of 40%-50% in future, albeit at a high cost. When all fai l, and the couple is desperate tO have a baby, adopti on is recommended.

ASSISTED REPRODUCTIVE TECHNOLOGY: AN OVERVIEW Assisted rep rod uctive tech no logy (A RT) comprises a group of procedures t11 at have in common the handling of oocytes and sperms ou ts ide of the body. The gametes or embryos are replaced into t11e uterine cavity tO establish pregnancy. These procedures, although benefited many infertile couples (20%-10% pregnancies), are stressful and very expensive with complications such as O HSS, multiple pregnanC). abortion and ectopic pregnancies. Although no gross fetal malformations have yet been reported, a long-tenn study is requi•·ed to detect subtle and late complications.

DEFINITION AJtr refe1-s to any fertility u·eaunent in which the gametes (sperms and ova) a•·e manipulated. Accordingly, ART p•·ocedures in volve sw'gical removal of eggs known as eggmtrieual. IVF is tl1 e most common ART procedure. It was fi 1"St successfull y used by Steptoe and Edwards in tl1e UK, leading to the birtl1 of first IVF baby Louise Brown in I978. Since then, mi llions ofbirtl1s have been ac hieved witll tl1e successful use of these techni ques.

INDICATIONS The co1runon indications for ART proced ures include the following: • Abnormal fallopian tubes: Blocked wbes or absent tubes (surgical removal). • Endometriosis-related infertility. ldiopatl1ic or Lmexplained infertilit). • Male factor infertilit). • Immunologic infertilit). • Failure of o,·ulation - donor ovum. Bilateral oophorectomy for diseased oval'ies, i.e. endomeu·iosis and ovarian cancer.

225

INVESTIGATIONS PRIOR TO ART • Semen analysis, semen culture and sensitivity. • Complete work up including t11yroid function tests, blood sugar. serum prolactin level. • Serum FSH on cia) 2/ 3 of C)cle. Serum oestradiol on day 2/ 3 of C)cle. • Test for ovarian reserve: Measurement of anliMulle•·ian hormone (AM II ) is considered the best test. This is indicated in women older than 35 ye:u-s, smokei"S, presence of only one ovary and unexplained infertility. It invohes standard day 3 laboraoory testS as mentioned abo,e, along with administration of IOO mg clomiphene citrate (CC) from clay 5 to day 9, repeat FSH on day I 0. FSH va lues must be the same as on day 3 of the eye! e. • Serologic evidence of chlamydia ! infection. Zona-free h amster oocyte penetration test to asses fe rti li zing capacity of sperm (op ti onal). • En hanced sperm peneu·ation tes t using TEST-yolk b uffer. • Tes ting both partn ers for antispe nn an l.ibodies. • Assess uterine cavil)' h)' hysteroscopy/ u·ansvaginal sonograph)'· • H)•drosalpinx reduces IVF success rates by 50%. Success rate increases to expected rates after surgical tying off or excision of hydrosa lpinx. Tying t11e medial end of the tube also reduces the risk of ectopic pregnancy. • Diagnostic laparoscopy to assess tubal patency and treat any subtle causes of infertility such as lysis of adhesions, treaunent of endometriosis etc. Excision of hydrosalpim: or ligation of medial end of the LUbe.

TYPES OF ART PROCEDURES IN CURRENT PRACTICE I. IVF. This is the most commonly done ART procedure. It im·olves ovulation induction, OOC) te reu·ieval :u1d fertiliation of the oocytes in the laboratO•)'; embryos are then culwred for 3-5 da)S followed by their transfer to the endomeuial cavity (ET). 2. GIFT. This involves ovarian stimulation and egg retrieva l, followed by lapa•-oscopicall y guided transfer of a mixwre of two ova and 50,000 sperms imo each of the fallopian tubes. This procedure came witl1 a big bang and popularity, h oweve •~ is no longer in use. 3. Zygote intrafallopian transfer (ZIFI). T his involves the laparoscop ic u·ansfe r of da)' I fe rti lized eggs (zygotes) in to the fallopian tube. 4. ICSI. This tec hnique was developed in the ea rl)' I990s. It aims at help ing coup les with severe ma le fac tor infertility. Under microscop)', one sperm i.~ directly iruected in to eac h mawre egg prior to inu·a ute line transfer of the fertilized eggs. The method yie lds 50%-70% successful fertilization rates. LndicaLions of ICSI in male infertility are as follows: • • • • •

Spenn count less than 5 million/ mL. Decreased or absent motilit) of sperms. Many abnormal spenns. Previous failed IVF. unexplained infertility.

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SHAW'S TEXTBOOK Of GYNAECOLOGY

The sperms are obmined by one of the following sources: • Semen washing in a normal male. • Sperms retrieved by testicular sperm aspiration (TESA). • Percumneous epididymal aspiration. However, a decreased m unber of sperms are available (PESA) wi th this teehnique. T his techni que can also cause u·awna to the epid idymis. • MJ::SA - the tis.sue can be cryoprese rved fo r fuwre cycles or fuw re pregnancy. Cryopreservation Cryopreservation of embryo, OOC)Les and sperms avoids need for repeat aspirations, reduces the cost of tl1e procedure and can be used in subsequent C) des as well as for fu•·t11e1· pregnancies. Cl)•opreservation is also useful in )Otmg men who have to undergo st~~·gery, radiotherapy or chemotl1erapy for cancer, or are frequenL travellers. 1. Ovum donation. Donor eggs are offered LO women witl1

poor egg num bers or q uality and elde rl y wome n. An egg dono r is sc ree ned fo r HI V a nd othe r d iseases. She is th en subjec ted to s timula tion p ro tocol for ind ucing superov ulation, fo llowed by standard egg reu·ieval. T hese eggs are ferti li.1.ed by the sperms of tl1e patient's male partner and tl1e embryos transferred to t11e patient's uterus which has been simultaneously prepared as per tl1e standard IVF protocol. 0 \'lun donalion is also required if botl1 ovaries are re moved or radiate'Y· Ovarian hypc111timul~tion syndrome. Reccnr Advdnccs in Obstetrics and GynaccoiOI,'}' 21 Ovarian hyper-stimulation synd rome. In: Bonnar ]. Re-cent Adv~ncc-s in Obstetrics and GynaccoiOI,'Y· 6:123, 2000, Churchill Uvingstonc: Elsevier.

CHAPTER 16 - INFERTILITY - MALE AND FEMALE Oa,id K. Gardner ct al. Textbook of Assisted Rcproducth·e Techniques. 5th c". Gynaecology, and \l'om~n"s llcalth.John Wiley & Sons, 2010. FOGSI Focm. lntr.t·Utcrinc in.cmination. 2010. I !art R. :-:orman R. Poi)C)'>tic O\'arian >-yndrome - progno.is and outcome.. In: Bot Pr.tctkc :md Re.carch: Clinical Obstetrics and Gpuccolg>. Vol 20(5): 751-778, Ebe\'ier, 2006. K Thoma> ct al. Surgical treatment of male infertility. In: Studd J. Prugn:ss in Ob.tetric> :md Gynaecolog), 15:363, 2002, Churchill Lhing;tone: Eb2000unlts • Muhlparous women

Medical Management (Injection Methotrexate SOmg intramuscular) Follow up with serum HCG

(

lapa IOSCOIJ'f

1

CHAPTER I 7 - ECTOPIC GESTATION

239

Postmedication Management Posunedication rnanagemen t comprises following: • Avoid use of alcohol • Avoid pregnane> until ectopic pregnancy resolves and serum hCC becomes undetectable. Use of banier methods of contraception is advocated during the follow-up. Response to mTX therap): Following mTX, a full in t.he level of hCC to 15% or below the init.ial level is considered a satisfactory resolution of a trophoblastic tissue. It is important however to note that there may be an initial 1ise in serum hCG le,•el in the first 4-7 days before th e decline, increase in the sit.e of the gestation sac and abdominal pai n due to release of hCC and sligh t bleeding during resolution . Ultrasou nd scanning therefore should be delayed t.mti l after a week. Follow-up with h CG a nd ultrasound is mandatory. Serum hCC sho uld be do ne every 48- 72 hours initiall y a nd the n weekly until the levels become undetec tab le.

SURGICAL TREATMENT All patients wi tl1 acu te ectopic pregnancy should be operated upon at the earliest once the diagnosis is made. The operation essentially consists of open laparotomy, identifying the affected tube, clamping the mesosalpinx and perfonni ng salpingectomy as described by Lawson TaiL in 1884. The pedicles are transfLxed and the blood present in abdominal cavity and pelvis is remo,ed. Before removing the affected fullopian tube alwa>s look at t11e contralateral fallopian Lllbe. This is imponant in case t11e patient has infertility and it is desired to presene t11e fallopian tube forsubsequemfertility. Most patients show immediate improvement in t11eir condition following su•-gical management. It is very impo•·tant to inspect the contralateral tube for two reasons.

A

8 Figure 17.16

(A) Salpingostomy. (B) Salplng otomy.

I. Rarel)' bilateral wbal pregnancy may be en countered or

the other fallopian tube is diseased/damaged. 2. Condition of t11e LUbe need5 tO be assessed tO ch eck the prognosis of future pregnancy. In most cases it is possible to preserve the ovary as it is separa te fro m t11e gestatio n sac in th e wbe. Rarely, if ovary is b l.lli ed in a tubo-ova lia n mass, salpingo-oop ho rec to my is pe rfo rmed . In t11e past t11e b lood in the perito neal cavity was used fo r auto u·ansfus io n. T he adva mages of autotransfusio n are that b lood is ava ilab le immediately witho ut any need for a cross-match. Also, there is no fear of u·an smission of I-I IV, malalia and hepatitis B.

lYPES OF SURGERY ON THE FALlOPIAN TUBE 111e surgical u-eaunent ma) comp•ise salpingec10my, panial saJpingectompalpingostOm) and milking of the tube (Fig. 17.16 ). • Salpingectom> if the gestation sac is >4 em, most of the tube is damaged and t11e other LUbe is healtl1y (Fig. 17.17 ). • Partial salpingectomy if more than 6 em of t.he tube can be preserved. Later, tubal anastomosis can be perfonned (Figs 17.18 and 17. 19).

Rgure 11.11 Total salpingectomy for a tubal pregnancy.

• Salpingostomy- Antimese nteric border is incised, co nceptus removed, haemostasis sec ured and the wo und left open for secondary healing. The pregnancy rate is better than with salpingotom> (Fig. 17. 16) and repeat ectopic pregnane> is low. SalpingotOm) - The wound is closed witl1 fine Vier) I suwres. • Milking of the tube is possible with fimbria] pregnancy, bul because of a risk of persistent inu-atubal bleeding and a persisten l trophoblastic tissue and an increased risk of recurrent ectopic pregnancy this technique is not

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SHAW'S TEXTBOOK OF GYNAECOLOGY

With improved awareness and screening proced ures, life-threatening ectopic pregnancy has changed to a benign condition. especially in t11e case of an asymptomatic woman in stable condilion at t11e time of diagnosis ( Llll ruptured ectOpic). Conservative medical treaunem then applied is safe and cost effective. It also improves the subsequent pregnancy outcome. The treatment of seconda•) abdominal pregnancy includes perfonning a lapa•·otOm)' and removing the fetus and placenta. Lf tlle placenta is adherent to a vascular organ, it may be safer to clamp the cord close to t11e placenta, leave the Iauer in situ and close the alxlomen without a drainage. Hreschchysh)'n et al. (1965) proposed adm inistration of mTX to resolve tl1e placental tissue. Ultrasonic monito•ing and estimating serum 1)-hCG level are mandatory in such a situation.

INTERSTITIAL PREGNANCY Figure 17.18 Partial salpingectomy for a tubal pregnancy.

TREATMENT Altho ugh an ex u·eme l)' rare variety of ec topic pregnancy, inters titial pregnanC)' can be assoc iated witJ1 massive intraperitoneal haemorrhage, rare ly a hysterec tom)' is indicated in ruptured inte rs titial pregnancy. In unru pu.1red pregnancy, conservative manageme nt may be possib le. Incision and emptying tl1 e gestaLional SllC following ligation of tl1e ipsilateral uterine artery, ovarian and round ligament. is followed by suturing t11e muscular layer. The risk of uterine rupture in subsequent pregnanC) mandates careful an Lenatal monito•;ng and caesarean delive•)· Recently, hysteroscopic removal oflhe sac has been attempted. Early imerslitial pregnancy has been managed witll local or intramtLScular mTX injection and a follow-up until serum 1)-hCG disappears. In all ectopic pregnancies if "oman is Rh-negative, it is achisable to administer 100 meg ami-D gamma globulin to the Rhnegative patient to safeguard against isoimmuniLation.

PROGNOSIS Rgure 17.19 Removing an ampullary t ubal pregnancy wit h conservatio n of t ube.

popularly used. With im proved tec hnique, lapa roscopically performed above-mentioned procedures have become the gold sta ndard in t11e treatment, with early recover)', less pain and a sho n hospital stay. T he future outcome is similar to Ul at of laparotomy. Most cases can be managed by lapa roscopy.

CONSERVATIVE TUBAL SURGERY Conservative tulk"ll surge!") is justifiable only if the contralateral tube has ah·ead) been removed or is diseased, because tllis t) pe of surge!") exposes t11e woman to a recurrent. ectopic pregnane). Fift) per cent women undergoing conservalive SLLrgery conceive and have ute rine pregnane>'·

Due to a delay in diagnosis or a fai lure to diagnose ectOpic pregnancy still remains a cause of materna l deatl1s. Ten per cent deaths in ectopi c gestatio n are primaril y d ue tO h aemorrhage. Following u·eaunc nt, 50%-80% of t11 e women conceive and of these 50% have in tra ute rin e pregnancies, 15% will have repeat ec to pic pregnancy. T he rest remain infenile, due to tubal damage.

UNRUPTURED ECTOPIC GESTATION Recent advances in im munoassays for hCG and highreso lution ulu·asound have made signifi ca nt progress in tl1e diagnosis and management of early unruptured ectopic pregnancy. ln tl1ese cases, t11ere has been a shift from ablaLive SLLrgery to conservative fertility-preserving tllerapy/ medical management. Schenker observed that 15% of ectopic cases will have recun·en Lectopic pregnancies and 60%70% have fertiliL) problems. To improve fuwre fertility, and LO avoid catasu·ophic haemon·hage, it is necessa•)' to make a

CHAPTER 17 - ECTOPIC GESTATI ON

241

Pregnancy test

+

Positive

Weakly positive

+

+

Maternal serum quantitative b-hCG

Missed abortion or Early EP or earty uterine pregnancy

>1000 lUll

+

US scan of pelvis

+

~

Repeat serum b-hCG 48 h later+pelvic US I

Ti tre falling, irregular gestational sac

+

Blighted ovum or missed abortion

l

+

Titre rising and gestation sac in uterus

Titre rising

buk66%

+

+

Consider EP

Normal pregnancy

+ TVS repeat+ diagnostic laparoscopy

False+ve pregnancy test or

+ Too ea rly scan

Repeat US scan in IVF pregnancy to exclude concomitant EP

...

Too early scan

Blighted ovum

Emply uterus

+ Repeat

+ Repeat

Laparoscopy

scan+serum quantitative b-hCG value

scan+ b-hCG value

+ + Mi ni mal

requisite Repeat b-hCG su rgery and scan Rgure 17.20 Positive pregnancy test: Features suggestive of ectopic pregnancy (EP).

di agn osis befo•·e the ectopic sac ruptures. This is possible with rotttiue tt!Jrruonic lemming in rarly jJrrgntmry. & rty 1iia[,rnOsis is tfte key to wu~eruative lll(ltWgrmml. if a woma n in the reproductive age complains of amenorrhoea, mi ld abdo minal pain and abnonnal uterine bleeding, she should be suspec ted of ectopic pregnancy. Early diagnosis of ec top ic pregnancy allows laparoscop ic conservati ve surge•)' or med ica l the rapy. T his not on l)' red uces mortalit)' a nd mo rbidity d ue to haemorrhage but also improves subseque nt fertility.

EXPECTANT TREATMENT (Fig. 17.21 ) The expec tant treaunent comprises follow-up with serial hCG levels and ulu·asouncl scannin g. It is applicable only if t11e gestational sac is less than 2 em and hCG levels are no t very high (< 500 mi U/ mL) a nd the a bse nce o fhaemoperiLO neum. in most cases pregnancies resolve witho ut any surgical o r medical manageme nt Howeve r, due to the Lmcertai nL) a nd a prolo nged fo llow-up, it is no t practical in Ia.-ge num be r of cases.

Table 17.4 Spie gelberg Criteria to Diagnose Ovarian Pregnancy • • • •

Pregnancy is in close relation to ovary. Fallopian tube on affected side Is normal. Mass is attached to uterus by ovari an ligament. Histologically chorionic tissue Is In Intimate contact with ovarian tissues.

OVARIAN PREGNANCY Ova ria n pregnancy co nstiLUte 0.5%- 1% of a ll ectopic pregna ncies. T he crite ria for diagnosis o f ovarian pregnancy we re desc ribed b) Spiegelberg ("la ble 17. 1) in most cases co nditio n comes to no tice at the time o f surgery for suspected tubal p regnane). The treatme nt co mprises e itJ1e r oophorectOm) or panial resection o f ovary with me reconsu·ucti on of remaining O\oal·ian tissues.

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SHAW'S TEXTBOOK OF GYNAECOLOGY

Medical management

Laparoscopy

Laparotomy

• Methotrexate local or systemic (1 mg/kg)+ leucovorum (0.1 mg/kg) • Prostaglandin F2a

• Salpingectomy • Milking fimbria! end pregnancy • Salpingotomy • Salpingostomy • Resection • Study opposite tube

• Salpingectomy • Salpingo-oophorectomy • Study opposi te tube

• RU-486 • KCI, hyperosmolar glucose

Follow-up With hCG (serial serum quantitative titres)

I Successful

hCG rising or plateau or bleeding

~

Laparotomy In laparoscoplc salpingectomy, the ectopic tube is removed using a tissue removal bag. Before removal, endo..foop Is slipped into the mesosalpinx and tightened. Diathermy knife or laser can be used in salpingotomy and salpingostomy to cut and secure haemostasis. Rgure 17.21

A treatment of ectopic tubal pregnancy (ETP).

CERVICAL PREGNANCY Cervical pregnanC)• is exu-emely rare (0.5%-1 %), though in Japan, the incidence is I / 1000 pregnancies and it is the second most common variety of ectopic pregnancy. The woman presents with profuse painless bleeding following a shon period of amenorrhoea. Pelvic examination r-eveals a patulous extemal os and products of conception in the cervical canal; the internal os is closed and the uterus is finn and normal in size. Ultraso und helps in a correc t diagnosis; clinically, the diagnosis of inevitable abortion is initiall)• made. Dopple r blood flow mapping and MRI im prove the diagnosti c acc uraC)'· T he risk fac to rs are previo us e ndocervical curettage and Asherman S)•ndrome.

ULTRASOUND Rubin's criteria for diagnosis of ce rvical pregnancy. • There should be no fetal tissue in llleri ne cavity. • There should be ce~ical gland~ opposite the placental tissue. • The sac and fetal tissue present in cervical canal should be below the level of reflection of peritoneum in the pelvis. Ultrasound cr-iteria a r-e as follows: • Empty uterus • Ballooned cervix • Gestational sac and fetal tissue below the level of internal os.

• lmernal os is closed • The blood flow in the cenix is increased • The absence of sliding sign - the pressure over the cervix causes sliding down of the gestational sac in a miscarr-iage, whereas the cervical pregnane)' remains static, because it is auached to the cervix.

TREATMENT OF CERVICAL PREGNANCY Because of a risk of profused bleeding during any surgical procedure, the trea un ent co nsists of liga ting the uterine vessel vaginally, suction evacuation and tampo nade by insertin ga Foley cathe te r in tJ1 e ce rvical ca na l for 24 hours. In case of profuse haemorrhage occasionally hyste rectOmy may be needed. I-I )'Steroscopic resection of the cervical pregnane)' using resectoscope has been described by Ash and Fan·oll in the USA mTX has also been ir~ ected locally, followed if necessary a week later witJ1 suction evac uation. Unlike in tubal pregnancy, i.m. mTX injectio n 50 mg may have tO be repeated weekly until ~hCC level disappears. Uter-ine artery embolilation has been auempted to reduce blood loss. prior to evacuation of cervical and caesarean scar pregnane).

CORNUAL PREGNANCY Comual pregnancy is a pregnane)• in the accessory horn or bicornuate utentS. Pregnancy may continue up LO

CHAPTER 17 - ECTOPIC GESTATION 14-16 weeks when a sudden rupwre inLO the pe1;toneal al\'ity resultS in features of acute abdomen. In most atSes diagnosis becomes obvious at the time of surgical management for suspected ectopic pregnancy. Excision of rudimental)' horn at laparotOmy or laparoscopy is the treaunent. Most cases in subsequent pregnancy should be managed by an elective caesarean section as a site of excision of rudimental) ' horn re mains a weak area in the ute line musculawre.

HETEROTOPIC PREGNANCY lleteroLOpic pregnancy, i.e. combined uterine and ectopic wbal pregnancy, is very rare in spontaneous conception C)cles; the incidence is not more than I :·1000 to I :7000 pregnancies. The incidence is howe\er higher in IVF programmes because of the higher number of embi)OS transfe1·red, with a possibility of one embi)'O migrating to the tube. The possibility is also related tO the amount of fluid i11jected ''1th the embi) 'O. At present, fVF centres have reported an incidence of I %-3% for heterotOpic pregnancy. T he d iagnosis is not easy. The serum 13-hCG may not be proportionately high. Ultrasound can visua lize multip le pregnancy in early pregnancy. A carefully clone lVS in early pregnancy may help to diagnose this condition.

TREATMENT Medical treaunent in the form of mTX, mifep1·istone and prostaglandin is contraindicated because of their adverse ef. fects on the normal uterine pregnancy. Glucose and KCI have been if!jected in the tubal pregnancy with the aim of continuation of inu·auterine pregnancy. A surgical app roach in the form of laparoscopic salp ingectomy mtl)' he lp to manage conditio n successfull)' allowing uterine pregnancy LO grow. In IVF programme, the fo llowing prophylactic measures have been suggested: • • • •

Bilateral tubectOmy prior to !VF. Transfer of not more than two embi)OS. A small amount of fluid medium to be u-ansfetTed. A routine ultrasound scanning in early pregnancy, in case conception follows.

CAESAREAN SCAR ECTOPIC PREGNANCY Caesarean scar ectopic pregnanC)' is recen tly reported in

6% of ectopic pregnancies. The ulu·asound shows an empty uterus and cervix and the gestational sac is attached low to t11e lower segment caesarean scat: Doppler imaging confinns the diagnosis. The woman presentS with clinical feawres of til reatened or inevitable abortion. The gestation sac is embedded in the m)omeu;um and fibrosis of the caesarean scar. MRI is a diagnostic teSL

ULTRASOUND Ulu·asound shows following: • Gesta tional sac located over tl1e lowe r ante rior uterine segmenL • The ab.~ence of sliding sign. • Increased blood flow over tl1e lower uterine segmenL

243

TREATMENT • mTX injection. • Surgery - Suction curettage may be risky even under ultrasonic guidance and the risk of caesarean scar rupture remains. A surgical removal of an ectopic site bearing area in t11e regional istl1mus witl1 reconstruction of uterus is t11 e preferred treaunent. • In a )'Oung woman desirous of childbealing, resection and s uturing of scar can be done but the risk of scar rupture in subsequent pregnancy is considerable. There is an increased 1isk of repeat scar ectopic pregnancy as well as placenta accreta. Hysterectomy is recommended in a multiparous woman.

PERSISTENT ECTOPIC PREGNANCY (PEP) PEP complicates conservative tl1erapy, especiall y milking of the wbe, when a portion of the conception productS is left behind. Following laparoscopic salp ingostomy, PEP is reported in 16% against l % following laparotomy. Persistent elevation of serum J3-hCG is a diagnostic. A repeat iqjection of mTX may help resolution of PEP.

RECURRENT ECTOPIC PREGNANCY Recurrent ectopic pregnancy is seen in about 15% of cases, irrespective of the method of previous treaunen t for ectopic pregnancy. Such an event is more likely in cases with previous PI 0 . When a woman suffers from a recurrent ec topic pregnanC)', it may be pn1dent to perfonn salpingectOmy and offer IVF as a treatment for subsequent ferti li t)'·

MORTALITY AND MORBIDITY Ectopic pregnancy is responsible for 11.5% matemal mon.ality mainl)• due to a dela)' in diagnosis or a failure of diagnosis. Early diagnosis and management can avoid maternal death. Morbidity includes following: • • • •

lnferti li t)' Rec urrent ectOpic pregnancy Pe lvic ad hesions and chron ic pelvic pain Psychological morbid ity and fear of future pregnane)' outcome

KEY POINTS • Of all t.he ecwpics, tubal p1·egnanC)' is the most common. PIO, previous tubal surgery and I UCO a1·e the common predisposing factors for ectOpic pregnancy. • Although an ac ute ectopic pregnancy is lifetllrea tening conditio n and requires an e mergency surgery, subac ute and ch ron ic ec topi c pregnancy may be managed medically or surgically afte r careful confirmation of d iagnosis.

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SHAW'S TEXTBOOK Of GYNAECOLOGY

• It is now possible LO detect an earl) unrupwred eCLopic pregnancy by uluasow1, Cp,aecology, and Women's I leah h. Page 295,John Wile)' & Son~. 2010.

Maya Chcuy, Janine Elson. Treating non·wbaitra, collection of Ptt> in thl' uterine tXJVity, can occur in endometrial carcinoma or following radiotherapy or when the cer.•ix gets stenosed due LO tubercular and senile endomeu·itis. The pain is localited in tl1e cenu-al portion of the lower abdomen and may or may not be accompanied with fever. Ulu-asound reveals an enlarged uterus with fluid in the cavity. Treaunem comprises cervical di lation for drainage of pus and antibiotics. A s ubsequent e ndomeu·ial curettage will help tO rule o ut underlying mali gna nC)' or tuberculosis. • Ouariau tuiiWUTl iu flderly, fJostmenoprn.t.wl wom(m art mostly malignrmt. T hey ca n present witlt ac ute abdom inal pain. • Sarcoma of uteru~. Afthough mre, .1-rtrcmnrt um develop in a ·t.tleru:, with fibroid~. A diognosis is mrzdil when th11jibroid starts grawi11g rapidly camiug pain, postmenopausal b leedin g or low grade fever (Chapter 13). • Retmtion of urine can occ ur in a postmenopausal woman due to bkulder 11Hk obstruction, prolapse uterus or urinary infection and requires drainage and appropriate management.

•

CHRONIC PELVIC PAIN Chronic peh·ic pain (CPP) refers to aqclical pelvic pain of more than &month dlll-ation. This t)pe of pain has been a recogni.ted as a spnpLOm of organic conditions such as

INCIDENCE

AETIOLOGY (Table 18.1) The causes of CPP are diverse. They may be gynaecological and nongynaecological. l. Gj?UU'coWgiml must.s are moSt!) organic but can be func-

tional at times. The well-recogni.ted organic causes are as follows: • Pelvic endomeuiosis, d1ocolate cyst of the ovaq (30%-35% ) • Ovaries - ovarian adhesions, residual ovarian syndrome, ovarian tumours (benign and malignant) • Tubal - chronic PID, tubal adhesions, postoperative adhesions, pa•-ameu·itis due LO infection or malignancy (24%) • Pelvic tuberculosis and adh esio ns • Uterine -uterine fibroids and adenomyosis, pyometra in menopausal women, nxed re u·ovened uterus 2. Pt.mct.ional cau~P~ include th e foll o"1ng: • Congestive clys me nordloea, Miue lsc hm erz and postcoital pain • CPPS, pelvic varicose o r d il ated ve ins (30%) 3. Nongynaecologiwl aw~e~ a111 asfollrnv~~ • lmestinalwberculosis, diverticu litis, colitis, append icitis, initable bowel S)•ndrome which acco unt for 20% cases • Carcinoma rectum • Chronic intestinal obstruction • Renal - ureteric colic, bladder stone, urinary tract inJection, C)Stitis, chronic retention of urine. • Skeletomuscular- joint pains (referred pain). • Hemias • Sickle cell disease, porph) ria • ew·ological- herpes LOSter, nerve enuapment, nerve compression, refen·ed pain • Scar- scar site pain, scar endomeu·iosis

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SHAW'S TEXTBOOK OF GYNAECOLOGY

Table 18.1

Correlation of History of Pelvic Findings and the Possible Diagnosis

History

Physical Finding

Diagnos is

Progressive worsening of dysmenorrhoea and

Tenderness and nodules in the posterior fornix and uterosacral ligaments

Pelvic endometriosis

dysp~eunia

Pelvic pain (postoperative)

Restricted mobility of pelvic viscera

Pelvic adhesions

Menorrhagia, dysmenorrhoea

Bulky uterus

Uterine fibroid or adenomyosis

Shifting pain on body movement

Normal pelvic f.ndings

Pelvic venous congestion

Dyspareunia, postcoital pain following surgery

Tender ovaries at the vault

Residual ovarian syndrome

Pain and bulge over the abdomen or scar

Hernia

Hernia scar endometriosis

----------------------------------------Bladder d istension or empty bladder Urinary frequency, dysuria urgency, pain suprapubic Cystitis Pain left iliac fossa

Tender colon

Colit is

Pain ri ght iliac fossa

Tender McBurney point

Chronic appendicit is

Referred pain, localized pain on t rigger points

Trigger points

Nerve and muscle pain

NO OBVIOUS CAUSE FOUND FOR CHRONIC PELVIC PAIN

CHRONIC PELVIC INFLAMMATORY DISEASE

ln q uite a few cases, no cause of C PP can be detected in spite of d etailed work up (35%). Eve n laparoscop ic find ings appear normal , and investigatio ns u ndertaken do not reveal a definite cause. It is a lso observed that even when a lesion is detected, it may not be th e cause o f the CPP, i.e. loose peritoneal adhesions, mainly postoperative adhesions do not cause chronic pain, a nd ad hes io lysis does not cure the spnptom.

C h ronic PLO causes c h ron ic persistem lower abdomi na l pain, dyspareunia , dysme norrhoea, menorrhagia and infertility. The uterus is reu·overtecl and fixed. Th ickened and slightly tender fornices o r a tubo-ovarian ma.'IS is noted. lf medical treaunent fails, the remo,oal of adnexa or hysterectomy may be needed.

ORGANIC CAUSES ENDOMETRIOSIS, CHOCOLATE CYST OF OVARY Endometriosis presents as dull lower abdominal pain associated \lith dysmen orrhoea, m e norrhagia and dyspareunia. lt is important to note that sm all lesions with fibrosis may cause only dull clwonic pain. l e nde r nodules felt in the posterior fornix a nd tender pelvic masses with the above history may h elp to recogni ze the clinical cond ition of endometriosis. Ulu-asound co nfirms the presence an d e xtent of the pelvic mass. Laparoscopic examin atio n is useful n ot o nly LO confirm th e unsuspecte d clini cal d iagnosis b u t also to s u rgically manage b)' coagula ti o n o n the lesio n. lf a c hoco la te cyst is no te d in the ova ry, it ca n be la pa roscop ically managed. Su rgical re mova l of c hocolate cyst b)' laparo to my may be necessary if the cys t is huge. A correlation of macrosco pic find ings with h isto logical and clinical find ings is rathe r poor: Severity of endometrio· sis does not always corre late with severity of pain. Small lesions near me rosacral ligame nts may cause more severe pain tJ1an caused by large c hocolate cyst.

OVARIAN ADHESIONS AND POLYCYSTIC OVARIAN DISEASE Polycystic ovarian diseases us ua ll) do not cause any pe Ivic pain, however, following su rg ical manage ment in tl1e fonn of O\oarian ch-illing a nd subsequem ova•·ian adhesions can cause chronic pelvic pain.

PERITONEAL AND POSTOPERATIVE PELVIC ADHESIONS ot all adhesions cause pain. Loose ad hesio ns which do not resu·ict mobilit) of abdominal 'isce•-a remain as)lnpLOmatic and do not •·equire adhes io lrsis. Rather, breaking tl1ese adhesions may result in reformation of denser adhesions which may cause persiste nt chronic pain late•: Dense adhesions and adhesions which resu·ict visceral mobility will lead to CPP. lf these adhesions enu-ap the ovaries, pelvic pain can result. It is obset·ved tllat som e adhesion tissue contains nerve fibres, and tJ1 ese adhesions whe n stretChed duri ng movement ofvisce1-a ca n ca use pain.

PELVIC TUBERCULOSIS Pe lvic tuberc ulosis is a com mo n cond itio n in Ind ia affec ting wo men of reprod uc ti ve age. Apart fro m c hro nic pa in, th e wo ma n ofte n s uffe rs from a me no rrhoea, o ligome no rrhoea a nd in ferti lity. Endome tria l c u reltings may in some cases reveal th e tubercular natu re of t11e infec tion. Laparoscopy ma)' be necessary to confirm t11e d iagnosis. An ti-T B treatment is needed. Po lymerase Chain Reac tion (PC R) on endometria l tissue and biopsies from pe lvic su·uctw·es he lps tO diagnose tuberculosis when histology fails to do so.

UTERINE FIBROIDS AND ADENOMYOSIS Uterine fibroids and adenOm) OSis ca use dysmenorrhoea and menon·hagia. Dull abdomina l pain is due to hea,~ness and pelvic congestion, a nd at times due tO associated PLD. Submucous fibroid can cause colic k) pain in the fonn of spasmoclic d ysme norrhoea. In te rstitial fibro icls can cause d ys menorrhoea m ore often Ula n subsero us fibro icls which cause more of hem iness a nd dull pain. Bimanual examination

CHAPTER 18 - ACUTE AND CHRONIC PELVIC PAIN

and ulu·asound wi ll he lp LO establish the ca use of the pelvic pain.

OVARIAN CYST OR TUMOUR Ln most cases ovaria n C)St or wmour ca uses dull aching pain or a sensation of heavi ness in lower abdome n. However, rapid increase in siLe of the wmour or d1anges such as haemorrhage, infection or LOrsion can cause pain. A dermoid C)St may cause dull pain due to infection and gradual tOI'Sion of iLS pedicle. Malignantw mour is a silemLUmour causing pain only in the achoanced stage. RESIDUAL OVARIAN SYNDROME Residual ovarian syndrome is seen when one or both ovaries are saved at the time of hysterectomy. These O\>aries develop adhesions with sun·ouncling su·uctures causing CPP and dyspareunia. Extensive and dense adhesion may require surgical remova l of tJ1 e ova lies. WitJ1 tJ1 e availabili ty of hormone rep lacement the rapy (HRT) , some believe in removing bo th ovaries a t tJ1e time of hyste rectOmy LO avoid occ urre nce of residua l ova ria n syndrome and the remote possib ili ty of ova ria n ca ncec DYSMENORRHOEA Congestive d)'Sme no •,·hoea is present in endometriosis, PLD and uterine fibroids. I L is felt as a dull ache in the lower abdomen starLing a few clays before mens u·uation and is relieved fo llowing tJ1 e o nset o f menses. The woman may also complai n of backache and heaviness, in tJ1e lower abdomen. D)'Smenorrhoea is related to menstrual cycles. OVULATION PAIN (MITTELSCHMERZ) Ovulatio n pain occurs in micl-qcle, is often acute, but at times a sha 1p pain is followed b) a dull pain las ting for several ho111'S. It may be clue to rupture of a Graafian follicle, timing co•·responcls to time of LH peak a nd generally noted 24 hours before O\lllation. It is postulated LO be due to contractility of ovarian perifollicular smoorn muscle mediated through PGF2a. In such cases, a nti-inflammatory drugs (nonsteroidal anti-inflammatOI)' drugs, NSALDs) :u·e effective. CHRONIC PELVIC PAIN SYNDROME CPPS is a condition characterized by CPP not associated "1th any cli ni ca l evide nce of pelvic pa thology. At laparoscopy, pelvic ve ins a re seen d ilated and some are associated ~,1 th venous stasis. T he woman is genera lly in reproductive age and compla ins of d ull ac hi ng pain in the lower abdomen; in rare cases, severe pa in which responds to postural aclj usune nt. Lying flat re lieves o r red uces pain, whereas standin g, walking o r bending worsens it. Other associated symptoms are co ngestive dysmenorrhoea (60%-70%), d)'S· pareunia a nd postcoital ac he. Polycystic ovary syndrome (PCOS) is seen in 50% of tJ1e cases and menorrhagia is presem in same num ber of cases. Shiftin g locatio n of pain witl1 body movemenLS is characteristic of this syndrome. Doppler ultrasound and 'enograph) he lp in tJ1e diagnosis. INTESTINAL CAUSES Chronic lower abdominal pain related to imestines :uHI sigmoid colon is seen in in·itable bowelS) ndrome :u1d bowel S)lnptoms such as constipation, chronic diarrhoea and

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colicky pain. Sigmoid colo n pain is fe lLin the left iliac fossa, lasts for a few minutes to a few ho urs. Intes tinal colic is often related to food and accompanied by flatulence. Appendicitis may present with chron ic pain in tJ1 e right iliac fossa. Irritable bowel S)ndrome and inflammaLO•)' bowel diseases :u·e nottmcommon in women in age group of30-40 yea rs, and may be associated with pelvic ve nous congestion (20%) . Stool examination for amoebiasis, sigmoidoscopy, colonoscopy and bal'ium enema may reveal the cause of abdomina l pain. lrl'itable bowel S)ndrome responcls to drotaverine and mebeverine.

URINARY TRAG Infection, cystitis and bladder stones cause CPP, but :u·e associated witl1 udna11' symptoms. Chronic retention of urine caused by bladde r neck obstructi on or a pelvic tumour causes chro ni c pain in the suprapubic region and difficulty in passing urine. A full bladder is palpable in th e suprap ub ic region. Ca tl le te rizatio n will empty tJ1e bladder and relieve tJ1e d iscomfort. Ch ro ni c reten ti on of urine with over flow is not unco mm o n in postmenopa usal wo man due LO narrowing of ure tJu·a o r senile ure tJ1ritis. Uri ne cul ture, cysLOscop)', rad iograph)' of pelvis for stone and ulu·asound are useful diagn os ti c procedures. PSYCHOLOGICAL FAGORS Some women with CPP appear neuro tic and this was considered to be t11e ca use in women witJ1 CPP. As mentioned before. now it is proved, that in many cases ne urosis is t11e result of CPP :u1d not vice versa. Some e leme nLS of ne urosis may eventuall) co ntribute to exaggeration of S)1npLOms. AntidepressanLS do not relieve pain in majority of these women, though when given along with medications do alle,·iate neurosis. PS)Chotherap) ma> also help. SKELETOMUSCULAR PAIN Diseases of bone and joints can cause CPP. Llioinguinal nerve may be trapped in a wide Pfannenstiel incision. Postoperative muscle pain is also possible. T•·igger points c:u1 be located b)' pressing a finger where the woman complains of pain. Pain following su•-ge•)' and accidents are the obvious causes of chronic pain. Referred pain from the spine is an identifiable ca use of chro ni c pain (Tahle 18. 1).

WORKUP OF A CASE OF CHRONIC PELVIC PAIN HISTORY CPP is common in re prod uctive yea rs. T he onset, type, d uration and location of pain will provide guiclance to th e probable cause of the pain. Ra dia tion of pain and its relation to mensu·uaLio n is important. Obsteuic and sex ual histo •)' is important. 1-listO•)' of use of intrauterine contraceptive device suggests possibility of pelvic infec tio n. Associated ttrinary and bowel S)1nptoms should be e nquired into . Some wome n with CPP also complai n of d)'Smenorrhoea and dyspareunia. A histo•') of tuberculosis and psychiatric problem wi U he lp. Histor> of cancer in the fami l) will suggest probable can cer phobia in the woman. General examination may reveal l)lnphadenopathy (lllberculosis), anaemia and swelling of feeL Abdominal mass, ascites and tenclemess suggest organic cause.

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Vaginal discharge is see n in PlD. Biman ual pelvic examination is necessary to rule out organic pelvic pathology. A full bladder is felt anterior to the uterus and is tender on palpation. Rectal examination may reveal a mass in the pouch of Douglas or a stricture in rectum. Pa in and restriction ofjoint movemems, especiall) hip joint or lumbosacral spine, suggest refened pain to the pelvis. Tendemess in the pelvis is caused b) endometriosis, adenomyosis, pelvic adhesion, PlD divea·ticulitis anclu a·inary infection. Ovarian pain is located at the junction of the middle and inner two-third of a line between the amea·ior superior iliac spine to the umbilicus, and tendemess can be elicited here.

INVESTIGATIONS A firm diagnosis and cause of pain cann ot always be elicited clinically. Ulu·aso und, diagnostic laparoscopy, Doppler ultrasound for pelvic congestio n, urine tests, barium enema, colonoscopy, sigmoidoscopy, rad iograp hy ofjoin rs and inu·aveno us pye lograp h)' (IVP) wi ll be needed in accordance with tl1e pa ti e nt's histo ry a nd exa min ati o n. CT and MRl may be helpful in so me cases. MRI can miss a small nodule, but it p icks up rcctovaginal endometriosis. Laparoscop)' detects s ma ll foc i in the pelvis sugges tive of endometriosis wh ich are undetected cli nically. It can detect pelvic adhesions and small in nammawry masses apart from obvious pelvic pathology. Therape utic treatment can be applied in tl1 e same sitting such as ad hesiolysis and cauteri.t.ation of e ndometriosis. Pe lvic venous congestion and dilated vessels are not alwa)S revealed because of a head low position and pressure of pneumoperitOneum. A poor correlation between macroscopic '~ew and histological evidence exists at laparoscop) and the ctiagnosis can be missed if pe.-itoneal biopsies are not taken. The bw-ntout healed areas of endomeu·iosis can also cause CPP due to fibrosis and entrapment of nerve fibres. £\en if a pelvic patl1ology is detected at laparoscopy, i.e. fi. broid or a small ovaaian C)Sl, adhesions, it may not be the real cause ofCPP; it could bejusta coincidental fincting. 'O:mscious pain nwj>jJing' at diagn(llfic laj>MUM:ofl)' muiPr local antJJJsthesia is t11JPfttl in d«iding the wr.Lle mullocatior1 ofrhrrmir pain. When laparoscopy fails to revea l any pathology and pelvic venous co ngestjo n is suspected to be tl1 e cause of pelvic pain, u·ansuterine pelvic ve nograph y is performed by injec ting tl1e dye myo metria ll )' or pelvic venography using comrast medium . In pe lvic co nges tio n syndro me, dilated ova ria n and ute rine vesse ls more t11an 10 mm with delayed clearance of dye are obse rved. Hyste roscopy p icks up intrauterine lesions.

MANAGEMENT The detection of pelvic pat11ology or cause for pain deter!lUnes tl1e therapy appropriate for the case. Negative investigations at least assure t11e woman that no serious pathology exists; this wa), cancer phobia can be eliminated.

Gonadou·opin-releasing hormo ne (G nRJ-1 ) can shrink the endomeuiosis and the pelvic veins. The rationale behind progestogen u·eaunent is that oestrogen causes dilatation of pelvic vessels and progesLOgens, by th eir antioestrogen ic effect, constrict the veins, reduce t11e blood flow and suppress ovulation. Medroxyprogesterone acetate (MDPA) up to 30 mg dail) (Provera) give n for 9-12 montllS relieves pelvic pain. Unfonu nately, pain may recur after stoppage of tl1e ch'ug and a prolonged tl1erapy can produce side effects such as increase in body weight, pain, bloating and menstrual irregularity; t11us, it is not desirable. Micronit.ed pa·ogesterone is a natural progesterone available in lndia as uu·ogestan 100 mg oral and vaginal tablet. ln a patient with liver disease, a vaginal route may be pa·eferred. lt causes diainess in a few cases, so one tablet daily is advocated at bedtime for I 0 days in t11e premensu·ual phase. For premenstrual tension, one tablet twice daily is recommended for I0 days premensu·ually. Mirena IUC D whi ch releases MDPA a t a rate of20 meg has e merged as an alte rnative LO prolo nged o ral progestogen tl1erapy. Mirena is very effec tive in relieving pain and effec tive for 5 years. 13esides, it acts as a co mracep tive when the woman is not desirous of pregnancy. Selec tive serotonin re uptake inhib ito r (SSI) nuoxetine 10-60 mg dail)'• or se rtrali ne 50~200 mg dai ly are drugs useful in some cases. ln tl1e past, people have u·ied dietl1yl ergotamine in tab let and if1jection fornlS to reduce pelvic pain ca tL5ed by dilatation ofvessels. Dieth) l ergotamine causes vasoco nstriction of veins and reduces pelvic congestion. Long·tenn use of this drug is not recommended because of serious side effects. Ligation of ov:uian ve i11S has been attem pLed wi tl1 variable results. Surgery in the fonn of hysterectOmy a nd bilateral salpingo-oophorectOm) may be resorted to if drug tl1ea-apy fajJs in elde.-1)' women. Ps) chothea-apy alone or combined with drugs will be usefu l in peh·ic pain S)nclrome and irritable bowel S)nclr·ome. Acupuncture and short-wave diathenny are adjuvantS, and are effective in some women. Presaca-al neurectomy and laparoscopic uterosaca-al n erve ablation (LUNA) are recommended in intractable pain in roung women. LUNA may lead to prolapse and bladder dysfunction. Ureteric damage ca n also occur. Presacral neurectOmy causes bleeding and haematoma in presac ral space. Stati c magne tic the rap)' for 4 wee ks o r transcutaneous nerve stimu lati on helps in so me cases. Varicosity of pelvic ve ins have been trea ted witl1 e mbolization of ovarian vesse ls o r laparoscop ic ia'Uection of sclerosing agents (sc lero tl1 erapy) using 5% e t11 ano lam ine maleate. Ge l foams and coils are also used. Omsciou~ pain rtwj>j>irtg. Conscious pain mapping involves laparoscopy under local anaesthesia a nd interaction with the woman on touching individual o rgans LO localize the organ of pain. This method he lps in improvi ng diagnostic accumcy. Backache is one of the S) mptoms ofte n accompanying CPP and is due to following ronaecological diseases:

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'tear, this protective effect lasts as long as 10 )'eal"S after stoppage of use of OCPs. The incidence of P10 is reduced, though it does not reach the same low level as seen witl1 tl1 e barr-ier method. This protective effect is due to the tl1i ck cervical mucus caused by progestogen, preventing the mi cro01-ganisms entering into the uteri ne cavity. Reduced inciden ce of ectopic pregnancy is d ue to suppression of ovul ation and red uction in PID. 1t protectS aga inst rhe umato id arthri tis. Reduces tl1e risk of anorec ta l ca ncer by 30%-40% . It is useful in acne, Po lyq•sti c Ova rian Disease (PCOD) and en do metriosis.

Side Effects with the Use of OCPs and Contmindications • lntermensu·ual spottingiscommon in the first3monthsof use of the pills, subsequently it gradually disappears. Freq uent spotting can be stopped by choosing a pill containing higher dose of oesu·ogen or other combinal.ion of honnones. Often menstrual bleeding becomes seamy and occasionall) a woman ma> become amenoni1oeic causing a fear of pregnane). Amenoni1oea lasting more than 6 months requires investigations. Postpill amenoni1oea is not 1-elated to tl1e t)pe, close or duration of pill imake. Those with p•-e,·ious mensu·ual irregula•·ity (oligomenorrhoea) a1-e mo•-e likely to suffer from amenoni10ea. • Genital tract candidiasis. Oral pills are associated witl1 monilial (candidial) vaginitis. • No documented association is seen witl1 carcinoma of cervix; however, dysplasia is more frequenL Recently an increase inciden ce of cervi cal adenocarcinoma and glandular abnormalities has been reported witl1 longterm use of OCPs. • No adverse effect has bee n noted on ute•·ine fi broids, and it is oesu·ogen singly tJ1at increases the ir size. • Breast. T he combined pills should not be offe red to a wo man suffering from ca nce r of the b reasL Some have reported the breast cancer in a nu lli pa rous woman (25%) who has taken oral contraceptive pills befo•-e tJ1e age of 24 )'Cars for over a pe riod of 4 )'ears. T h i.s sho uld be considered whi le presc ribing oral pills tO a young n ulliparous woman. There are some repo rts indicating higher incidence of breast cancer among users of OCPs. Petiodic breast examination and necessary investigations in a user of OCPs will he lp to detect breast cancer at an early stage. Progestogen component also conu·ibutes tO the potential of development of breast cancer. However, if breast cancer de, elops, it is well differentiated witl1 good prognosis. The risk of malignancy disappea•-s after 10 >e;u-s of stoppage. • Pituitary adenoma was att.-ibuted to the use of the pill but itS exact role in its dC\elopment is not clear and doubtful.

CHAPTER 19 - TEMPORARY AND PERMANENT METHODS OF CONTRACEPTION

• Breast mil k amount in lacta ti ng woman who chooses tO use OCPs is reduced. T he combined pills may preferable be avoided during the first 6 mon ths after delivery if a woman is lactating. llowever, progesterone only pills (POP) do not suffer this disadvantage and can be safely used du.-ing the first 6 months of lactation. ausea and vomiting are common initiall) mainly due to oesu·ogen and subsequent!) disappears. It can be avoided by taking the pills at bedtime. If ,·omiting occurs witl1in l hour of taking pill, repeat dose. • Lh·er. Adenomas have been reponed and though they are benign rarely a napwre of a hepatoma can be futal. Because tl1e hormones are metaboli Led in the liver, chronic liver diseases and recemjaundice contraindicate tl1e use of pills. • Gall bladder fun ction may be adversely affected. • Carbohydrate metabolism. Ca rbohyd rate tOleran ce may be reduced . T herefore, combined oral pills a re con train· dicated o r given ca uti ously to a d iabe ti c woman. • Lipid metabolism. Oestrogen i n crea~es tl1e high-density li poprotein (II DL) a nd lowers low-de nsity lipoprotein (LDL). Some progestoge ns have a reve rse effec t a nd the overall effec t o n t11 c myoca rdial function and lipid metabolis m depends upon t11e co mbined effec t of bo th hormones. Rifampicin, an a ntib iotic p resc ribed for a tuberc ular infection, red uces the abso rp tio n of drugs in the pill; hence, OCPs are contraind icated in a tube rnLiar patient on .-ifarnpicin. OtJ1er drugs interfering with OCPs are tetracycline, amiconvulsants, antifungal, cephalospo· rin and phenobarb. Ritonavir for HIV also interferes witl1 absorption of OCJ>s. • Headache. migraine, depression, irritability, increased weight and letharro can occur due to progestogen. • Thromboembolic disorders. Pulmonary embolism and cerebral thrombosis, both venous and arte1ial, are 7-l 0 times mo•·e frequent in the pill u5ers than in the nonusers in the first )Car of use. This is due to an increased clotting mechanism (platelet aggregation and increased fib•·inogen factor VII, VIII and decreased fibrinolysis) caused by tl1e oestrogen component of t11e pill. T he effect is dosedependen 1, and the reduction of the oestrogen content of the pill from the original 100-30 meg in currently used pills and of late a newe r o ral pill (Femilon) which co ntains 20 meg 1!.1:: 2 revea l a n improved safe ty a nd tolerance profi le, a nd at t11c sa me tim e retain its contraceptive efficacy. T he incide nce ofthromboe mbolic d iso rders has tl1Us dropped witJ1out d iminish ing the efficacy of the p ill. A wo ma n o lder than 40 )'Ca rs, a woman witl1 stro ke, heavy smo ke •; a card iac and hypertensive pa tien t, a wo ma n with fami lia l h)•pe rlipoproteinaem ia a re a ll high-risk cases for tJ1is complicalion. T he pills co ntaining desogestre l and gestodene (thi rd generation) a lso ca n·y a higher lisk of venous thromboembolism t11an the pills containing LNG. • Sickle cell anaemia patients can develop thrombosis and crisis. • A woman who wears contact lenses should be warned of oedema and irritation of eyes (tJHombosis of optic vessels) - it is a relathe contraindication. Combi ned oral contraceptive (COC) pill do not protect a woman against HIV and sexually transmined infections. This is imponant while counselling a woman at a high risk for these infections. Barrier methods reduce tl1e risk of

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transmission of HIVand other infec tions. In HfV patien ts a d Ltal method of banier contraceptive wi th OC Ps are recommended. • Pills have no ad,erse effects on thyroid funCLio ns. Contraindications to the Use of OCPs l. Cardiac disease, h) penension, smoker o lder than 35 years. 2. Diabetes. 3. History of thrombosis, m)Ocardia l infurction, sickle cell anaemia, seve1·e migraine. 4. Chronic liver diseases such as cholestatic jaundice of pregnancy, cirrhosis ofliver, adenoma, po•·phy•·ias. 5. B•·east cancer, gall bladder disease. 6. G•·oss obesity. 7. Patient on em.yme-i nducing drugs such as rifum picin, and anti epilepti cs except sodium valp roate. 8. 4-6 weeks plior to a pla nned surgery. 9. Lacta ting wo ma n. A wo man can ta ke OCPs regularly up to tlte age of 35 )'ears, and thereafte r liiHil 45 yea rs if she is healthy, no nobese a nd nons mo ker. ll oweve •~ she s ho uld remain under th e supervision of t11 e doc to r and have Pap smear do ne regularl)' to cl1ec k on cervical dysp lasia. Return of Menstruation and Fertility. Ninety-n ine per cent of women wi ll have normal menstrual cycles within 6 months after stopping use of OCPs but return of ferti lity may be slightl) dela) eel due to delayed return of ovulation. inety per cent ovulate within 3 months of stopping the drug. There is no evidence of increased fetal malfonnations or increased rate of abortion in t11ose who conceive while on pills. Triphasic Pills. Witl1 tl1e aim of further reducing tl1e amount of honnones du•·ing OCP use, t11e biphasic and triphasic pills were intmduced. The composition of pills in initial part of menstrual crete is different from the pills given in tl1e last I 0 days, tltis way the total amount of oesu·ogen and progesterone in a month is reduced. The triphasic prepa•·ations cur-rently in usc co ntains E ~ an d LNG in an amount 30 meg ££.2 plus 50 meg LNG durin g tl1e fi rst 6 days of tJ1 e cycle, for the nex t 5 days 40 meg EE 2 plus 75 meg LNG, and duri ng tl1 e last I0 days 30 meg EE2 and 125 meg LNG. Nex t pac k of triph asic pills is sta rted afte r I wee k. T hese p il ls have no adve1'Se effect on ca rbo hydrate a nd lipid metabolism; the refore, t11 ey ca n be presc ribed to d iabe tic wo men and witho ut expecting any increased ris k of myocardial infarc L Th ey are as effective as the monop hasic oral p ills but no t reco mmended in woman witl1 me no n·hagia an d for o tl1er ind ications. How to Maintain Compliance with the Use of Oral Pill? • Three-monthly course of pills. 'Seasonale' which co ntains £~plus LNG is available as a packet containing 84 tablets (witJ1 a gap of 7 da)S), which means only four menstrual cycles in a )ear. and has been attractive to many working women especial!) in the USA. However, some may face the problem of prolonged b•·eaktJ1rough bleeding. Yearly continuous pills are under uial (one pe•·iod a )Car)- L)brel is effective for I >ear.

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• OCPs containing only 10 meg Ef...? (ul tra low dose p ills). • Once-a-montJ1 pill containing 3 mg quinestro l and 12 mg megestrol acetate, popular in China and Latin America. Two tablets in tJ1e first montJ1 are followed by one tablet month!). • ~ + drospirenone (Yasmin, Tarana,Jan>a) contain 21 tablets in a packeL Janya contains 24 tablets (gap of four tablets in a C)cle), and contains 20 meg EE2 • • EE2 + C)proterone acetate (Dianeue) 35 meg EE2 is more useful in women with PCOD, hirsutism. • Quackiphasic pills containing E2 + dienogeSL, daily- no pillfree days, beuer tolerated and a good conu·ot of menses. • Chewable tablets containing 35 meg EE2 and 0.4 mg norethindt·one. • Lybrel-continuous dai ly use for I year contains 20 meg ££2 + 90 meg LNG in a tablet. Newer Pills with Antiandrogenic Properties. Drospirenone red uces fl ui d reten ti on and has no adverse effect ofspiro nolac tone, has an ti mine ra locorticoid (3 mg d rospire no ne is eq ui valent to 25 mg of spiro no lac to ne, cures ac ne and hirsutism. It reduces fl ui d a nd sodiu m re te m ion, and has no adve rse effect rn g of Iauer), has anti rn ineralocorticoid and with an tiandrogenic activity. It inhib its ovu latio n, and has no effect on bone mineral densit)'· It also prevents obesity and maintains good li pid profi le. Because of this property and relieffrom acne, it is also been called 'beauty p ill'. Main side effect is potassium reten Lion because of which it is contraindicated in renal and liver disease and in a woman with previous thromboembolism. Different Generations of Oral Pills. Depending on the progesterone co men tin an OCP, oral pills have been called the first generation, second generation, third generation and fourth generation. • Frrst generation - contains norethindrone progesterone and 50 meg or more of t::E • Second generation - contains LNG, norgestimate, norethindrone progesterone fonnulation and 20, 30 or 35 meg EE. • Third generation - contains gestodene, desogestrel progesterone formulation and 20, 30 or 35 meg££ • Fourth generation - contains spironolactOne, dienogest or cypro terone acetate. Progestogens. Progestogens a lo ne have also being successfull y used as hormone comraceptives. Besides being devoid of oesu·ogenic side effect these co ntracep tives can be used du ring lac tati on, d uring menses and in woman where oestrogen are conu·aind icated. Progestogens are availab le as oral pills (minip ills), intramuscular i t~ections, implants, pa tches, vagina l ring and Mirena IUCD. Progestogen-Only Pill (PO P - Min.ipill). The to,,"C.lose POP (noretJ1isterone 350 meg, norgesu·el 75 meg or LNG 30 meg) has been introduced to avoid the side effectS of oestrOgen in the combined pills. The tablet is taken daily without a break. The pill should be slatted within 5-7 days of the menstruaLion and taken at tJ1e same Lime with a leewa)' of 3 hours on either side of tlle fixed time each da)'· If this regime is not obsen·ed any day, the woman continues with POP but

observes exu·a precaution for next 48 ho urs. The mode of action of progestogen has ah·ead)' been discussed earlier. PO P is started 21 da)S postpanum and soon after abot' Lion. The woman needs LO take precaution in the first 48 hottrs in tJ1e first C)cle. Minipill does not ha\e some of the major side effects of the combined pill and it i.s rwll 5uited for u:tetating women; some progestogens, in fact, increase milk secretion. However, it has a higher pregnancy rate of 2-3 per 100 womanyears which is higher than that of the combined pill though comparable to an IUCD and is higher in obese women. Strict daily compliance is a drawback. Other drawbacks are it·regular bleeding (20%), amenorrhoea, depression, headache, migraine and weight gain, ectOpic pregnancy, functional ovarian cysts besides a higher fai lure rate. The use of newer gener·a tion of synthetic progestogen, namely desogestrel in PO l~ It has no androge nic effect, no adverse effect on ca rbohyd rate and lipid metabolism, and is considered to be safe, especially for lacta ting wome n. H muever, lite incidmce of thromhoembolimt is higher witlt this progestogm.

Contraindications. Con u-a ind ica Li ons to PO P are p revious ec topic pregnane)', ovalian cyst, breast and geni tal cancers, abnormal vaginal b leeding, active liver and a n e tia l d isease, porp hyria, liver tumolll; valproate, spirono lactone and meprobamate. BectlliJe of ruteofJenUI, it is ccmtrt1imliwted in adolescent~ a rut )'Otlllg women. AdLmttages of Progestogen-Only Pill. Advantages of POP are that they can be recommended to: • • • •

Lactating women. Women older tJ1an 35 )ears. Those with focal migraine. Those illloleralll to oestrogen or oestrogen conu-aindicated. • Diabetic, hypenenshe woman, sickle cell anaemia. As regat·ds to t·eturn of fenility, it is faster than in COC users because ovulation is not suppressed in all cases (suppressed in 40%)

Mode ofAction of Minipills • Cemzette which contains dcsogestrel in a dose of75 meg s uppresses ovul ation in 97%- 100%, whe reas otJ1er POPs s uppress ovu lati o n in onl)' 40%. • It forms a tJ1ick p lug of mucus in th e ce rvical ca nal and acLS as a barrier to spe rms. • It alters tubal pe ristalsis and ferti lized egg reac hes th e uterine cavil)' too earl)' for imp lant.atio n. Cerazette containing 75 meg desogestrel has the fo llowing advantages over other POPs: • Stringent Lime compliance not necessary, as it suppresses ovulation in 97%, through pituitary hormone suppression. • o androgenic effects such as acne. • o ectopic pregnanC), no effect on carbohydrate or lipid metabolism. • Failure rate only 0.21 per 100 woman-> ears. It acts through metabolite etonogestrel which binds to progesterone receptors

CHAPTER 19 - TEMPORARY AND PERMANENT METHODS O F CONTRACEPTION

ide effects: (I) weight gain, (2) in·egular mensu·ual bleeding. (3) depression, (4) breast cancer and (5) thromboembolism. Depot Injections of Progesterone. Although not ve1)' pop ular in Ind ia depot ir\jeetio ns of progesterone (Depot med rOX)'progestero ne aceta te, DMPA; norethistero ne ena ntl1ate NET-EN ) are two co mm o n!)' used imramusc ula r injec ti ons of progestero ne. In fuct, in more than 125 countries these are available in the Family Planning Pro· grams. Ease of adm inistration, 1·epeating action at 2-3 monthly imervals and high efficacy have made tl1is mode of administralion of contraceptives 'ery popular. To overcome the inconvenience of daily compliance, depot injections of progeswgens have been de,eloped. DMPA is given in a microcrystalline aqueous suspension and ET-EN in a castor oil solution, both by deep intramusCLllar injection (subc utaneous preparation of OMPA is also ava ilable in 104 mg). Late!)' a mo nthly DMPA combined wi th 25-50 mg of medroxyp rogestero ne acetate combined with 5 mg oesu·adio l is ava ilab le a nd is co nsidered to be mo re effec tive "1th lesser menstrual distu rba nces. O ther preparati ons in usc are tl1e DMPA 150 mg 3-monthl y, DMPA 300 mg 6-momhly and NET-EN 200 mg 2-montl1ly. After stoppage, the contraceptive effect of DMPA lasts longer than tllat of lT-E . Menstrual irregularity though common is accepted by puerperal woman as ph) iological. The injection should be started within a month of delivel)' in a nonlactating woman and during tl1e third month in a lactaling woman because ovulation is delayed up to atleastlO weeks in lactating mothers. Pregnancy rate is 0.'1 per 100 womanyea rs for OMPA and 0.6 per 100 woman-years for NET-EN. Injecti on DMPA has rece nUy bee n introduced free of cost in tl1e Na tional Fa mil y Pla nni ng Programme of India "1th tl1e name of'An tara'. T he iryection should be adm iniste1·ed wi tl1in 7 clays of menstruation with a grace period of 2 weeks for DMPA and I week for NET-EN for a repeat injection. Action lasLS 12-14 weeks of the first injection for DMPA anciS-9 weeks fo1· ET-£1

Advantages • Iryections are easy to administer and there is no worry over 'missing p ill'. They are long-acling and reversib le. • T he compliance is good and the woman rema ins unde r regular medical supervis io n. • The side effects on li p id and ca rbo hydrate metabolism are avoided. DMPA is least androgen ic. • It is suited to lactating women. • The incidence of PlD, ectOpic pn~gnancy and functional ovarian C)SLS is low, so also endomeuial cancer. • A'oids oestrogenic side effects. • Can be given LOa woman with sickle cell anaemia. • Relllrn of fertility is slight!)' dela)ed in DMPA group compared to ET, but 80% conceive within a )Car (5 months for DMPA and 3-4 mon ths for NET-EN). • Independent of coitus. • T hey tu rn o ut to be mo re cost-effecti ve for mass usages. Disadvantages • Once ad mi nistered, the side effects, if any, need to be tolerated until tl1e progeswgenic effect of tl1e injection is over.

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• Mensu·ual irregularities are common in the form of amenon·hoea or in·egular bleeding. Amenon-hoea is reponed in 20%-50% LLSers of DMPA at the end of I )Car and are more common with DMPA tJ1an NET. Heavy and irregular bleeding is repo t1.ed in I %-2% users and is more commo n with the use of NI::'I: • Do not preve nt STD a nd 1-1 IV. • T here is a delay in re turn of fenili ty b ut 80% are expected to conceive by end of I yea r. WitJ1 DMPA, ovulation returns in 5 months, a nd with NET wi thi n 3 months of the last injection. • The side eff'ects in tlle fonn of weight gain, depression, bloated feeling and masralgia can occur witll injecrable progestogen. • Prolonged DMPA LLSe, by vinue of antioesu·ogenic action, ma) reduce bone densit) mass and induce osteopenia. • Conu·aindicated in breastcance1: • It does increase LDL b ut does not adverse!)' aff'ec t th e b lood pressure. • It rn a)' decrease lib ido, ca use d 1)' vagina. Because of risk of osteopenia, tJ1is conu·acepti ve is contraindicated in adolescenLS, and should not be used for more than 2 years in otllers. Lately, subcutaneous i1~ections are under de,elopmem to enable self-administration by tJ1e woman. Once-a-Month Injections. O nce-a-month intramLLScular injections of combined oestrogen and progestogen are available in some CO Ltntries. T hese are as fo llows: • Mesigyna - ( 1/2 mL con taining NET 50 mg witl1 oestrad io l va lera te 5 mg) is given by deep in tramusc ular irtiec· tion once a month with :!: 3 days. T he low fai lure rate of 0.4% at the end of 1 year is encouraging. • Cyclofem and Lunelle - l / 2 mL contains 25 mg DMPA and oestradiol cypionate 5 mg. The failure rate is 0.2% at the e nd of I )ear. The menstmal irregularity is less tJ1aJ1 with progestogen-alone i11jections. • Marvelon - Desogestrel 150 meg with El::-1 30 meg. • Femovan - Gestodene 75 meg with E£.1 30 meg. • Anafertin - Dihydroxyprogesterone acetophenide 75 mg + esu·ad io l enan tll ate 5 mg. It should be re membe red that the first me nstrual period co mes 10-15 days after the firs t i11jection b ut tl1 ereafter every 30 days and lasts for 5 days. Failu re rate of 0. 1%-0.4% is reported. Ovulation returns in 6 months.

Subdermal Implants

In the quest to find altemalive routes of gh·ing hormonal conu-acepti,es. subclennal implams were discovered. Wilh tl1is me tJ1od, tJ1e progeswgens are delive red in to general circulation with a slow and StLStained release manner with lesser side effects. T here are two types of subdennal imp lants, b iodegradab le and no ndegmclable. Once imp lanted Llle)' re lease drug slowly over a pe riod of 1-5 )'Cars depend ing upo n the implant. T he subdermal implan t has no 'nuisance value' of continuous compli;u1ce which often adver'Sely affects

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motivation. Besides, being nonora l it avo ids 'hepatic first-pass effect and Llws, reduces systemic side effects'. Norplant 1. Norplant I (Fig' 19. 11- 19. 16 ) was Ll1e first subdennal implant imroduced for contraception containing six silastic capsules, it has now been wil.l1drawn from the market and replaced b) a single rod implanL orplant ll (Jadelle) was the second implant system inu·oduced for conu-aception. It consisted of two rods ead1

..

Figure 19.14

Norplant I and Norplant II.

containing 70 mg LNC wil.l1 a daily re lease of 50 meg and provides conuaception for 3-5 )'Cars. The implants suppress ovulation in 50% of Ll1e cycles but the main mechanism of action is suppression of endomeuium. Insertion of Implants. The implants are insened on Ll1e first day of Ll1e menstntal C)cle or wil.l1 in 5 days of abonion, and 3 weeks after the delivery. The woman needs to use banier contraception or abstain in Ll1e first 7 days after inse•·tion. It takes 5-I 0 minutes to insert under local anaesthesia. It is best insened on Ll1e medial aspect of the upper arm. The capsules are nonbiodegmdable, so they need removal at Ll1e end of its use or earlier, if side effects are imolemble. The insertion and •·emoval is made easier using a single rod system called lmplanon (40 X 2 mm), wh ich contains 68 mg etonogestrel and docs not require an incision tO insert. It releases 30 meg of Ll1e hormo ne dail y a nd is effective for 3 years. T he re has been no fa ilure tO date. It preve nts ovul ati o n a nd is reversible wil.l1in I mo nth of re moval. With the use of lm planon, a me no rrhoea is co mmo n at the end of 1 >•ear. Acne is red uced and it has no effect on bone densit)'· Advantages. The advantages of imp lants are as fo llows: • They are long-acting wil.l1 sustained effect- compliance is good • Coital-independent wil.l1 no 'nuisance' of daily oml or frequent i•~eCLions. • Pregnanq 1-ate varies between 0.2 and 1.3 per I 00 womanyears. The failure mte is higher in obese women weighing more than 70 kg. • S)stemic side effects are few and Ll1e first-pass effect on the liver avoided. • Return of fertility is prompt (within 4-12 weeks). • Can be used by lactating mothers and women older than 40 years.

Figure 19.15

Insertion of Norplant.

Disadvantages • Breakl.luough bleeding, in·cgular q •cles, amenonhoea occur as seen with other progesterone onl y contraceptives. • Other side effects of progcstogens are seen . • Ec topic p regnancy is reported in 1.3%. • Local infec ti on at the s ite of insertio n may occ uc • Req uires insertio n and removal wil.l1 nonbiodegradable im p lants; however, it is a mi nor surgical proced ure. • T he imp lants are expensive. • l nfertili q• may be seen in a few cases after Ll1e removal of imp lant. Contraceptive Vaginal Rings (CVR)

Figure 19.16 Removal of Norplant.

Anoll1er route which has been tested and found suitable for delivery of hormonal con u-aceptive is in the form of contraceptive vaginal rings. In an attempt to reduce the side effects of systemic hormonal con tracep1ion and the surgical method of insertion of implants, silasl.ic vaginal rings canying progestogens in differenL doses have been u;ed. The ring is 50-75 mm in diamete•· and 5-9 mm thick. 1l1e ring currenl.ly a\oailable contains L G released at a rate of 20 meg of honnone daily. The •·ing needs a change after

CHAPTER 19 - TEMPORARY AND PERMANENT METHODS OF CONTRACEPTION

3 momhs. Anotl1er ring which contains both oesu·ogen and progesterone is available in the market by the name of NuvaRing cont.'lining 11.7 mg eLOnogestrel and 2.7 mg ethinyloestradiol. NuvaRing is effective for I montl1. Advamage of uvaRing is that incidence of breakthrough bleeding and spotting is less compared to vaginal ring comaining on I) progesterone. Failure rate is 1.8 per 100 woman-> ears. Recently, a lot of •·esearch is going on in this field, some p•·ogestin ears (WI 10, 1985). A ring releasing 30 meg E£2 with ei tl1er 120 meg desogestrel or 650 meg n orethisterone is under tl'ial. Other rings are as follows:

+ 15 meg E£ 2 daily release can be re moved during inte rcourse but not for more than 3 ho urs at a tim e. 2. Nestorone - 150 meg progeste ron e + 15 meg E£ 2, effective for 1 )'ea r; fai lure rate is 1.2 pe r 100 woman-years. I. NuvaRing - 120 meg eto nogestrel

Advantages of Contraceptive Vaginal Rings • Self-insertion and removal, good compliance. • Otl1er advantages of progesLOgen con u·aceptives. • Quick reversibility. Disadvantages • Expe•lSive; Rs 700 per ring per cyde. • Local irritation is felt b) few, vagin itis 5%. • Expulsion can occur especially in woman with vagi nal prolapse. o S)stemic side effects of progestogens have been noted in some women. IUCDs Containing Progestogen. Another route of delivering hormonal contraceptives which has been successfully emplo)ed is in the form of I UCD impregnated witl1 progestoge•lS. Progest.'\Sel·t and Mirena are two such devices which have been extensively used. Mirena contains 52 mg LNG in tl1e vertical ann ofT device and elutes 20 meg daily. The effect lasts for 5 years. T he fai lure rate is 0. 1% similar to oral combined pills. Though primari ly used in AUB, its con u·acep tive benefit is also appreciated. The me nsu·ua l irregularity in the first 3 months settles down to norm al C)'Cies and dysmenorrhoea is also cured. The incide nce of PI D and ec topic pregnanC)' is red uced. The inse rtio n is however difficu lt d ue to the thick vertical stem. Amenorrhoea is reported in abo ut 20% at the end of I year. Mirena costs Rs 7000. Skin Patches

Hormonal Patch (Orth o-Evra). Another route of hormonal contraceptives which has been tested in clinical practice is a skin patch impregnated in hormone. A Ortl1o Evra Honnonal patch releases 6.00 mg norelgesu·omin ( GMN) and 0.75 mg E.E. A patch lasts 7 days. Three patches are required in each qcle followed b)' !-week patch-free imer,oaJ. The patch should be applied within 5 da)S of menses O\'er tlle buttocks or abdomen but not over tl1e breasts.

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The failure rate is 1-2.8 per 100 woman-years. Compliance of90% is reported. The breakthro ugh bleeding ( 18%), skin reaction (20%) and breast discomfort are L11e side effects. The other S) ln ptoms are headache, nausea and mastalgia. The site of patd1 should be changed often and is conu 1ears. POPs are not. prefer-red O\er COC, because oft.he irregular bleeding, amenon·hoea, a higher fai lure r-ate and ost.eopenia. Three-monthly ir~ections or implantS, skin patches and vaginal rings may be acceptable to young man·ied adolescentS, and side effects tolerated. Occasional failure may be backed up witJ1 MTP facilities. Sterilization should not. be offered LO young couples. The Government of India has passed a law t11at t11e surgical procedure should not be pcrfo nned in a woman younger than 25 years wi tl1 two or less chi ld re n and the yo ungest chi ld less than 2 yea rs old. MT P and e merge ncy contracep ti o n sho uld form th e backup procedmes in t11 ese girls.

Table 19.3 Comparison of Mlrena and TUbectomy Mlrena • Effective • Reversible Bleeding, dysmenorrhoea less Cheaper than surgery No Surgery, anaesthesia complications avoided Ectopic pregnancy (0.2/1 000) Ovarian function not compromised

Tubectomy Effective Surgically reversible success 70% Menstrual Bleeding may increase in 15% Costly Surgery, anaesthesia required Risk of ectopic pregnancy slightly increased May be compromised

PERMANENT STERILIZATION AFTER CHILD BIRTH A multiparous woman rn a)' be counselled on sterilization or vasect.Om)'· T his is done any time after 2•cin ma)' face a highe r failure rate due tO inte rac tio n with rifamycin and antiep ileptic drugs excep t sodium valproate. Similarly POP is conu-aindicated in liver diseases, vascular disorders and breast ca ncer. It is safe in sickle cell anaemia. EmergerlC) contraception ( L r tablets) is safe in a woman with medical disorders. Conu-aception for a Woman witl1 Ps)d1 iatric Disordel'. lf a woman is considered unfit to bear children, a nd permanem method considered, a wr·itten opinion regarding psychiatric pr·oblem should be obtained. The written consent should be obtained from the husband or guardian, as the ps)chiauic patient may not be mentally aware of tile nature of ster·iliation. EmergenC)' contraception is no bar to a woman witi1 a medical disorder, as onl y two tablets are given in 24 h ours.

WHO CONTRACEPTIVE WHEEL WHO has introduced a small whee l-like device wh ich can help doc tor to decide whethe r a particular method of contracep tion is safe for a woman who has so me assoc iated disease. Recen ti)' WHO has co me out witll an easy to use disc like device called Contraceptive Wheel. It helps clinician to choose a safe me tl1od of co nu·aception in th e presence of a signifi cant medical/surgical condition. Each contraceptive has been categorized into four categories with a range where category I means safe to use witi1out an)' health risk. whereas categor) II indicates use of a method is more advantageous than risk, category Ill indicates risks are more ti1an usual. howe,er, method of co ntraception can be used with caution whereas categor) IV means ti1at use of conuaceplive method is absolute !) contraindicated in a give n health condition which women might be suffering. This contraceptive wheel is user friendly and makes cliniciaJl decide the best conu-acepti'e for a woman.

CHAPTER 19 - TEMPORARY AND PERMANENT METHODS OF CONTRACEPTION

MALE CONTRACEPTION There have been attempts to find out a safe method of conu-aception for males other than vasectomy. Till now there is no proven method of ma le conu-aception because of several reaso ns such as hi gh count of sperms in ~ac ulate, a lo ng period of 72 days for spermatoge nesis and high incidence of s ide effects. Fo llowing approac hes are being tested for ma le contraceptio n.

METHODS BASED ON SUPPRESSION OF SPERMATOGENESIS GOSSYPOL Its use as a male comraceptive 11as discovered in China. Gossypol is a yel low pigment isolated ft'Om couonseed oil. It is administe red orally 10-20 mg dai ly for 3 moml1s and thereafter 20 mg twice weekly. T he action is direc tl y on the seminiferous wbul es inhibiting spermatogenesis witl1o ut altering FSH a nd LH levels. T he side effects such as weakness, hypo· kalaem ia and pennanentstetilit)' in 20% of cases limit its use.

TESTOSTERONE ENANTHATE ·n~stosterone enamhate 200 mg injection weekly causes aLoospermia in 6-12 montllS. ·n~stosterone bucidate 600 mg 3-mom.hly is also effecti1 e through negative feedback mechanism without loss of libido. • Instead of weekly il'tiection, testostemne decanoate 1000 mg i.m. followed by 500 mg 4-weekly is more convenienL • Four implants of 200 mg ead1 of testOStetune every 4-6 montl1s witll 300 mg medt'OX)']) t'Ogesterone 3-monthly is successful in 96% of cases witl1 count less tllan I mi llion/mL.

•

Side effects - osteopenia, liver and li pid metabo lism dysfunction, prostate enlargement.

GNRH 111e continuous administration of analogues of gonadotmpin· releasing honnone (GnRH ) causes a fall in the sperm coum and spenn motility. The level of testostetune also falls. The loss of libido and osteopomsis make this regime w1accept· able over a long period. Besides, it is very expensive and needs to be given subcutaneo usly.

MEDROXYPROGESTERONE ACETATE Medroxyp rogesterone acetate 250 mg i.m. with 200 mg noretl1isterone given as weekly it'tiections is reported to suppress spermatogenesis witl1 97% success.

DESOGESTREL It has androgenic property. 75-300 meg daily with subcuta· neous pellets of testostemne 300 meg causes oligospermia, 11ithout altering tl1e level of HDL. The hormonal suppression of spermatogenesis causes loss of li bido and is toxic in hi gh closes. Besides, the injec tion of hormones is inconvenient 10 ad minister regul arly. T he acne, weight gain and dec reased HDL are other side effects. Immunological methods of suppressing spermatogenesis have not )'et been successful.

277

S) mhetic hormone - 7 alpha-meth) 1-nonestosterone (M£ T) used as substitute of testosterone-no side

effects.

KEY POINTS • Fam il )' plannin g and contraception has gained mome nwm wo rld overwitl1 an urgent need to con u·ol the wo rld pop ulation as we ll as to promote woman's healtl1. • This has resulted in continuous effort to discover newer metl10cls and new modes of deli1el') with optimal effectiveness but with minimal side effects. • Bat-rier methocls, bOLll male and female, apan fmm their conu-aceptive effect, ha1e the ach antages of preYenting u-ansmission of STDs, HIV and reducing the incidence of cancer of the cervix. A high failure rate of 10-14 per 100 per woman-year use t'S with barrier methods ca n be imptuved by a backup method s uch as usc of eme rge ncy contraception if unpro tec ted intercourse occurs around ovulation. These advantages along wi tl1 ilie low cost and excellent reversibilit) can e nhance tl1e use of tl1is metl1od in preveming an unwamed pregnancy. • ewer formulations containing extreme!) small dose of oesu·ogetlS and an effecti1e progestogen has reduced t11e failure rate and side effects of oral contraceptive pills. • I UCD is an established method of female contraception in India on account of one-tim e insertion, low cost a nd long efficacy. Progesteroneimpregnated IUC D has a n added advantage of red ucing me ns u·ual b leedin g, but it is expe ns ive . T he re mova l rate of 5%-10% on acco unt of s ide effects is acceptable. • Newer drug de livery systems are continuous!) on uial, and tl1eir advamages, disadvantages, effecti1eness and rC\ ersibilit) are being studied. This has resulted in availabilit) of implants, vaginal lings and conu-aceptives skin patches. • OCPs offer a number of health benefits in addition to conu-aception. • POP are particularly useful when oestrogen is contraindicated or its side effects are intolerable. POP is as effec tive a~ I UC D but less effec ti ve th an COC. It can be used by the lactating woman, unlike COC. • Centchroman as an oral con traceptive pill is available in India. It is cheap and needs to be taken once a wee!... • Vasectom> and tubecwmy are tl1e surgical metl1ocls offered on I) when a pennanem method is desired by the couple. • EmergenC)' contraceptive also known as postcoital contraception is an il1novati1e technique of preveming conception if t-ape or unprotected intercourse occurs around ovulation. This method has a 95%98% success rate and thus avoids MT P. • A wide range of contracepti ves allow a wider selec ti on of cho ice to the couples a nd improves tl1 c acceptabilit)' of one or more methods.

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SELF-ASSESSMENT I. Discuss

2. 3. 4. 5.

6.

Lhe advantages and disadvamages of oral combined con tracepLive pills. WhaL are 1.he con traindicalions 1.0 oral combined pills? WhaL is 1.he role of minipills in contracepLion? Discuss 1.he complicaLions and conu-aindicalions of inu-auLerine device. Wt·iLe shorL noLes on: • H ormonal implanLS • VasecLomy • Barrier conu-acepLives Discuss Lhe uses of Mirena and Copper-T.

SUGGESTED READING Ali>ott Scott, Anna Cla.ier: £,idencc b'• incomplete evacuation, haemorrhage, cervical laceration, perforation, infection and anaestJ1e tic complications. If pregnancy was not confirmed by ulu·aso tmd, an ecwpic pregnancy may be missed. A failure to evacuate is due to following reasons: I. Too earl) a pregnane). 2. Ectopic pregnane). 3. Uterus bicomuate, aspiration being can·ied out in a nonpregnant horn.

Rh anti-D globulin 50 meg i.m. should be given tO an Rh-negative nonimmuniLed woman with pregnancy less than 12 weeks. Medical Abortion Of late termination of cady pregnancy (less t11an 4~63 days) is being carried out with the use of mifepriswne ( RU486) and misoprostol. T his mctl1ocl avoids need for a surgical me tl10d suc h as menstrual regulation. In Ind ia termination of pregnancy up to 49 clays has been perm itted fo r the use of a med ical me tl1ocl. In a co nfirmed pregnanC)\ the wo man is in itia l! )' given a t4lb le t of mifep r isw ne co nta ining 200 mg of drug, followed by vagina l adm in is tratio n of 800 meg of misoprosto l. In most cases, abo n.ion is successful \\~thin few hours after adm inistration of misoprostol. Most women experience continuation of bleeding for a period of 7-14 days. A repeat ulu·asound after 14 days is carried o ut tO d1eck for any retained products or possible continuation of pregnancy. Some patients may require suction evacuation for heav) bleeding after medical abortion. Prophylactic antibiotics are ghen for a period of 48 hours to 5 days. Rh-negative woman should receive ami-D i11jection. \'\'oriel over tllis metJ1od has taken over tJ1e surgical evacuation for tennination of earl) p•·egnanC)'· To avoid complications on a rare occasion, it will be good idea to ,·isit a doctOr and avoid self-administration of drugs. In India, regulations

VaCLmm evacuation is the most efficiem method of tenninating pregnanq• up to 12 weeks of gestation. It has gained rapid acceptance worldwide. The operation can be generally undertaken under local anaesthetic, paracen~caJ block, coupled witJ1 some sedation if necessary. Apprehensive patients may need general anaestllesia. The procedure involves examination of the patient in the operation theatre observing full aseptic precautions. The gestation size and the position of the uterus are carefull y assessed. After administering a paracervical block, the cervix is h eld with an Allis/vulsell um forceps and dilated by mea ns of Hegar's or some o tJ1 er metal di lators until adeq uate dilati o n is ac hieved w perm it in trod uction of the s uction cannula of the appropriate size (diameter correspo nd ing to the wee ks of gestati o n) in to tl1e ute rine cavity (Fig. 20.2) . A standard nega tive sucti on of 650 mm (65 em) of Hg is created a nd the prod ucts are asp irated. Wh en tJ1e p roced ure is co mp le ted, a gra ti ng sensation is fe lt all a rou nd th e uterine caviL)'• no further tissue is asp irated and the internal os begins to grip the Karman cann ula wh ich may also reveal a blood-stained froth. There is no need to follow this up with a check curettage with a sharp cureue, as tl1is step can be traLLmatic and lead to complications such as perforation, synechiae (Asher man S) ndrome), and predispose to placenta accreta in a fuwre pregnancy. In case me pregnanq exceeds 8-week gestation siLe, the patient is nulliparous or there is presence of a uterine scar, gene raJ anaestJ1esia may be preferred. ln case of large uterus of 10- to 12-week gestation size, or nulliparous cervix, p.-iming tJ1e cervix with prostaglandin gel or suppository, at least 4 hours earlier helps tO soften the cervix so tl1at it yields more easily and undue force is avoided during cervical dilatation. This precaution safeguards against complications such as ce•vical tear, lacerations and injur-y to the intemal os leading to incompetent ce•·vix; 200-400 meg misoproswl pessary is inserted in the vagina (prostaglandin E.).

.,'

""'~

.:§

F~ure 20.2 Suction evacuation - aspiration of the products of conception.

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SHAW'S TEXTBOOK OF GYNAECOLOGY

Vacuum aspiral.ion as a melhod of MTP has a very low failure rate (< 1% ). Complical.ions such as incomplete evantal.ion, infecl.ion, uterine perforal.ion and excessive bleeding occur in less than 2% of cases. The mortality is less than 2 per 100,000 procedures. NonimmuniLed Rh-negative mothers must receive 100 meg of anl.i-0 immunoglobulin after tmdergoing MTP. Failure to end pregnancy is due to a ver')' earl) pregnane). unrecogniLed ectopic pregnancy and pregnane)' in a rudimentary hom. Preoperative uluasow1d is useful in pre,enting these complications.

MEDICAL ME1HODS Prostaglandins and RU486 ha,·e been extensively used as medical methods of MTP in early pregnane)'· Acting singly, the)' are not as effective as "11en used in combination. The medical melhod avoids hospitali zation but the prolonged observation, occasional need of surgical te nn ination (failure) and the cost of t he drugs are some of th e disadva ntages. Prostaglandins

Prostaglandi n Injecti ons (Prostin, Ca rboprost-p rostagla nclin F2cx) 250 meg given i. m. every 3 ho urs up tO a maximum of 10 closes has been found LO be effective in initiating the process of abortion. It has not been pop ular in the fi rst u·imester because of an unaccep1.a bly high inc ide nce of incomplete abortion (20% ) req uiring surgical intervention to complete the proced ure, and lhe high rate of unp leasant side effects such as nausea, vomiting, diarrhoea, cramping abdominal pain, bronchospasm and mild fever at times. Mifepristone (Mifegest - RU486)

First invented in France, in 1980, RU486 stands for Roussel Uclaf 486 (laborator1 number). It is a S)nthetic steroid, a derivative of 19-nortestosterone,

"ith antiprogestogenic eff'ecL It also has antiglucocorticoid and weak antiandrogenic action. By competing with progesterone receptors, it reduces the endometrial glandular activity, accelerates degenerati'e changes and increases su"Omal aCLion, thereby causing sloughing of endometrium. It thus preventS or disturbs implantation of the fertilized O\um through luteolysis. l t also causes utel'ine contractions, softens and slightly dilates the cervix. Used singly, it is effective in 83% cases, and ca uses incomplete aborti on in 10%-20% cases. Addin g prostaglan din yields a success t' :.can the >)lllbol or log in

286

I()

Insertion ot cardinal ligament

Rectum Uterosacral_~-~~

ligaments

Vaginal vault -~~~~~~~~~~~=r_ Symphysis Pubocervical fascia "Ji::;:::::=::;:;~,....._.,...~ Urethra Levator ani -:::::7"-....1...._ 1 7"=~--- Perineal body (Pubococcygeus) Figure 21 .2

rour account on \\ '"'·~fcdEnat"l .mlll

Various supports of the uterus.

CHAPTER 2 I - GENITAL PROLAPSE

Clinica lly LUHecogni:t.ed da mages and breaks in these suppo rts ca n be de tected by ulu·asound and MRl.

AmOLOGY OF PROLAPSE UTERUS (Table 21 1) Wea kness o r injut) to no rmal s uppo n s o f ute rus results in u te rovaginal pro la pse. In most cases, d am age LO suppons occ urs as a r esul t o f a mis ma naged c hildbin.h. H oweve r, a conge ni ta l d efect o r weakness of suppo rts of uterus can resul t in prola pse of uterus a nd vagina. \>\r. thdrawa l of h o m10n al suppo rt, especially oestrogen , foll o wing m e no pa use is an impo rta nt fac to r for the onset of sympto ms of pr·olapse. Ra rely pelvi c trauma or nerve dam age to p elvis ca n resu lt in prola pse ute rus. Raised intraabdo min al press ure, ch ro ni c co ns tipatio n, ch ron ic obs tn.tctive airway di seases also p lay a role in th e develop· ment of p elvi c orga n prola pse . Mismanaged childbirth: Unsupe rvised or wro ng practi ces d uri ng labour o r pue rpe rium ca n p redi spose a woma n to s ubseq ue nt develo pme nt of ute rine pro lapse. Prolo nged bearing down effo rts in tJ1e fi rst s tage of labo ur before the full d ilatatio n of ce rvix result in und ue s u·e tc hing or tears in Macke nrodt a nd ute rosac ral ligame nts. Sim ila rly, app licatio n of fo rceps befo re the full dila tio n of cervix res ul ts in tears in cervix a nd Mac ke nrodt ligame nts with subsequent risk of ute rine prolapse. Birth o f a big-size baby can also predispose to prola pse ute rus by dam aging ce rvix and s upporting liga me nts. Fo llowing a c hildbinJ1, poor re habilita· Lio n in puerperitun, earl) resumptio n of physical acti,~ty, li fting hea' ') we ig hts can pred ispose woman LO pro lapse ute rus. As discttssed la te r, p•·o la pse of uterus due to a mis man aged c hildbi rtll is mostly see n in wo m en in repro ductive age. T h is t) pe has been called uterovagina l pro lapse a nd has elonga ti o n of supravaginal po rtion of cervix, vaginal mucosa is well e pi theli ali Led and associa ted witJ1 good tone of le,m or muscles. Me nopause: Me no pause is cha ra ctetized by declining levels of oesu·ogens. Al l tJ1 e suppo rts of uterus at·e under the effect of oesu·ogen during reproductive years. Declin ing le vels of oestroge n after me nopause resul t in loss oftone of m uscula r s uppo rts a nd relaxa tio n of ligame m o us s upports of uterus. T hese c ha nges predispose a wo ma n to uterine pro lapse in the prese nce of preexis ting weakness in s upports of ute nts .

Table 21.1 Atonicity Birth injuries

Other causes

287

Prolapse ute rus see n afte r me no pa use is clinically characte rized by a troph y o f vaginal mucosa, the presence of e nterocele. poor to ne of levatOr muscles and tl1 e a bse nce of cemx elo ngatio n.

CLASSIFICAnON OF PROLAPSE (Figs 21 .3 and 21 4) Ute rine pro la pse has bee n classified in a number of ways. Howeve r, recently for the plll·pose of a unifo nn repo rting and compa t·ison of resul ts, a n ew classification has been proposed by lntem ati o nal Society fo r Swdy of Vulvovaginal Disorde t-s. Foll owing sectio n desctibes two comm only used classification systems of prolapse, namely Uterovaginal Prolapse System and Pelvi c Organ Prolapse Qua ntifica tio n Syste m (POP·Q). Uterovaginal Prolapse System

A Anterior vflginal tv(lll (Fig. 2 1.5 ) Upper two·thi rds---C)'Stocele } . Cys to ure throcele Lower o ne- U11rd- Ure tJu ocele

B. Posterior vaginal wall Upper o ne- tJ1ird - Ente rocele (tJ1e po uc h of Do uglas he rnia) (Fig. 2 1.()) Lowe r two- tl1irds- Rec tocele C. Uterine de~cent • Desce nt o f the cerv ix in to the vagina • Desce nt of the cerv ix up to the in troiws • Desce nt of the cervix o uts ide tJ1 e illl.ro itLIS Procidentia - Entire uterus is ouiSide tJ1e introitus (Figs 21.7-21.9).

CYSTOCELE Prola pse of upper two-thirds of a n terio r vaginal wall is called C)Stocel e. The bladde r is s u pported by puboce tv ical fasci a whi ch exte nds laterall y to the arcus tendineus and

Aetiology of Prolapse • Menopause Congenital weakness Prolonged labour Perineal tear Pudendal nerve Injury Operative delivery MuHiparity Big baby Raised intraabdominal pressure Chronic bronchitis

gh Figure 21.3 (Sou~ee:

Pelvic organ prolapse quantification system (POP..Q).

From Rgure 2 1 9. larl Symonds arid Sabaratnarn AnJkumarar~:

Essential Obstetrics and Gynaeoology, 5th Ed., Elsevier, 2013.)

288

SHAW'S TEXTBOOK OF GYNAECOLOGY

A

Bp Ap

B

Ap

+3Aa

+6ea

+2c

-3 Aa

-3 Ba

4 .5gh

1.5pb

6,..

4.5g.

1 pb

-3Ap

-2Bp

+3 Ap

+5Bp

Profile A

·6c

a,..

Profile B

Rgure 21.4 Pelvic Ofgan prolapse quantification (POP-Q) system !Of staging pelvic Ofgan prolapse. Aa, Point A anterior; Ap, Point A posterior, Ba, Point B anteriOf; Bp, Point B posteriOf; C, Cervix or vaginal cuff; D, PosteriOf fOfnix (if cervix is present); gh, Genital hiatus; pb, Perineal body; tvl, Total vaginal length. (Source: From Figi.Xe 1 11 . VICtOf Nitti: \f.aginal Surgery fOf the Urologist. Saunders: Elsevier, 2012.)

1

I

( I

\

\

\"........

_

Rgure 21.5 Prolapse of the oervix, anterior vaginal wall and blad· der. The cervix is elongated and hypertrophied. The anterior vaginal wall and bladder have prolapsed outside the vaginal orifiCe. The cerviX is also prolapsed. In this case, the ligamentary supports hold up the body of the uterus. Note that the almost vertical direction of the uterosacral ligament from the cervix to the junction of the second and third sacral vertebrae. Compare this f1Qure with Fig. 21.8.

fuses with the leva tor ani muscle below. T he ureth ra is supported by the posterior urethral liga me nt whi ch is fixed to the pubic bone. ln prolapse of tl1ea nte ri orvagina l wa ll, tJ1e upperpartof the an terior vaginal wa ll descends and in advanced cases it may prou·ude outside the vagina l orifice. In these cases, tl1e vesicle and vagina l fasciae are tl1inn ed o ut and fa il to s upport tl1e b ladder, so that tl1 e bladde r pro lapses with the amerior vaginal wal l. This condiLion is te rmed as cystocele . l n mild cases, the lower portion of the anterior vaginal wa ll does not prolapse, and the urethra is well supported by the posterior urethral ligamem. When the urethra along wit11 the lower one-third of tlle anterior wall prolapses, it is termed uretllrocele, and t11e patient invariably complains of su·ess incontinence. When t11e C)StOcele protrudes outside the vulva, owing to friction, the vaginal epithelium becomes thickened, h)pem-ophied and keratiniLed. Ulceration can occur over t11e vaginal wall. Senile 'ault at the time of h)Sterectomy, 1>ault prolapse can be prevented. Sacrocolpopexy is considered the gold standard surgi cal procedw·e for vault prolapse.

5. Describe the surgical procedw-es for repair of ge nital prolapse. 6. A 50-)ear-ld woman pt-esenLS with third-i> operation: A report of 58=~.,. Amj Obstet Gj-necol 113:1114,1972. Scigword1 CR. Vaginal \"ault prolap.c with c\CI">ion. Obstet Cynecol 54:255,1979. StuddJ (~>d). Progress in Obstetrics and C)11aCCOiog) 17:381. Churchill Lhing>tonc, Ebe\ier Sturdec D. Year Book of Obstetrics and GyrM~'Cology Year Book of Ob>tcuic> and Cp>aewlogy. 61-70,200 I.

Displacements of the Uterus

Introduction 302 Retroversion 302 Inversion of the Uterus 304

Key Points 306 Self-Assessment 306

INTRODUCTION 1l1e uten.lS is kept in place by a cro&'\-fo rmation offour ligameniS (pubocervical ligaments, uterosaO if it precedes pr-olapse or if prolapse caLLSes reu-oversion. Sometimes, t.he displacemem of the uter·us is caused by twnours such as ant.e ri or wall m)omas and ovarian C)'SIS in tlle peh·is, which push tJ1e uterus backwards.

CHAPTER 22 - DISPLACEMENTS OF THE UTERUS

303

BACKACHE More likely, the backache is due to an ot·tJ1opaedic cause and not due to the reu·oven.ed utet·us.

Long axis of the vagina Retroflexion

Retroversion

Retroversion Rgure 22.1

Normal and retroverted uterus.

ReU'oversion is commonly noted in women afLer childbirth. Such displacements often con·ect themselves sponUineousl y on ce the patiem's muscle tone im proves.

FIXED RETROVERSION Fixed retroversion means th at the ute rus is bo und down b)' ad hesions o r tumo urs in the reu·ovcned positio n. Most fixed retroversions result from pelvic in nammatOt)' diseases (PID) such as salpingo-oophoritis and pelvic tumot.u·s. In salpingo-oophoritis, tlte oedematous, tlte distended fallopian tubes prolapse behind t11e uterus and, partly by tlteir weight and partly through fonnation of adhesions lO the pos~.et·ior surface of ilie uterus, pull back the uterus. ln the process of healing, adhesions fonn which bind the utems firmly in its retroverted position. Fixed retroversion is also ca used by chocolate cysts of the ovary and pelvic endometriosis.

SYMPTOMS The sign ificance of retroversion pe r se in clinical practice has dec li ned during the last few decades. This is due tO the apprec iatio n of the fuct t11atthe spnptoms earlier auriblllecl to tJ1is displacement are not to it, ramer tltey are related to tJte aeuo logical factors causing reu·oversion. Therefore, as)mptomalic retroversion does not need treatment, and treaunem of symptomatic fixed retro,ersion is direcLed towards tJ1e disease that causes it.

DYSMENORRHOEA Both congestive and spasmodic dysmenorrh oea have been ,wo ngly a Ltributed to mobi le retroversio n. The incidence of d)'Smcno rrh oea is the sa me in women with the re u·ovened ute rus as it is in women wiili an an tevertecl uterus. The fixed re u·ovened uten.LS can cmt.Se dysmenorrhoea. MENORRHAGIA Meno rrh agia associated witl1 mobile reu·oversion is eiilier due to m)Oh)petplasia or abnormal uLet·ine bleeding (AU B). A manual or surgical cotTection of reu·oversion will not relieve the menstrual symptoms. In fixed reu·oversion, menoni1agia is due to pelvic congestion caused by pelvic patltology. PRESSURE A norma l-sized retrove n ed uten ts does not ca use pressure on the rec tum or o n the bladder.

DYSPAREUNIA Of all the symptoms of rell·oversion, dyspareunia may be one which is genuine and attribu table to retroversio n. Outing vaginal exam inati on, the bod)' of the retrove rted lllenL~ is te nder and tlte patient ma)' wince when it is touched. Besides, the ovary may prolapse in the pouch of Douglas and tllLIS cat.J.Se dyspare unia d uring coin.LS. Fo Uowing coitus, she may complain of a dull ac he in tlte pelvis tl1at persists for 12-24 hours. This mll) lead to ftigidi cy and marital dish;u·mo n). INFERTILITY To implicate reu-o,ersion as a cause ofinfet·tility, it is necessary to perform all ot11er investigations for infertility. In ilie past a lot of emphasis has been given to retrovet-sion in a woman with unexplained infenility. Sims-Huh ner test (poStcoital test) "1tJt abundant motile spenns see n in tJ1e vaginal pool and cervi cal mucous rules out reu·ove ts ion as a cause of infertilit)'· On tlte conLJ be in the fonn of cystS, LLLrnour masses or infections. Following section describes these conditions which are seen in clinical practice.

BROAD UGAMENT CYSTS Broad ligament C)'Sts are fairly common. However, they are small and are of no clinical importance except the paraovarian cyst which may attain a la•·ge size and undergo torsion.

ANATOMICAL CONSIDERATIONS Vestigial remnantS of the Wolffoan d uct (mesonep hri c duct) are see n in th e broad liga ment, lying between the fallopian tube and the hilum of the ovary. T he mesonephric d uct ex tends from the outer aspect of th e ova•')\ parallel to the fallopian wbe in an inward and downward direction unti l it enters tl1 e myometriwn in tJ1 e region of the cervix. Its low· ermost limit is the region of the hymen. It should be rememebered tl1 at wo lfFian d ust is same as mesonephric duct or gart.ners duel. Associated with the mesonephric duct and opening into it are tl1e tubules of the upper pan of the Wolffian body, tl1e epoophoron or parovarium (sometimes called the organ of Rosenmi:JIIer). The) are siLUated in the broad ligamem acrecning, t~.ttment, and follow-up. Cynecol Oncol 199-1: 55:54. Swdd.J. et al. l'r%rn:;s in Ob.>tctriC> and Cp1aecology 17:306, EJse,·ier, 2006. Studd, J. et al. ProgrtetriC> and Cyl>aecol!,'Y 18:299- 313, Else,icr. 2008.

Benign Diseases of the Ovary

Nonneoplastic Enlargements of the Ovary 312 Polycystic Ovarian Syndrome or Diseose PCO, PCOS, PCOD 31 4

Key Points 317 Self-Assessment 3 18

O varies can be s ite o f a va ri e ty of d iseases. T hese diseases includ e f u nc ti o na l C)'SLS, ova ri an e ndome u·iosis, polycys tic ovaries a nd neop lastic diseases. In Lhis c hapte r; fun ctio nal C)'SLS and po l)'C)'Sti c ova ries a re d esc ribed. Ovaria n e nla rgeme n1.s, C)•Stic o r solid, may occ u r at an y age. F rm c tio na l a nd infl a mma to ry e n la rgemenrs of the ovary d evelop almost exc lus ive ly d uring the ch ildbearing yea rs. T hey may be asym ptomatic o r p rod uce local disco m· fort. menstrual d istu rba nces, infe rtility o r in rare cases cause acute S) mp to ms d ue to co m plicatio ns s uc h as hae m· orrhage. ru ptu re or torsio n . T he oval') is complex in its embryology, his to logy, ste· ro idoge nesis a nd has the poten tial to deve lo p malignancy. T he refore, oval"ian neoplas ms exhi bit a wide v:uiatio n in su·uctw·e a nd biologica l be ha,·io u r. t.:nlike the cervix a nd uterus, the ovaries are not cl inica lly accessibl e, :u1d the refore, sui table screening m eth ods for detecting ovarian neoplasms are n ot avail able. The ovary, a fter the ce rvix, is the second m ost commo n s ite for d evelopment of gynaecologi· cal m alig na ncy, with a dism al p rognosis. O varia n tum o u rs may occur at a n y age. Ln ado lescents, the ovari an tum o urs are m ostl y ma lignant and a re o f germ cell o ri gin. In pe rimeno pausal and post· men opa usal wo me n they te nd to be e pitl1eli al in o rigin. Du ring tl1e ch ildbea ri ng age, t11ese ova ri an e nl argemen ts are functi ona l in 70% of cases, neoplasti c (mostly benig n) in 20% of cases and d ue to O\'tl ri a n e ndo melli oma~ in 10% of cases.

NONNEOPLASTIC ENLARGEMENTS OF THE OVARY (Table 24.1 ) Enlarge me nt o f ova ries can be as a resul t o f pe lvic co ngestio n as seen in a pe lvic in flamma to ry disease, o varian endome triosis caus ing a c hocolate cyst o r pe rsiste nce and enLarge me n t of p hysio logical struc wres in t11 e ovary such as the Graafia n follicle or corpus lu te um. Th e lesio ns due to in flammator) co nd itions a re discussed in tl1e c hap ter o n a pe lvic in flammatoq d isease, a nd e ndome triosis affecting the ovary is d ea lt in Chapte r 27. In this c ha p ter, no nneoplas· ti c enlargeme n t of the ov;u·ies, a nd poi)C)"SLi c ovari:u1 S)11· dro me ( PCOS) are described in detail.

312

Table 24.1

Varieties of Cystic/neoplastic Enlargements of the Ovaries

1. Functional cysts

2. Inflammatory

• Follicular cysts • Lutein cysts • Multiple functional cysts Corpus luteal cyst (PCOS) Salpingo-oophoritis Puerperal , abortal, IUCD related

3. Metaplastic

Endometrioma

4. Neoplastic benign and malignant

Benign Borderline tumor Malignant

FUNCTIONAL CYSTS IN OVARY O varies ca n be tl1 e site of functi o nal cysts such as folli cular cyst. t11eca lutein cyst o r· co rpus lute um cyst. T hese cysts us ua ll y form beca use o f no nregressio n o f f unc ti o nal cysts in ovary. 1u define a funct.ional l)~l., it~ size must. be at l&.zst 3 C11~ b u t no t more than 7 e m .

FOLUCULAR CYSTS Fo llic ula r cysts a re no t u ncom mo n. T hey may be s ing le or m ul tip le, m ay be b ila te ra l a nd vary in s ize fro m s mall ble bs to cysts o f large s ize bu t ge ne ra lly d o no t exceed 5.0 e m in dia me te r (Fig. 2 1.1 ). They fo rm as a result o f fa iiLtre o f a bsorptio n of the fl uid in an in co mple te ly d eve lo pe d fo llicle o r a novula ti o n . They a re us ua lly asympto ma tic unless haemorrhage, ru pw re o r to rs io n supe rve nes, in whic h case S)lnptoms a nd sig ns of an ac u te a bdo me n d eve lop. Large :u1d mul tiple cysts may caLLSe pe h,ic pain, d ys p:u·e u· n ia :u1d irregular bleeding. The e nlarged ovary may be reco g ni a ble cl ini cally or docume n ted o n sonogra phy.

CHAPTER 24- BENIGN DISEASES OF THE OVARY

Figure 24.1

313

(A) Corpus luteum cyst. (B) Transvaginal ultrasound showing polycyst ic ovary.

Ovarian neop las ms, infl amma to ry ad nexal e nlargement and e ndo me u·iosis must be cons ide red in the differentia l diag nosis. Most fo llic ula r cysts disappear spontaneously within 4-8 weeks. In t11 e presence of sympto ms s uch as amenorrhoea ad ministering o ra l meclroxyprogesterone 10 mg twice a clay over a period of 5 clays will generally bring o n menstruation. Norethisterone tablet (Primo lut N) 5 mg Li.d. for 5 da)'S also induces menstmation. O ra l combin ed pills administered for 3 montllS he lp resolve the persistent cyst in most cases. If (Ill)' cy:.t per..ists for lo11ger tlum 3 numths, or size increases to > 7 em, the jJOJJibi/it)' of a neopln.stic cyst must be kept in mimi,

ami the patient iiiVI'.IIigMal.

FOLUCULAR HAEMATOMAS (FOLLICULAR CYST WITH HAEMORRHAGE) Small follicular haematomas are commo n. To the naked eye, the ova•-y con tains h aemord1agic cysts. Old cysts appear to con tain tan-y materia l and a re likely to be mistaken for endometriosis. Ma ny of t11 ese a re asymptomatic and of no clinical sig nifi ca nce except for t11e ra re case, wh en the C)'St ruptures into tl1 e peritoneal cavity ca us in g ac ute abdom en, and is mistake n fo r a n ec to pic pregnancy.

co urse of tim e. li e nee obse rva ti o n is reco mmended whenever this cond iti o n is s uspected. As it resemb les unruptu red ectop ic pregna ncy sonograp h y and se rum quantitative estima tio ns of 13-hCG can he lp to make a correct diagnosis. Uluasound reveals a sp ider web-like stm c ture with o r witllOut a clot. Dopp ler shows increased vascularization with a hig h blood flow ve locity.

THECA LUTEIN CYSTS These C)'Sts can sometimes enlarge to several centimeu-es in diameter. The) are usuall) bi lateral and filled with su-awcolottred fluicl Theca lutein cysts are oflen noted in cases of hydatidifonn moles, cho1iocarcinoma. Induction of ovulation witll gonadotropin (hCG) and clom iphene can also result in tlle formation of t11eca lutein C) St. The cy:sts spon taneously •·eg•-ess after evacuation of ilie mole, ilierapeutic curettage and treaunent of choriocarcinoma. In a case undergoing induction of ovulation ,,1t11 gon adotrOpin or clomiphene one should avoid giving hCG i-:jection tO prevent furm er enlargement of ova1-y. Functiona l cysts are distinguished from neoplastic C)'Sts b y the fact tlwt they uever grow more than 7 tm in size, am unilucul~lr with cltmr fluid wul rf'{,ITf:JS (ifier some t.ime. T he hypers timu la ti on syndro me by c lo miph e ne t11e rapy has been described in tl1 e c hapte r on Infe rti lity: Ma le a nd Female.

LUTEIN CYSTS OF THE OVARY Two l)'pes of lute in cysts a re recognized: • Granulosa lute in cysts found witllin the corpus lu teum. • Theca IULei n cysts associated with a trophoblastic disease and c horio nic gonadotropin therapy.

CORPUS LUTEUM (GRANULOSA LUTEIN) CYSTS Corpus lu teu m C)Sts are functiona l, no nn eop lastic e nlargements of the O\'al'). Persistent corpus luteum C)'Sts may cause local pain, tenderness or dela)ed mensu·uation. These C)'Sts are often pa lpable clinicall)'· Unless complicatiOilS such as torsion or •·upwre lead to an acute abdomen requiring surgicaltreaunem, most cysts will resolve in due

MULTIPLE FUNCTIONAL CYSTS Multiple func tio na l cysts are us ua lly ca used by following concli tio •lS: • Fo llicle-stimulatin g hormone (FSH )-secretin g pituitary adenoma. • O varian h)perstimulation S)ndrome (OHSS) • PCOS

PITUITARY ADENOMA ln pituitary adenoma, ovarian C)Sts measure more tllaJl l em; FSH and oestrogen le,·e ls are raised, but lute inizing hormone (LH ) le,el is low. Othersig•lSofh)perstimulati on

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such as hae moconcenu·aLion and coagulation profile are not present. Amenorrhoea, oligo menorrhoea and infertility are the clinical feawres. Pituitary adenoma may require transsphenoidal excision of th e ade noma, but no surgery is reqtLired for th e ovaria n C)SIS. These eve ntually resolve.

OVARIAN HYPERSTIMULATION SYNDROME O HSS is omsed main!) b) ad ministration of human chodonic gonad otropin injection in a wo man undergoing control ovarian stimulation with gonadotropin or clomiphene. The folli cul ar sit.e is usually more than 3 em. POLYCYSTIC OVARIAN SYNDROME PCOS is characterit.ed by multiple small cystS less than 1 an; LH is raised and LH / FSH ratio is ~ 2. This condition is fairly common affecting 5%- 15% of adolescent girls. It may also be seen among women in rep roductive age suffering from inferLility, mens trual irregula rit.i es or hirs utism. Following sec ti on desc ribes in de ta il about aetiopathogenesis, diagnosis and manage ment of this co nd itio n.

POLYCYSTIC OVARIAN SYNDROME OR DISEASE PCO, PCOS, PCOD PCOO is a heterogeneo us, mu ltisyste m endocrinopathy in women of reprod uctive age with the ovarian expression of various metabolic diswrb;1nces and a wide spectrum of clinical feaLUres such as obesity, menstrual abnormalities and hyperandrogenism. This disease was descdbed by and named as Stein-Leventhal S) ndro me in 1935. 1o diagnose PCOS. adrenal and androgen-producing ovarian nunour shotLld be excl uded.

INCIDENCE Current incidence of PCOS (5%-15%) is increasing fast lately due to change in lifeSt) le and stress. It is also becoming a common p•·oblem amongst adolescentS, developing soon after puberty. Amongst infertile women, about 15%20% of infertility cases are due to anovulation caused by PCOS. Some of the women who develop a cardiovascular disease, hypertensio n, endomeu·ia l cancer and type 2 diabetes later in life appea r to h ave suffered from PCOS in earlier years. AETIOLOGY AND PATHOGENESIS T he exac t aeLio logy of !'COS re ma ins unknown. A number of t.h eolies have bee n postul ated in the ge nesis of PCOS. Some of tJ1e well-known facto rs which may infl uence the onset of PCOS are lifestyle changes, sedenta•)' life, d iet and su·ess. ln itia ll)', tJ1e ovaries we re thought tO be the primary sight which setS tJ1e series of d1anges in the endoa·ine pattem resulting in PCOS. Genetic, fami lial and environmental factors (autosomal dominant inherited facwrs) were later added as aetiological facLOrs in the development of PCOS. The environ men tal facLOrs ma> function in utero or in early adolescent life, manifesting clinically a few years later as PCOS. CYP~ 1 gene mutation has been ident.ified in iliis connecLio n. Familial occu•,.e nce has also been reponed where a sex-linked mode of inheritance has bee n postulated. AnotJ1er ,•iew held for the de,·elopment o f PCOS is an enhanced serine phospho•1 lation unification acti,~ty in the

ovary (hyperandrogen) and a red uced ins uli n receptor activity peripherally (insulin resistance). Obe~ity is related to PCOS. At leas t 50%-70% of patientS with PCOS te nd to be obese or overweight. The adipose tissue (fat) is considered an endoc rine a nd immunomoclulaLOry organ; it secretes leptin, ad ipo nectin and cy1.0kines which interfere witJ1 the ill.SU/ill .Sigt~(l/lillg pathways in tlle liver and muscles resulting in i11.su/in n'Sistrmce, and hyperinsulhwemia. Increased binh weight in obese and PCOS moth· ers can also cause PCOS in their adolesce m daughte rs. Raised LH secretion by insulin ca n cause infertility or misca•·riage through improper oocyte matura tion. Obesity is characterit.ed as the condition "11en bod)' mass in· dex > 30 kg/ m2 and waist line > 88 em; waist/hip ratio > 0.85. Endogenous !3-endorphin also stimulates insuli n release and ma y contribute to insulin resistance. Hyperandrogenism and resultin g anovulation were initi al!)' tho ught LO arise plimaril y in th e ova ries. It has now being proved that insuli n resista nce with resul tan t h yperins ulinaemi a in itiates PCOS in 50%-70% cases, tJw ugh hypothalamic-pilltita•r-ova ri an ax is, ad renal glands also play a ro le in the genesis of PCOS to so me ex te nt.

OVARIAN STEROIDOGEN ESIS IN PCOS Insuli n ind uces Ll-1 to cause theca-cell hyperp lasia and secrete androgens, testostero ne and epi-androstenedione which are converted to oesu·ogen in the gran ulosa cells. £pi-androstenedione is co nve rted in tJ1 e pe ripheral fat to oestrone. This leads to lise in tJ1e oesu·ogen and inhibin level. These in turn cause high Ll l surge. While oesu·one level increases, oesu-adio l level remains nonnal with tJ1e result Ulatthe oestro ne/ oestradio l ratio lises. Hyperandroge nism lowe rs tJ1 e level of hepa tic sex hormone-binding globulin (SI IBG), as a res ult levels of free testosterone in se•·um rises leading to hirsutism. AJUlrogen also wpprlllle:. the grmutlt of 1111' domill(lllt folliclt' wul pTl!Vt!nt.s apoptosi~ of smaller follicll'~ whiclt lln' non1lflll)' dP.stined to disa~ pmr in the lme foUicu/(lr pluJJe. PCOS may set in early adolescent life, but clinically manifest in the rep•·oductive age with long-tenn complications such as diabetes, hypenension , hyperlipidaemia and a cardiovascular disease; this cluster of disorders is known as the ' X syndrome' or 'metabolic syndrome'. Endocrinological changes in PCOS are as follows: l. Oestro ne/£2 level rises. 2. LH level is ra ised over I0 IU/ m L. FSH level re ma ins no rma l, but FSH/ LH ra ti o falls. 3. SHBG levels fa ll d ue to hypcra nd rogenism. 4. Tes tosterone and ep i-androstened ione levels rise. 5. Fasti ng b lood glucose/ fasting insuli n < 4.5 suggestS insulin resistance. 6. Triglyceride level > 150 mg/ dlrhyperl ipidaemia High Density Lipoprote ins (HOL) < 50 mg/ d L. Testosterone > 2 ngl mL, free T > 2.2 pg/ mL (Normal level 0.2-0.8 ng/ mL) onnal androstenedione. Raised Oeh)droepiandrosterone Acetate Sulfate (OHEA-S) level 7. Pro lactin is mildly raised in 15% of cases. 8. Fasting insulin le,·els are 1-aised (> IOmlU / L in 50-70% cases of PCOS).

CHAPTER 24 - BENIGN DISEASES OF THE OVARY

Rgure 24.2 Bi lateral enlarged ovaries w ith a smooth and thickened capsule. (Source: From Figure 22.3A . R. Jeffrey Chang: Polycystic Oiary Syndrome and Hyperandrogenlc States. Jero me F Strauss a nd Robert L Barbieri: In: Yen & Jaffe's Reproductive Endocrinology: Physiology, Pathophysiology, and Clinical Management, 7th Ed ition . Saunders: B sevier, 2014.)

9. Th)•roid f1m ctio n LeSlS may be abnormal (h ypothyroidism) . 10. Urin ary co rtisol < 50 mcg/ 24 hours.

PATHOLOGY Mac roscopicall), bo th ovaries are e nlarged. The ovary shows a thick white caps ule of wnica albuginea. The ovarian surface ma) be lo bulated but the pe rito neal surface is free of adhesions. Multiple cysts ( 12 o •· more) o f 2-9 mm siLe are loca ted pe •·iphera lly along the surface of the ov:u·y gi,•ing it a ' necklace' appearan ce o n ul traSound. These are persistemalt'etic follicl es. Theca-ce ll h) pe •·plasia and stromal hyperplasia a ccount for the increase in the siLe of the ovary which a mounts to m on~ than 10 em' in volume. The laparoscopic view of th e pol)'C)Stic ovari an disease is shown in Fig. 21.2. CUNICAL FEATURES (Table 24.2} The pathoge nesis appca•'S to be initiated either in utero or in earl y adolesce nt life. Earl y adrenarche in the form of earl y pube rta l ha ir and ca rl)• menarche is observed in some Table 24.2

315

of tl1ese girls. Me nstruatio n for t.he initia l few years may be no rmal, but as clinical fea tures of PCOS develop the cycles beco me o ligomenorrheic (87%) o r they deve lop a short pe riod of a me no rrhoea (26%) fo llowed by pro longed or heavy pe riods (a co mmo n complaint in a majo ri ty of cases) . Drsme no•·rhoea is abse nt. ln the reproducti' e )Cars, infertili t) is see n in a numbe•· o f these women. This is du e to anovulatOI')' q cles. lf a woma n with PCOS conceives, she d evelo ps ca rbohrdra te intolerance , diabetes and h) pen ension. Pregna ncy loss occurs in 20o/o -30% cases due to aborti ons. Hypera nch-ogenism a ppears in the form of acne (30%) and hirsutism. Facial hair appea rs over the upper lip, chin, breasts and thighs . Baldness is sometim es noted, but virilism does not develop. Histol')' of lifestyle, diet and smoking and exogenous hormon e adminisu-a ti on sho uld be enquired. Family history of diabetes and hypertensio n should also be asked.

EXAMINATION OF A GIRL WITH PCOS Look for • Obesit)', especially waistJinc . Waist LO hip ratio > 0.85 is abnormal; 50% of wo me n are obese. • Bod)' mass index betwee n 25 and 30 - overweight; and above 30 - obesit)'· • Thyro id e nlargeme nL. • Hirsutism and ac ne . • Hype rinsulinae mia which ma) manifest as acantJ1 osis nigricans (5%) ove r tJ1e nape of tJ1e nec k, axilla a nd below the breasts; 75% of obese PCOS women have h)'Pe rinsulinae mia. • Blo od pressure in obese wo men . Peh·ic findings are usually nonnal, and it is not easy to palpate the enlarged ova.-ies.

DIAGI'OSTIC CRITERIA FOR MAKING A !lAGI'K)SIS OF PCOS For the di agnosis of PCOS, th e Rou erdam u iteria (2003) a•·e genera lly followed. It states that at least two of three crite.-ia should be p•·esent. These c•·iteri a are as follows: • Oligo/ ame norrhoea, anovulati on , infertili ty • Hi rsutism/ acn e • Ultrasound findings (sec sec ti o n ' Investigations')

Clinical Features of PCOS

Clinical Features • Young woman • Central obesity BMI > 30 kglcm2 Waist line > 88 em Oligomenorrhoea. amenorrhoea Infertility (20%) Hirsutism Acanthosis nigricans due to Insulin resistance; thick pigmented skin over the nape of neck, i nner thigh and axilla Most androgen come from OVflrl t fasting insul in > 10 miU/l

Sequelae

Hormonal

•

t~ level

• Diabetes (15%) • cardiovascular Disease (CVO) Llpidaemlas Hypertension fAndrogens Endometrial cancer Testosterone, epi- androstenedlone, dehydroepiandrosterone Breast cancer Premature ovarian failure following 17-a·hydroxyprogesterone > 300 ng/dl Testosterone > 2 nglml surgery Prolactin t Sex hormone-binding globulin (SHBG) l l E:!oestrooe (E 1) ratio F. glucose/insulin ratio < 4.5

• t LH levels t FSHILH ratio

t

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DIFFERENTIAL DIAGNOSIS Although the diagnosis is easy in most cases. congenital or adult adrenal hypetplasia, Cushing disease and ovarian mascui in i£ing tumottrs should be considered in differemial diagnosis especially, if a woman isex u·emelyobese or had features of virilism. With irregular C)•cles in yo ung girls, hormonal assays wi ll idemify a hypo thalam ic-pitu ita t)•-ovarian dysfunction. Thyroid function testS may be called in for a few cases. INVESTIGATIONS Ultrasound is diagnostic of PCOS. • • • •

It confil"lns the enlarged ov:uies, their sit.e and increased su·oma. Ov:u·ian volwne will be mot·e tl1an 10 nun~. It shows 12 or more small follicles each of2-9 mm in size placed peripherally. It helps to rule o ut ovarian ttunouc It can also show endomeu·ial hyperp lasia, if present.

In a case wi tl1 suspicious adrena l tum our/adrenal hyperplasia, abdominal scan, estimation of O il ~, 17-0H hydroxyprogesterone level will help in d iagnosis of these conditions. 'lb make a diagnosis of PCOS, ultrasou nd should preferably be perfonned in tl1e early follicular phase. An increased blood flow is sometimes revealed on Doppler uluasow1d Ulu-asound is also used to watch the response of medication and to decide when to stop lhe drug therapy. Sometimes, onl) one ov:uy may show features of PCOS. These ovarian d1anges cannot be relied upon if a woman is on combined oral pi lis, as tl1ese pills change tl1e ovarian morphology. • Hormonal stud)' mentioned ea rlier is not performed ro uti ne l)', bm specific hormonal swdics are undertaken in a woman as and when requ ired. All ho rm onal studies are not needed as a ro utine. • Thyroid function testS in an obese woman. • Laparoscop)' is reserved for a t11erapeutic purpose. ln most cases diagnosis can be confirmed on uluasound. Laparoscopy reveals enl:u·ged bilateral ovarian cystS.

TREATMENT The aims of u·eaunem are as follows: • • • •

To cure a woman with menstrual disorders To treat hirsutism To treat inferti lity To preve nt long-term effec ts in t11e form of X syndrome in later life. The lrtYJiment sfwttkt be tailomlto thrreqttiremeu/. oftlte umnan.

loss. Weight loss of more than 5% of previous weight alone is beneficial in mild hirsutism; it restores the honnonal milieu considerabl)'· \\'e ight loss increases the secretion of tl1e SHBG, reduces insulin level and testosterone level. • Lifestyle changes. Cigarette smoking should be stopped. It lowers E~ level and raises DHEA and androgen level. • Hormones to regulate mensu·uation are as follows: • Oral combined pills (OC) • OC containing cyproterone acetate or drospirenone • Spironolactone and OCs • Ketoconazole 200 mg dai ly reduces testosterone secretion. •

~l!ight

Oesu·ogen suppresses androgens and adrenal hol"lnones (DHEA). It raises tl1e secretion of SHBG in the liver, which binds witl1 testosterone, tllLLS reducing free testosterone. It also suppresses LH. It is best given as low-dose combined pills, having progestogen witl1 lesser androgenic effecL Fourtl1 generation of combined pills wh ich comains30 meg E..~ and 2-3 mg drosp ircnone (progestogen witl1 an ti-androgenic acti on) are best for PCOS (Yasm in, J anya, Tarana). IL helps to reduce acne and further development of hirsutism. It preventS water retention and reduces weight; it maintains a lipid profile. • Progestogen may be required to induce menstruation in an amenorrhoeic woman prior to initiating a ho.-n1onal C)clical tl1erapy. • Oral Conu-aceptive Pills (O CP) con r.ain ing C) proterone is prescribed, if the wom:u1 has hirsutism (see Chapter 9). • EAorinthine cream topicall)' prevents hair growtl1. Hinuti~m. Ami-androgens used are described in detai l in chapter o n llormone T herapy in Gynaecolog)'· Acne can be managed by a clindamycin loti on I % or e rythromycin gel 2%, if pustules form. For severe acne, isou·etinoin is used, but it is ter-atogenic and pregnancy should be avoided whi le on this medication. The drugs take 3~ IIWnlhl before imjntruemmt in Mnttli.!m il noltxi. Dexamethasone (0.5 mg) at bedtime reduces androgen production, and is used in some infer·tile women if DHEA-S is raised abo'e 5 ng/ mL l nfertilit)'. For managing infertility in a PCOS wom:u1 Cibmip11Pnl' is the firlllirw of ln!tllment. It induces ovulation in 80% and yndrome. Obstct Cynccol 2009; 114:936. American College of Ob.>tetricians and GynecologistS O:nnrniLLee on Gynecologic Practice. Coonmitttoe Opinion No. 477: the role of the

ob.>tetrician-gynecologbt in the early detection of epithelial ovarian cancer. Ob.>tct Cynecol 20 II: 117:742. American College of Ob.>tctrician.> and C~11ccologists. ACOC Practice Bulletin. Management of adnexal ma>>t'.>. Obstet C~necol 2007; 110:201. Bonnar J. Recent Ad.-ance.> in Ob.>tctric.> ;u1d Cpuoet"OIgj Vol 19:121, 1995. Bonnar J. Recent Ad\ance.> in Ob.>tctriC> and C,naecology 21: Ill, 2001. Fauser BC. Tartalris BC. Rebar R\\', et al. Con .en>& IS on women 's health aspectS of poi).C)'>tic oval") .>yndrome (PCOS): the Amsterdam ESIIRE/ ASR.\1-Spon;,on:d Srd PCOS Consen>&IS Workshop Croup. Fcrtil Steril 2012: 97:28. Goodman NF. Cobin Rll. Fuucn,eit \\', et al. American association of clinical endocrinologi>~•. american college of endocrinolj.,')', and andrQ!, ;,ocicty di.case state clinical ,..~,iew: Guide to the best practicIIS on dias.:nostic criteria and long-term health risks related 10 polycy.>tic ov.try .>yndrome. Fertil Steril 2004; 81:19. Studd J. ProbttL..S in Ob.>tetrics and Cyn accoloj.,'Y 11:851, 1994. Studd J. ProbttL..S in Ob.>tetrics and Cyn accoloj.,'Y Vol 16:227, 2005

Benign Diseases of the Vulva

Introduction 319 Benign Diseases of the Vulva 319 lnAamrnotory lesions 319 Ukers 321 Atrophy 322

Vulval Dystrophies 322 Cysts and Neoplasms 325 Key Points 325 Self-Assessment 325

INTRODUCTION A \'3.-iety of developmenLal, trophic, innammaLOry, allergic and neoplastic diseases can occur in the vulvar skin and iLS appendages. 1l1e common n•lvar diseases affecting Lhe vulva are as follows:

t. 2. 3. 4. 5.

1-:pidenni~ and dennis. Common dermatological disorders, a lle rgies, infections, naevi, d)'Siroph ies, ulcers and new growll1s. Sltin r•fJfJendages. Folliculitis, sebaceous cysLS, hid radenomas, Bartholin's cyst or abscess and Paget disease. lldj(ICtml stmctures. Li pomas, fibromas, haemangiomas, vadcosities, carcinomas, sarcomas and endometriosis. DevelopmmJaL Vulvovaginal C)Sts, imperforate hymen, vulval anus and intersex problems. Homw11aL Vulval au·ophy in menopausal women. • Despite ll1e fact that vulvar diseases are not tmcommon, and the \ulva is easily accessible to clinical examination, ll1ere is oft.en a delay in arri~i ng at diagnosis dLte to delay in seeking medical advice out of a sense of modesty wh ich prevails and pre,·e ms the patielll from seeking early advice. • T he symptoms most commonly produced by vulvar lesions are excoria ti on, swelli ng, ulceration or altered pigmentation wh ich may be accompan ied b)' itching, pain or bleeding. An accurate diagnosis can usually be made by inspection, palpation, smear and culture examination and biopsy.

BENIGN DISEASES OF THE VULVA Benign conditions of the vulva may be classified as follows:

• lnjllmmwtory• lesions. (a) Skin diseases, (b) sex uall)' ~ransm it­ tcd diseases, (c) contact vulviLis and (d) vu lvar infections associated wi ll1 vaginitis. • Ulcer.,. (a) Simple acute ulcers, (b) tubercu l at~ (c) 1raumatic ulcers and (d) malignant ulcers.

• A~rophy. • D)Strophies. • Crsts and neoplasms.

INFLAMMATORY LESIONS

SKIN INFECTIONS INTERTRIGO AND FOLUCULITIS I ntenri go and fo lliculitis are common I)• seen in obese women, using tight garments whi ch prevent evaporation of the moisture from tllese parts leading to chaffing followed by bacte•·ial and fungal infection. Pyogenic bacteria, sLaphylococcus can cause folliculitis. The treaunem involves weight reduclion, use of loose undergarmenLS, ad,·ice •·egarding personal hygiene, tLSe of a bland soap and an unmedicated protective d1LSting powder. Anlimicrobial ointments may be tLSed iniliall) to control secondary bacterial infection. Occasionally, oral antibiotics may be needed. Local app lication of 0.5% hydrocortisone o inunentthree to four times dail)' he lps LO re lieve itching in intertrigo. TINEA CRURIS Tinea cruris or ringworm of the thigh, vulva and groin is not infrequent!)' encountered in the tropics. The causative organism is TriclwfJh)'I011 rubru11L It tends to be chronic and frequently •·elapses after u·eaunenL The characteristic e11 tJ1 ematOlLS circumscdbed areas are found in the skin flexures of ll1e ll1ighs and outer aspect of the labia. A fine papular rash is LLSually seen sharply demarcated from Lhe adjacent healthy skin. Patients experience intense itching; scratchin g leads to superimposed infec tion. Treatment co nsists of metic ulo us hygiene, t11e use of freq uently chan ged light underclothes, dustin g will1 a fungicidal powder or app lica ti on of a fungicida l o illlment co nLaining benzoic and salicylic acids. Oral ad ministra ti on of griseofulvi n is also high ly effective. 319

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THREADWORMS Enterobit~:> ven11icuktm may seco nclalily infect the vulva from t11e anorectal area, particularly in d1 ildren. The diagnosis is easily established on sLOol exa minalio n. The treaunem is with anthelmintic drugs such as pipem2ine o r mebendazole. VULVOVAGINITIS Vulvovaginitis in children may be nonspecific due LOa foreign body accidentally inu·oduced in the vagina or due to threadwonn infeCLion. Gonococcal and fw1gal infection may rarely be due to sexual abuse or contamination. Ban.holinitis is mostl y gonococcal but other cocci may also be responsible, and pr·e sent with a painful and tender swelling over the labia m 23.() and 25.7). • Goolama l e t a l. showed tha t this lesio n is linked to a utoimmune diseases in 40% o f cases a nd is seen

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SHAW'S TEXTBOOK OF GYNAECOLOGY

•

•

Figure 25.6 Lichen sclerosus et atrophicus of the vulva (SOU"ce: Juan Rosai. Rosai and Adears of age; genetic and familial tendency is also noted. During the acute phase, the lesion may appear dusky im ohing the vulva, perineum and per·ianal area

•

•

•

•

in an hour-glass pattern (figure-of-eight). The skin is papery thin and wrinkled. As the disease progresses, the labia minora blend into the labia majora thus causing a narrow introitus. Although the lesion is essen tiall) atrophic in lo ngsta nding lesions areas of dysplasia and malignanq ma> occur in I %-5% of cases. Longstanding Lichen scle rosus is a wellrecognit.ed predisposing factor for developmem of carcinoma ,•ulva. All suspicious areas must be biopsied. The chief S) mptoms are intense prur·itus, d ys uria, d yspareunia and local discomfort. Biopsy reveals hyperkeratosis, thinning of the epidermal epithelium, flattening of the rete pegs and hyalinit.ation of the tissue beneath the epidermis. Treatment with bland creams is recommended. The condition responds well to local application of steroids, such as oestrogen cream and testoster·one propionate. Two per cent testosterone oinu11ent in a whi te petrole um jell y resolves pruritus in 6-8 weeks. Andractim gel (5 g) dose can be grad ually reduced beca use of the risk of virilization and acne. About 80% response is reported. Testosterone by converti ng to d ih yd roteswste rone brings abo ut favo urable skin changes. Excision of the areas to re lieve pr uriLUs is often fo llowed b)' recurre nce of th e lesion aro und the excised margins. Hypertrophic changes may fo llow, for which biopsy is advis.'lb le. Lichen sclerosus is now treated with 0.05% clobe tasol (Dennovate) ointment for 8-12 weeks followed by Trimovate (clobetasone plus n)Statin and oxytetracycline) to maintain S)lnptomatic relief. Oesu·ogen and testosterone creams are useful in older women. Vitamin A is useful, and reti no id analogues have been administered. Twenty to thil'l)' milligrams aciu·etin given for I montJ1s is effecti'e in 60%-70% of cases. It can cause ell") ness of skin, e>e irritation, hair loss and mya lgia. Its teratogenic effect prevents its use during pregnancy, and you ng women should use contraceptives to prevent pregnancy. lntralesional intPr.frrrm is successful in some cases. It must be emphasit.ed that before medical treatment, multiple or selective biopsy is mandatory to rule out malignancy or preinvasive lesion, as 5%-10% ofthese lesions show concomitant malignancy or develop these changes in d ue course of tim e. Pap smea r is also desirable to check on tJ1e cervical histology. S·urgery is rarely empluyed lmd is not. t ll.mble. Fresh lesio n may appear in tJ1e vicin iq• of the excised area. Ski nn ing vulvectOmy, cryoablati on and laser ab lation and vulvecwmy in o lder women have been employed. The treatmenL th e refore, is d irected LOwards symptomatic re lief, preve nLi ng ca nce r by reg ul ar fo llow- up and improving the appearance of the vul val skin. This indicates the ne ed for prolonged and continuous follow-up. Mixed variet) shows histological changes of hypertrophied as well as atrophic d)Stroph) at different sites in ilie same lesion. The treatment is also based on predominance of t)pe of lesion seen. De nervation ofvulva b) ' Me ring' procedure with a curved incision around the vuh' vaginal cell (Fig. 2().2). The nucleus is pyknotic. The maximum level of cornification is usually seen in the late prolife1-ative phase of a nonnall)' menstmaling womatl when oestrogen production is maximum near the Lime of ovulation.

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~

• d

Figure 262 The layers of vaginal epithelium of the well- oestrogenized adult. The superliclal layer contains surlace cells that are cornified (squamous) with eosinophilic cytoplasm and pyknotic nuclei (a) as well as large intraepithelial cells that are also karyopyknotic but basophilic {b). The intermediate zone oontalns basophilic cells that have less cytoplasm and intermediate-size nuclei (c). Parabasal and basal cells have successively smaller amounts of basophilic cytoplasm and more vesicular nuclei {d, e). (Source . From Rgl.le 15-29. Mark A Sparing: Pediatric Erdocrirology, 4th Ed. Saunders: Bsevier, 2014.)

PHYSIOlOGICAl CHANGES IN THE VAGINAl EPITHEUUM It is possible to demonsu-ate C)clical \'31·iations in the \ knotic. The cells :u·e sepat-ate. and tlle cornification index is the highesL 4. Early secretory pbase. The squames become clumped togetller in clusters. They are less mature, tlle crtoplasm is now largely basophilic, and t11e nuclei are bigger, less

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SHAW'S TEXTBOOK OF GYNAECOLOGY

dark-staining and vesicular. The cells are no longer flat but appear to be folded with a crinkled or o·wnpled appearance. Some are pointed and characteristically spear shaped. The cornificatio n index falls. 5. Late secre tory phase. Intermediate precomified cells predominate. There is lack of com ification. Cytoplasm is basophilic- the cells are o ·umpled and folded. The nuclei are large, pale staining a nd vesicular. Pyknosis and concentration of nuclear su bsta nce are absenL Polymot·phs are on the increase. The background is mud.'}' (diny). The C)clical ch anges in the vaginal epithelium show that the activity is at its maximum during the week before the onset of mensu·uati on. Br0\\11 staining of the vagina, when t11e walls are painted with Lugol's iodine, gives a rough indication of tl1e gi)'Cogen co nte nt of t11e cells li ning tl1e vaginal epitl1elium, and thereby the oestrogenic tiu-e of t11e pati ent's blood. T he maximum glycogen co nt.e nt in t11 e vaginal epitlleliu m is found in the vagina l forni ces, whe re it is prese nt to th e ex tent of 2.5-3.0 mg%, and it is at its lowest in the lower tl1ird, whe re its va lue is 0.6-0.9 mg%.

NATURAL DEFENCE MECHANISM OF THE VAGINA The skin of the vagina is a tough stratified sq uamot.LS epitllelium devoid of glands. It presents a smootJ1 unbroken surface to the aLLack of pat11ogenic organisms. There are no crypts where organisms co uld multiply unlike in tl1e endocervix. The p H is low and the high acidity mitigates against bacLetial growth. The thickness of the epitJ1elium and the hostile p H depe nd upo n oestroge n, and therefore, it is only in extreme young girls, befot·e puberty, and in senescence, i.e. after menopause, tl1at bactetial inroacls are likely. There are following cen.ain phases when the p H is raised: • During menstruation, when th e cervi cal and the endometrial dischaq~e, which is alkaline, tends to neutralize tl1e vaginal acidity. • After abortion and childbirth , wh en the alka li ne lochia h as a similar elfecl. • An excessive cervical discharge, such as occ urs in endocervicitis, has the same effect. Apa tt fro m these excep ti ons, the vagina is na turally selfs Lerilizing under the ac ti on of DOde rle in's bacilli.

CYTOLOGY OF THE VAGINA Cornification of the vagina is well marked in the vagina of t11e newborn because of th e high oestrogen level wh ich has been transferred from the mot11er. After about 10 days, the vaginal epithelium beco mes thinner and remains in tl1is state until the approach of puberty. At puberty, the functional la)er increases in t11 ickn ess. In t11e first half of a normal pregnanc), t11e co rnifi cation index is low and shotLid not exceed 10%. In the presence of progesterone deficienc) tl1 ere is a t·ise in the comification index, and if the index tises over 25%, the patiem is likely to abort. ln late pregnancy, the cornification index falls even lower and at tet·m, it may fall below 10%. Aft.er menopause, altl10ugh the ovat·ies haYe ceased to function, some degree of comification is usually present, the oestrogens probably being derived ft·om tl1 e adt·en al cortex and from conversion of androstenedione (fi·om ovary) to oestrone in the pet·ipheral adipose tissue. After menopause, th e vagina l epitheli um atrophi es with witl1drawal of the oestrogen supporL T he epithelium becomes tl1in and parc hmem-like and is prone to infection (sen ile vaginitis). T he vagina l s mea r shows ma inly the basal basop hi lic rounded cells with la rge nucl ei. T he bac kground shows le ucocy ti c infi ltrati on . T he s uperfi cial sq uames are absent and th e inte rmed ia te cells are few and far between.

VAGINAL ACIDilY The vaginal acidity is due to lactic acid, which may be present in a variable amount The pH value is 5.7 in the newhom and reaches 6-8 in children , and falls tO 4 at puberty. Ottring pregnane), the pi ! value is usually 4. After menopattSe. tl1e p H rises to 7. The normal pH in healthy women dwing the childbeal'ing period is about 4.5. It is important to understand that DOderlein's bacillttS is the only organism which will grow at a pH of 4-4.5. As the acidity of the vagina falls and t11e pH tises, nonresident pathogens are able to thti\e.

FLORA OF THE FEMALE GENITAL TRACT In healtl1y women, the fa llopian Lubes, tl1e cavity of the utentS and the upper third of the cervical canal are free of microorganisms. The lower third of t11 e cervical canal always comains microorganisms, as does the vagina. a. Lactobacilli (Doderlein's bacilli)- mainly responsible for the production of h)drogen peroxide whid1 is toxic to anaerobes. The> also protect against bactet·ia and candida. b. Facultative organisms (low, nonpathoge nic numbers) ( 1) Diphthei'Oids (2) Coagulase negati' e staph) lococci (3) Streptococci (gt·oups Band D) ( 4) &cherichilt coli (5) Url!ojJla~11U:t tlrtXt~'licwn (6) Mycoplr~"u:' lwmini~

c. Anaerobic organisms (poor concentration) ( I) Peptosu·eptococci (2) Bactemidll.l (3) Ft.tsobacteriwn species In healtl1y wome n, Dode rl e in's bacillus is tl1e o nly o rganism found in Lhe upper two-tl1ircls of the vagina; b ut in tl1 e neighbourhood of tl1e vulva, both sap rop h)'tic and parasitic organisms can be de monstrated. Docle rle in's bacilli have been fo t.Uld in tl1e vagina of the newbom witl1in 9 hours after de livery, a lthough the usual Lime for them to appear is 15 hours. The vagina of the newborn is probably inoculated dttring parwrition. Otuing tl1e pueq)erium, ac idity of the vagina is reduced and foreign organisms such as colifonn bacilli and otJ1er patl1ogens can grow. Vaginal discharge increases aro und 0\1.tlation, during pregnancy and intercourse. Antibiotics and bat-rier contraceptives also make vaginal secretion mo re alkaline. Outing the climacteric a nd after menopause, the number of DOderlein 's bacillus is reduced and sometimes, tl1is

CHAPTER 26 - BENIGN DISEASES OF THE VAGINA

organism cannot be demonstrated in the vagina. The importance of Dode rle in's b.1cill us is that its presence is associated witJ1 tl1 e production o f lactic ac id contained in tl1e vagina and tl1 is acid it) inhibits tJ1e growth of o tJ1er organisms. Ln multiparous women, when the vaginal orifice is patulous as a result of childbirth, foreign organisms may be found in tJ1e lower part of tJ1e vagina which by producing a low-grade vaginitis give rise to discharge.

lEUCORRHOEA The tenn leucorrlwea should be resu·icted to tl1ose conditions wh en m e nonn al vagin al secretions are increased in amounL Ln such patients, tJ1ere will be n o excessofleucocytes present "hen tl1 e disch ar-ge is examined under tl1e microscope, and tl1e dischar-ge is macroscopicall y and microscopically non pun.denL Purulent disciHu•ges due to specific infections such as gonorrhoea, u·icl1omoniasis and mo niliasis. Ulcerated growtJ1s of th e ce rvix and the vagina and d isch arges caused by urinary fiswlae arc of a d ifferent type and sho uld be excluded from tl1e term ' leucorr·hoea'. Some cl inicians use the term to describe an)' whi te or yellowish-white d isc harge fro m tJ1e vagina. An increase in t11e norma l vaginal secretions is ph)•siological at p ube rty, d uring pregnane)', at ovulation and, in some women, during t11 e pre me nsu·ual phase of the mensu·ual cycle. During pregnancy, the nonnal discharge is ina ·eased in ;unotu1L because of ina·eased vascu larity of the female ge nital tract. During the latte r part of the menstrual cycle, tl1 e h)'Peru·oph ied premensu·ual glands of tl1e endometri tun secrete muco us whid1 is discharged through the ce rvix into the vagina. The leuco ni1oea of pubeny is probably caused b) the increased vascu larit)' of tl1e ute n.IS, cervix and vagina at that time. It is of shon duration and needs no u·eatme nL This secretion contains proteins, polysaccharides, ;unino acids, en0mes and immunoglobulins. onpathogenic leuconi1oea, merefore, ca n be classified into: (i) cervical and (i i) vaginal.

EXCESSIVE CERVICAL SECRETIONS (CERVICAL LEUCORRHOEA) Mucous discharge fr·om t11e endocervical glands increases in such conditions as chroni c cerv icitis, cervical erosion, mucot.IS polypi and ecu·opion. When t11e mucous secretions of tl1e cervix are produced in excess, it u ndergoes little ch ange in the vagina and appea rs as m ucoid discharge at the vulva.

EXCESSIVE VAGINAL SECRETIONS (NONPATHOGENIC VAGINAL LEUCORRHOEA) T his form of leucorrhoea is seen when t11e disc harge origi· nates in tl1e vagina itse lf as a transudation tl1rough the vagi· nal walls. Nom1ally lac tic ac id o f the healtl1y vagina is formed from tl1e glycogen co nta ined in tl1 e kerati nized cells of the vaginal mucosa and the vagi nal portion of tl1e cervix. These cells are co nsta nLly being desquamated when tl1eir glycogen liberated is fermented b) DOde rlein's bacilli, whid1 produces lactic acid This process is under tl1e con u·ol of oestrogen, the level of which determines tl1e pH of L11e vagina. Local co nditions in pelvis with an increase in blood flow to me pelvic organs as see n in pregnancy, acq uired reu·oversio n and prolapsed congested ovar·ies, duonic peh~c inflammator)• disease (PID ) and chro ni c constipation are causes of an increased ' -aginal secretions.

329

Leucorrhoea must be distinguished from specific vaginitis by perfom1ing bacteriological examination and care mLISt be taken to differentiate between L11e cervical discharge of chronic cerv icitis and excessive '-aginal sec retion. A specLLium exami nation of the 'aginal discharge in bactet·ial 'oaginosis are as follows (Amsel's criteria): • White, milky, nonviscous disd1a1-ge adherent to the vaginal wall. • p H of the discharge is more than 4.5. (p H 5-7). • Fishy odour when mixed with 10% KOH is due to a mino-metaboli tes from vario us o rga nisms (a mine or whiff test). • Presence of clue cells - the epithe lia l cells have a fuzzy border due Lo ad here nce of bacteria (Fig. 26.4A and B) . • Increased numbe r of G. vagina/is and o th er microorganisms and reduced number of lactobac illi and le ucocytes. The woman has minima l vu lval irrita tion. The diagnosis is based on wet smear and c ulture. The smear reveals clean background with few inflammatory cells and other organisms. but scant) lactobacilli. Many epi thelial cells presem a granular C) to plasm caused by small Cramnegative bacilli adhel'ing on their surface, the so-called clue cells. Free floating clumps of Gt~rdnerellll are seen. Cram stain is 90% sensitive and 83% specific. D A probe for G. vagina/is is now avai lable. Cas liquid chromatOgraphy is useful.

CHAPTER 26 - BENIGN DISEASES OF THE VAGINA

331

DOderlein's -~•o( bacilli

Figure 26.3 (A) Normal mature vaginal cells wit h D&lerlein's lactobacilli. (B) Clue cells with very few DOderleln's bacilli.

Bacterial voginosi~ ca n ca use PID, chorioamnion itis, premature n.tplllre of memb r,lne (PROM) and pretenn labour.

TREATMENT The 7-day course of metronidazole 400 mg twice daily is effective in 85% of cases, whereas a single dose of 2 g cures only 45% of cases. Ampicillin 500 mg or cephalospori n 500 mg b.i.d. for 7 da)S is also effect..ive. Tetracycline 500 mg four Limes ada). dox> C) cline I00 mg twice a day and sulphafumLole for 10-1' be co nside red supe rior tO the laue t: Metron idazo le to u·eat bacteri al vaginosis may be avoided in first uim este t:

A

PROBIOTICS Ecoflora

, · ·~

..'

·"

:~-

~-~

Figure 26.4 Bacterial vaginosis. (A) Vaginal smear showing DOder· lein's bacilli. (B) Clue cells suggestive of bacterial vaginosis.

Ecoflora capsule contains Lal'tobacillus rhmmuJSus GR-1 and Lactobacillu~ reuteri Rc-14. These are probiotic age nts, effective against Gram-negative pathogens a nd resistamto spermicides. Th ey also have anti-inflammatory ac tivity. They secrete collagen-binding proteins that prevent pathogen adhesions. The ecoflora adheres to the epithelial cells, prevent adhesion of other pathogens and produce 1-120 2 , thus maintaining p i-1 in the vagina. One to two capsules daily for 30 days are followed by one capsule daily for another 30 da) s. The drug is, howe,·er, contraindicated during pregnancy.

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SHAW'S TEXTBOOK OF GYNAECOLOGY

MISCELLANEOUS CAUSES OF EXCESSIVE VAGINAL DISCHARGE

The infection is more common fo llowing menstmation or following in te reo u rse.

a. Excessive physiological discharge (1) Comm on causes Sexual excitement Cervical erosion Ovulation lime Ps) chological factors (2) Management Clinical evaluation to exclude pathology Counselling and education Electrocalllery of erosion cervix b. Other infections ( 1) Common microorganisms suspected include Chlamydia tradwmati~ Gonorrhoea Herpes Foreign body Chemical irritation Senile vagin itis c. Management options Advice abo ut personal hygiene. Avo id use of il,.itants such as do uches, vaginal comraceplives (chem ical creams, foam tabletS) if they are the cause. Remove foreign body- retained condom, tampon, pessaries) Chlamydia - treat with tetracycline/ doxycycline/ erythromycin. Gono1·rhoea - treat with penicillin/ ceftriaxone/ ciprofloxacin. cefiXime. Herpes -treat with aC)clOvir and allied de1ivalives.

DIAGNOSIS

INFLAMMATION OF THE VAGINA

Diagnosis is established b) smear and cuiLUre of vaginal discharge.

TREATMENT Treaunem \oa1·ies according to the infecting organism and is general as well as local.

GENERAL All measures a1·e designed to improve tJ1e gener·al healtl1 of the patient.

LOCAL T he correction of the vaginal p i I to 4.5 by a waterstetrlcal and G~aecological Pathology, 3rd ed., London: Chtxdlil Ul.ingstone, 1987, pp. 411-456.)

Subacute PLD results from inadequate treaunent or from reinfection by the infected panne r. Tube rculosis also manifests in the form of rec un·ent pelvic infec ti o n due to secondary infec ti on.

CHRONICPID Failure of acute pelvic infection to resolve or end resu lt of ac ute infec tion results in chro nic wbo-ovarian masses. These masses man ifest in the fo llowing forms: • • • • •

Hydrosalpinx Chronic p)Osalpinx Chronic imerstitial salpingitis Tubo-ovarian C)St and TOA Tubercular tubal-ovarian masses

Hydrosalpinx ( Fi~ 27.6 ond 27.7)

H)dro.salpinx is the distension of the fallopian tubes by coUecLion of fluid in the lwnen. If a p)Osalpinx or TOA responds to antibiotics, the pus contained therein becomes ste•ile within 6 weeks of the initial auack, but the damage to the tube persistS presenting as chronic p)osalpinx or h)drosalpinx. A hyd•·osalpinx •·epresents the end result of a previous acute salpingitis, and is often bilateml. It is retort-shaped

Rgure 27.6 Right-sided hydrosalpinx. The left appendage shows less obvious but well-marked chronic salpingitis.

Figure 27.7 Hysterosalpingography showing bilateral hydrosalpinx.

swelling of th e wbe d ue to enormous d ilatati on of the ampullary region fi lled with a clear flu id and ma)' be as large as 15 em. The fimbria! end of the fa llopian tube is usually closed; fimbliae are indrawn so that the o ute r SUJface of the hydrosalpinx is smooth and rounded. The interstitial end of the tube is curiously paten L, as Lhe dye can be visualized in the ILtmen during hysterosalpingogram (Fig. 27.7). The wall of the hydrosalpinx is thin and tmnslucenL At Limes, the hydrosalpinx is mobile and can undergo torsion. Quite often, however. the outer surface is covered with adhes ions which fix the h)drosalpinx to the back of the broad ligamem and the pouch of Douglas (POD). Histology reveals flauening of the tubal plicae and exfoliation of the lining epit11elium (Fig. 27.8). Chronic Pyosalpinx (Figs 27 4 ond 27.5)

A chronic p)osalpinx is thi ck-walled swelling of the fallopian tube, surrounded by dense adhesions and filled ''1th pus. The inner wall is •·eplaced by a granulation tissue. A pyosalpinx is often fixed to t11e POD, poste•·ior surface of t11e broad ligament and t11e uterus by dense adhesions.

Figure 27.8 The wall of a hydrosalpinx. Note the flattening of the plicae (X360).

CHAPTER 27 - PELVIC INFLAMMATORY DISEASE

Table 27.2

3.41

Stages of PID

Stage I- Acute salpingitis without peritonitis- no adhesions Stage II - Acute salpilgitis with peritonitis - purulent discharge from tubal ostia Stage Ill - Acute salpingit is with superimposed tubal occlusion or tubo·ovarian complex Stage IV - Ruptured tubo-ovarlan abscess Stage V - Tubercular salpingit is

Chronic Interstitial Salpingitis

In chronic imerstilial salpingitis, the wall of the fallopian l.llbe is thickened and fibrotic, but there is no accLumtlation of pus in tJ1e ILtmen. Involvement of the ovary in adhesions resu ll.S in chronic salp ingo-oophoritis. Tubo·Ovarian Cyst

In Utbo-ovaria n cyst, a hyd rosa lpinx co mmunica tes with a fo ll icul ar cyst of the ovary, whi le in TOA, pyosalpinx com· municate with an ovarian abscess. It is difficult to identify a normal ov;u·ian tissue in these pathological conditions. Tuberculous Form

Pelvic tuberculosis is described in Chapter 28.

STAGING The spectrum ranges from mi ld-to-moderate and severe PI D. Depending upon the severit)' of lllbal damage, Ga inesville has described five stages of PID (Table 27.2).

SYMPTOMS AND SIGNS OF PID ACUTE PELVIC INFEGION A )Otmg, sexually active woman is prone to PlD. The most common S)mptom of acute PLO is alxlominal pain. It is bilat· era! and restricted to tJ1e lower abdomen. Pain spreads upwards if generalized pe1i1.0nitis ensues. It is severe in me acute stages and is accompanied with high-grade fever. Vomiting may also follow. The sexually U"l!nsmitted organisms may cause dysw·ia and vaginal discharge. Mensu·ual inegularity, if any, is d ue to preceding endomeu·itis in a case of ascend ing infec ti on or clue to the amecedent aborti on or de livery. T he pmie nt may develop abno nn al ute rine b leeding at a time when mensuuation is not expected and the bleeding is often profuse and prolonged. In criminal abortion, tJ1e patient may deliberately conceal me history ofamenoni1oea, making tJ1e diagnosis more difficult. ln case of a pelvic abscess (Fig. 27.9), in addition tO me above S)lnptoms, the patient develops se· ve•·e dianiloea and passes small and frequem loose motions clue to rectal initation. ln chkmrydial infoction, symptoms are li!ss pronounced and often tm asymptomatic course. The patient witll acute PID looks ill with high temperature ( I 03-104°F). Tachycardia is present, and the tongue shows deh)•dration and is coated. Abdom inal examination shows distension co mbined with te nde rness and rigidity in the lower abdo men . It is rare for an abdom inal swelling to be palpated in ac ute salpingo-oop horitis. Late •~ as me tenderness becomes less witJ1 treaw1ent, a tender fixed mass

Figure 27.9

Ult rasound showing pelvic abscess.

arising from th e pelvis may be palpable. Speculum examination shows pLtrulem discharge from the ce•,•ical canal. A torn cervix or damaged tissue is evident in postabonal sepsis and criminal abortion. Swabs should be taken fi·om the cer· ''ix and high 'oagina for culture. In an acute stage, cen•ical movement tendemess and tendemess in tJ1e fomices are the onl) evidence of peh~c infection. Later (Fig. 27.10), tender pelvic masses are felt in the lateral fornices. These ma~es are fixed and at times palpable behind the utenLS in POD. A pelvic abscess prod uces a n uctuating Lender swelling in the POD, bulging into th e posterior fornix. TOA fo 1mati on occ urs in 30% of the cases of PLO and is a freq uent reason for hospitalizati o n.

DIFFERENTIAL DIAGNOSIS ACUTE APPENDICITIS In appendicitis, the pain is initiall)' central, arow1d tJ1e umbilicLLS and men localizes to the right iliac fossa. Vomiting is severe, buttempera[Ure is not as high as in PIO. The

Rgure 27.10

Ultrasound showing a pelvic mass.

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SHAW'S TEXTBOOK OF GYNAECOLOGY

lower margin of Lhe append icular mass can be reached, but tl1is is not so in case of PI D. Vagina l discharge and menstrual irregulariLies are absent in acute appendicitis.

EGOPIC GESTATION Amenoniloea followed b) irregular uterine bleeding and abdominal pain are tlle characteristic features seen in ectopic pregnane). Cervical movement pain and a tender mass dLUing per vaginal examination are tlle feawres of ectopic pregnancy. Ca·iminal abo•·tion with history of amenorrhoea may mimic ectopic pregnancy. Mostly temperature is normal or only slightly raised in ectopic pregnanC)'· The signs of internal bleeding are absent in PID. Vaginal discharge, leucocytosis and 1-aised erythrocyte sedimentation rate (ESR) go in fuvour of a diagnosis of PID. Ulu-asound may reveal bilateral tubo-ovarian masses. DIVERTICUUTIS Di verti culi tis may s imulate t11 e clinical p icture of PID, but it usually seen after the age of 50 yea rs, whe reas PID is a d isease of the yo ung, sex ua ll y ac tive fe ma les. T he signs of infec ti o n are co nfined to the left iliac fossa in diverticulitis. A TWISTED OVARIAN CYST A twisted ovarian or paraova•ian C)'St (fimbria! cyst) causes sudden pain in tile abdomen with vom iti ng, b ut pyrexia is usually absent or of very low grade (Fig. 27. 11 ). Menstrual irregularity and vaginal discharge are absent, and an abdominal lump is felt distinctly, which is usually tender. The nonnal-sized uLerus is felt separate from the lump. Ulu-asound is helpful in making a diagnosis. l nflammatoq bowel diseases and urinary u-act infection are associated with bowel and tuinal') spnpLOms, and do not usually ha,•e high fever o•· vaginal discharge. RUPTURED ENDOMETRIOTIC CYST Rupture of an endometriotic C)St is not a common event; however, in ra•-e situation a ruptured endomeu·iotic cyst can be mistaken fur PID. The patient with endomeu·iosis will have suffered dysmenord1oea, meno•-rhagia and pelvic pain before this acute episode. 13esides, the patient is afeb1i le and has no vaginal discharge.

SEPTIC ABORTION Septic abortion may mun1c Lhe clinical features of PID; amenorrhoea preceding tile abdominal pain is present in septic abortion. A detailed clinical evaluation will help in establishing a diagnosis of septic abortion. The treaunem with antibiotics is similar in boLh t11ese conditions. CHOLECYSTITIS Occasionally, a woman witll PID complains of acute rightsided upper abdominal pain simulating cholecystitis. This is due to a fib•·ous band extending from tlle right adnexa to the under surface of the liver in PI D caused by gonococcal and chlam)dial infection. This goes by the name of Fiu.-H ugh-Cunis S)•nd•·ome.

INVESTIGATIONS Clinical diagnosis of PID is acc urate in o nly 65%-70% cases, a nd specific investi ga tions arc req uired to co nfirm the diagnosis as we ll as to identi fy Lhe offe nding o rga n isms. • Haemoglobin. • Blood co unLS reveal rise in tot.a lle ucoc)•te co unt. • ESR is also raised. • Ceroical and high vagi11al swab wltnw for both aerobic and anaerobic organisms is necess.1ry. Urethral swab culture should be done, if gonorrhoea is suspected. For chlamydia! infection, a long-wire swab tipped witll calcium alginate is used to collect the specimen from t11e tube, tLretJHa and endocervix, and this is inoculated on cycloheximide-treated McCo) cells for culture. Serological microfluorescence test for detection of lgM and lgG antibodies is useful. Pol) me1-ase chain reaction (PCR) test is now a\ and to establish tile diagnosis of a pelvic abscess. • LapMosropic examination though recommended and pmcliced b) some should not be used in routine p•-actice. This investigation is limited to cases in which diagnosis is uncertain and it is not easy to aspimte pus for cultw·e. T he pus extruding fro m th e fimbria! end and peritubal

•

Rgure 27.11 Laparoscopy revealed torsion of fimbria! cyst (paraovarian cyst) to be the cause of acute abdominal pain.

CHAPTER 27 - PELVIC INFLAMMATORY DISEASE

adhesions is a sure sign of P ID. O th er signs of pelvic infection besides e xudates are hyperaemia of tl1e fallopian LUbes, oedema a nd fibrinous band of adhesions in peri hepatic space (Fit:t.-llug h-C urtis syndro me ) mentioned above, seen in 15% of cases. • Gm-1droe protein, an acULe-phase reactam protein generated in response Lo innammation, is increased to 20-30 mg/ dL or more, and it helps LO diSLingu.ish between infective and noninfective mass. • Ultrasound, computed tomQgraphy (C!J amlmagnd.ic Tl!SlJIIfJIIce imaging (MRJ). TOA appears on ultrasound as a complex C)Stic adnexa l or cukle-sac mass with thick in·egul:u· walls a nd septations. ILoften contains imemal deb•·is :u1d echoes (Figs 27.9 and 27.10). This is safer and noninvasive compared LO laparoscop>: 3 D and 4D ultrasonography is used nowadays LO define Lubo-oval'ian masses. CT s hows a sp he ri cal o r tubula r strucwre, with a low atte nuation cen u·e, in add itio n to thi c k walls a nd septations, but it is diffic ult to diffe re nti ate it from e ndometriosis. Inte rn al gas bubb les, if see n, a re pa thognomon ic of inflammato ry mass. MRI does not provide mo re specific info nna tion than ultraso und , and is muc h more expensive. It iJ importtmt to te~t the all msfs of PID for HfV and other sexually tran~mittl~l infectiom. The parme r s ho uld also w1dergo inves tigations fo r sex ually u·ansm ined infections. In a menopau&"\1 woman, who-ovarian mass indicates probable malignancy a nd sho uld be invest.igated accordingly.

CHRONIC PELVIC INFLAMMATORY DISEASE The hisLOq of pre' ious pel' ic infection helps in tl1e diagncr sis, but often this history is not fo•·thcom.ing and not recalled by the patienL The patiem complains of constam lower abdominal pain which geLS worse before mensu·uation. Low backache and deep d)spareunia caused by pelvic masses prolapsed in the POD are common compla.ims. Vaginal discharge may be absem and if presem, may be due to chronic cervicitis. Meno•·rhagia, polymenon11agia, and congestive dysm e non·hoea are aw·ibuted to chronic pelvic congestion. Infe rtility results fro m blockage of the fall opian tubes. Rectal irrita tio n may be complained of by few patientS. T hese cle bilita ting symptoms ac t upo n the general health of th ese patie nts. Abdom ina l pa in is due to pelvic adhesions o r s upe rimposed infec tio ns. Pe lvic exa mina ti on in c hro ni c PID is less painfu l than in th e ac m e stage of the disease. The appe ndages are fo und to be tender, thi c ke ned and fixed, a nd a n assoc iated fixed retroversion of ute rus is a very co mmon finding. At times tl1 e uterus and appendages are dense ly ad herent tO each other, so the uterus ca nnot be defined separately from t11e pelvic masses, thus forming a fix ed hard mass. A ' frozen pelvis' is tl1 e descriptive term used in these cases.

DIFFERENTIAL DIAGNOSIS Ectopic Gestation

Chronic ectopic pregnancy ma>' be easil)' mista ken for PID. Pregnancy Lest, ulu-asound a nd laparoscopic examinat.ion "ill confirm the diagnosis of ectopic pregnancy.

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Uterine Fibroids

The sympLOms are very simila •~ so also tl1e pelvic findings if appendages are adherent to th e ute rus, giving ll1e impression of at1 irregular e nlarged utems. Fixi ty and tendemess however go more in fmour of c hro nic PI D. Pelvic Endometriosis

Pelvic e ndometl"iosis produces similar clinical features as chronic PIO. Laparoscopic examination will confinn ll1e diagnosis. Ovarian Tumour

A benign ovarian tumour is often unilateral and causes neitl1er menstrual pmblem nor dyspareunia. A malignant ovarian wmour usuall y occu•-s in elderly women and is rapidl y growing; he nce, sympto ms com e up faste•· than in chronic PI D. T he te ncle mcss is abse nt in a n ova 1i an tumo ur. Ultrasound examina ti o n, CA-125 a nd fine-needle aspiration cytology (FNAC) ca n be useful. Tubercular Tubo·Ovarian Masses

Tubercu lar tubcrovali a n masses may present as rec urrent or chronic PIO. It is some tim es uni la te ra l. Laparoscopic e xamin a tion, endo me uia l b iopsy a nd c ulture he lp in establishing the diagnosis. PCR tes ting of e ndomeu·ial tissue can also be done.

TREATMENT A.im is to u·eaL infectio n, minimi:te wbal damage and prevem adhesions. thus avo iding sequel of tubal damage.

TREATMENT OF ACUTE PID The mild cases of acute PID are u·eated at home with antibiotics. Moderate a nd se'ere cases of acute PIO need hospitali.t.ation. Treatmem modalities comprise following: • Medical treaunent, antimicrobial • Minim al invasive surgery • Major surge•-y Syndromic mat1agem ent - labo rato r-y tests take tim e and may delay the trea tme nt. To avo id sequelae s uc h as blocked tubes, chronic pelvic pain a nd infe rtili ty o r ec top ic pregnancy, tl1e mode rn manage me nt is to initiate antibiotics whi le waiting for the fina l reports. This ha~ a s ma ll risk of unn ecessaq' u·eaun e nt o r ove rtreaune nt, but is worthy. Hosp ital manage ment consists of followin g: • Rest. • lnu·avenous nuids in the presence of dehydration or vomiting and correction of e lectrolyte imbalance. Ryle's rube aspiration may be needed in periwnitis or distension of abdomen. in which case correct intake-output d1art should be maimained. • Analgesics. o nce the diagnosis is co n finned. • A11tibioticJ.. Because of the damaging effect of gonococci and cldamydia o n tl1e fallopian wbes a nd pol)lnicrobial nature of tl1e infection, it is mandaLOI)' to instiwte antibiotic ll1e1-apy at the earliest and not wait for the cultw·e resultS.

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l n most cases of PI D, bo th ae robes and anaerobes form t11e bac terial flora, hence it is essemial to administer combinatio n of a ntibiotics to cure the disease and preve nt permane m damage to the fallo pian tu bes. Initially, intraveno us route is resorted to, but as the infection settles down, o ral me rap) ma> be started . When t11 e cui LU re re port is available or if the patient fails to respo nd to the antibio tics, an appropriate change in the antibio tic tllerapy will be needed. Antibioti cs effective a •·e as follows: • • • •

At.ithrom)cin 500 mg for 14 days. Oox) C)cline 100 mg b.i.d. for 14 days. Clindam)cin 450 mg q.i.d. for 10 da)S. Gemamyci n 80 mg IM 8 hourl y for 5 days.

For managing a case of PI D, t11e guidelines given by CDC are extremely useful a nd h elp in bette r management of a case (Table 27.:~).

Table 27.4

Subacute Cases Who Can Take Antibiotics Orally (the fo llowing regimen have been suggested by CDC)

Recommended Intramuscular /Oral Regimens Ceftriaxone 250 mg l.m. In a single dose PLUS Doxycycline 100 mg orally twice a day for 14 days WITH or WITHOUT Metronidazole 500 mg orally twice a day for 14 days

OR Cefoxltin 2 g i.m. in a single dose and Probenec id, 1 g orally administered ooncuiTently In a single dose

PLUS • Doxycycline 100 mg orally twice a day for 14 days WITH

or WITHO UT

• Metronidazole 500 mg orally twice a day for 14 days

OR • Ot her pare nteral t hird-generation cephalosporin (e.g. ceftizoxime or cefotaxlme)

PLUS Table 27. 3

CDC Guidelines for Treatment of PID (2015)

• Doxycyc line 100 mg orally twice a day for 14 days WITH or WITHOU T • Metronidazole 500 mg orally twice a day for 14 days

Recommended Parenteral Regimens • Cefotet an 2 g l.v. every 12 hours

PLUS • Doxycycline 100 mg orally

or l.v.

every 12 hours

OR Cefoxltln 2 g i. v. ei.'Bry 6 hours

PLUS Doxycycline 100 mg orally

or I.v.

every 12 hours

OR Cllndamycl n 900 mg l.v. every 8 hours

PLUS Gentamicin loading dose i.v. or l.m. (2 mgl kg), followed by a maintenance dose (1.5 mg/ kg) every 8 hours. Single daily dosing (3-5 mgl kg) can be substituted. Alternative Parenteral Regimen Amplcilln/Sulbactam 3 g J.v. every 6 hours

PLUS Doxycycline 100 mg orally or i.v. every 12 hours

However, fo r subac ute cases or tllOse wh o can take antibioti cs orall y, a regime n has been suggested by CDC as given in ·rable 27.1 . T he side eJJects of clincla m)•Cin are skin reac tion, nausea and vo miting. O tl1e r anti bio ti cs useful a re cep halosporins, and pe ni cill in witll be ta-lact""mase inhi bitors. T he fo llowing are the newe r antib iotic regime ns: 1. Cefoxitin 2 g i. v. &-ho urly+ Doxycycline, 100 mg i.v. fo llowed by o ral ro ute . 2. Azitl1romyc in 500 mg i.v. &-ho urly for 2 days, then orally fo r chlam)'di(~ 3. Ofloxac in 400 mg orally b.i.d . for 14 days. Cefo tetan 2 g i.v. 12-ho url) plus clOX)Cycline 100 mg b.i.d. o rally/ i.v.. Drugs are co ntinued fo r at least 48 ho urs after the clinical imprO\eme nL After the discha rge from the hospital. dOX)C)cline is co ntinued 100 mg fo r 10-14 days. 4. Levofloxacin 500 mg b.i.d. fo r I I days with or witllOut meu·o nida.t.Oie.

5. Clindamycin 900 mg i.v. every 8-ho urly plus gentamicin in a loading dose i. v. or i.m. (2 mg/ kg) fo llowed by maintenance dose (1.5 mg/ kg) 8 ho urly (regimen co ntinued for at leas t 48 hours afte r tl1 e clinical improvement) . After discharge fro m tl1 e hospi tal, do xycycline is given 100 mg b.i.d orall) fo r 10- 14 days or clindamycin 450 mg orall) ulcerate and cause a d isdlarging sinus. Mia·oscop)rre,•eals the L) picai LUbercula r g.-anul oma. Ulce ralive vagina l lesions whenever prese nt :u·e always found to co-exist with ceni cal d isease. Tubercul:u· vaginitis has also been re ported. The di agn osis has been made on

Figure 28.5 Hypertrophi c tuberculosis of vulva. Note considerable oedema of labia majora and elephantiasis-like appearance of labi a minora. (Source: From: Madeod and Read, Gynaecology, 5th eel. Ch.lrchill, 1955.)

ce rvico-vaginal smears. Ulcerative lesio ns o ften heal by fibrosis ca usin g vaginal stenosis. l?.ecw-vaginal fistula is a rare co mplicaLion of ge ni ta lw berc ulosis.

CLINICAL FEATURES OF GENITAL TUBERCULOSIS It is an important obsel"\'lltion t11at about I0%- 15% o f women suffering fi·om genital tuberculosis a re asymptomati c and 15% of them may have successfully conceived earli er. However, the leading presen ting complain tS in women suffering from geni ta l tubercul osis include infertility, menstrual irregularities, abdominal pain, vaginal discharge and suspicion of neoplasm. Fistula fonn ation is a .-are occurrence. Sometimes general symptoms of low-grade feve•·, weight loss, faligue a nd a feeli ng of lis tl essness ma y raise the suspicio n of hitJ1e rto unsuspected d iagnosis of geni tal tubercul osis. Pelvic examinalio n often reveals no tJ1ing significant; in 20% of cases tJ1e ad nexae ma)' feel tJ1icke ned or co rd-like, tubo-ovarian masses ma>• be palpable. T hese may be te nder if seconclalil)' infec ted. In cases of no nhealing sca rs following surge ry, a lwa)'S suspec t tJ1e possibilit)' of tuberc ulosis and b iops)' fi·o m the scar tissue will reveal tJ1e d iagnosis. Clinical features of female genital tuberculosis are as follo-w-s: • • • • • • • •

lnfe rtilit) Me nstrual i1·regulari L) Abdo mina l pa in Vagina l discharge Abdo mina l mass Fistula forma ti on Ectopic pregnane> As)lnptoma ti c in LOo/o-20% cases

CHAPTER 28 - TUBERCULOSIS OF THE FEMALE GENITAL TRACT

Infertility (pri mary or secondary): Th is is an important presenting symptom. In fact, in 35%-60% cases infertility may be the on I) complaint for which the patient seeks medical auention. Of these women, about 75% present with primaq infertility and 25% give history of previous conceptions. In almost half of these cases, there ma> be a histoq of a past infection or contact with a person suffering from tuberculosis. In any suspicious case, it may be wise to obtain a histological repon on the endometrium early in the course of the work up for infertility. Infertility is attributed to tubal damage and endometrial adhesions (Asherman syndrome), and at times ovarian damage. Menstntal ir regularity(amenorrhoea, hypomenot-rhoea, menorrl1agia): It has been obser-ved in 10%-40% of cases. T he menstrual diswrbances reponed include menorrhagia, menometrorrhagia, intennenstrual bleeding, oligomenorrhoea, hypomenorrhoea, ame no rrhoea a nd eve n postmenopa usal bleeding. In the West, dysftm cti o nal bleeding is more freq uen tl y enco untered, whereas in Ind ia oligome no rrhoea a nd hypo menorrhoea a re seen mo re freque ntly assoc ia ted with genita l tuberc ul osis. T his has been aw·ibuted to the higher associa ti on with pul mona ry disease in our country. Tuberc ulosis sho uld be suspected if pubeny me norrhagia does not respond LO med ical therapy. Chronic pelvic pain: This pain may be d ull ac hi ng in type, sometimes aggravated premensu·ually, or it might be intermittent in nature. Vaginal discharge: Blood-stained vaginal discharge, postcoital bleeding, leucorrhoea and serosanguinous/ seropuntlent discharge from ulcers are occasionally encoLunered from lower genital tract tubercular lesions. Abdominal mass: Some women may present with a mass in the abdomen, which consistS of rolled-up omentwn, with dense adhesions to the uterus and adnexae. The history of associated mensu·ual disturbances accompanying the presence of fixed abdomino-pelvic mass should raise the suspicion of genital tuberculosis. Encysted ascites, matted intestinal loops, uterine pyometra and adnexal masses ma>' p•·esent as lumps. A doughy feel on palpation of the abdomen is suggestive of wberculous periton itis. Other symptoms include dysmenon11oea, dyspareuni a and repeated episodes of pelvic infla mmatory disease ( PID). ln a yo ung, unmarried girl presen ting with a pelvic inflamm atory mass, it is almost alwa)•S of a tube rcul ar o rigin . PID whi ch fa ils to respond LO the sta nda rd u·eatme nt and rec urren t P10 is ofte n d ue to w berculosis. Fistula for mation: T his co mplicati o n ge ne rally follows s urgical in terven tions such as d raini ng of a n abscess, or abdom inal h)'Sterectomy. Ectopic pregnancy: Women witl1 genital tuberc ulosis rare ly conceive. Howeve t; patien lS successfully treated for the disease have a high risk of ectopic pregnancy. The high risk is attributed to residual tubal scarring ca using narrowing and disLOrtion of the tube. Prospects of future childbearing: Treaunent of patientS with genitalwberculosis for infenility has generally rielded poor results. In case pregnanq occurs, t.he t-isk of eCLopic pregnanq and abottions is substantially high. However, Jive pregnancies have been reported. In women wit.h a LUbal disease but ha,'ing recepti,,e endomeu·ium and a nonnal ute•·us, cases of successful pregnancy outeomes have been reported with assist.ed reproducti'e t.echniques. However, in

351

case of t.he endomeuium being unfavourab le and nonreceptive, surrogate pregnanq• may need to be considered.

INVESTIGATIONS General: Routine imestigaLions ma> reveal nothing significant. I. Complete blood count: A differential leucocyte cow11. ofi.en shows the presence of lymphlX)•wsi5.

2. Er)'t hrocyte sedimentation rate (ESR): This is frequently

raised. However, f.SR is a nonspecific investigation. 3. Mantoux test: A posiLive test is indicative of exposure to

tubercle bacilli in the past. It has been reported lO be positive in mot·e than 90% of cases. A negative test goes against tuberculosis. QuantiFERON test is supetior to Man LOI.LX leSt. 4. Hysterosalpingography reveals fea tures suggestive of ge ni talwberc ulosis in man>' patients, whe re e ndo me u·ial b iopsy has fa iled to reveal the d iagnosis. Hysterosalpingograp hy sho uld not be pe rform ed if geni tal tube rculosis is suspected because of risk of sp read of infec tio n. If performed in an asymptomaLic woman, it may show th e following patterns( Figs 2!l.G-28.8 ): • A tigid nonpetistaltic pipe-like tube (lead pipe appearance) • Beading and variation in the fi lling • Calcification of the lUbe • Cornual block • A jagged fluffiness of the wbal outline • Tobacco-pouch appearance of hydrosalpim: and pyosalpinx 5. The enzyme-linked immunoabsorbent assay (ELISA) tests - lgC and IgM: In recemtimes, ITI)CObactet·ial purified protein antigens used in ELISA have been favourably evaluated. 6. Ultrasound examination: It can reveal an abdominal mass, but cannot identify its nature. However, ulu-asound guided nne-needle aspiration cytology (FNAC) from the adnexal mass is feasible, as is USC-guided u-ansvaginal

Figure 28.6 Tuberculous tubes and uterus injected after removal. (Source: From: Stallworthy, 1952, JObst Gynaecol Br Emp.)

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SHAW'S TEXTBOOK OF GYNAECOLOGY

Rgure 28.7 Beaded appearance of the fallopian tube and extravasation of the a.;e in pelvic tuberculosis.

Rgure 28.8 HSG showing a reduced size of the uterine cavity with irregularity of lumen outline and adhesions suggestive of Asherman syndrome. (Co!rlesy: Dr K.K Saxena. New Detll.)

tri-cut biopsy of the peritoneum as an altemative to laparoscopic biopsy of the peritoneal tissue. 7. Endometrial histology and PCR testing: Endomeui um tissue is obtained by D&C/hystcroscop)•i> of 1he nlh"a. Obstet G)nec:ol 1978: 51:225. Chhabra S. Genital tuber~·uiO>i> a baffiing di>ea.e. J Obstel Gynaec:ol India 1990: 40:569. Cocttcc LF. Tubera•lou; \aginith. S Afr ~!edJ 1972; 46:1225. Clcemobilsky B. Endorneuiti> .md infcnilit). Fenil Steril 1978; 30:119. Dalal AR. \'enkatesan R. M.magernent of genital tubercuiO>is. In Tank OK, Sar.ura l:B. Patel MK (ed>). Po>tl-,•r.tdltate Frontiers in Obstetrics

CHAPTER 28 - TUBERCULOSIS OF THE FEMALE GENITAL TRACT and Cyn ac"t:ology. 2nd Ed. New Delhi, FOGS! Publications, J. P. Brother.., 1999. DalyJW, MonifGRG. lnfcctiotl> di>c>o.sch it tl, Belac'>ch·AIIart .J C. Gen ir>tl tuberculosis-in fertility tre-ate-d "it h IVF-ET. J In Vitro Fert Em bryo Transf 1985; 4:184. Gu pta N, Arora I lL, Gupta A. Tubercul osis of th e female genital tract. J O bstet Gyn accol lndia 1991; 4 1:238. Gu rg"an T Unn an B, Yar~li I I. Ge nital tuberculosis. Fe rtil Steril 1996; 65:367. llalbrcecht I IV. ll calcd ge nital tuberculosis. O bstct Gyn ecol1957; 10:73. Jcdbcrg II. A study on genit al tuberculosis on women. Acta Obste tric Gynccol Scand 1950; 31(Suppl): 11 7 Khcrdckar M, Kh cr A, Sh ann a AD. Tuberculosis of the end ome trium: A h i>topathological study of 355 c>o.s 1954: 69:618. Manjari Mridu. Khanna S. ~hlan SK. Genital tubera tiO>is. Indian J Pathol Microbiol 1995; 42:227. ~Ieise Is A. Fortin R. Genit•il tubcrculo.i> Acta C)10I 1975; 19:79. ~lerchant RJ. Geniti> and infertility.] Reprod ~led 1989; 34(7):468. ~lill:tr JW. llolt S Gilmour I 1~1 . e1 al. \'uh-ar tuberatlosis. Tubercle 1979: 60:1 73. Munshi MM. Chiddanvar S, Patel A. Tuberculosis in gynaecolog)•. lndi:.nJ !"athol Microbiol 1993; 36:3.?6. l'\a1,.-pal M, P..d D. Genital tuberculo>i>= A diagnostic dilemma in O PD patients. .) Obstct Gynaccol l ndia 2001; 51:127. Nogali>: A 31 year stud y of 1436 cases. Obstet Cynecol 1979; 53:422. Nov-ak ER, Woodru lf J D. 1ov-dk's Gynaccologic and O bstetric P.a thology, 8tlt Ed. Philadelph ia, WB Saunders, I 979. Parikh FR, Nadkarn i SG, K:un at SA, ct al. Genital tuberculosis in infertilit y. Fcrtil Stcril 1995; ()7:497. Prcrni IlK, Kum ar A, Kum arS. Cervical tubcrculosis..J O bste t Gynaecol India 1990; 40:826. Ridley CM. Re-cent Ad v-.m ccs in Vulval Disease. O turchill Livingstone, Edin burgh, 198.'>.

Sexually TransmiHed Diseases Including HIV Infection

Vulvar Infections 356 Genital Ulcers 358 Vaginitis 362 Human lmmunode~ciency Virus Infection 365 Contraception 368 Sexually Transmitted lnfec~ons and Infertility 369

Practical Approach to Common Vaginal Infections 369 Hepatitis B Virus 369 Key Points 369 Self-Assessment 370

The term 'sexua ll)' u·ansmitted d iseases (STDs)' refers to a \'• remain aspnptomatic.

363

Table 29.4 Treatment of Gonorrhoea (CDC-2015) Recommended Regimen Celtriaxone 250 mg l.m. In a single dose PLUS azith10mycin 1 g orally in a single dose Alternative Regimens If ce!triaxone is not available: Cefixime 400 mg orally In a single dose PLUS azith10111ycin 1 g orally in a single dose

lABORATORY INVESTIGATIONS These include Gram Stlasma grmitalitml is sexually u-ansmiued. It colonizes in the cervix, ascends upwards and causes PlD in the female. It is difficult to culture because it takes months LO cultivate and ot11e1· mycoplasmas overgrow in the meantime. Now witl1 PCR, it is possible to detect this organism.

369

Disad,·rultage is perhap> the woman wi ll •-eceive unnecessary multiple tJ1erapies if only one organi.sm is involved.

HEPATITIS B VIRUS HBV is a DNA vil'llS tltat can be u-ansmiued sexually, tJ1ough the partner ma> remain the as)lnpwmatic ca1-rier. This infeCLion can be a'oided by proph)lactic vaccination "~th I mL of hepatitis B \' u·act during ID naecological operations

PELVIC TUMOURS Pelvic tu mo urs lll CI)' ca use co mpression a nd obstructio n the ure ter, and this is especia ll y tr ue of the myoma whi ch lies fi rm ly embedded in t he pelvis. Ovarian cysts, benign and malignant, pelvic endometriosis and inAammawry disease, and b•'oad ligament tumours produce the same picwre. Such patientS should have thorough urological investigations befo•·e operation because roughly half of them would show some ureteric obstruction and this may well account for postoperative urin:u·y infection. Removal of these wmours will reswre the urinar>' tract tO normal in 70% of cases. The worst offenders are those in whom the obsu·uction is due to pelvic inAammator> disease or advanced cancer of the cen~x where permanent stricture fonnation may have occun·ed in a segment of the ureter. LO

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SHAW'S TEXTBOOK OF GYNAECOLOOY

CARCINOMA OF THE CERVIX Although the ureter is guarded by a tough sheath in the ureteric canal against acwal malignant infiltration, itS simaLion in this wnnel is a gr·m e danger because it is particularly subject to compression. It is an absolute dictum that no case of cancer of the CCI'\ ix should e'er be treated b)' surgery or radiation therapy until a preliminary urographic study has been conducted. Those patients who show LU'etelic obstruction have a de fin itel) poorer prognosis. and it must be remembered that in 70% of cases, patients with carcinoma of the cervix die not of their plimaq disease but of bilateral ureteric obstnaction. In these patientS, the surgeon's knife has been regarded in the past as a great menace to the uretet~ b ut effective irradiation of an infiltrated parametria.un is an eq ual if not greater menace, because the resulting fibrosis eve nLUally strangles l11 e ure ter. This posu·adiation proces.~ is not immed iate but ma)' develop over months or even )'ears, and the patient may we ll be cured of l11 e local d isease to succu mb at a later date to l11 e ure tetic obstruction (see l11e chapter o n Cervical lnu·aepi ll1elial Neop lasia, Ca rcinoma of Cervix).

OBSTRUCTION AT THE SITE OF FISTULA Many ureteric fistulae heal spon Laneously and, alll\Ough this is a gratifying pa"Ocess to the sw-geon and l11e patient, the net result of such a cicau·ix may be disastrous to the affected kidney. By llle same token, ureterouretetic anastomosis of a ureter it'\iured too high to be implanted into the bladder is unfortunately often followed by stricture formation at l11e site of the junction. uch a patient should be carefully followed up b)• a competent urologisL A periodic dilatation may well save the kidne), but man) of l11ese patientS end up with a nephrectOm).

canal by dextrorotation and dextroposition of the pregnant uterus, which is so ft·equent a finding at caesarean section.

KEY POINTS • IJ•·inaq S)lnptoms a•·e commonl) encoumered in g) naecological practice. The g) naecological diseases, peh'ic operations and difficult vaginal delivelies con tribute towards most of the lllinat') complaints. • Neurological disorder ma> also be t11e underlying cause, so the mnaecologist must excl ude the neurological cause before undertaking surgery for Ltlinary complaints. • Apan from postoperative and puerperal retention of tHine, other obsu·uctive co nditions are haematocol· pos, retroverted gravid uterus, fibroids, and an ovatian wm our and bladder neck obstmc ti on in o ld women. • Ure t11ra l syndrome is noticed in posunenopausal women d ue to oesu"Ogen de ficiency and is effec tive!)' u·eated witl1 s hort-te rm oesu·ogen vaginal cream. • Urinary fistu la in deve loping co unu·ies is mostl y obstetric in origin. In developed counuies, urinal')' fistula follows u·auma to t11 e bladdet· during difficult surget')'·

SELF·ASSESSMENT I. How would )Oll investigate and u·eat acute UJinary t-eten-

tion in a woman? 2. Oesctibe llle u•-ethral S)ndrome. How would )Outreat it? 3. Oesctibe the management of dysuria. 4. OiscLLSS llle management of u.-inar) incontinence in middle-aged women. 5. What are the clinical manifestations of infection of the female auinary system? OiscLLSS itS managemenL

PREGNANCY AND URINARY PROBLEMS Al l gynaecologists are conversant with the fact l11at pregnancy has a profound effect on the ureter and kidney. Th is is cl ue to the specific action of progesterone on a ll smoo th muscles throughout th e bod)'· The gasu·ointestina l tract and the ga ll b ladder, l11e muscu la tu re of the ve ins, and the liga ments of the spine and the pelvis are a ll affec ted. T he changes are most remarkab le, however, in l11 e urin ary tract a nd appear by the fo unh month to reach a maximum at term. After pregnancy, this process of hyd rourete r slowly resolves an d returns to normal by l11e end of the puerperium, certainly by the lllircl month. lf, h owever, a severe infection occu rs, such as in pyelon ephritis of pregnancy, the process of involution may never be completed and permanent damage may result in chronic pyelonephritis. The cause of this ureteric dilatation is not the compt·ession from the growing utems because it occurs before such an obstruction can operate. It is more frequently noticed on the right than on l11e left side and is probably due to some distortion of the uretelic

SUGGESTED READING Allen R£, tloskcr CL, Smith ARB, cl al. Pchic floor damage and childbinh: A neurophysiological .tudy. Br J Ob.tcl Cynaccol 1990; 97: 770-9. American Collcb'C of Obslclrician• and Gync-cologi>J.>. Ccniwurinary Fistulas. ACOC Technical Bulletin 83. Wa>hingwn, DC, ACOC, 1985. Bhatia NN, Bergman A. Cystomcu-y: Unstable bladder and urinary tract infection. Br.J Urol 1986; 58: 134-7. Burgio KL, Mauhcws rtet C)11L'C Surv 1990: 45(Suppl): I 5-4 iS.

Urinary Fistula and Stress Urinary Incontinence

Urinary Fistulae 379 Stress Urinary Incontinence 384

Key Points 395 Self-Assessment 395

T he urinary syste m a nd th e fema le ge nit.a l system are closel)' re lated e mbryologicall y, anato mi cally and functionally. It is therefore not surprising t11a t urinar")' fis wlae resu lt from obste u·ic and gynaeco logical o perations and gynaecological diseases. A uri nary fis tu la is o ne of tlt e most distressing conditions for a woman , fo r her family members and equally for a gy naecologist who looks after such a patient

URINARY FISTULAE ur;naJ] fistulae are abnormal epithelialiLed corrumutication u-acts between tlte genital u-act and t11 e urinary u-act (Fig. 31.1). Injur-i es tO the urethra, bladder and ureter can occur during childbirtl1 or during pelvic surge ry. Genital u-act malignancy in its ach>ancecl form is known to involve t.hese pelvic organs and catLSe fistulae. Finally, radiat.io n tlterapy ca n cause tissue necrosis and may result. in fistula formation.

Vesicouterine fistula

Figure 31.1 Diagrammatic representations of urethrovaginal, vesicovaginal and vesicouterine fistulae.

In developing co unu·ies, the vast m ~jo li ty of genit.al fistulae cominue to be obste u·ic in origin. Even in tlte present times in rur-al Indi a, it is not uncommon to enco unter obstetric emergency cases of prolonged, neglec ted and obsLructed labo w·. These potentially infected and dehydrated patients may often nan·ate the history of attempted manipulation or vaginal insu·ume ntatio n which has failed to accomp lish childbirtlt or resulted in a difficult u·auma tic delivery witl1 poor perinatal o utco me. In such women, the bladder and vaginal walls which have undergo ne prolonged ischaemic changes ultimately e nd up witl1 tissue necrosis and fistula fonnation. ln developed countries, o n t11e co nt.rary, ope rative u-alltna dw·ing pelvic surge r1 constitutes t.he most com mo n cause of genital fisw lae.

AETIOLOGY The common causes of geni tal fistulae are as follO\\S:

OBSTETRIC CAUSES Prolonged obsu·ucted labour; difficult insu·ument.al or manipulative delivel'ies such as forceps delivery or forceps rot.ation can cause injury to t11 e bladder neck and tl1 e ure tJ1 ra. T he surgeon must ta ke ca re to avoid injury LO me urinary bladder during caesa rea n seCLion. The bladder is most vttl ne r-able (pa rti cul arl)' if it is not empty) during its mobi li zati on from tl1e front of t11e lower segme m before making a u·ansverse incision o n t11e su·etched lower segment to deliver tl1e fetal head. Bladde r injury ma)' follow as a resul t of ex tension of tlte lowe r segment incision amerio rly to the bladder during de livery of a deep ly im pacted fetal head in tl1e pelvis. The bladder o r urete r may be inadvertently included in tlte suture li ne whi le suutrin g the lower uterine segment. Wo me n undergoing repeat caesarean sections are at a higher risk for bladder injury. The tL5e of cranial perforatOrs and spicules of bone during craniotomy and symphysiotOmy also cause ia~U t"). Rupture ofuLenLS is anotl1e rcause of urinary fistulae if tl1e bladder is invo lved OPERATIVE INJURIES The bladder and tl1e pelvic ureter are vulne r-able tO ir~Ut")' during g)naecological surgery. These may result from poor

379

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exposure of the organs, faulL) technique or due to distoned anatOm)' caused b)' LUmour or fibrosis, or pre,~ous surgery. In Western countries, operathe inju•·ies during a gynaecological operation accoum for most of the unnllr)• fistulae. Bladder injury may ensue during its dissection from the cervix in abdom inal or vaginal hysterecto my and during caesarean secti on when the bladder needs to be d issected from tJ1e lower uterine segment. The inj ury is most like ly to occur in a woman with previous caesarean section. Other causes are pelvic adhesions, cervical fibroid and sli ng operaLions for su·ess urinary incontinence (SU I). Ureteric injuries. Most of the ureteric injuries occur dUiing ID naecological surge•")\ especiall) cancer surgery. rete•ic inju•·ies can be serious if not recogniLed at operaLion. Only a third of the ureteric i•'\iuries are detected during surgery and repaired. Others are discovered only in the postoper·ative period. The ca uses of ureteric fistula are as follows: • Congenital fistula is rare and occurs in double ureters. • Direct injury such as cutting (partial or complete), clamp ing, ligaturing or including it in a suture to obtain haemostasis. • Devascularization of ureter. The ureter receives rich vascular supply on the lateral aspect of the ureter below the pelvic brim, and the dissection on the lateral aspect can cause avascula 1ity. Devasculariation follows denuding of the ureter and stripping it off its blood supply during cancer sw·gery. • Thermal injury (camery or laser cautery during laparoscopic surgery).

Sites of Ureteric Injury are as Follows • At the infundibulopelvic ligament. • In ureteric tunnel. Wertl1eim hysterectomy while dissecting the ureter in the parametrium. • Near the cervix and vaginal vault, as tl1e ureter is close to it and the ute•·ine vessel also is proximal to it dUJing hysterectomy. Clamping the utel'ine ,·esse! may indude the ureter anteriorly. • Near entry of the ureter in the bladder during bladder dissection. • Near the pelvic brim, during ligation of the internal iliac arte ry. • Near the uterosacral ligament. During laparoscop ic uterosacra l nerve ablation, vau lt closure d win g hysterectomy and in endometriosis. The risk of injury is high when the surgery is undertaken for peh~c endomemosis, pelvic in Aammatory disease, cenl)'les, the following special teSIS are useful in planning surgical procedures: .-ine cultut·e is mandatOt')' before surgery, and infection should be treated. The lll·ine is collected by

CHAPTER 3 1 - URINARY FISTULA AND STRESS URINARY INCONTINENCE

catlleLerization in case of VVF or by us ing urine which collecLS in tl1e well of a sterile Sim's spec uh.un. Cy~trucofJ>•: CystoscOp) witl1 indigo carmine excretion test (5 mL intravenous!)) enables visualiLation of the dye from each uretedc orifice indi,~dually (Fig. 3 1.7A and B) and identifies which ureter is damaged. It helps in kno,~ng Lhe site and number of fiswlae. During sonography of Lhe kidne>•s, ureter and bladder, a C)Stic mass (tu;noma) due LO collection of urine can be identified.

• Descending intratH'IIOtL! jt)Y'logmphy (IVP): f\IP may reveal h)dronephrosis and h)droureter and indicates tl1e exact site of ureteric obstruction. • Ureteric catheteriuttion will detect the side and site of ureter damage. • ln case the fistula is small and not clearly visible, methylene blue test is applied. • Methylene blue - 'f'ltlf!N,uah left. A ca tlleter is introduced into the bladder thro ugh the urel11ra. T he vaginal cavity is packed wi tl1 three steri le swabs; 50-100 mL of d ilu te me tl1 ylene blue d)•e is injected intO tl1 e bladder through tl1e catl1 eter. lf tJ1ere is a WF present, tl1 e me tl1ylene blue d)•e stains tl1 e midd le swab. If the lowermost swabs geL stained, tl1e leak is from tJ1e ure tJ1ra. lf the swabs do not take up the stain b ut geL wet wi tJ1 urin e, the leak is from tl1e ureter. Oral Pyridium (p henazopyrid ine) (100 mg) stains urine orange and is easily recognized in the vagina; however, iL does not identify tl1e site of fistula. • Metal catheter not onl) identifies a fistula but also confi nns the patenq of the uret11ra.

MANAGEMENT VESICOVAGINAL FISTULA ln case bladder damage is suspected following a difficult childbirth, an indwelling catheter for 3-4 weeks is recommended for prolonged draining of the bladder, and antibiotics and supportive tllerapy are recommended. Spontaneous healing of small fistulae is known to occur. However, in case of an established fistula, it is beuer LO wait for about 3 montl1s for all tissue inflammation to subside, tissue vasculalization to improve and local infection to be cleared before su r'gery is undertaken. ln case of a fiswla following ca ncer, a biopsy sho uld be taken from tl1e edge of tJ1e fiswla and tl1e presence of cancer ru led out prio r tO surgery. • Most VVF can be repaired vagina ll )'· T he Latzko procedw·e involving den ud ing of the vaginal epitl1eliu m all around tl1e fisu.do us edge, fres hening the edge and approximating the wide raw surfaces witll rows of absorbable suwres is often successful. This techn iq ue is suitable for post- hysterectomy fistulae. It, however, leads to narrowing of the upper vagina or atresia. • ll1e Chassar Moir technique of widely separating L11e vaginal and bladder mucosa all around by tl1e flapsplitting metl\Od and suturing tl1e bladder and vagina separate!) in two la)ers is the most commonly used metllod. Absence of tension on the suture line promotes healing. IL is preferable to see that tlle suture lines on tl1e bladder and vagina do not o'·erlap. Haemostasis should be meticulous to ensure success. In cases of extensive fibrosis,

383

omental grafts, interposil.ioning of Marti us graft or gracilis muscle graft between the bladder and vaginal walls improves the blood supply aL t11e site of repair and promotes healing. Flap-splitting surgery has L11e advamage of tension-free sutures. If one attempt fails to heal tl1e fistula, a second vaginal repair can be undertaken after a pe,;ocl of 3 montllS. In case of a large fiswla dose to or invoh~ng the uretelic orifice, vaginal repair ma) be difficult; also in cases of failure of previous surgical attempts to repair L11e fistula by the vaginal route, transabdominal approach is recommended LO achieve successful closure. • ln case of exLensh e loss of bladder tissue, previous repetitive faillli"CS to close t11e fistula or radiation fistula which fails Lo heal, the sur-geon must consider procedures for uti nary dive1-sion such as implantation of tl1e urete•-s imo the sigmoid colon, creating an ileal loop bladder imo which tl1e ureters arc implanted, or a rectal bladderan operation in which the term inal sigmoid colon is brought out as a colostOm)'· The d istal end of the rectosigmoid is sulltred and closed and the ureters im planted into tl1e term inal rec tal po uch, which ac ts as a ulin ary receptac le. T he da nger-s of ureteric implantation into tl1 e large bowel include a high incidence of ascend ing infection to tl1e kidn eys and the risk of elec trOI)•te imbalance leading to hyperchloraemic acidosis as well as su·icture at the s ite of implantation. • lf tl1e fiStula r-epair fai ls, one sho uld wait for at least 3 montl1s before auernpting a second repair. A fistula located at the vaginal vault following hysterectOlll)' is tl1e most difficult LO repair. • Fistula caused b) cancer cervix may require ame.;or exenteration. Postoperative management after VVF •-epai•·: • Continuous bladder drainage for 14-21 days. Some prefer suprapubic drainage. • Antibiotics - Urine infection should be treated adequately. After removal of t11e catheter, the woman is advised Lo pass udne f•-equently as the bladder capacity may have been r·educed. No vagina l o r· speculum examination or imercoUJ-se is allowed for 2 months after the surgery. In the nex t pregnancy, a caesarean sec tio n is ind icated following successful fistu la repair. Stress inco nLin cnce fo llowing VVF repair may be noted, and it results from ligid ure t11ra, loss ofvesico urethral angle, small bladde r and short ure tl1ra.

URETERIC FISTULA (Fig. 31.3) Most t.u-e teric fistulae are traumatic; rare ly, ectopic ureter cmJSes dlibbli ng of urine apart from passing urine from me otl1er kidney. Only one-third cases of ureteric trauma are recognized intraoperative!). In case of total obstruction following bilateral ureteric ligation, anuria will ens ue; sonography will reveal bilateral h)dronephrosis and dilated ureters up Lo the site of the block. The renal function tesLS reveal a rise in creatinine levels. If tl1e obsu·uction is detected early, the offending ligatures removed and the urete•-s sLemed, recovery is possible. However, if L11e ureters are damaged, tl1ese should be implanted imo L11e

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bladder. In case the diagnosis is delayed, as happens in cases of unilateral ureteric block, the symptoms of loin pain and fever gradually subside and the kidney on the affected site undergoes atrophy. A procedure of percutaneous nephrostOm) (PCN) can save the kidney functions before reimplamation of ureters is undenaken at a later date. In case of urete•·ic transection, partial or complete, a p)elography fails to show pan or whole of the ureter on the transected site and there may be pooling of the urine in the peritoneal cavity. The immediate u·eaunem is percutaneous nephrostomy and reu·ograde d)e iryection under fluoroscopy to help identify the site of transection. If the injury is partial transection, cystoscopic catheterization and steming of the ureter at the site of inju•)' may be attempted. ln case of complete u-ansection, urina•)' diversion by nephrostom y is advisable to tide over the crisis, followed later with repair surgery. In case the transec tion is recognized during surgery itse lf, the surgeon must eithe r undertake anastomosis at th e site of inj uq• o r implant the cut end of the ureter into the b ladde r o r perform a Boari flap ureteroneocystostomy. Ure terourete ri c anastomosis is also so metimes possible, but tl1 e risk of stricwre sho uld be re membered. Fixing the dom e of tl1 e b ladde r to the psoas muscle re lieves tension on tl1 e im plan ted ureter. Urete•ic sui cture a nd infection are the sequ e lae of urete ric implantation and need to be observed. When ureteric damage goes unnoticed, following the hectic postoperative period, fever settles down, but patient starts dribbling urine from t11e vagina around the 10tll-14tll day. Urine collects in the vagina, but tl1e woman also micrurates and oliguria is noticed. It is difficult to visualize the fisttLlous opening. Melll) lene blue test recognizes the ureteric fistula. Cystoscopy with retrog•-ade catheterization shows the absence of urine coming from the affected side and the site of blockage, respectively. IVP will be required to detect hydroureter/ h)dronephrosis. U•·ine culture and kidney function tests are also required. One should not wait for t11e kidney damage to occur and perform laparotomy; it sh ould be performed at tl1e eadiest, once tl1 e inflammation and infection subside. The surge•)' for urete•ic if!jtuies comprises tl1e following: • Ure teroureteral anastomosis with tl1e ure teric stent inserted • Imp lanta ti on of tl1 e ureter into the bladde r • Psoas muscle stitched to tJ1e dome of the bladde r to avo id su·etchin g a nd te nsion on tJ1e ureter • Boali operation • Ileal bladder Prophylaxis

In a difficult gynaecological su•-ge•)' where inju ry tO ureters is likely, it is prudent to trace the ureter from tl1e pelvic brim downwards before damping any vessel or cutting tl1e tissues. ll1e ureter is identified by its position (may be disLOrLed or abnonnall) placed in pelvic diseases), pale glistening appearance and peristaltic movement when su·oked. In a difficult case, some mnaeco logists prefer to insen the ureteric stem befo•·e sta•·ting the stu-ge•)'. but tl1is does not always p•-e,·ent tn·ete.-ic clamage if devascularization occurs during its dissection.

Blood supply to the pelvic ureter co mes from the latera l side, so dissection of the ureter should be done on itS medial side and devasculalization and isc haemia should be avoided.

VESICOUTERINE FISTULA Vesicouterine fiswla is a 1-are variet) of fistulae where there is a communication between utentS and bladder, usually caused during caesarean section or ute•·ine mpture or placenta acueta. The patient's S) mpLOms are unlike those of lower u•·inary u-act fistula. The patient remains continent, as urine does not d.-ibble into the lllerine cavity. The patient, however, complains of crclical haematu•·ia mensuual blood trickling through t11e fistula imo the bladder (Youssef synd•·ome). The other cause of crclical h aematuria ru·e bladder endomeu·iosis and rarely an intrauteri ne contraceptive device (I UC D) perfo•-atio n into tl1e bladder. Cystoscopy wi ll reveal tl1 e true pathology. Methyle ne blue injec ted in tO the uterine cavity wi ll s how a lea k imo the bladder. Occasional prolonged b ladder ca the te rizati o n may close tl1e fisw la; o tl1erwi se, t11 e treaunent is by abdom inal repair. Ome ntal or graci lis graft is so metimes req uired. URETHROVAGINAL FISTULA T he patient is continent and dry b ut dribb les t.LJine onl)' during the act of micturition. A speculum examination will show tl1e fistulous opening clea rly. Vaginal repair is often Sttccessful, but urethral su·icture may fo llow. A big fisu.tla may need a graft technique. The ure tiH-al fistula is encountered following surgel') for paravaginal cyst and uretl1ral diverticttlum. Penetrating iryul') following a fall or during criminal abonion can cause uretl11"al fistula. Urethral reconstructive sttrge•) is required.

STRESS URINARY INCONTINENCE SUI is a fairly common condition affecti ng 25o/o-40% of women. It is more commonly seen among women older than 40 years. The conditi on may be seen in association with genital oq~an p•·olapse or may occur as an isolated condition. It is a very disu·essing problem, especially among working women, limiting their social activities. T he u·eatment, often a surgical repair, may fail to provide relieffrom symptOms. T he exact ae ti oiOg)' of SUI remains unknown; howeve •~ a number of hypotheses have been put forward. Urina ry incontine nce ma)' be stress inco m inence, urge inco ntin ence or true inco ntinence. The co mm on type of stress incon tinence is assoc iated witl1 cystocele and ge nita l prolapse when tl1 e woman voids a small quantity of urine invoh.tn tari l)' wh ile sneezing, coughin g o r laughing. The condition also develops during pregnancy and soon after delivery. Stress incontinence is confused witl1 urge incontinence. In ttrge incontinence, the woman wants to pass urine at a moment's notice, and unless she is quick abo ut it, she passes u.-ine in lru·ge quantit) before reaching tl1e washroom. The amoum of urine passed is considerable. In stress incontinence, tl1ere is no desire to pass u•ine, but escape of a small quru1tity of u.-ine occurs during coughing, sneeLing, lifting heavy weight or change of postu•-e. Both are bothersome symptoms and affect tl1e quality of life.

CHAPTER 3 1 - URINARY FISTULA AND STRESS URINARY INCONTINENCE

Uti nary incontinence may indicate a symptom, a sign or a condition. The patient complains of invo luntary leakage of ttrine, which is socially and hygienically unacceptable. The sign is the objective demonstration of urin e loss, and the condition is the underlying pathophysiologic mechanism responsible for the urine leak. The S) mptom of involunta•") urine loss may be associated with stressful aCLi' it) such as coughing, sneeLing, su30°

Resling

Valsalva

Rgure 31.12

Diagrammatic representation of Q-tip cotton swab test. fSouroe: Hacker NF, Ga11bone JC, Hobel CJ, Hacker Md Moore's Essenlials of Obstetrics and Gyneoology, 5th ed. Phladelphia: Elsevier, 201 0.)

UrethrocystometTy

o.-.nal findings are as follows: At rest, 150 mL of urine causes 2-8 em H~O pressure, which •ises to 15 em H 2 0 at filling. Urethral pressure averages 40 em H2 0 , and less t.han 20 em H 2 0 pressure leads to incontinence. UroflowmetTy

Measmement of u.-ine flow rate and volwne provides an objective, noninvasive measure of voiding function . Micturition Cystourethrography

Normall y, a contine nt woman demonstrates a well-marked posterior urethrovesical angle of about 100•. Loss of postelior ureth rovesical angle ca uses stress incon ti nence in many women. Colposuspension and s li ng operations are based on restoring tl1is angle s urgically. Uroprofilometry

Uroprofilomeu'Y measures the dynamic urethral pressures and diagnoses urethral instability and uretJ1ral diverticulLtm. It is a gold standard in the diagnosis of GSL The normal flow is 15-25 mL/ s. Flow below 10 mL/s occLu·s in atonic bladder and during obst.ruction, which is confi1med b) C)StomeU). Increased bladder pressw·e of more than 50 em H 2 0 and low flow suggest obsu·uctio n. Urod)namic study may not be needed in all cases of uri11M)' incontinence; however, it is desirable when diagnosis is

in doubt or lhe patient continues surgical intervention.

LO

have symptoms despite

UltTasonography

Ultrasonography is useful in measuring the bladder volume and residual urine. A bladder wall tJ1ickness of more tl1at1 6 mm suggests Dl. Bladder stone can be seen. Videocystourethrography

Videocystourethrography is th e new gold standard urodynamic in vestigation to s tudy the lowe r urinary t.ract dysfunction. It combines the pressure studies wi tJ1 th e video position of the bladder nec k and ure tJ1rovesical a ngle. MRI Studies

MR! studies tl1e defects in the pelvic floor muscles and the supporting fasciae. Appropriate surge•)' to b uttress the bladder neck wi ll cure incontinence. Sophisticated neurofJII)•~iowgical testing is requi red when the neurologica l component for stress incontinence is suspected. ResidLtal urine on ult.rasound scan shows incomplete voiding.

TREATMENT It is impo•·tam to rule out Dl before any smgery for SUI is undertaken; otherwise, tJ1e S)lnpLOms will worsen.

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SHAW'S TEXTBOOK Of GYNAECOLOGY

Table 31.3

Conservative

Management of Stress Incontinence Drugs

First line of treatment • Oestrogen cream in • Young women menopausal • Frail, old women women • Postpartum, previ· ous fail ed surgery • Venlafaxine 75 mg daily Kegel pelvic floor • Imipramine exercises x 4-6 1D-20 mg b .d. months Electric/magnetic stimulation for nerve damage, magnetic stimulation Artificial urinary sphincter in neurolog leal condit ion I Vaginal cones

Surgery If others fail • Vaginal (Kell y) • Abdominal MarshaiiMarchetti- Krantz and Pereyra Burch Combined vaginal and abdominal suspension Slings Tension-free s ling Transobturator tape Laparoscoplc suspension of the bladder neck

Treaunemcomprises t11e followin g (Table 3 1.3): • Conse•vative t11erapy • Surgical repair The main aim ofu·eaunem is to imp•·c:>Ve the quali ty oflife.

CONSERVATIVE TREATMENT Cou~ervative

treatment should be the .fin.t li11e of tr&.!lmll1l~ espein younger women. It is cheap, has fewer co mplications and does no t co mpromise future surgery if so required. Conse rvative therapy is also app lied to the e lderly and frail women unfit for surgery and during the 6 mont11s after tl1e delivery. It is also applicable in tl1ose with previo us failed surge') a nd in women desirous of child bearing. The trea unen t complises me following: cial/~•

• • • • • • • •

Drugs a -Adrenergic drugs may help to constdctthe bladde r neck and •·educe the frequency of stress incontinen ce. Oesu·ogen cream is useful in menopausal women. Phenylpropan olamine enh an ces uretl1ral pressure. Ven lafa.xine 75 mg dai ly is a se rotonin (5-hydroxytt}'ptamine [5-HT]) and noradre na line re up take inhibitor and is th e lates t drug of choice. It ca n cause mild u·ans ient nausea and mi ld cardiac effect. Imipramine at a close of 10-20 mg b.cl. is a lso effective. lntraurethral and Vaginal Devices These have been tried with some success. A ring pessary in ge nital prolapse may reduce stress incontinence in so me women. Contifonn is a silastic vaginal cone ava ilable in India. It is placed du•·ing the day and rem01•ed and cleaned at nighL The con e needs changing eve•}' 6 weeks. It is successful in 85% oft11e cases. Vaginal cones weighing 20-100 g are ava ilable. A small cone is used initially, with larger ones used later. The co ne is inserted in tl1e vagina and held in positio n by co ntraction of the levator ani muscles a~ long as possible, the reb)' to ning up these muscles. The)' are not useful in menopausal women with weak levator ani muscles or in the presence of vaginal scar. Toxic shoc k S)'ndrome can occur if retained for a long period. Electric Stimulation Electl"ic stimulation ofthe pelvic floor muscles has also been tried dul'ing physiomerapy if the stress incontinence is caused by clenervation of the pudendal nerve during delive•"Y· Magn etic stimulation is lately empl oyed. It is especially useful in old women witl1 weak pelvic floor muscles. Artificial Urinary Sphincter Artificial urin al)• sp hincter (AUS) (Fig. :31. I:1) model-800 is used in Lhose with ne urological conditions and in th ose with previous surgical failure and sphincteric dysfunction. AILhough an 80% success rate is reported, equipment is

Physioth erapy Drugs lntraurethral and vaginal devi ces Elec u·ic stimulation Artificial urinary sphincter We igh t l os.~ exercises Red uced caffeine in take and smoking cessmion Bladder u·a ining and timed voiding

Physiotherapy Suited for Grade I GSL Pelvic floor exercises for 4-6 monms with or witho ut elecmcal stimulation make patient's life tolerable in 60% of cases. Bom weight loss and exercise are beneficial. It takes 8-12 weeks before any improvemem is seen. Kegel pelvic floor exercises work best in younger women and in those witl1 mild stress incontine nce associated wim ure thral hype •mobility with no da mage to imernal sph inc· te 1: It is also effective in th ose wi tl1 urge inco minence, as tl1ese exercises wne up t11 e leva to r ani muscles a nd in ternal sp hincter.

Figure 31.13 Artificial urinary sphincter. (Source: R Gonzalez, L Piaggo. Pediatric l.Xology. Artificial umary sphi'lcter. Sau1ders: 2010.)

CHAPTER 3 1 - URINARY FISTULA AND STRESS URINARY INCONTINENCE

expensive, can cause infec tion and mechan ical fai lu re can occur. Genuine Stress Incontinence

Posune nopau.s.'\1 women with senile changes in the vagina, hypoto nic urethra and mild stress incontinence may benefit immense!) with oesu·ogen replacement therapy, preferably a ·eam applied locall). Women with chronic cough, COilStipation and alle1-gic rhinitis or excessive ph) sica! activity may benefit with medical measures. Avoiding aggravating fucwrs such as smoki ng, straining or undue physical exertion also plays a complementary role. Successful surgery for GSI restores the relationship between the bladder, urethra and t11e urogenital diaphragm. The goals of su•-gi cal repair of GS I include tl1e following: • Repositioning the proximal ureth ra tO a high retropubic position to maximize proper ureth ral compression. • Preserving vesico ure thral angle tO facili tate ureth ral compression. • Preserving comp ressibili t)' and pliability of the ure th ra. • Preserving integrit)' ofLhe sp hi nc teri c mec han ism.

SURGICAL REPAIR OF STRESS URINARY INCONTINENCE Various sur-gical proced ures (> 100) have been designed over tl1e )'ears; some of Lhese existing proced ures are discussed here. lt is, however, recomme nded that any sur(.,rery should be defemd in a )'OIIrtg tuonum and C01lSI'TVtttive method employed initiall)'. Future pregnane) ma) mar t11e good result of surgery. Primal') stu-gel) offers the best resultS; tl1erefore, selection of cases and tl1e procedure should be most appropriate. Vaginal Operations

These include a nte •·io•· colpon·haph) with plication of the bladder neck (Kelly's repair) or apposing the medial fibres of the puborectalis mttSCies in the midline under tl1e bladder neck region to ele-.'l\te the same (Pacey's repair). Abdominal Operations

391

palpated and guided into a sma ll mid line transverse suprapubic incision in tl1e abdominal wall. A similar paraurethral tissue sling can be pulled up on th e other side with a helical sutLLre. After appropriate traction which ele\'lltes the bladder neck adequate!), t11e he lical sutures are fixed to tl1e aponeurosis of the anterior abdomina l \\' mpametic nen·es.

AETIOLOGY OF DETRUSOR INSTABIUTY DI may be: • Functio nal and pS)Chosomatic. • Deu·usor hyperreflexia (neuropatl1y) in certain medical conditions such as diabetic neuropatl1y, a cerebrovascular accident, multiple sclerosis, spinal ir'\iut)' and Parkinsonism. • It occ urs following s urge ry fo r GSI if Lhe b ladder neck is placed LOO high and LightJysuw red. IL is seen in 1% of th e cases following anteri o r vaginal wa ll repair, 5.8% afLer e ndoscopic bladde r nec k suspensio n and 10% fo llowing colposuspension and sling operati on. • ld iopa t11i c. l e n pe r cent of men and 30% wo men older Lhan 40 yea rs have Dl. • Uti nat)' infectio n.

PATHOPHYSIOLOGY lnneased a-adrenergic and cholinergic activit)' is responsible for this condition.

Potemial reasons for failure include the following: • Surgical failure - suttu·es cut out because of poor placement of sutures, inadequate mobiliation of me bladder neck and proximal uremm, postoperative haemaLOma fonnation / infection. • Incon·ect choice of operation - mainly the result of incomplete or incorrect preoperative assessment of the cause of urinar> incontinence. • Developmen l of incontinence due to otl1er causes such as fiswla formation, DI or pipe-stem uret11ra previously not present With the pass;1ge ofLime, the resu lts of all kinds of incontinence surge ry Lend to deteriora te. Long-term follow-up data s uggest (Tab le :H.tJ ) cure rates of different surgical procedures.

Table 31.4 Cure Rate of Different Surgical Proced~res Operation for Repair of GSI

Long-Term Cure(%)

Bladder buttress operation

67.8

Ma-shaii- Marchetti-Krantz operation

89.5

Colposuspension

89.8

Endoscopic suspension

86.7

" Vaginal sling operations

93.9


e. Ol»tet Cpwcol 1996; BB: 47(}...78. Leung AS, fanner R.\f, Leung EK, et al. Ri.>k factors associated "ith uterine rupture during I rial of labour afh:r ct:sar~~n delivery: A case

control st udy. Am.J ObSif:t Gynecol 1993; 168: 13!\8-63. Pokorn y SF. Long-term intr.tvaginal presence of foreign bodit"> in chil· dr~:n . A prelimin ary siUd y.J Reprod Med 1994; !\9: 931-35. Robcruon I' A, Laros RKJr., Zhao RL. Neonatal ~u1d mate mal Ot.llcorne in IOI•'pclvic and midpclvk oper.1th'e dcli,·cries. Am .J Obstct Gynccol 1880; 162: 14!\f>-42.

Smith NC, Van Coc,·erde n d e Groot JIA, Gun.>ton KO. Coital ityurie;; of the \".tgina in nomirginal paticnl.>. S Afr J.ft'Copy. ~OtNnrgical repair. GaslJ'Ointe>t Endo.c 1989; 35: 54-56. Krebs liB. Intestinal hyury in gynecologic surgery. A ten }ear experi· ence. Am j OI>Stet Cynecoll985; 155:509. 'icholl.> 0 11 (ed). Oinkal Problems, Injurie• an d Complicativns of Gynecologic Surgery Baltimore, Williams & Wilkins, 1983. Pasnlka PS, Bistrian BR, Benou.i PN, ct al. 1l1e rbks ofsul){ery in obese patients. Ann lnt Mcd 1986; 104: 540. Reich I I. Laparoscopic bowel injury. Surg Laparosc En dose 1992; 2: 74-78. RU»ell TR. Gallaghar 0~1. Low rect.ovaginal fistula. Am .J Surg 1977; 134: 13. Schaefer G, Graber EA (eds) . Complication• in ob>tctric and grneccr logic •urge'). I lagersiO\\n, ~m . llarper & Row, Publishers, 1981. Shellj ll Jr, ~f)Cr> RCJr. Small bowel inju') after laparo.copic sterilization. Am J Ob>tet Crnecol 1973; 115: 285. Thomp:.on 811, Wheeless C RJr. Gastrointestinal complications oflapa· roSCOJ>)' >terilil.ation. Obstet C tnecol 1973:41:669-76. Whedc» CR. Thennal gastroin testinal injun~.,. In Phillips J~l (ed) . LaparO>COJ>)', Bahomore, Williams & Wilkin;. 1977,231-35.

GYNAECOLOGICAL MALIGNANCIES

33 Preinvasive and Invasive Carcinoma of Cervix 34 Cancer of the Body of the Uterus 35 Pathology of Ovarian Tumours and Benign Ovarian Tumours

37 Vulval and Vaginal Cancer 38 Gestational Trophoblastic Diseases 39 Radiation Therapy, Chemotherapy and Palliative Care for Gynaecological Cancers

36 Ovarian Malignancies

407

Preinvasive and Invasive Carcinoma of Cervix

Epidemiology 408 Cervical lnlroepilheliol Neoplasia (ON) 409 Cryosurgery 4 18 Invasive Cancer of the Cervix 420

Carcinoma in Pregnancy 429 Endocervical Adenocarcinoma of Cervix 430 Key Points 430 Self-Assessment 431

Carcinoma of tl1e cen~x is t11e t11ird most common cancer among women worlcl"1dc and is now awibutable LO infection "~tl1 human pap ill oma,~rus (HPV). H owe,·e i~ it is the most common genital cancer among wo men in Ind ia. In certain parts of tl1e COLUlU")', it remains even more common than carcinoma breast; however, in most oftJ1e large meu'Opoli tan cities in India, it now ranks second to carcinoma of tl1e breast amongst cancers in women. The median age at diagnosis is 48 years, and tl1e majorit) of cases are diagnosed betwee n 35 and 55 years. 1l1e universal application of Pap smears in Western communities has led to a drastic decline in t11 e number of invasive cancers of th e cervi x and a higher detection o f preinvasive lesions. Howe, er, tl1is has not happened in India because of lack o f uni,•ersal screening; a chive agai11SL this preventable cancer must continue to keep tl1e d isease under control. Every year 530,000 new cases and 275,000 deatl1s are reponed annuall y worldwide. In India alone, 130,000 new cases occur witl1 a dea tlltoll of 70,000 cases every year. Cancer of tl1 e cer vix accounts for 15% of all ca ncers in women. Prevalence I-ate is 2.3 milli on annual ly globally. In India, it is 13-24 lakh per year and at diagnosis more tl1an 75% are in tl1e adva need stages.

Tabl e 33.1

Predisposing Factors for Cancer of the Cervix

• Coitus before the age of 18 years • Multiple sexual partners • Delivery of the first baby before the age of 20 years Multiparity with poor spacing between pregnancies Poor personal hygiene Sexually transmitted diseases Poor socioeconomic status Circumcision: ExposU'e to smegma from uncircumcised p..-1· ners was considered an Important factor, accounting for tower incidence of cancer of the cervix; now It Is realized that the inci· dence of human papillomavirus (HPV) is low in circumcised men, and that is the reason for tow Incidence of cancer in their wives Smoking and drug abuse, including alcohol \Nomen with STD, HIV infection, herpes simplex virus 2 infection Immunosuppressed individuals (following transplant surgery), viral infections and HIV \Nomen with preinvasive lesions of cervix • \Nomen who never had screening for cancer cervix • Use of oral contraceptive pills

- - Cervical intraepithelial neoplasia - - Invasive cervical carcinoma

EPIDEMIOLOGY (Table 33.1 ) T here are man)' conditiOI1S wh ich predispose a woman to development ce rvi cal ca nccc Most im portan Lamong these is earl)' age at start of sexual ac tivit)'· Multi ple sex parUlers, low socio-economic st.alllS, m ulti parit)', sexua lly transm itted diseases and poo r pe rsonal hygiene are some of these factors. Average age of development of cancer cervix is 35-45 years in India. However, disease can be seen any time between 2165 years of age. The precancero us lesio n of cervix usually oc· mrs I0-15 years earlie r. There is a pe1iod of 10 years or larger whe n a precancerous lesion can p1'0gress LO imasive cancer. ow a definiti\ e relationship has bee n established between HPV infection and developmem of cancer ce rvix. (Fig. 33.1 ). ~ To

408

16-20

26-30

36-40

46-00

5fHIO

66-70

7fHIO

Age (years) Figure 33.1 Al;}e incidence of cervical carcinoma in situ and invasive cervical carcinoma.

\iew the k-cturc noJe> :.can th e >pnbol or log in to rour accoun t o n "'"'·~lcdEna. lishing diagnosis. Occasionally, a diagnosis may be made by a Pap smear in case tll ere is no visible lesion on cervix but the patient presenl.'l witl1 S)lnptoms of irregular vaginal bleeding. In a Pap smear, invasive cancer shows tadpole cells, fibres and malignant cells and haemorrl1age, and necrosis in the background. Common!) two t}pes of carcinoma of the cen·ix are seen; first and mo•·e common \'lll·iety is the epidermoid carcinoma. lt arises from tl1e stmtified squamous epithelium of the cervix, and accounts for almost SO% of all cancers in the cen~x. The second \'lll·iety, endocen •ical carcinoma, arises from the mucous memb1-an e of the endocervical canal, and accounts for 20% of all cervical can cers. Histologically, 95% of cervical cancers are squamous ca1·cinomas and only 5% are adenocarcinomas. T his is beca use t11e column ar epitheli um of the endocervix often undergoes sq uamous metaplasia (Figs33.2 l-33.2 1), before undergoing maligna nt change. Incidence of endoce1v ical ca ncers of the ce rvix has rece ntly increased beca use of prolonged use of oral comb ined co ntraceptive pills and progestogen pi lls which have a profound effect on gla nd ular epitl1eli um (Fig. 33.22).

If a pa tient is in the midd le of a vaccina tion course, when she gets pregnant, all furt11er vaccinations sho uld be stopped unti l after the de live I)'. Med ical te rm ination of pregnancy is however not required. The woman can contin ue with remaining vaccination after delivery and to continue breast feeding following vaccination.

HISTOLOGICAL CLASSIFICATION

HPV Vaccine for Males

Squamous cell cancers of the ectocervix appear as prolifemtive growths. ulcers or Oat indu1-ated areas. The common prolifemtive or cauliOowel'like growth is vascular, friable and bleecls on touch. It undergoes ulce 1-ation and necrosis, which is associated witll an o ffe11Sive fo ul-smelling \'llginal discharge. The mu coid discharge is often blood-stained.

The vaccine is also an applicable prophylaxis for male adolescents. Anotl1er pro p h) lax is is the use of ba1Tier conu-acepLives to prevent u-a11Smission of ' 'i1-al infections and other sexually trai1Smitted infections from man to woman.

• • • • •

Squamous cell carcinoma Adenocarcinoma Adenosquamous carcinoma Clear cell carcinoma Rare t)pes such as ne uroendocrine carcinoma

CHAPTER 33 - PREINVASIVE AND INVASIVE CARCINOMA OF CERVIX

421

Figure 33.23 Large fungating carcinoma of t he cervix In a case of proci dentia.

Figure 33.21 (A) Keratinizing squamous cell carcinoma of cervix: nests of atypical squamous cells infiltrating Into the stroma. Keratin pearls are seen. (B) Carcinoma in- situ (GIN IIQ (Source: tor (B) Dr Sandeep Mathur, AIIMS)

Figure 33.24 Ulcerative carcinoma of cervix , the specimen was removed by radical hysterectomy. Note also the parametrium and 2 em of vagina removed.

The endoce•v ical growth remains confined to the cervical canal for a long time causing a barrel-shaped enlargement of the ce•vix, a nd onl y at a late stage growth protrudes beyond the external cervical os and become visible.

MODE OF SPREAD

Rgure 33.22 Endocervical adenocarcinoma: tumour is composed of malignant glands lined by columnar cells with moderate nuclear pleomorphism and focal intra::ellular mucin. (Courtesy: Dr Sardeep Mathur, AIIMS.)

Histologically, the tumour is graded as well-differenti ated (showing epithelial pearl formation- see Fig. 33.2 1), mod· e rately d iffere ntiated or poorly differe ntiated. A sq uamous cell carcinoma of cervix us uall)' is non keratinizing b ut at times can have keratin pearl formation.

ln initial stages, the cancer of cervix spreads by its co ntin ui ty to acUoining su·uctures (involving the vagina, parameu·ium and bod) of uterus); in advanced stages. it spreads to urinary bladder and rectum. Lymphatic spread occurs to draining I) mph nodes (parametrial nodes, obwrator, h) pogasuic and rarely distam nodes). Vascular spread occurs in late stages to distant sites such as lungs, liver, bones, kidneys and brain. Ovmitm metoMa1·is occurs in only 1% in ctlM'l of lquamJHIS cell wucer b11t. ()('(111') in 10% in cases of tUienowrrinmn(l of tervix.

CUNICAL FEATURES Most patie nts with invasive cancer of cervix present with th e complain ts o f irregular menses, menometro rrhagia, continuous bleeding, postcoital b leeding, leuco n·hoea and

422

SHAW'S TEXTBOOK OF GYNAECOLOGY

blood-stained or offensive discharge. It is not uncommon to encounter disease in postmenopausal women where the presenting spnptom is posunenopausal bleeding. On per speculum examinatio n, ce rvix reveals a growt11 which bleeds o n toucll or a n ulcer with edges that bleed on touch. On per vaginal examination , the uterus may appear bLLiky becaLtse of p)Omeu-a in the advanced stage when the cervix gets blocked b) growth. In lateral fomices indw-ation is felt, and o n per rectal examination thickening of ULerosac•-al ligaments may be noted. In all suspected cases, a biopsy is needed to confirm the diagnosis. Tissue biopsy in a case of frank invasive cancer reveals loss of su-atification and cellular polarity; the cells show alteration of mo•·phology, th e nuclear:cyLOplasmic 1-atio is increased and th e tumour cells show hyperchromatism. Thickening of th e nuclea r mem b rane, cl ump ing of the chromatin mate 1ial, pe netration of the underlying base men t membran e and prese nce of the ca ncer cells in to the unde rlying s u·oma arc no ted (Figs 33.25 a nd 33.26).

Figure 33.26 Adenocarcinoma in situ. The superficial p arts of t he crypts are li ned by epit helium whi ch shows loss of polarity and nuc lear atypi a (x 155). (Source: From: Haines & Taylor's Obstetrical and Gynaecological Pathology, 3rd eel. Churcl'liU, 1987.)

DIFFERENTIAL DIAGNOSIS T he cervical growth and ulcer may at ti mes be m istake n for tuberc ular and S)'p hili tic ulcer, mucus and fibro id polyp an d rare!)' sarcoma of the cervix. Biopsy helps in mli ng o ut other conditions.

STAGING OF CANCER OF lHE CERVIX (Figs 33.27- 33.39; Table 33.6) Staging of cancer of cervix is based on revised FICO staging given in >ear 2009. This staging is a clinical staging. For t11e pw-pose of staging. a careful clinical e xamination of the patient including per vaginal examina tion, per •-ectal examination and a combined per rectal-per vaginal examination is perfonned. Commonly done investigations include cl1est X-ray, an ulu"3SQund of the abdomen and pelvis and liver and kidney fw1ction test. Presence of h) dronephrosis makes a clinical stage as stage Ill b. Use of newer imaging techniques such as CT scan, MRJ and positron emission tomography (PET) scan is not•·outinely recomm ended nor is the cli nical stage changed based on results of these investigations. Early invasive ca ncer of cervix (stage Ia) is diagnosed by histological examination of biopsy. Depending o n the depth

of stromal invasion and hori:t.onta l exten t of the spread, the d isease is fw·ther classified as SLD-gf.ucose is useful in the determination of p.-imary disease, lymph node detection and local recun·ence detection. The test is based on the fact that malignan ttissue exhibits greater glycolysis than normal tissue, and FOG accumulates in th e malignam tissue resulting in increased tum ou r contrast. Whi le Cr and .MRI show anatomical changes, PET shows bioch emical changes in the tissues. A combi natio n of PET and CT would predict the presence of malignant tumour and its anawmy beuer than either s ingly. FDG-PET is now considered a gold standard in th e investi gati on of ca ncer ce rvix.

TREATMENT OF INVASIVE CANCER Treatment depends on the stage of th e disease. However, in case tl1ere is a need to preserve fertilit)', a conservative surgical procedure is possible in early stage disease. Better understanding of early lesions has permitted a more conservative surgical treaunen t without compromising t11 e success, at t11e same Lime reducing the morbidi ty and retaining the fenilit) potential in yo unger women. SURGICAL TREATMENT Stagewise Treatment of Cancer of the Cervix

• Stage Ial : The diagnosis is by cone biopsy. The lymph node imohement in this stage is only 0.5%. Therefore, Internal os

~

conization witl1 a clea r margin is co ns idered adequate and is diagnostic as we ll as therapemic. HysterectO my in a yo Lmg woman is considered rather a radical surgical approach witl1 increased morbidity but without improved Sttrvival. Hysterectom> (extrafacial hysterectomy- Type I hysterectom)) is appropriate in e lderly a nd parous women, or those ha' ing an associated disease in the uterus. L) mphadenectOm) is not required, but long tenn follow-up is necessa•y L)lnphatic or vascular channel infiltration however mandates treaunem as in Stage lb. • Stage Ia2: Lymph node imolvementand recurrence rate is 2%-7%, provided vascular and lymphatic channels are not involved. Extended h)-sterectomy and lymph node sampling are recommended (Type II hysterectOmy) . Nodal involvement requires postoperative radiotl1erapy. In a yo ung woman desirous of chil d-beari ng, conservative u·eatmem comprising lapa roscopic lymp hadenectOmy followed by vaginal u·ac helecw my inu·oduced by Daniel Darge nt( 1987) is approp riate and does not co mpromise on iLS success. Fertility-conserving trachelectomy consists of who le or at least 80% re moval of t.he cervix and upper vagina and cutting Mackcnrodt's ligame m on eitl1e r side. lnvolvemem of l)'mphatic or vasc ular chan nel needs similar treaunem as in Stage lb. Be fore conservative surgery, MRI mapping for local extension a nd lymph node involvementis needed. Obturator gland is the se ntinel node- if negative, no further 1)1nphadenectomy is requi red. Injection of blue d)e into t11e cervical tissue before surgery identifies 1)1nph nodes. Conception rate of 30%~0% at the end of 1 )ear, with miscarriage (20%-30%), prete1m labow· (18%) and chorioamnionitis, is reported. Recurrence rate of 5% is also reported Contraindication LO fertilit)·presening operation is a lesion more than 2 an. Cen~cal cerclage at the time of ptimary surge•) ' may reduce the pregnancy complications of abo•·tion and preterm labour (Fig. :n. tO). Isthmus uterus

Paracervical and paravaginal tissues

b ; Rgure 33.40 The technique used for radical trachelectomy. Area of tissue for resection (shaded) including cetvlx and upper vagina with pa-acervical and paravaginal tissues up to the level of the uterine isthmus.

CHAPTER 33 - PREINVASIVE AND INVASIVE CARCINOMA OF CERVIX

• Stages l b and lla: The treaunem options are as fo llows: • Radical Abdomina l hysterecLOmy (Type lll radical hystereCLomy) • Sd1auLa's vaginal h)Sterectomy (known as Mitra operation in india) and Taussig's or Iaparoscopic lymphadenectom> • Plimal") mdiotherap) with concun·em chemotherapy • Combined stu·ge•1 and radiotherapy Injection of blue d)'e into the cervical tissue before surge•)' identifies lymph nodes during surgerr (sentinel lymph node). Negati'e sentinel lymph node (obturator lymph node) helps a\oid extensive pelvic lymphadenectomy. Wertheim's hysterectomy, also known as Meigs-Obayashi hysterectomy, is the surgical treaunem in SLage la2, with lymphovascular invasion and tumour size of 2 em. Whereas for Stages lb and lla is sli ghtly more mdical procedure (Type Ulradical hysterectomy). It complises exploratOry laparotomy, removal of the e ntire uterus, botl1 adnexa, pelvic lymp h nodes, media l one-tJ1ird of tl1e parame u·ium on e ither side and upper one-tJ1ird of tl1e vagina, spa ring sacral gla nds. T he ovaries are invo lved in on ly I%, so tl1 ey may be reLained if appear heal U1)' in a you ng patien 1.. In s uc h a case, tJ1e ovalies ma)•be u·ansposed outside the pelvis LO avoid damage in case radiotl1erap)' is requ ired later. L.'lte l)', rad ical hysterectomy is performed laparoscop ically by expert~, a robotic rad ical hysterectomy is done in specialised cenu-es. Schauta's operation is an extended vaginal hysterectomy consisting of removal of the entire uterus, adnexa, most of tJ1e vagina and medial portion of tJ1e parametrium. This is combined witJ1 pelvic l)mphadenecLOmywhich can be done by extraperitoneal approach. The original vaginal radical hysterectom> has been •-eintroduced witJ1 modification by a number of surgeons in France where a laparoscopic approach or laparoscopic-assisted operation is done. Alternatively, postoperative pelvic radiotherapy may be employed. \>\lith the possibility of laparoscopic lymphadenectomy and lesser morbidity of vaginal approach, tJ1is modified laparoscopic-assisted radical vaginal h)sterecLOmy is gaining populality among many oncologists. Complications of Radical Hysterectomy

• • • • • • •

Haemorrhage during surgery Trauma to tJ1e bladder and ureter ( I %-2%) causing fistula Dysfunction of bladder because of nerve damage Damage to tJ1e obwrator and gen itofemoral nerve Sepsis T h romboembolism, p ulm onary and wi nary u·act infection Parai)•Lic il e us, periton itis, wo und sepsis, burst abdomen and scar hern ia • Lymp hOC)'St formation in tJ1 e broad ligament • Lymphoedema ( I0 %-20% )

A radical abdominal hysterectomy is a major surgical procedure associated witJ1 major and minor complications as mentioned above; this procedu•-e also has a risk of primary mortal it) in the region of I% . ot all centres and not all sw·geons are capable of doing this major surgical procedure. Radiotherapy

Ad,•;mces in radiotherapy techniques have made it possible to treat cases of cancer cervix with equally good results

427

as seen witl1 surgery. In addition, radiotherapy is app licable in sLages sud1 as Stages Ji b, II Ia and Ili b where surgery is not feasible. Prima11 radiotherapy consists of imracavity brachytherapy and external radiation to tJte pelvis. It yields the same 5-)ear cure rate as that of surgery, i.e. SOo/o-90%. It is, however. obsened tltat many surgical cases show positive l)lnph node metastasis which requires additional postoperative radiotJ1erap) anywa), and this combined therapy increases the mo•·bidity in the woman. Therefore, some oncologislS prefer to a'oid surgical approach and employ prima•1' radiotherap)' (see chapter 39 on Radiation Therapy and Chemotherapy). Addition of chemotl1erapy with cisplatin 40 mg2 weekly to radiotJ1erap)' imp•·oves the radiation effect, as cisplatin acts as a 1-adiosensitit.er agenL Current SLandard of radiation therapy is to combi ne it with weekly cisplatin when the patient is unde•·going extemal beam radiation. Young women in tJ1is group warrant specia l consideration because of risk of desu·uc ti on of ovaries, stenosis of vagina and occ u rrence of pyomeu·a fo ll owing radiotherapy. Prima ry s urgery therefore is tJ1e trea un e nt of c ho ice in yo ung women. In case of a large lesio n, externa l rad iotherapy is used first, followed b)' two app li cations of brach)•tlt erapy 2 weeks aparL This s hrinks the tumour, a nd a llows insertion of internal app licator. The advamages and dis.'ldvantages of s u rgery and rad iotherapy are mentioned in Table :tl.7. Indications for Postoperative Radiotherapy ln case surgeq was tJ1e first line of treaunent of early stage

cancer cervix. postoperative radiotJ1erapy will be needed for the following indications: • Positive l)lnph nodes fo•· metastasis • Positive resected margin of"agina or parameu·ium • Evidence of l)lnphovascular invasion or deep su·omal invasion • Poorly differentiated tumour P•·eoperative Chemotherapy Currently giving p•·eope•-ative chemotJ1erapy to a case of ca•·cinoma of tl1e cervix is not a sLandard method of treatment; however, people are explo ring this as a mode oftreatment in women with bulky disease. • Neoadjuvant paclitaxe l 90 mg and injecti o n ifosfam ide 2000 mg p lus mes na 400 mg weekly for three cycles • C isp la tin 50 mg week ly fo ll owed by s urgery yie lds 94% s uccess in earl)' s Lages Recurrence of Cancer

Advanced stage diseases suc h as Stages liB, Ill and rv are at a risk of recuiTences. Rec urrence can also occ u r in early stage disease managed by surgery or chemoradiation. Most patients tend to develop recurrences in t11e first5 years after ueaunent. Chemomdiotherap) can improve tJ1e survival and allow tJ1e woman to spend a comfonable life or increase the duration of remission. A cenu-ally placed ~·owth , a bladder and rectal fiStula ma> be subjected to exenteration operation. Recent trend is to u·eat stage lib with chemo•-acliation or chemotherapy for tl1e first 3 months followed by surge•1'·

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SHAW'S TEXTBOOK OF GYNAECOLOGY

Table 33.7

Advantages and Disadvantages of Sw-gery Compared with Radiotherapy

Surgery

Radiothera py

Advantages Survival rates for surgery and radiotherapy a-e similar Applicable to all stages between Stages IB and rJ OPD procedure No immediate mortality

Accurate surgical staging possible Pelvic lymphatic glands can be removed Conservation of ovaries - transposition of ovaries in case postoperative chemotherapy is required A more pliable, but short vagina retained Applicable if fibroids, adnexal masses present Failed surgery can be treated with radiotherapy Disadvantages • • • • • • • • •

Surgical mortality - 1% Anaesthesia compli cations Haemorrhage, trauma d uring surgery Sepsis - wound, pelvic, c hest, urinary tract, burst abdomen Bladder atonicity, fistula, ureteric Injury, bladder dysfunct ion because of denervatlon Paralytic Il eus, thrombophlebitis, embolism Lymphocyst formation Many require radiotherapy postoperatively Scar hernia, pelVIc adhesions Obturator nerve damage

• • • • • • •

Anaemia Ova-ian destruction Pyometra Decreased libido because of ovarian failure Vaginal stenosis Bladder - cystitis, fistula, ureteri c stenosis Bowel - chronic diarrhoea, proctitis, rectal stricture, fistula - skin burn • Avascular necrosis of femoral head • Not applicable in the presence of ovarian tumour, adnexal mass, fibroids, prolapse • Risk of sarcoma a few years later

Recurrent Lesion

Management of Recurrences

Twelll) to twenL)·fh e per cent of early lesions recur with in 2 years of prima11 treaunent. This may be cenu-ally located or on the lateml pelvic wall with l)lnph node invo lvememor distal in Lhe pam-aonic nodes, lungs, liver or bones. Most recUJ·rences are related to the siLe of the primary growt.h of more than 2 em, st.age of cancer, lpnph node involvemem and tissue dilfel'·e ntiation. T he srmptoms appear late, but are similar to t.hose of earl)' cancer. The development. of sciat.ic pain, lymphoedema of the leg and fistula are sure signs of recun·ence. It. is import.ant to differentiate infla mm atOry from malignant, parameu·ial tl1i cke nin g. On pelvic examinatio n, in flammatory infiltraLion is s moo th, whe reas malig na nt infiltratio n is nodular.

Recun·em growth following •-adiotherapy can be t.reated by hysterectom) in a small cenu-al growtJ1 or exente1-ation opemLion. Most recun·ences a•·e cenu-all) placed and 30% are fit to be managed by peh·ic exente1-ation opemLion. Amerior exente1-ation comp•·ises hysterectomy a nd removal of the bladder with ureteric implantation in t11e ileal conduit. Posterior exeme•-ation removes the utems and t11e rectum with low rectal anastomosis, avoiding permanent colostomy. In total exentemtion, both bladder and rectum are removed in addition to t11e uterus. Vaginoplasty ma y be required in youn g women. Exememtion operation is indicated in recurrent a nd resid ual tum o urs centrally located. Exenteration s w·gery ma kes t11e li fe of t11e woman comfo rtable, witJ1 5%-15% s urgica l mo rta lit)' but 60% !).year c ure ra te. T he follo~,1 ng are t11e co nu;1indica ti o ns LO t11i s opera tio n:

Follow-Up of a Treated Case of Cancer of the Cervix

Pap s mear is diffic ult to in terpre L. T he ce lls appear large with C)'toplas mic vacuo lation, multinucleation a nd nuclear shrinking wi tJ1 in flammatory cells in th e first few months of radiotherap)'. Cli nical exam inatio n and combination with investigations if indicated can detect rec urrences. Fineneedle aspiratio n C)'tologr (FNAC) and tricot needle biops)' confirm tl1e recurrence. Cystoscop)', sigmoidoscopy, CT, MRI and PET are required to study the extent of the gt"OWth . MRl is superior to Cr in idenLifying malignam infilu-ation in Lhe pammeu·ium, but in case of difficulty, MRl is repeated 3 momhs later; PET also helps. Cr is specific in 60%-70% of cases, but MRJ is specific in 70o/o -90% of cases. PET-CT is more specific than t.he two.

• • • •

Age over 80 )'ears Woman not accepting colosto m)' Presence of l)'mph node o r distal me tastasis Fixed tumoms

Lateral recurrence is ma naged by racliotherap)' in a previous SLtrgical case, but repeat •-adiotherapy can cause fistula unless mdiotJ1erapy was applied more than I year ago. Distal met.astasis has a 5-)ear survival rate of o nly 5%, but chemotJ1e1 90

Stage IIA

>80

Stage liB

> 65

Stage lilA

About 45

Stage IIIB

About 35

Stage

w

< 15

gery and radiotherapy. Co ni:t.atio n \\1th externa l radiotllerapy is recommended.

PAlliATIVE TREATMENT IN TERMINAL STAGES OF CANCER OF THE CERVIX • Pa in re lief with morphin e and tramaclo l; ora l mo rphine 5-60 mg • Vomiting: Dehydration a nd e lec trOI)•te imbalance correc ted; neuu·openia, uraem ia and chemoradiation are the causes of vom iting • Ha lopetidol 1.5-3 mg (dopam ine rgic antagonist) • Appetite improved by metoclopramide, domperidone and corLicosteroids for bowel oedema (60-100 mg daily prednisone); dexamethasone 4-S mg daily for 3-5 days • Lymphatic leg oedema stockings, garments a nd massage • DiLLretics and spironolactone for ascites • Vaginal discharge - Betadine douche or metronidazole irrigation • O ndat1seu·on I mg Li.d. for 111diation vomiting • Ascites tapping For profuse vagi nal bleeding, packing and adminisu11tion of tranexamic acid 500 mg i.v. &--8 hourly are helpful. Rare!)•, emboli:t.ation / Ii gation of imem al iliac artery is needed.

FUTURE DEVELOPMENT A new line of approac h in th e form ofVEGF fitcwr such as bevacizumab is be ing u·ied alo ng with sta ndard u·eaun e nt prow col to ac hi eve be tter stuv ival ra tes. Otl1er forms of chemotherapy such as pacli taxe l + ca rboplatin are also being evaluated for trea tme nt of adva nced d isease. Gene therapy ma)' have a role in locall y adva nced d isease. It is possible for tl1e direct iqjection of DNA-liposomal comp lexes and human leucOC)'Le antige n, which may promote a favourable cytotoxic immune response. T his may have a ro le in reducing local recurrence.

KEY POINTS • Carcinoma of tl1 e cel'\ ix is the most com mon genital U11Ct cancer in women and 111nks next tO breast Catlcer. It is a disease of )Oung " omen betwee n the age of 35 and 50 )eai"S.

CHAPTER 33 - PREINVASIVE AND INVASIVE CARCINOMA OF CERVIX

• H uman papillorml\irus (H PV) infeclion is now proved to be the most important cause of preinvasive and invasive cen ical cancer. It is sexually transmitted. Ot11er con u-ibutOI) factors are earl> age of sexual acti,~t:y, multiple partners, poor h)giene, multiparity and immunosuppressi'e conditions such as I-I IV. • lJse of ban·ier contracepti\ es prC\ems transmission of 'iral infection to a ''oman and prC\enLS preinvasive and irwashe cenical cancer. Prolonged use of oral combined pills increases t11e r·isk of cancer cenix, especially endocen•ical cancers. • Ninety per cent of young women witl1 H PV infeclion show spontaneous resolution within 2 years and do not develop cancer: Only those \\ith persistem infection after the age of 30 years are at a high risk for preinvasive and invasive ca ncer. • Stepwise development of ca ncer cervix from HPV infec ti on and iLS persistence leading LO preinvasive an d invasive ca ncer takes I 0-15 yea rs. T his lo ng period all ows ro uti ne screening and u·eaune m of preinvasive cance r; so that invasive ca nce r does no t develo p. • Ro uti ne Pap smear and colposcopic su.rdy and b iopsy p ick up preinvasive lesions (C IN) effeclive ly in 90% of cases. Add ing HPV testing further improves the pick-up rate. • Ab lative therapy for early stage d isease is a successful fertility-conserving therapy in yo ung women, b ut lifelong follow-up is necessal) to detect recurrence. Hysterectom> is reser\ed for elderly and multiparous women. Follow-up is necessal) irrespeclive of treatment for preinvasi'e cancer. • Endocer\ ical cancer is difficult to diagnose in iiS early stage, as the tissue is not available for cywlogy and colposcop). Endocenical scrape and cone biopsy are required for diagnosis. Treatmem is chemoradiation followed by Wenheim 's hysterectomy.

431

• Radiotherapy is app licable in all stages of invasive cancers. 1-lowe,er, because of ovarian atrophy, vaginal stenosis and p)ometra, primal) surgery is preferred in )Oung women. • Prognosis in invashe cancer depends on the size of the lesion. stage of t11e disease, imohemem of lpnph nodes and cell differentiation. • Proph) lactic vaccine againstllP\1 is now available. Given before the start of sexual acti' it), t11e vaccine is expected to reduce the incidence of cen ical cancer in futw·e.

SELF-ASSESSMENT I. Discuss tl1e causes of carcinoma ofthe cervix.

2. Discuss the clinical feawres and management of prein vasive cancer of the cervix.

3. Describe the clinical features of invas ive cervical ca ncer and the d ifferen ti al d iagnosis. How will yo u inves ti gate a case of ca nce r of the cervix? Disc uss the manage men L of st.age lb ca nce r of the cervix. Describe the FICO staging of cancer cervix. Disc uss the d iagnosis and management of endocervical cancer: 8. Discuss management of a case of cancer cervix witll pregnancy.

4. 5. 6. 7.

SUGGESTED READING DuncanJ. Shulman P. Yearbook of Ob.tctric., C)naecology and Women's llcalth: 40: 42!1. 2010. Studdj. liP\' role in cancer cenix : In: Progreso in Obstetrics and C)naL>Colg) Vol: 14. 2000. Studd J. Prognosis in cancer ccn i x. Progres. in Obste trics and C)naecology 15. 200!1. Studd J. Progress in 0 b;tctric> a nd Cp mecology 7: 1989. StuddJ. Screening cancer ccr,ix. PrOf..'Tes> in Obste trics and C~naecol­ ogy 16: 32!1. 2005.

Cancer of the Body of the Uterus

Endometrial Cancer 432 Sarcoma of the Uterus 438 Endometrial Stromal Tumours 439

Key Points 440 Self-Assessment 440

T he body of tl1 e ute rus is the site of e ndomeu·ial cancer, the most freque nt ge nita l tract ca nce r in rich countries; howeve t~ it ranks tl1ird in India after cancer of cervix and cancer of oval')'·

ENDOMETRIAL CANCER Endometrial cancer has recently emerged as the more frequelll.l) encoumered ID naecological ca ncer accoLmting for 20%-25% of all genital cancers in tl1e developed countries. notonl) because oft11e longerSLLrvival of women, but mainl) because of the marked dedine in cervical cancer b)• screening programme (Fig' 31.1-31.5). In developing countries including India, tl1e incidence has remained low at 5%-7% of all genital cancers; cervical cancer continues to predominate and is seen in 1.8 per I 00,000 population. T he majority of tl1e endometria l cancer is seen in the 55-70 years age gmup, 20%-25% of cases occur in perimenopausal women and only 5% of cases develop in women youn ger tl1 an 10/HPF). (Courtesy: Or Sardeep Mathur, AIIMS)

CHAPTER 34 - CANCER OF THE BODY OF THE UTERUS

Metastasis occurs relatively early; the spread OCC tLrs by t11e bloodsu·earn, by l)~nphatics, by d irect spread and by an implantation. As a result of bloodstream dissemination, it can metastasize to lungs and kidneys and ot11er organs. Lymphatic spread invo lves pelvic lymph nodes in 35% of cases in Stages I and II, and para-aortic glands in 15% of cases. Di rect spread into the peritoneal ca,~ty leads w multiple metastases over the peritoneum with accompanying ascites and large depositS in tlle omemum. Most patientS ha'e poor su rviva l after tlle diagnosis of leiomyosarcoma is made, with an average duration of life of about 2 years from t11e commencement of symptoms. ln most cases, a diagnosis of a sarcoma comes to light on t11e basis of histopathology of a specimen of the uterus or myoma removed at myomectomy or hysterectomy. Failure to respond and shrink in size follo,,1 ng GnRH administration in a case of fibroid should stro ngly suggest t11e possibili ty of malignancy. Positron e mission tOmography (PET), Doppler ulu·asound and MRI may help in t11e d iagnosis. Witl1 subm ucosal wmow-s which produce co ntinuous bleeding, a histological exa minati on of cure LLings may e nabl e a diagnosis to be made. Again, a rap id enl arge me mofa quiescent myo ma in a woman ofposunenopausal age is almost pat11ogno monic of a sarcomatous change. A sa rcoma of t11e ute n1s usuall)' causes a rapid en largement of the uterus witll profuse and inegular vagina l b leedin g. Pain is present in 60% of cases and fever due to degeneration or infec tion may also occ tu· in about one-tl1ird of the patientS. If t11e tumour has encroached upon tl1e ca~ty of t11e lllenlS and caused posunenopausal bleeding. diagnosis ma> be made by curettage. The imerpretation oftl1e histoloro is vel') difficult becatt.Se of the presence of degenerative and infective changes. However·, a mitOtic cotUH more t11an 10 per 10 high-powered fields and an atypical cell would suggest a diagnosis of leiomyosarcoma. Staging of leiomyosarcoma Stage I

lA lB Stage II

llA liB Stage Ill lilA

lllB lllC Stage IV IVA LVB

Tumour limited to the uterus 5cm Tumour extends to the pelvis Adnexal in volvement Tumour extends to extrauterine pelvic tissue Tumour invades abdo minal ti ssues (not just prou·ud ing into the abdomen) One s ite More tha n one site Metastasis to pelvic and/ or para-aortic lymph nodes Tumour invades b ladder a nd/or rectum Distant me tastasis

439

be imolved. This is followed by radiation t11erapy. The &-year cw·e rate is under 30% and large ly depends on t11e type of growth, being t11e wor-st in the round cell variety where the growth originates in t11e e ndomeui um. Metastasis sud1 as ILmg. liver or brain metastasis is a contraindication to surgery. Radiotherap) is ineffective in distal metastasis. Chemotherapy is the onl) hope and comprises a combination of cyclophosphamide, vincristine, doxorubicin and dacarbaLine or vincristine, actinOm) cin and C)clophosphamide (VAC). lt reduces t11e recurr·ence rate. The conservation of ovaries does not ach·ersely influence the prognosis, and it is a wise decision to leme them behind during h)'Sterectomy in a young woman. Br-east can cer is seen associated witl1 leiomyosarcoma, so it is pr·udent to screen t11e woman's breasts. Rhabdomyosarcoma is a rare, highl y malignant tumour in children. lt is now managed by ch emoradiotl1erapy. The prognosis is poor with a 5-year survival rate of 40%. A 50% response is reported ''1th docetaxel a nd gemcitabine. Progeswge n an d am matase inhibitor hold future promise.

MAUGNANT MIXED MUllERIAN TUMOURS These uncomm on tum ours of t11e uterus co mprise elements of mesodermal a nd ec todermal o rigin. In tl1e past, these twno urs were comm only named as carcinosarcomas; however, now a preferred te nn is malignan t mixed Mullerian tLUllo w·s (MMMT). Although the ute n.L~ is a common site for these tLUllOLu·s; howeve t; t11ese can be seen in vagina, cervix or ovaries.

MESODERMAL MIXED TUMOUR (INCLUDING BOTRYOID AND GRAPE-LIKE SARCOMA) Uterine sarcoma arises t) picaII) in t11e body of the utent.S, whereas a sarcoma of the cen ix is ' e r1 rare. Eight per cent of cases follow peh·ic racliotherap)'· Pathologically, t11e tumour-s should be regarded as mesocler·mal mixed wmours as tlley often contain canilage, striated muscle fibres, glands and fat. The su·oma is embl')Onic in type, similar LO t11e embr)'Onal mesench>•me. A grape-like sarcoma of the cervix arises typically in adult women, metastases develop rapidly and local recurrence follows their removal. Somewhat similar LUmours are known 1.0 develop in t11 e vagina in children at a ver) ' ea rl y age, and such tumours contain su·iated muscle fibres and a n embryo ni c stroma. Rat11er similar wmo ut'S some tim es develop in t11e bod)' of the uterus in o ld wome n, and in t11is way three types of mixed tum o w'S, namel)' the vagina l tumours of children, the grape-like sarcoma of t11 e ce n•ix and t11 e mixed tumours of the bod)' of tl1e ute rus of old women can be distinguished. ln all cases, the prognosis is bad a nd a rap id recurrence follows t11e ir re moval.

ENDOMETRIAL STROMAL TUMOURS

TREATMENT l11e u-eatmem of a sarcoma of t11e uterus consistS of total hysterectomy with bilateral salpingophorectomy, followed by a full course of radiation therap). If t11e growth is in the region of t11e istl1mus or cen·ix, a radical hysterecwmy of t11e Wertheim t) pe with a bilateral I) mph node excision probably offer'S the best chance of cure, because in many cases t11e glands may

Sarcomas can arise rarel) from t11e su·oma of endomeuium. ll1ese su·omal tumours ha'e a variable course and have been classified as follows: l. Stromal nodul es/ su-omal h) per·plasia 2. Low-grade su-omal sarcomas 3. High-grade su·omal sarcomas

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SHAW'S TEXTBOOK OF GYNAECOLOOY

In most cases, diagnosis is made on the basis of histOlogy of hysterectomy specimen conducted for irregular, abnormal uterine bleeding. Sometimes diagnosis can be suspeCted on the basis of D&C matetial submitted for histOpathology in a case of abnormal utetine bleeding (AUB). Although a low-grade stromal sat·coma does not require any acljuvant treaunent, patients with a high-grade stmmal s:u·coma require radiotheraP> and chemotherapy as an acljuvam treaunenL A high-grade stromals:u·coma is associated with poor prognosis. Staging of endometrial stromal tumours (FICO 2009) Stage I LA

IB

IC Stage II ILA JIB Stage Ill li LA III B

IIIC Stage IV IVA IVB

Tumour limited to the uterus Tumour li mited to endometrium/ cndocervix with no m)'Omeu·ial invasion Less than o r eq ual to half myometrial invasion More th an half myomeu·ial in vasion "1\tmour ex tends to the pelvis Adnexa l invo lvement Tumour extends to extrauterine pelvic tissue Tumour invades abdominal tissues (not just pt·otruding into the abdomen) One site More than one site Metastasis to pelvic and/or para-aortic l)lnph nodes Tumour invades bladder and/or rectum Distant metastasis

• Alll10ugh simple endomeu·ial hyperplasia leads to endomeu·ial cancer in 2% of cases, atypical hyperplasia leads to endometrial cancer in 8%-29% of cases. • Early stage of endomeuial cancer is treated by h)'Sterectomy, bilateral salpingoo()()phorectomy. L) mphadenectomy is required in case of deep m)omeuial infiltration, endocel"\ical imohement, poor!) differentiated tumours. • Cf, MRI are helpful in mapping tl1e m)ometrial in\'asion and l)lnph node imohement. • Surge I") is the primal") mode of u·eaunent. PostOperative radiotl1erap) is required in the advanced stages, and for reducing the recurrence in tl1e vaginal vault. • Progestogen and Mirena can prevent endometrial hyperplasia. Progestogens are effective in 30% of cases wit.h lung meLTt"SS in Obslclrics and Cynaccology 7: 1989. S1uddj. Pr!,>Tt"SS in Obslclrics and Cynaccology 16: 343,2005.

Pathology of Ovarian Tumours and Benign Ovarian Tumours

Pathology of Ovarian Tumours M 1 Tumours

of the Surface Epithelium

442

Borderline Ovorion Tumours 444

Benign Ovarian Tumours 452 Ovarian Tumours Associated with Pregnancy 456

Germ Cell Tumours 444

Ovarian Cyst in a Menopausal Womon 456

Sex Cord Stromol Tumours 447

Ovarian Remnant Syndrome 456

Feminizing Tumours 447

Ovarian Tumours in Adolescents 457

Virilizing Tumours 448

Key Points 457

Tumours Arising from Connective Tissues of the Ovary 449

Self-Assessment 458

PATHOLOGY OF OVARIAN TUMOURS Ovaries can be the site of a variety of benign and malignant tttmours. These wmours can be cystic or solid, often a combination of the two. Th~ can val) in siLe from as small as 3-5 em to as big as equal to a fu ll-term pregnam uten.lS. They can be seen in an) age group starting from prepubertal 1.0 adolescent du.-ing reproducti,·e life and postmenopausal age group. Malignant tumours can develop in any age group. Ovaries are the site of th ree common types of tumours: (i) epithelial tumours: those which arise from surfuce lining of ov;u·ies; (ii) germ cell tumours: those which arise from germ cells within ovaries; and (i ii ) sex cord stromal tumours: those which ar·ise fr·om sex cords present in ova ries. O varian tumour is nota single entity, but a complex wide spectn.rm of neoplasms in volving a variety of histOlogical tissues ranging from epithelial ti ssues, connective tissues and speciali zed horm o ne-sec re ting cells lO germin al an d embryonal cells. The most common are epithelial tumo urs forming 80% of all tumours. Eighty per cent are ben ign tum ours and 20% a re ma li gnant. Of all the malignant tumours, 90% are epithelial in origin, 80% are primary in the ovary and 20% secondary from breastS, gastro intestinal u·ac t a nd colo n. Be nign tumo urs can become secondaril)' maligna nL Mucinous cyst becomes ma lignant in 5%-9% but papillary cyst adenoma becomes malignant in 30%-50% if left un treated. Unfortunately, patients with ova rian tumotu·s are often S)'lnptom-free for a long time, and the signs are often nonspecific. B) the time diagnosis of ovarian malignancy is established. about two-thirds of t.hese are already fur advanced and the prognosis in sud1 cases is unfuvourable. An ova.-ian tumou r· in adolescem and posunenopausal women is more often malignanL Most genn cell tumour-s occur in )Ounggirls )Ounger than 25 )ears of age.

PATHOLOGY ln an attempt to standardi:t.e the nomenclat.ure used in desc.-ibing the diverse varieties of ovarian uuno urs, the World Health Organiation (WHO) devised a classification listing nine major groups for benign and malignant tumotu'S (Table 35.1 ). Epithelial ova.-ian neoplasms ar·ise from the mesoepithelial cells on the ovar·ian surface. Epithelial cance r'S constitllle about 80% of all ovar·ian cancer'S. The most common histological t)pe is the papillary serous cystadenomas and carcinomas accounting for almost 50% of a ll epithelial mmow-s. MucinotlS tumotu'S account for 12%-15% of the cases, clear cell and endometrioid combined about 10% of the cases, and the unspecified types 25%-27% of the cases. lf the li ning of tumour-s resembles the lining of epithelial tumout'S of fallopian tubes, they a re labelled as serous tumours; if th e lining of epitheli um resembles e ndocervical epitheliu m, they a re labelled as mucinous tum o urs; if the li ning of epithe liu m resembles e nclome u·iu m, th ey are labelled as enclometrio id wmours; and if the lining of epitheliu m rese mb les b ladder epithe lium, Lhey are called clear cell va rieq•. The degree of cellula r d ifferentiation of the epithe lial ovarian neoplasm expressed as histo logical grade has an important sign ificance in prognosis as we ll as in identifying malignancy. The criteria of grading used include mitotic count, stratification, cellular pleomorphism, nuclear atypism and proportion of solid areas within ll1e tumour. Grade '0' tumours, also known as borderline malignancies or wmours of low malignant potential (LMP), may demonsu-ate papillar> wfting, stratification, epithelial atypia, exfoliation of cellular· cltlSter'S and minimal mitotic acti,~ty, but no stromal invasion. The 5-)ear surviva l of patients with Stage I Gmde '0' tumour'S is more than 90%

441

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SHAW'S TEXTBOOK OF GYNAECOLOGY

Table 35.1

WHO Classification of Ovarian Tumours (Major Groups)

I. Common epithelial tumours: • Serous t umours • Mucinous t umours • Endometrioid tumours • Clear cell (mesonephroid tumours) • Brenner tumours • Mixed epithelial tumours • Undifferentiated carcinoma Unclassified epithelial tumours II. Sex cord (gonadal stromaQ tumours: Granulosa stromal cell tumours, theca cell tumours Androblastornas: Sertoli-Leydig cell tumours Gynandroblastomas Unclassified Ill. Lipid (lipoid) cell tumours IV. Germ cell tumours: • Dysgerminoma • Endodermal sinus tumour • Embryonal carcinoma • Polyembryoma Choriocarcinoma Teratoma Mixed forms

benign coun terparLS. Histologically, tlle benign variety shows C)'Stic spaces, and the lining of the tumour consistS of tall columnar ciliated epithelium resembling tJ1e endosalpinx. The loculi contain a serous straw-coloured Auid, which may be blood stained when malignant transfonnation occurs. Unless cell ular atypia exceeds four-cell-layer tJ1ickness or stromal invasion occ urs, the tumour is classified as borderline or ben ign (Fig. 35.1).

MUCINOUS TUMOURS Mucinous wmours are multilocttlat.ed cysts lined by epit.helium resembling the endocervix (Figs :~5.2 and 35.3). Former!). th~ were refeJTed 1.0 as pseudomucinotlS C)'SLS, as their contentS are not. chemically u·ue mucin. The cut. surface shows multi loculi and hone> comb appearance. The t.umours are not infrequent, can grow 1.0 a large si£e and oft.en weigh as much as 5-10 kg; tJ1ey are often pedunculated. These may be combined with a dermoid cyst or a 13renner tumour (Fig. 35.'1 ). T hey are us ua ll y tmil at.eral; only 5%10% are bilat.e ra l. T he tumours are most.ly benign; only 5%-10% beco me malignam and 10%-15% a re of LMP. 13ilate ra l wmours are often metastatic from t.he g.lsu·oimestinal u·ac4 mainly mucocele of appendix or prima•)' adenocarcinoma of appendix or stOmach.

V. Gonadoblastoma: Pure Mixed with dysgerminoma or other germ cell tumours VI. Soft-tissue tumours not specific to overy VII. Unclassified t umours VIII. Secondary (metastatic) tumours IX. Tumour-like condit ions

compared to 54% survival for patientS with SLage I Grade 3 serous cystadenocarcinomas. Besides hisLOiogical LLunour grading, Aow C)'lOmeu·y analysis of wmour DNA comelll provides another method of assessing wmour differentiation and prognosis.

TUMOURS OF THE SURFACE EPITHELIUM SEROUS CYSTADENOMA AND CYSTADENOCARCINOMA Serous cystadenoma and cystadenocarcinoma are amongst the most common of cystic ovarian neoplasms, acco unting for about 50% of all ovarian tumours; of t.hese, 60%-70% are benign, 15% borderline and 20%-25% are malignam. Se•·ous C)'St.adenomas occur in the thi•·d, fourth and fifth decades of life; malignam C)'Stadenocarcinomas tend to oc· cur more frequently with advancing age; however, no age is ban·ed. In about half of the cases, they are bilateral. Delicate papilla•) ' excrescences may be seen on the surface and with in the loc uli in a benign cyst. In ca~e of sero us cystade nocarcinoma, coarse papilla•)' growths sp read to tJ1e periLOneal surfaces. T he papillae are friab le unlike th eir

Figure 35.1 (A) A papillary form of serous cystadenoma of t he ovary. The epit heli um, t hough hyperplastic, Is un doubtedly ben ign (x 60). (B) High-power serous cystadenoma (Source: tor (A) Rao KA: Textbook of Gynaecology. India: Elsevier, 2008. Courtesy (B) : Dr Sancleep Mathur.)

CHAPTER 35 - PATHOLOGY OF OVARIAN TUMOURS AND BENIGN OVARIAN TUMOURS

443

Rgure 35.4 A combined Brenner tumour {solid area) and multilocular mucinous cystadenoma.

Rgure 35.2 Mucinous tumour.

Mucinous lltmo tu-s occur in women between 30 and 60 )'ears. They have a gliste nin g surface, and th e cut section reveals loc tJi fi lled with mucinous co me ms (Fig. 35.5) . Lfthe tumour n.tptures, it may lead LO fo nn aLion of pseudomyxoma peritonei and tJ1e viscera show extensive adh esions. Appenclicec tom)' at the Lime of primary surgery preventS pse udomyxoma peritonei, as often mucocele of appendix is known to cause tJ1is complication.

ENDOMETRIOID TUMOUR Endometrioid wmours are moSU) malignant and accoLUH for about 20% of all ovarian cancers. They are lined by a glandular epithelium resembling the e ndometriLUn.

~.

Rgure 35.3 (A) Mucinous cystadenoma. (B) Mucinous cystadenoma. High power shows cells resembling endocervix. (Courtsey: !X Sa1deep Mathur)

Figure 35.5 A mucinous cystadenoma with its mu~icystic appearance and delicate septa. (Sour09 The Female Genftal Systen1 and Breast. ~bins Base Pathology, Bsevier, 2007)

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SHAW'S TEXTBOOK OF GYNAECOLOOY

The tumours are of moder-ate size, and are essentiall y solid, with cystic areas in between filled witl1 haemorrhagic fluid. In 15% of cases, ovarian endometriosis may coexist. They are associated witl1 endometrial cancer in 20% of cases.

CLEAR CELL (MESONEPHROID) TUMOUR Mesonephroid tumour, also called clear cell carcinoma, is an tmcommon wmour of the oval). It is composed of large cuboidal epithelial cells witl1 abtmdam clear cytoplasm characteristically forming wbules, glands and small C)'Stic spaces lined by clear cells showing large, dark n llclei prot.ntding into the lumen (hobnail cells). The LUmour is highly malignant.

BRENNER TUMOUR Brenner tumour is an un common solid fibroepithelial tum our acco unting for abo ut 1%-2% of all ovarian neop lasms. On gross appearance, it resembles a fibroma of the ova ry (Fig. 35.'1 ); its cut Stll'face appears griuy and yellowish grey. It is generall)' uni latera l, small to moderate in s ize, mostly ben ign and has no e ndocrine function. Brenner t umour ca n occasion all)' be ma lignan t. T he tumour is generally seen in women at·otmd menopause, and causes posunenopausal bleeding. Occasionally, it may be associated with ascites and hydrotl1orax (pseudoMeigs S)'ndrome). In rat·e cases, it becomes malignant. Histologically, the tumour shows a background of fibrous tissue - interspersed within it are nests of transitional epitllelium (Walthard cell rests). These cells demonstrate a longitudinal groove t·esembling puffed wheaL As mentioned earlier, this tumour may be combined witl1 a mucinOLIS adenoma of the ovaq.

SPREAD OF EPITHEUAL TUMOURS OF THE OVARY When these tumours become malignant and extend through the capsule, llle) may be seeded on to the peritOneal s urface, omentum and intestinal viscera and by transcoelomic spread reach the subdiaphragmatic space. The asc itic fl uid is often b lood-stained and shows the presence of cltL~te rs of tumour cells. The tumour cells ma)' spread to ll1e para-aortic lymp h nodes, and metaStaSize to tll e liver, lu ngs, gasu·oin testinal u·acL and other areas. In over half of ll1e cases, the opposite ovary is also in volved.

BORDERLINE OVARIAN TUMOURS Borderline ovarian tumour'S or ovarian epithelial tumours of LMP were first dcsctibed by Taylor in 1929. There is a broad agreement that a categor)' of borderline tumour existS. Histologically, these tumours are intermediate between u·uly benign neoplasms and tl1ose witl1 invasive charactet·istics. Clinically these tumours tend to have LMP. They are pre, be dela)ed for many years. Kotuneier reported that malignant recurrence occurs in 50% of granulosa cell tumours and the term gra nulosa cell carcinoma is justified. There is a cenain con-elation between the histo logical appearance and malignancy. A well-differentiated follicu-

T his tumou r is usua ll y seen after me nopause. lt is nearly a lwa)'S unilateral and forms a solid mass. T he cut surface is >•e llow in colour and, if stained selec tive ly, lipoid materia l is characteristically present. The tumour consisiS of spindle-shaped cells reminiscent o f an ovarian fibroma LOgetJ1er witJ1 fat-lade n pOI)hedral cells which resemble the t11eca lutei n cells of the Graafian follicle. The tumour is imensely oesu·ogenic and causes posLmenopausal bleeding. lt usual!) runs a benign course but malignant fonns have been described. IL has been shown that both gra mtlosa cell tumout-s and theca cell wmours mar show lute init.ation of their cells, witJ1 the result that progesterone is secreted and secretory h)penrophy can be demonstrated in the endomeLrium.

VIRILIZING TUMOURS The ovarian tumours which produce male sex hormones are called viri lizing Ltunours. Virilizing mesen ch)'moma and o th er virilizing wmo urs of the ovary are grouped together here for convenience.

ARRHENOBLASTOMA (SERTOI.HEYDIG TUMOUR) ArrhenoblasLO ma are rare tumours th at secrete androge ns which cause defeminizaLion fo llowed b)' masc ulinizatio n. Women in t11e childbearing age may comp lain of altered body comours, Ratten ing of th e breasiS, and scanty and irregular mens u·uatio n endin g ultimately in amenorrhoea. Later signs of masculinization sucl1 as increased hair growt11 on t11e face (hirsutism) appeat: Coarsenin g of the features, enlargemem of the cliLOris (Fig. :33.13) a nd even breaking of the voice ma> occur. Removal of tJ1e tumour reverses most of t11e above-mentioned features of e ndome u·ial carcinoma except the voice change. The gross appearance of the wmour is like Lhat of other mesenchpnomas. Gene mil)', ontr one O\'llt) ' is affected. LIS

CHAPTER 35 - PATHOLOGY OF OVARIAN TUMOURS AND BENIGN OVARIAN TUMOURS

449

TUMOURS ARISING FROM CONNECTIVE TISSUES OF THE OVARY Of Llle innocent connective tissue tumours of the ovary, fibromas are the most common.

OVARIAN FIBROMA

Rgure 35.13 blastoma.

Hypertrophy of the clitoris In a patient with arrheno-

assoctauon with pregnanq• has been reported. The incidence of malignant transformatio n is rmed to be higher than with feminizing wmours. Histological!). the tumour reveals a ll grades of differentiation from the testicular adenoma showi ng perfecLly fo1med seminiferous tubules to a sarcomawus anaplastic variety, wherein lipoid-containing cells are seen. The diagnosis is usually made on the basis of the endoc1·ine behaviour of the tumour.

ADRENAL CORTICAL TUMOURS OF THE OVARY Adrenal cortical tumours ohhe ovary have a resemblance tO the adr-ena l cortex when examined microscopically and have been called hypem epluo ma, masculinovoblastoma, vili li zing luteo ma or clea r-celled tumours. T hese various appellations show tJutt tJ1 e constituent cells resemble the large clea r cells of the adrenal con ex or lute in cells of the corpus lute um. Whateve r may be tJ1 eir u·ue origin, they are very rare uun o u1'S. The)' a re so metim es masc ulinizing.

HILUS CELL TUMOUR A rare viri lizing wmo ur a lising from cells in the ovarian hilum has bee n described in women after menopause. One interesting feature of tJ1 e hilus cell tumour is the presence of Reinke crystals in tJ1e cells, a distinguishing featLu·e ofL11e Leydig or interstitial cells of tJ1e testis.

Ovarian fibroma comp1·ises about 3% of ov:uian neoplasms :md has no pa1·ticular age incidence. The twnour is oval in shape with a smootJ1 surface and large veins always noticeable in the capsule. The consistency is firm and harder tJum that of a uterine m)oma. The tumour frequently undergoes degener-ation so that cystic spaces are found tOwards tl1e centre. Calcareous degeneration is not uncommon. Th e tumours are usually about 15 em in diameter but sometimes become much larger than tJ1is and may weigh as much as 25 kg. Torsion may occur with tJ1 e larger tumo urs. Microscopic examina ti on shows tJ1e LUm our to be composed of a network of spind le-shaped cells wh ich closely resemble the spin cUe cells of tJ1e ovalian co n ex. The cell ular pauern is striking!)' uniform and there is no aue mpt at nuclear ac tivit)'· Th e association of Brenne r LUmo urs with ovarian fibroma is known. In large tumours, tl1 e connective tissue cells are elo ngated and a n inte rcellular matt·ix becomes prominent. The tumours are ofte n accompan ied by ascites. Sometimes, the patient has hydrothorax. T he combination of an ovarian fibroma with ascites and hydrothorax, usually right-sided, is known as Meigs syndrome. It is now accepted Ll1at the diaphragm is porous e ither by reason of minute foramina or' ia the l)lnphatics. Meigs S) ndrome can occLLr witJ1 other solid ovarian wmours such as granulosa cell tumour and Brenner tumour. Three t) pes of fibromas are recogniLed. In the first type, the tumour takes tJ1e form of a su1-face papilloma on tl1e ovary. Ln the second type, tJ1ere is a small encapsulated fi. broma arising in an ovary so tJ1at nonnal ov:uian tissue c:u1 be recogniLed at one pole of the tumour. In tJ1e third type, the fibroma replaces tJ1e ovary completely.

HISTOGENESIS OF OVARIAN TUMOURS FIBROMAS Small ovarian fibromas form white, ro unded excrescences in tJ1 e co rtex of the ovaq•. The tum our a rises from the s u·o ma cells of th e ova ri an co rtex. H istologicall y, a fibro ma a nd a Brenner wm o ur have a close rese mb lance, apart from th e inclusion of the epithe lioid Wa ltJ1 ard restS in the la tter. With subseq ue nt growth , a ca psule becomes differentiated and tl1 e wmou r grows at the expense of the normal ovarian tiss ue, so that fina lly tJ1 e ovary is completely replaced by the fibroma. The structure of a large ovarian fibroma is not unlike tJ1at of the stroma of the ovarian cortex. except that the constitue nt cells are more primitive in type.

GYNANDROBLASTOMA

PAPILLARY SEROUS CYSTADENOMA

A g) nandroblastoma combines the characte1·istics of Llle granulosa cell tumou1· and an arrhenoblastoma. This rare LUmour sometimes arises in d) sgenetic gonads.

Papillary serous qstadenomas almost certainly ongmate from downgrowths of the su1-face epithelium of tl1e ovary into the cortex. Small down~·o"ths of this son :u·e

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exu·emely common, even in normal ovaries, and small cysts, only recognized b)' microscopic examination, are fairly frequem. Papilla!") forms result from inrracystic growths inLO these wmours. Papillary serous carcinomas of the ova11 arise when the imracystic growths become malignanL The origin of the wmours from downgr0\\1.hs of Lhe surface epithelium of the ova11 is generally accepted and Lhe LUmours are regarded as examples of ov:uian Mullerianosis, with epithelial cells resembling endosalpinx.

GRANULOSA CELL TUMOURS Granulosa celltumotu-s consist of cells identical to the granulosa cells of Gt-aafian follicles and theca cell tumours similar to the theca interna cell (Fig. 35. 11). As both types of tumours may at·ise after menopause, ,,11en there at·e no Graafian follicles in the ovaries, the wmours can not be regarded as being derived from mature cells of this type. They are therefore regarded as oliginating in mesenchymal cells which are differen tiated sexually. The ard1enoblasLOma is regarded as being derived from mese nchyma l cells of the male type. The theca cell is rega rded as the ma~ter honnone prod ucer in th e oval)'·

TERATOMAS Teratomas probably arise from totipotent cells, i.e. cells which are capable of producing ectodermal, mesodermal and endodermal su·ucture.

MUCINOUS CYSTADENOMAS The cells of the tumour resemble those of the cervix and tJ1e large imestine. ·n1e two presem-day tJ1eories are (i) Lhe tumour represents an example of ovarian Miillerianosis, with metaplasia of tJ1e ovarian surface epimelium into cen~­ cal epimelium and (ii) the tumour at·ises from l:u·ge intestine elements of a dennoid C)'SL

BRENNER TUMOUR Brenner tumours are often associated witJ1 a mucinous cystadenoma, whet·e tJ1et·e is probably some relation between tJ1eir origins. The similarity to Walthard inclusions has al-

ready been noted and this suggests that Brenner tumo urs, like WaltJ1ard inclusions, are derived from the genninal epitJ1elial layer of the ovaq•.

COMPLICATIONS OF OVARIAN TUMOURS (Table 35 .2) AXIAL ROTATION: TORSION Torsion of an ovadan cyst is a common complication, and occurs in about 12% of cases. Dennoid cyst is me most common ov:uian cyst to undet·go torsion. Chocolate cysts and malignant ov:uian wmotu-s are usually fixed by adhesions, so it is very rare for these ovarian tumours to undergo LOrsion. On me conu-ary, paraovatian C)'Sts and broad ligament cysts at·e the most likely pelvic tumours to undergo tOrsion, probably because tJ1ey develop in the outer pan of the broad ligament and come to lie above the infundibulopelvic fold and above the pelvic brim so that they have a greater degree of mobility than otJ1e1· ovarian tumours. In most cases, tJ1e cyst is about 10 em or more in size when it undergoes torsion. Because of the hi gh incidence of mucino us cystadenomas, dermoid cyst torsion is most frequen tJ y seen \\1 \Jl these tu· mours. There is no particular age incidence. The right and left sides are involved witJ1 eq ual frequenq•. Usually, the tumour rotates so tJ1at its ame rior surface turns towards the patient's tight side. It is not uncommon for the twnour to be rotated tJuough tJu-ee or mot-e complete circles. As a result of rotation, tJ1e veins in tJ1e pedicle become occluded, the tLunour becomes congested, and there is interstitial haemorrhage in tJ1e wall of tJ1e tumour and imo the loculi. The increased tension causes severe abdominal pain and the signs of petitoneal irlitation. SubsequentJ), adhesions fonn wim sunuunding su·uctures, so that tJ1e omen tum and intestines become attached to the tumou.-. On occasions, me cyst may become infected. The most pt·obable explanation of rotation of an ovariru1 cyst is haemod)namic. It is suggested tJ1at some violent movement, a history of which is almost invat·iably obtained, initiates tJ1e twist and as a result the ovarian artet)' itself becomes twisted. The pulsation in the vessel will then cause a series of tin)' impulses to be u-ansmitted to the pedicle, each of whicl1 will aggt-avate the twisL After a time, the degree of torsion will be such that tJ1e veins in tJ1e pedicle become occluded and tJ1e patient compl ains of severe abdominal pain (Fig. 35.1 5).

CUNICAL FEATURES OF TORSION OF OVARY The woman often presents witl1 ac ute abdom inal pain, fever and vomiting. Sometimes, she complains of inte rmittent abdominal pain referred along the ob turato r nerve to along

Table 35.2

FIQure 35.14 Granulosa cell tumour, folliculoid pattern. (Crurtesy: 0" Sandeep MathlJ", AIIMS.)

Complications of an Ovarian TUmour

Torsion Rupture Haemorrhage Infection Pseudomyxoma peritoneum Malignancy

CHAPTER 35 - PATHOLOGY OF OVARIAN TUMOURS AND BENIGN OVARIAN TUMOURS

451

Figure 35.1 6 Ovarian cyst obstructing labour. (Sowce: From Eden and Holland's Manual of Q)stetrics.) Rgure 35.15 The pedicle of an ovarian cyst showing the relations of the ovarian vessels, the ovarian ligament and the fallopian tube, together with the anastomosing branch of the uterine artery.

the medial aspect of the thigh. SpnpLOms may start after empt)ing of bowel in the mom in g. Ultrasound shows a swollen oedemaLOus ovary, globular in shape, and free fluid in the peritoneal cavity. The pelvic findings re,eal a tender mass separate from the utet·us. This is an emergency requiring tu·gent laparotomy. The appearance of torsion of the ovati an tumour does not correlate with the ova.-ian viability, even when the LUmow· appears blackish. The refore, one is advised LO try and conserve tlte ovary if possible, unless ga ngrene h as set in. DetOrsion of tlte ovary and ovariopexy, after remova l of tlte tumolll~ should be attempted. The ova ry sho uld be observed fo r colo ur cha nge fro m bluis h blac k appea rance to its no rmal appearance. The tJ teo re tical risk of embolism with detOrsion does no t normall )' occ ur. The ova ry recove rs and becomes functional. T his approach is especial!)' important in a yo un g woman.

RUPTURE Rupture of an ovatian cyst may be u•xoma of the peritoneum develops (pseudomyxoma peritonei).

HAEMORRHAGE Haemorrhage may occur in a n ovarian cyst. It mostly occ urs spontaneously, giving rise to ac ute pain s imilar to pain because of torsio n . Occasiona l! )•, haemo rrhage in cyst can occur fo llowing asp ira tio ns of cyst. PSEUDOMYXOMA OF THE PERITONEUM In this condition, tl1e pe ri to neal ca vit)' is fi lled wi t11 coagulated mucinous mate ria l ad he rent to the omemum and intestines. The findings at lap.-·uotomy almost exactly resemble a boiled sago pudding. The mate tial cannot be removed completely at operation because of itS auachment to t11e bowel, and the condition tends LO recur after operation. Pse udom)'XOma of t11e peritoneum lL~ ltally occurs with a mucinous C)Stadenoma of the ovary, but it has also been reponed with a mucocele of the append ix and carcinoma of tlte large intestine in men. In pseudomyxoma of the peritoneum, the mesothelium of the pet·iLOneum is converted, in part, inLo high columnar cells which are

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histologically sim ilar to those lining a mucino us cystadenoma oftl1e ovary, and these cells secrete mucinous material into the peritOneal caviL). The prognosis in pseudom)'XOma of the peritoneum is bad, even afi.er tl1e ovaries and the appendix are removed, as it is to recur again and again. It is now believed that mucocele of the appendix may induce secondaf) ovarian tumour. Tlum:fore, there is a tendtmC)' amon~t gyrwecologiJI!. to rrmmw tilt appemli-Y tiS well, when encoulltered tuith muci11011.1 IJII(Iritm tumour, a11d trooid pseudom)'X-

oma of the peritolleum. Pseudom>xoma may be treated witl1 palliative chemotl1erapy. INFECTION Infection of an ovarian wmour is infrequent. Most cases follow acute salpingitis or when the cyst becomes infected during the pue1·perium as pan of an ascending genital tract infection. Infection may also follow torsion when, as a res ult of ad hesions to the intestine, th e tu mou r becomes direc tly i nfec ted. Infectio n by the bloods u·eam is vef)' unco mm on. Infec ted ovarian wm o urs are always adh e re nt to adjacent viscera and occasionall y disc ha rge the ir co nte n ts into th e rec llt rn. Sebaceous ma te rial in a de rmo id cys t also causes infection in t11e tu mo ur; it may also cause periton itis. EXTRAPERITONEAL SPREAD Some ovarian tumours b urrow ex u·aperitOnea lly d t.Lring tl1eir development and may spread upwards into tl1e perinephric region. The removal of these wmours is extremely difficult and there is danger of injuring Lhe ureter. During dissection and removal of such a cyst, large vessels may be tom in the retroperitoneal space and subsequent leakage of blood will form a retroperitoneal haemaLOma gi'1ng rise to shock and requires drainage. Malignant change : Secondary malignam changes occur in 50% of serous qstadenomas and 5% of mucinous cystadenomas, but only in I. 7% of dermoid cysts. A longstanding ovarian cyst may become me site of malignant change.

Figure 35.17 A very large beni gn mucinous ovarian cyst wh ich weighed about 50 kg. Note the prom inent veins, displacement of the umbilic us and oedema of the lower abdomen.

BENIGN OVARIAN TUMOURS T hree commonly seen benign ova ri an tumo urs are Sero us Cystadenoma, Mucino us C)'Staclenoma and Benign Cystic Terato ma. T hese can be see n in any age group, however, more co mm only seen between 20-25 yr of age. T hese three common benign tu mours ca n prese nt witl1 a variety of symptoms such as lu mp abdomen, pain abdome n o r detected inc idemally at Ll1e Lime of ul traso und being done for some other ind ications.

Figure 35.18 A lateral view of the same patient as In Fi g. 35.18. Note the lumbar lordosis.

SYMPTOMS Altl1ough benign ovarian cysts occasionally attain enormous lllmours. the) catl.Se relat.ivel) few symptoms. Indeed, in innocent ovarian tumours, t11e patient's attention is first directed to the abdominal swelling. The average pseudomucinOLIS cystadenoma removed at operation is about Ll1e size of a football, and it is not until the tumour has read1ed Ll1is size mat it causes sufficient alxlominal enlargement tO make Ll1e patient real ice mat sometJ1ing is wrong (Figs 35.17 and 35.18; Table :l5.:l).

MENSTRUAL IRREGULARillES Ov;u;an tumours. e'en bilateral, do not generally affect the menstrual C)cles. The onl) tumours caLISing menorrhagia are granulosa and t11eca cell wmours by \1rtue of Lheir oestrogen honnone secretion. Similarly, masculinizing tumours cause amenorrhoea and \'iriliLation. Postmenopausal bleeding may occur in benign Brenner ru1d femini.dng wmours.

CHAPTER 35 - PATHOLOGY OF OVARIAN TUMOURS AND BENIGN OVARIAN TUMOURS

Table 35.3

453

Featwes of Benign and Malignant Ovarian Tumours

Benig n Ovarian Tumours

Malig nant Ovarian Tumour

History Not related to age or parity, though most common during childbearing period Slow-growing tumour, no pain. No menstrual disorder unless it is a feminizing tumour or masculinizing tumour

Seen most commonly in adolescents and elderly women- mostly after 50 years of age; low pa-ity or infertile woman Rapidly growing tumour, pain in advanced stage; postmenopausal bleeding Family history of breast, ovarian or colonic cancer

Examination Usually unilateral, cystic, well-defined and mobile; no ascites (except in Meigs syndrome); no nodules in the abdomen or pouch of Douglas

• May be bilateral and solid, fixed; ascites may be present; metastatic nodules may be fe~ per abdomen; nodules In the pouch of Douglas

Ultrasound • Cystic well defined w it h or without echoes; no ascites (except In Meig s syndrome)

• Often soli d and bilateral fixed wit h Internal echoes, ascites may be presen t; metastatic nodules may be seen

Doppler Ultrasound • No increased vascularity

• Increased vascularity • Pulsatile index < 1 • Resistance index < 0.4

MRI andCT • Similar to ultrasound findings • CA-125 normal

• Metastatic and enlarged lymph nodes may be detected • CA-125 raised more than 35 IU/ml

Operative Findings Well-defined ovarian cystic or solid tumour; no ascites or metastatic nodule; often mobile

• Fixed solid tumour, often bilateral - with blood-stained ascites; metastatic growth over the omentum and peritoneal cavity; lymph nodes may be enlarged

PRESSURE SYMPTOMS The O\' increase the .-iskofabortion, whereas laparotom) in the tJ1ird u·imester increases tJ1e surgical difficult) becalLSe of tJ1e growing utenLS; pretenn labour is also a possibility. The tumour discovered late in pregnancy should be remo,ed in early pue•·pe•·iwn to avoid torsion and infection. The malignant O\' of these are malignam potential. The tumours are often as)lnptomatic to begin with, and are often fur ach anced b) the time the) are diagnosed. These tum out-s can be C) stic or solid. ln young girls below the age of 25, most tumours are germ cell tumours. Conservati'e surgery followed b)' chemotherapy (BE.P) helps to cure these tumours. Sex cord tumout'S have a potemial to secrete hormones which may present with clinical S)'mptoms such as precocious puberty, mensu·ual disturba nces and postmenopausal bleeding. Vi.-ilizing effectS may be observed in masculi nizing tum ours. Bilate t-al tum ot u-s, rapidly growing tum o urs and presence of asci tes are suggesti ve of malignancy and require investi ga ti ons. Tum o ur market-s s uch as C'A- 125 and CEA are particula rly useful in postme nopa usal wo men suspected of having a malignan t. epit.helial cell uuno ur. Markers such as alp ha-fet.opro te ins, LOH and hCG are helpful in making a d iagnosis of germ cell tu mours. Imaging moda li ties such as ultrasonogmp hy, CT scan and MRI he lp to detect ovarian neoplasms, and assist in staging of ovarian cancers. It is important to differentiate between benign and malignant en largemen LS of the oval') to instirute time!) and effecti'e treaunent wit.hout dela). Benign O\'a.-ian tumours are surgicall) dealt with by ovarian qstect.Om). ovariotOm), laparoscopic dissection of the C)St in a )Oung woman and hysterectomy with bilateml remo,oal of adnexa in an older woman.

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SELF-ASSESSMENT I. An l 8-yea1'-0id girl prese ms with a n a bdo minal tLunoLtr

and slight a bdo min al pain. DisctLSS the differential diagnosis and manage men L 2. A 36-)ear-old parous wo man preseniS with ascites and alxlo minal lump. Discuss the diffe rential diagnosis. 3. A 30-yeai'"Oid 110man, pru-a 2, preseniS 11ith menorrhagia of 6 months' dw-ation. An abdominal twnour is palpable abdominally. Discuss the differential diagnosis and managemenL

4. Write sho rt notes o n: • Brenner tumour • Mucino us epithelial wmo ur • Arrhe noblastoma • Theca cell tumo ur

SUGGESTED READING Sengupta S. Chauopadh)il). \'anna. Cp1ac') for Postgraduate and Practidoners. 2nd Ed. El,.,1icr, 2007. Studdj. T he ad nexal mas.. In: Prl>""'" in Obstetrics and C p1aecology 17: 306. 2006.

Ovarian Malignancies

of Ovary

dinicol Features 465

Germ Cell Tumours

Screening for Ovarian Cancer 466

Sex Cord Stromal Tumours 469

Investigations 4 66

Fallopian Tube Cancer 469

Surgical Treatment of Carcinoma Ovary 467

Key Points 470

Chemotherapy for Ovarian Carcinoma 467

Self-Assessment 471

Ovarian cancer is u1e fouru1 most common cancer among women afler breast cancer, cervical cancer and gall b ladder cancer. ln India 45,23 1 ovarian cases occ urred in 2015 and estimated 59,276 cases wi ll occur in 2020. Ovarian cancer is u1e second most common of all geniLal cancers with high case-fatality rate and accounts for 10%-15% of all gynaecological cancers in developing counu·ies including 1ndia. Over the past two decades, u1ere has been an increase in the incidence as well as SUIVival rate amongst women with ovarian cancer. The l'isk of a woman developing cancet· of the O\' 10 mm IIIA2: M icroscopic extrapelvic peritoneal involvement - p ositive retroperitoneal lymph node 1119: Macrosooplc extrapelvic, peritoneal metastasis > 2 em - positive retroperitoneal lymph node, extension to capsule of liver/spleen

Stage IV: Distant Metastasis IVA: Pleural effusion with positive cytology IVB: Hepatic and/ or splenic parenchymal metastasis, metastasis to extra-abdominal organs (inguinal lymph node, lymph node outside abdomen)

Source: FIGO gtidelnes.

CHAPTER 36 - OVARIAN MALIGNANCIES

•

•

•

•

• CA-125 is a glycop ro te in surface antigen raised in 80% epitl1elial wmours, but is no t very specific, as it is also raised in abdomina lwberculosis and endomeu·iosis as well. It is normal in 50% Stage I epithelial carcinoma. Some have observed raised CA-1251evels, 18 montllS to 3 )ears before clinical detection of malignam ovarian tumours. AFP, hCG, B/ 701 (tJu·ee C)cles) after smget) '· SECONDARY DEBULKING SURGERY lf a treated case of carcinoma O\>ary develops recun-ence, she can be managed by a second operation witl1 tll e aim of removing recurrences. However, witJ1 wide spread t-ecur· t·ences treatment with tl1e second-line chemotherapy is usuall y the preferred approach. PROGNOSIS Ovarian cancers are o ne of th e most le tJ1al wmours. In spite of max imum possible surget) ' and che motherapy, a great majority of women ex pe ti e nce recurre nces and may die subsequen tly of disease rec urrences. AltJ1ough rec urrence rates depend on stage of disease at d iagnosis, s urgical proced ure and chemo th erapy, but up LO 80% pa tientS experience recurrences within 3 years. Fo llowing Table 36.3 shows stagewise 5-)'ear surviva l rates.

CHEMOTHERAPY FOR OVARIAN CARCINOMA After initial surgical management almost all cases need 'adju\'lllll chemotllemp) '. On I) patients who can be kept o n follow-up b) avoiding postoperative chemotherapy are the o nes who had Stage Ia disease. Patients who were t-eponed w have 'bot·derline O\'lltian malignanC)•' on histopatllology are also kept on follow-up only without gi,·ing any chemotl1erapy.

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SHAW'S TEXTBOOK OF GYNAECOLOGY

Table 36.3 Staging

FIGO Staging and 5- Year Survival Rate in Carcinoma Ovary 5 year Survival Rate

Stage 1:

90%

Ia:

94% 92%

lb: lc:

Stage II: IIa: lib:

85% 70% 78% 73%

lllc:

39% 59% 52% 39%

Stage IV:

17%

Stage Ill: lila: lllb:

been tested in ovarian ca ncers a nd is being tried in other tumours also (breast cancer). Drug is initially given weekly for 20-21 C)cies, but can be exte nded up to 22 weeks. At present, high cost of u·eaunem with bevaciZLUnab prevents itS routine usage.

FOLLOW-UP OF EPITHEUAL OVARIAN CANCERS Cases of epithelial ovatian cancers u·eated b)' surge•) ' and chemotherapy are seen at regular interval of 3 montl1s for initial 2 >ears and subsequently e' ery 6 month for next 3 >ears for any t-ecun·ences. Clinical examination and serum CA-125 evet)' 3 months help in detection of recurrences. Imaging swdies are catTied out in case of any suspicion of recun·ences.

GERM CELL TUMOURS OF OVARY

In the past, several chemOLhe rapy drugs either give n s ingly or in combination have been ttied with va riable success rates. Current!)' most common!)' used combination of drugs in t11e u·eaunentof epithelial ovarian cancers is Paciit.axei + Carboplatin. These drugs are given intraveno usly every 3 weeks for six cycles. Doses and side effectS of these two dntgs are given below: Paclitaxel: Dose 175 mg/ m2, intravenously over 3 hours. Main side effect: eurotoxicity. Ct•rboplatin: Dose is calculated b) area under curve (AlJC) which is generall) taken as 5--6. However, in suqjectS witll compromised renal function a smaller dose is given. Side effectS: ephrotoxicity, bone marrow suppression.

Ge tm cell tum o uts of the ovar)' comprise 5%-10% of ali ovarian ma lignancies. The)' te nd to a tise from germ cells with the ovary. AILI1ough Llle)' originate from t11e ovat)', tl1 ey differ from epithelial ovarian ca nce rs in many respects. Most often these tum o urs are seen in )'Oung ado lesce nt girls, it is rare to find t11ese twnours afte r t11e age of25 years. Most of these tumours are usually fast growing and highly malignant, )'et witl1 tim e ly diagnosis and appropriate surgical managemem good o utcome can be expected. Current!)' postoperative management of L11ese patjentS witll chemotherapy in the form of BleOm)Cin ELOposide-Cisplatin (B£P) has almost ensured cure for these wmours. Witll effecli\'e and time I) chemotl1erap), most of these young girls can be expected to resume Llleir normal menstrual function and achieve reproducr.he outcome in the fonn of nonnal live birtllS.

OTHER CHEMOTHERAPY REGIMENS

STAGING SYSTEM

l. Paciitaxel 80 mg/ m2 every weekly + Carboplatin eve•·y tlu·ee weekly. 2. Paclitaxel 60 mg/ m2 + Carboplatin AUC-2 given weekly. 3. Docetaxel 6~75 mg/ m2 + Carboplatin AUC 5-6 every tl1 ree weekly.

For staging of germ cell tumours of the ova t) ', same staging system as given by International Federation of Gynaecology and Obstetdcs(FIGO) of ova ri an cancer (20 14) is followed.

DRUGS USED FOR CHEMOTHERAPY

NEWER DRUGS FOR TREATMENT OF EPITHEUAL OVARIAN CANCER In case patient is found to be platinum resistant, fo llowing newer drugs can be used: l. Topotecan 1.5 mg/ m2/ day X 5 days

2. Pegyiated ii posomal doxorubicin (PLD) 50 mg/ m2 orally X 28 days. 3. Gemcitabine 1000 mg/ m2 on clay I , 8 and 15. 4. Nanoparticle albumin bound Paclitaxe1 (Nai>-paciitaxel) 5. ELOposide 50 mg/ m2 orally X 2 1 days 6. Trabectedin 1300 mcg/ m2over 3 hours every tllreeweekly. 7. Bevaci.wmab (Avastin): It is an anti-angioge nic ' Human Monoclonal Antibod) to VGEF (vascular growth endotllelial factor)'. It is not chemotherap)•, but addition of tllis agem to tl1e standard chemotllerapy helps in improving result of chemotherapy. This new approach has

PREOPERATIVE WORK UP In additi o n to co mm o n!)' done investi ga ti o n such as haemogram, c hes t X-ray, imaging of abdo me n by uiu·asound a nd CT / MRI; a pane l of tests including hCG, AFP a nd LDH are cond ucted. T hese in vestiga tions he lp in kn owing t)•pe of germ ceil wmour. R.1ised AFP is noted in yo lk sac tumo urs, raised hCG points towards choriocarcinoma. Raised LOl-l is noted in dysgerm inomas. A combination of tumour markers, when raised, poin tS LOwards t11e possibility of embryo nal care inoma or mixed germ cell tLUtlOUr.

SURGICAL MANAGEMENT Surge•)' is the first line of treatment in most cases of ov:u;an germ cell tumours. Majot·it)' of cases are )Otmg girls, so presenoation of Ll1e utet·us and nonnal O\'llt) ' or O\'llt·ian Lissue is desirable. 'v\l'ith a careful approach and surgical efforts it is

CHAPTER 36 - OVARIAN MALIGNANCIES

always possible to preserve normal-looking ova rian tissue in one or both ovaries.

SURGICAL STEPS Same surgical steps are followed as described for epithelial ovarian cancers. l. Vertical micUine abdominal incision.

469

SURGICAL TREATMENT SLLI'ger)' remains the cornersLOne of u·eaunent. Removal of ovary harbouring tumour will suffice in most cases. However, in case of bilateral tumours or tumours witl1 spread tO other su·uctures an operative procedure on 1!1e lines of epithelial ov;uian cancers is can·ied out in t11e form of tOtal alxlominal hysterectom) witl1 bilater"al salping~ophoreetomy and infracolic omentectomy.

2. Peritoneal washings/ ascites fluid for C)l.ology. 3. Exploration of alxlominal and pelvic organs. 4. Unilateral salping~ophorectomy with preservation of the uterus and normal-looking ovarr 5. Pelvic and para-aortic lymph node sampling. 6. l nfraclitaxel + Carboplatin) and BEP have been used. However, a response to chemoth erapy varies and is not as good as for germ cell tumours. Prognosis: Most patients have ea rl y stage d isease a t diagnosis and have good prognosis. However in tl1 e advanced disease and recurrences prognosis is co mpromised.

FALLOPIAN TUBE CANCER Cancer of the fal lopian tubes is rarest of a ll gen ital tract malignru1cies. More often the fallopian tubes are invo lved by extension of disease from ovaries or uterus. Primary carcinoma ofthe fallopian tube is uncommon and accounLS for only 0.3% of all cancers of t11e female genital l!'act, though metastatic growths from t11e uterus, ovaries and gasu·oimestinal l!'act are common. The tlLmour is bilateral in one-tl1ird of cases \\11en it resembles a pyosalpinx or tuber-cular lesion. The tLUnour is often atl adenocarcinoma tl10ugh chor·iocarcinoma may develop in a tubal ectopic pregnancy or in a wbal mole. The tumour is highly malignamand spr-eads rapidly tO tl1e SLUTOLUlding areas, and via lymphatics to tl1e pelvic or·gans. Ver)' often, Lhe tumour is in the advanced stage when diagnosed and mostly it is diagnosed only on a histological study after tl1e surgery. The distal portion oftJ1e tube is t11e common site of cancer. Staging of fallopian tube carcinoma (FIGO) Stage Description 0 I lA

IB

!C

II

STAGING SYSTEM Asimilarstagingsystem as given for epithelial ovarian cancers is used. In most cases, disease is unilater' multiplii or adequate biofJ~)'· 4. Elderly women should be dealt wil11 by simple vu lvectomy. A lifelong follow-up is required in all cases. Follow-Up

RecLLn·ence around the excised lesio n or fresh recurrence occurs in 20%-30% of cases. Five to ten per cem of cases progJ·ess to invash e cancer in 8 )Cars, after which invasion is less likely, unlike that in ca•·cinoma in situ of the cer,~x which may take 10-15 )Cars to cJe,·elop to ill\• if it is more tJ1a n I em. Restrictin g unnecessa ry lymph node dissection reduces the s urgical morbidiq• in ea rly ca ncer. Howeve•; LO do this, determination of tJ1 e ex tent of primal')' lymp h node (se ntinel) invo lvement is neceSSi\1')'· Lymphatic mapping and sentinel node biopsy (froze n sectio n) before or d urin g surgery help in carrying o uL an adeq uate surgical proced ure will1 good prognosis. Mapping is done by: • An inu-aoperative intradermal u-uectio n of blue dye amund the tumour (Fig. :l7.5); a detection rate of 100% is reported. • Labelling tissues with 1-adioacti'e tmcer and localiat.ion with a handheld detector. • L)mphoscintigraphy has also a 100% detection 1at.e.

CHAPTER 37- VULVAL AND VAGINAL CANCER

477

Rgure 37.5 A picture showing Infiltration of methylene blue dye into the subdermal tissue of the tumour to facilitate sentinel lymph node identification.

Microin vasive vu lval cancer S1.a ge lA is app licable on ly to a single lesion of squamous cell carcinoma up to 2 em in size and less than I mm invasion below the epitl1elium with no evidence of vascular space invasion and lymph nodal involvemenL Adenocarcinoma and melanoma are not included in this group of tumours, because of their high propensit) for nodal involve me m. Microinvasive LUmours can be treated b) local excision with a margin of 2 em beyond tl1e lesion, pro' ided the sun·ounding skin is not dystrophic. Lf it is d) u·ophi c, vulvectOlll)' is recommended because of the possible recurren ce of cancer in the dystrophic tissue. Multiple foci do not come under this classification and n~qui•·e more radical surgery. Treahnent

TI1e traditional u·eau11ent by radical vulvectomy with bilateral lymphadenecLomy of inguinal, femoral and pelvic nodes, as described by Way and Taussig in 1935, has undergone a radical modification in the rece nt )'ea t'S. This is based on the observa· lion of high prim;uy mortali ty of radical surge•)', a high per· centage of nega tive lymph node invo lvemem and satisfactOry 5-)•ear cw·e raLe wiLJl the conservative app roach (Table 37.5). Besides, im,asive ca nce r encountered in )'Oungwomen has also

Table 37.5 FIGO Staging

Results of Treatment and 5-year Survival Rates for Cancer of the Vulva 5-Year Survival Rates

Stage I

90%

Stage 11

80%

Stage Ill

About 50%

Stage IV

About 15%

Total

About 60%

Fig ure 37.6 (A) Radical vulvectomy specimen of carcinoma of the vulva. (B) Post vulvectomy reconstruction.

welcomed this cotlSCrvati'e su•·ge•)', Lhere is a multidisciplinary approach for Lhe treaunent and it should be individualized (Fig. 37.6). The factors to be considered before individualizing tl1e surgical treaunent are the general condition of tl1e woman, stage and site of the tumour, wmour histology and diffe•·entiation. The surget)' is now performed with a separate groin incision rather than extensive skin incision over a wide area which is mutilating and diff1cuiL to heal. Primary mortality of surge•)' is 1%-5%. Stage I. Stage ! A- Ulleral lesions can be dealt with by simple partial vulvectomy with a margin of at least 2 em beyond the growLh, o r unilateral vulvectomy, accompanied by ipsilateral inguinal node dissection . If the frozen sec tion reveals the absence of involvemenL of glands, nothing more is required. This is because, in Lhis case, 1.he conu·alateral lymp h nodes are invo lved in o nly 0.4% and extensive surget)' will not improve survival, but add to morbidity. Ipsi lateral lymph node involveme nt demands contralateral removal of inguinal glands. The pelvic lymph nodes are removed onl) if the gland of Cloquet (femoral) shows malignant cells. Ahe rnativel), a woman is subjected to postoperative radiation. in place of e xtensive peh~c node dissection. A cenu-al tumour requires bilateral inguinal node dissection. Stage 11. Radical/modified radical vulveCLomy and bilat· eral inguinofemoral l)mph node dissection. If tl1ese are

478

SHAW'S TEXTBOOK OF GYNAECOLOGY

positive, pelvic node dissection or postoperative radiotherapy is required to th e pelvic nodes. l fLhe wmour is more than 11 em in size, poorly differentiated or it is a me lanoma or adenocarcinoma, nothing less than radical vuh ectOm) and bilateral lymphadenectOmy with pelvic node dissection are required. A separate vulval incision and two groin incisions are e mplo)ed. Stnge m. Mega,oltage rad iotherapy 4000-5000 rad O\'er a pe•·iod of 5 weeks causes sl11inkage and at times the tOtal disappeamnceofthe tumour. Local excision of the shrunken tumour is then adequate and eliminates the need for exenteration operation. Loca l recurrence can be dealt with b)' chemotherapy. Forty per cent survival and 30% recurrence have been reponed. Stnge IV. It is u·eated by d1emot11erapy or radiot11erapy. Anal involvement is satisfactorily treated wit11 infusion of 5-FU and mitom>•cin·C, followed by radiot11erapy 3000 rad, over 3 weeks. Local excision of residua l tumour may be required. Chemotherap)' avoids exenteration operati on with its assoc iated high mona !it)' and morbid ity. Fifteen per cent 5-year surviva l is reported. Other chemotherapy agents used area as fo llows: • Bleom>•cin 5 mg days 1-5 • Metho u·exate 15 mg da)'S 1-4 • Tmstuzumab 4110 rng days !).7 This regime is administered weekly for 6 weeks.

BARTHOLIN's GLAND TUMOUR Bartholin's gland tumo ur is a rare unilateral tumour, common!) an adenocarcinoma, and carries a poor prognosis. Radical vulvectom> is the treatment of choice. VULVAL SARCOMA Vuhoal sarcoma is a rare tumour which occurs in younger women (Fig. :l7.7). Treatment is local excision. MetaStaSis is common. The p•·ognosis is poor. VULVAL MELANOMA Malignant melanoma accounts for 3%-5% of all vuhoal tumours. lL occurs at all ages, and may develop in a mole or occur de novo. The lesion is pigmented a nd presents as eitller nodular or superficial spreading tumour. The edges of t11e lesion are ofte n irrcgul a •~ and freq uently ulcerate and

bleed. The u·eaunent is managed by vu lvectOmy and bilateral node dissection. Postope rative radiotherapy may be reqLtired Prognosis is poor.

RODENT ULCER This uncommon lesion presents as an ulcer which keeps invading the deeper tissues of the vulva. Biopsy shows basal cell carcinoma. It is locall) malignant and responds well to "~de local excision. PERSISTENT CANCER (RESIDUAL) Persistent cancer is one whi ch develops witl1in 6 months of primary treatm ent. Local excision with \\ide margin is required. SECONDARY GROWTH OF THE VULVA Secondat-y growt11s of the vulva are metaStases from choriocarcinoma, endomeu·ial and ova ri an ca nce r. They are treated by radio therapy or chcmo t11e rapy. Distal metastati c growths arc rare. T hey are treated with radiot11erapy and chemo tlt erap)'· Fifty per cent recurrent growths are seen at the local site within 2 )'Cars of prima•-y trcatmem, and occur witl1 large growt11s and l)•mph node invo lvement. The)' are u·eated by exenteration operation, radiotherapy and chemo therapy. Rewmmt growth.!>. Rec urre nt growtlts occ ur in 30% of cases within 2 years. Local rec urrence is seen in 75% cases. Lymph node and distal metastasis are rare. If the growth is small, local excision with a wide margin over 2 em is adequate; otlterwise, radiotherap) or chemotherapy is employed as palliative treaunen L Exenteration operation with removal of bladder/ rectum with vulvectom> is ve11 rare I) perfo rmed t11ese days. PROGNOSTIC FACTORS Prognostic fuctOI'S are tlte sit.e of t11e tumOLII~ grading, histOlogy, lymph node im·ohrement and immune status of the woman. Groin node status is the best prognostic predictOr. When the lymph nodes are not involved, 5-year swvival is 90%. Lymph node involvement diminishes tlte survi,oal rate proportionate to t11e number of lymph nodes involved. VULVAL CANCER IN YOUNG WOMEN Vulval imraepithelial neoplasia is mostly encoumered in young women. Using barrier co ntraceptives and maintaining h)•giene can reduce the transm ission of HPV infection which normally ca uses VIN. 8\ dy d iagnosis and conservative therapy can cm e th e d isease, avoid mutil atin g surgery and improve the survival rate. II PV vaccine can prevent malignanC)' in tJ1ese cases in future.

VAGINAL CANCER

Figure 37.7 Sa-coma of the vulva.

Primary vaginal cancer is a rare cancer acco tmting for less than 0.2% of all cancers in women. It occurs in elderly women often older tJ1an 70 >ears when sexual acaivity has genemlly ceased. Unfonunatel), onl) about o ne-t11ird of the patientS have regional disease at the time of diagnosis; t11erefore, late diagnosis is not un common (Fig. 37.8). An LLilusual tumour clear cell adenocarcinoma was seen in )Oung women who were themselves exposed to diet11) lstilboesu'OI (DES) in utero.

CHAPTER 37 - VULVAL AND VAGINAL CANCER

479

Table 37.6 Vaginal Cancer Staging Stage 0

Rgure 37.8 Carcinoma of t he upper-third of the vagina removed by extended hysterocolpectomy.

Vaglnallntraepithelial neoplasia (VAIN)

Stage I

Carcinoma limited to the vaginal wall

Stage II

Carcinoma extending beyond the vagina, but not extending to the pelvic side walls

Stage Ill

Carcinoma extends up to the pelvic walls

Stage NA

Carcinoma extending beyond the true peMs/or involving the bladder and/or rectum, or evidence of distal metastasis

Stage NB

Spread to the distal metastasis

exposed to DES in utero, whe n the upper o ne-third vagina is involved, following trophi c ulcer'S in women wit11 procidentia, foll owing prolonged and neglected use of ring pessar) ' fo r prolapse or as spread fro m othe r pelvic o rgans. VinJs infectio n may be a causati ve facLOc lL may also d evelop >•ea rs later foll owing rad ia tio n for cancer of th e cervix. T he lesion is sq ua mous cell carc inoma in 90% cases, rare l)• adenocarc inoma a rising from vagina l adenosis in )'Oung girls. The wmour in th e u pper vagin a drains in to pelvic lymph nodes and that in the lower part drains in to inguinal lymp h nodes (Fig. :l7.5 ). Vaginal intraepithelial neoplasia (VAJN) is rare, and always progresses to invasive cancer.

STAGING Refer to Table :l7.6.

Rgure 37.9 Carcinoma in a case of prolapse. (Source: From: Sengl.4)ta et al. Gynaecology br Postgraduates and Practitioners, 2rd ed. Elsevier, 2007.)

H owever, such cases arc fast disappearing with withdrawal of the drug. C'..ancer of th e ce rvix , bladder and urethra, vulva and lower bowel may spread LO involve the vagina. MetaStaSes from ca nccr ofLhe ute rus, ova ry a nd trophoblasti c tum o ut'S have bee n known LO occ ur in the vagin a. Cancer over a d ec ubitus ulce r in pro lapse is a lso known to occ ur (Fi g. 37.9).

CLINICAL FEATURES Vaginal cancer is generally asymptOmatic in itS earlier stages. The usual complaints are the presence of watery discharge, or postcoital bleeding; the lesions may be diffuse, raised velvety patches bleeding on touch, a whitish pateh or ulcer: Cytology/ Schiller's iodine test/colposcopy and biopsy help settle t11e diagnosis. The lesions are often multifocal and in the upperthird of the posterior wall. The extent of spread may be determined b) combined vaginal and rectal examination. Diffuse spread ma)rimolve the w·ethra and bladderamer·iorlyand t11e large bowel posteriorly when urinary and bowel spnpwms may occur. Cancers may a rise de novo in )Ounger women

DIAGNOSIS Suspicious areas of plaque/ white patch should be su~ected to Schiller's test and colposcopic biopsy. All gross lesions such as nodule, papule, ulcer or mole should be biopsied. Local application of oestrogen in old women enhances a colposcopic view. Colposcopy is d ifficult on account of a large vaginal area, multiple lesio ns and vaginal folds.

MANAGEMENT PRETREATMENT WORK-UP Compl e te histOr)' and exa m ination, WBC, urina l)•Sis, blood s ugar es tim a ti on, li ver function tes t (LIT), renal function test (RFT), chest radiograp h y, t::CG, cystoscop)\ p roc toscopy and bari um ene ma may be req uired. CT and MRI are done for a nodal study.

TREATMENT VAIN. It is treated with loca l e xc is ion biopsy, COt laser and local application of 5-fluorouracil cream. Electrocautery ru1d c r1 otherap) are best avoided. Invasive cancer is u·eated wit11 local radiotherap), Wertheim hysterecwmy with total colpectOm), or exenteration operation for the advanced cases irwoh'ing bladder/ bowel. O verall sun~val is 30%-10%. Creation of neovagina is required in young women.

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SHAW'S TEXTBOOK OF GYNAECOLOOY

Pmp!tylaxi~. Treati ng a decubitus ulcer and proper care of a ring pessary in a prolapse can avoid cancer of vagina. SarromEt. Sarcoma botr")Oides is a rare tumour seen in children. This tumour arises in l11e mesenchymal tissues of tl1e vagina and in rare cases, in the cervix before the age of 2 )Cars. It presents as a haemon-hagic grape-like po lyp o r as a flesh)' mass and consists of rhalxlom)oblasts with vacuolated C)'LOplasm, myxoedema a nd su·oma with fusifonn cells. The tumour spreads b) local infihratio n. lymphatics and bloodstream. £xami1Uttio11 is done under anaesthesia; biopsy confirms tl1e diagnosis. CT and M R1 indicate its spread. Trt!(t/mmt. C he mothe rapy wil11 VAC (vincristine, adriamycin and cyclop hosp ham ides) is the gold standard in treating tlus u.unour. Othe r drugs used are cisplatin, actinom>•cin, cyclop hosp ha mide and ifosfa mide. St.u·ge•")' is li mited to l11e local resid ual twno ur. Interstitial rad iati on is used in the advanced stage.

KEY POINTS • Prein vasive ca ncer of vulva (V LN) is caused b)' human papilloma virus in )'Oung women. • VIN is usua ll y a multifocal lesion in young women, but a single lesion in older women. • In )Oung wom en , 90% reg•·ess, 10% progress to invasive cancer within 8 )Cars. Careful follow-up is recommended. • VI in older women invariably progresses to imasive cancer and should be treated b) \uhectom>'·

• The conservative surget")' ablative as well as local wide excision is adequate in )Oung women. Simple vulvectOmy should be performed in elder!)' women. Follow-up is necessa•")'· • Radical \llhe cLOmy is required if tl1e regional lymph nodes are imo hed. • Prognosis depe nds o n the l) mph node in,olvemem which in tum depends upo n the site. sue and depili of ll1e lesio n. • Vaginal cance r is rare a nd difficult to diagnose in its early stage. • Radical surger) is usuall) required. Radiotherapy is palliative in the advanced stages.

SELF-ASSESSMENT I. A 55-year o ld woman prese nts wi th a vulva l ulcer. Disc uss the diffe renti al d iagnosis and manage men L 2. Disc uss the manageme nt ofv1 Jva l cancer Stage l. 3. Disc uss the manageme nt ofv1 Jva l cancer Stage U.

SUGGESTED READING BonnarJ (ed). Recem Ath-.-lllCt.c trics. GynaecoiOj,')' and Women's llealth 1989; 417:7, 2010. jonathan S (ed). Cplee> in 10 •m~-cological oncology: I n: AB ~ladeao, et al. Progress in Ob>tcLric> and C rnaccology Vol 12: 403, 1996.

Gestational Trophoblastic Diseases

Hydatidiform Mole .48 1 Invasive Mole .483 Placental Sile Trophoblastic Tvmovr .483 Persistent Trophoblostic Disease .488 Treatment of Persistent Trophoblastic Disease .488 Perforating Mole (Chorioongiomo Destrvens) .488

Recurrent Molar Pregnancy .488 Coexis6ng Molar Pregnancy .488 Choriocorcinomo .489 Key Points .493 Self-Assessment .493

Gestational u·ophohlastic diseases (GTDs) comp tise a variety of biologically interrelated conditions wh id1 form a clinical spectrum from a benign partial hydatidifonn mole at t11e one end to the highly malignant choriocarcinoma at t11e other witJ10ut an) precise line of demarcation. This specu·um extends from a very early pregnancy (hydatidifotm mole) to )Cars afte r t11 e pregnancy is over (choriocarcinoma). Trophoblastic tumours ma> be categoriLed imo tJuee broad gro ups ("Iahle :38. 1): I. Hydatidiform Mole: It may be a complete or a partial

mol e. The tumour sometimes invades the wall of the uterus and the surrounding su·uctures, when it is called an invasive mole (chorioadenoma destruens). 2. Persistent trophoblastic disease (P1D), also kn own as residual u·ophoblastic disease (RTD), incl udes the invasive mole. 3. Ch oriocarcinoma: T his is U"ttl y a malignant tum our. It co ul d be a nonm eL iv over/2hr

Day 2

Etopocide 100mg/m2 iv infusion over 30 min Actinomycin - D 5001Jg/iv stat Folinic A cid 15mg im x 4 does every 12 hr

Day 8

Vincristine (On covin) 10mg lv stat Cyclophospham ide 600mg lv Infusion In saline

*Next course repeated after 2-3 wks.

the resui ts ru·e good a nd rad io th e rapy causes exte nsive fibrosis. MetJ1ou-exate 12.5 mg can be i ~ected inu·a rhecally at every 2-4 weeks' interval until hCG level becomes negative. Newer d rugssuc h as Taxol, t)'J)Otecan and ge mcitabine (a ntimetabolite) have been used in resistant cases. Gemcitabine I250 mg/ m 2 o n da)S l-8 wiLh cisplatin is effective. Rarel)'• leukaemia has been reponed with tJ1e use of Etoposide se,•e t-al ) ears late.-.

SURGERY Surgery is mrely indicated in the managemem of chotiocarcinoma. H)Stet-ectomy is indicated in tJ1e following conditions: • • • • •

High-tisk cases older th an 40 rears, multiparous Chemothempy ineffective/chemotJl et-apy •-esistance Haemorrhage beca use of ute rin e perforation Large-sized growtJ1 in the ute rus Whe n placenta l site u·op hoblasti c disea~e does not respond to chemo tJ1e rap)' and hysterec to my is the only solutio n

Hysterecto m)' is us uall y fo llowed b)' chemothe rapy. T here is no need to re move th e ova ries as ova rian metastas is is rare and can be effec tive ly trea ted by chemotherapy. Hysterectomy reduces th e number of chemoth erapy cow·ses. Role of radiotllempy is limited to only ac ute bleeding from vaginal metast."l.Sis, brain and live r metastasis. The postradiotJlerapy fibrosis is tJ1e disad,oantage. A solitaJ') lung metastasis can be dealt witJ1 by tl10racotomy a11d lobectom). CraniotOm) is t-arely resorted to in a solitary brain wmour. The role of high dose chemotJlet-ap)' wiLh autologous bone marrow u-ansplant is being explored.

CHAPTER 38 - GESTATIONAL TROPHOBLASTIC DISEASES

Table 38.8 Management of Metastasis Vagina

Vaginal pack for bleeding, avoid excision, chemotherapy

Lungs

Chemotherapy, Lobectomy if the growth is localized or resistant to chemotherapy

Liver

Chemotherapy, Radiation

Brain

Chemotherapy Intrathecal chemotherapy Surgery Radiation

CEREBRAL METASTASIS (Tobie 38.8) A focal lesion detected b)' CT/MIU can be excised to prevenL haemorrhage in tJ1e wmour and dea tJ1. A large lesion is trea ted with rad iation given in a dose of 30 Gy in 10 fracti ons 5 clays a week for 2 wee ks along with EMA/ CO and th is yields 80% response. Liver metastasis sho uld rece ive wholeorgan rad iation over 10 days in a dose of20 Gy. Lobectomy is required in a chemotJ1erapy-resismnt case. FOLLOW-UP OF A CASE OF CHORIOCARCINOMA Serum 1)-hCG is done every week till it becomes negative. Once negative it is •·epeated eve•]' 2 weekly for 3 momh, tJ1ereafter every month for one year and t11en 6 montl1ly for •-est of life. PROGNOSIS Overall cure rates in recem years have been excellem witl1 chemot11erapy alone, and surge•] ' is undertaken only in selective cases described earlier. With chemotllerapy, 100% success has been claimed in low-•·isk group (J Lewis, 1980) and 90% success in high-risk group. A successful pregnancy has followed treatment with chemo t11erapy. However, it is ad,~sable for the patiem not to conceive for 2 years after the drug u·eaune nt is ove•~ The lifelong follow-up ofthe woman, however, should be e nco uraged.

• Serum hCG level is tJ1e key marker in follow-up. • Histology is not able to indicate tl1e potential of molar pregnancy for dC\elopment of malignancy. Therefo1-e, follo\\•up witJ1 sen.un 13-hCG is necessa•]' for 2 years. The•-eafter, tJ1e •·isk of malignancy is negligible. • Persistent trophoblastic disease and cho1iocarcinoma are treated effecti,el) b) chemothempy. Surge•]' is rare!) required. • Choriocarcinoma and metastatic growtllS dC\•eloping se' era! >ears after pregnane> render t11e diagnosis difficult • Placental site trophoblastic disease wit11 low hCG but raised H PL Ie,el fails to respond to chemot11erapy and req uires hysterectOm). • Following molar pregnanC)', tl1e woman needs co unselli ng regarding recurrent mo le and choriocarcinoma, and should be cow1selled for follow-up. • Prognosis has greatly improved beca use of specific hCG ma rke r and effec ti ve chemo tl1erapy. • Cho rioca rcino ma is unco mm on, but highly malignant. • Chori oca rcino ma may follow a molar pregnancy, aborti on, te nn pregnancy and ec topic pregnancy. • Fifty per cen t cases of choriocarcinoma occ ur following molar p regnancy and occur within 2 years. • T he long interval of yea1-s between pregnancy and cho•·iocarcinoma makes tl1e diagnosis difficulL • P1ima•]' treaunent of d10docarcinoma is chemotllerapy and is effective in 90%-100% of cases. Surgery is reserved for selecti' e cases. • P•-egnancy is possible following treaunem with chemotherapy. Howe,er, conception should be dela)ed for 2 >ears to a'oid te•-atogenic effect on me fetus.

SElf-ASSESSMENT I. A 25-year-old woman presents with 3 montllS' amenor-

2.

KEY POINTS • Trop hoblastic d iseases comprise a spectn.1m of clinical cond itions va•]•ing from hydati d iform mo le, in vasive mole and choriocarcinoma. • Hydatid ifonn mole is more prevalen t in Sout11east Asia, d iagnosed cli nicall y and confirmed by ulu·asound scan and •-aisel.ic dbca> naecological malignancies. ItS specific curative role has been established b~ a nd doubt in the ma nagement of cervical cancer, the most commonly seen g) naecological cancer in clinical practice. Radiation treaunent may also be curative for locali.wd endometri al cancer and when surgery is not possible. It improves prognosis if used as adjuvant postoperative therapy in adva nced cervi cal and endometl"ial cancer. The scope ohadiation the•-apy has been enhanced in tlte man agement of cancers of the vulva and vagina. ln selected cases of ca ncer of tJt e ova ry, postoperative adjuvant radiotherapy may be benefi cial in conu·olli ng t11e disease. In many cases, a judicio us co mbination of rad iotherapy and cancer chemo tJte rap)' has co ntributed sign ificantly in im proving tlt e patie nt's prognosis and surviva l period. Cell dea tl1 in term s of rad ia ti o n bio iOg)' is defined as the loss of clonogenic ca pac ity or 'cell rep rod uctive potential'. Ion izing radiation produces free rad icals wh ich d isrupt the reproductive integrity o f DNA-prod ucing cells and thus conu·ol cell division and neoplastic growth. Rad iation affects bo tl1 normal cells a nd LUmo ur cells. However, the dividing mitotic cells are most vulne rable. Hence, by grading tJ1e dose of irrad iatio n, a differential effec t can be attained by forcing tl1 e cancer cells to differentiate and UlLLS lose !Jle ir malignant potential, stimulating angioblastS and fibroblastS to grow into tJ1e LUmour cell mass, dividing tl1em into smaller nests of neoplastic cells and, finally as tl1e connective tissue fibroblasts consu·ict, cutting off !Jle tumour cell blood supply causing tumour necrosis. Anaplastic tumours !Jlerefore respond beuer compared tO well-' that is transferred from the radiation so urce to tl1e target tissue being irradiated. The tlt erape u tic activ it) of rad iatio n is mainly related LO the process of ioniation. The re are two fonns of ph(}tons (quanta of rad iation whose e nergy is proportional tO their fi·equenq a nd imersely proponional to their wavelength). One fonn of ioni.t:ing 1-adiation is e lectromagn etic, which refers to X-l'li)'S. These sources of energy have no mass and no electdcal charge. They are produced in discrete quanta or photons. A second source of photon radiation comes from the production of gamma l'li)'S (similar to X-l'li)'S) which 1·esult from the decay of 1-adioactive isotOpes. Electromagneti c •·adi ati on witJ1 shorter wavelengtllS has a higher frequency, he nce hi gher ene rgy. The energy produced is measured in electron voltS (eV); I eV = 1.6 X 10- 12 e rg. T he X-ray radiothc rap)' units ca n range from 50,000 eV (50 kV ) to ove r 30 mi llio n eV. Photon radi ati on is measured in curies (Ci). One curie is de fined as 3.7 X 10 10 d isintegrati ons/seco nd, wh ich is eq uiva len t to tl1e disintegration of I g of rad iu m. Irrespective of the source of elec u·omagnetic o r photon radiation, tl1e tran smitted e ne rgy dive rges from the source of origin and diminishes inversely as the sq uare of the distance u·ave rsed (I I d·) . X-rays and photons can be generated a5 a result of rapidly accelerated elec u·ons in vacuum sui lUng a target. Modem generators tl1at accelerate tJ1ese e lectrons LO a high speed mtl)' do so in a circular fashion (betatrOn) or linearly (linear acceleratOr). Another t)pe of rad iatio n energ>, known as particulate .-adiation, is produced b) subatomic particles ha,~ng a discrete mass. These panicles a 1·e de1·ived as a result of disintegration of 1-adionuclides. Four differelllL) pes, name ly alpha particles, neutrons, protOilS and elecU'OilS, are produced.

CHAPTER 39- RADIATION THERAPY, CHEMOTHERAPY AND PALLIATIVE CARE FOR GYNAECOLOGICAL CANCERS Neutro11~ are high ly penetrative and have no d1arge b ut have a large mass. They cause high-energy collisions witl1 atomic nuclei, principall) hydroge n in the tissues. The resultant recoil proton loses e nergy to the surrounding tissue by ionization. causing cell death. Plwwm are posithel) charged panicles and can be produced directl) b) ge nerators. The high-energy beams produced are used for special applications such as the u·eaunem of pituitary tumours. Alplw particles (helium nucleus) have very liule penetrating po\\er and therefore are not of much practical use. Electrons, also referTed to as beta rays, can be produced at different energies b)' machines for v:u·ious therapeutic uses.

495

Fractionation of radiation treaunent pennits effective treatment of tl1e tumour, and minimizes complications which could result from exposure of nonnal tissues (bone marrow. nonnal intestine) to a single large dose. The more effective repair of normal tissue occ urrin g between treatment fractio11S allows recovef) of no rmal cells which is a therapeutic advamage. The clinician must be familiar with the unit of measureme m of amoum of enerm•absorbed b)' the tissue, called t11e rad. Rad is defined as 100 ergs of enerm•absorbed per gram of tissue. Lately the term gra-)' ( I j / kg) has been introduced. One gray (Gy) is equivalent to 100 rad. Summary

RADIATION BIOLOGY Photons (gamma rays or X-rays) act by dislodging orbital electrons of th e tissue through whi ch they pass. Th is colli· sion prod uces a fast elecu·on (Comp to n effec t) which th en io ni zes mo lec ul es along its path prod uci ng secondary elecu·ons and free hyclr'OX)'I (011 ) rad icab. T his p rocess co ntinues until the p ho ton loses all of its e ne rgy. Abo ut SO% of the cell contains wate r; so cell ul ar rad iation damage is mediated b)' the ionization of water and prod uction of free rad icals, h)•drogen (H ) and h)•drox ide (01-1 ). The free 0 1-1 radical causes DNA cell damage. The effect may be lethal and ki ll the cell or it may be subletl1al, in whid1 case tl1e cellular DNA may undergo repair and the cell recovers. The free molecular 01 1 radicals react with molecular oxygen to fonn peroxides, which in tum ftu·ther damage t11e tissues. OxylJim i~ theTfjOTf imJXJrUmtto mlumce plwton effects. Large tLUnours witl1 poor blood suppl) have poor photon effect in h)poxic areas and are radioresistant R£uliation in the frTl!SimCil of (IIWemia, infoctum am/ 5amulti!JIU' produas poor rmths. The Idle of loss of enermr of an ioniLing particle as it traverses a unitlengtJ1 of medium is known as linear energy transfer (LET). In case of photons, energy tl'allSfer from an X-ray or electromagnetic source, the LET is low; hence, multiple tissue bom bardments are required lO achieve alethal dose. In case of particulate irradiation with large pru·ticles (neutrons), t11 e ionit. ation achieved is high, leading to high LET, more intense ionilation and production of more tOxic hydroxyl radi cals, achi eving greater lethal tissue effect independent of tissue oxygenation. Successful racl iothe r"iip)' req uires a good balance between t11e dosage to the wmo ur and to that of t11 e surroundin g su·ucLU re (radiati on to lera nce) so that least damage is in· flic ted to tl1e no rma l tissues, whi le max imal radioeffect reac hes the twno ur cells. The a im is to de live r a high dose to the u unour and minimal dose to t11e no nnal tissues. Radiosensitizers, cisplatin and &-n uorourac il, en hance the letJ1al effect of radiation when given concomitantly. This combirwtion i~ wiled chemoradiation. An important principle to re member is that a given dose of radiation kills a co rlStant fraction of tumotu· cells; hence, each repetitive sitting ac hieves a similar reduction of rumotu· cell activit). There are four phases of a cell cycle: resting phase, RNA and protein S)lllhesis, D A S) nth esis and cell di,~sion or mitosis. Rapidl) clh·iding cells are the most radiose11Sitive. This explai rlS the higher respo•lSC of anaplastic tumours compared to a well-differentiated one.

Radiation biology pr·oduces the following effectS: • Radiation (photons or gamma rays) is u-ansferTed from t11e rad iation source to the tissues undergoing in·adiation. T he process of ionization occurs (Compton effec t) along the patJ1 of radiati on. T he free racl icab liberated produce tissue damage. Mitoti c cells are ki lled (le tJ1al effec t) or tmdergo differen ti ati on (rendered non lethal). Pr-oliferation of angioblasts and fibrob lasts breaks up the mass imo smaller islands of tissue tumow·s. Finall)', the fib r-oblastsconsuictand cause nea·osis o f tissue by way of dec reasing vasc ularity. • The effect of traJ1Stnitted energy, ir1·espective of t11e source of irradiation as it diverges fi-o m t11e source of origin, rapid I)' diminishes inverse!> as t11e square of the distance travelled • Success of radiotJ1erap) requires a good balance of dosage between tl1e tumour tissue and 1J1e healthy surrounding tissue.

RADIATION SOURCES: EXTERNAL AND INTERNAL THERAPY ln general, two techniques are utiliLCaginal radiation via colpostat, vaginal vault recurrence drops to 2% from the previous 13%. • The survival improves in Stages IC and ll when postOperative radiotl1e1-ap) is administered to sterilize the pelvic lymph nodes. Radiation is indicated in uterine sarcoma, altho ugh outcome is poor. • lt is used to treat patienLS who are unfit for surgery. • lL helps to treat palienLS with vaginal / pelvic recun·ences. • lt is performed for palliation in cases of nonresectable intrapelvic or metastatic disease.

OVARIAN CANCER The primary ll'eaunent for O\>arian cancer is C)•LOreductive surgery( total abdominal h}sterectomy, removal ofbotl1 O\>aiies and omemectomy). In advanced cases, maximal debulking surgery is followed by chemotherapy in epithelial llllllOtli'S, and most of tl1e otJ1er maligna nt ova ria n tumours. In few selected cases radiation tJ1erap)' in tJ1e fo nn of ' Moving Suip' technique is applied to para-aortic lymph nodes and abdominal metastasis. Dysgerminoma and gra nulosa cell tlUl1ow·s, altl10ugh hi ghl y racUosensiti ve are not being routinel)' used as advances in chemotherapy has resulted in chemo tl1erapy being tl1e first line of u-eaunent for these u.uno urs. ln the 'moving-suip' technique, a su·ip of2.5 em area is irradiated front and back over 2 days, and tJ1e su·ip moved upwards, w1til tl1e entire abdomen receives radiation. Witl1 the liver and kidneys shielded, tJ1e tota l tumour close of 26002800 cGy is administe1-ed. CT and MRI are useful in detecting para-aortic lymph node involvement p1ior to racliotl1erapy. The earlier instillation of radioactive gold, tl1iotepa and otller chemotherap) drugs at the end of surgery is not widely used. because the drug needs to be even ly disu·ibuted tO avoid imestinal adhesions. Besides, C)clophosphamide needs to be acti,>ated in the liver before iLS effect is felL Therefore, S)'Stemic chemotherapy is more effective. Five )Cars survh>al mtes in ovarian cancer depend on a nwnber of factors including residual wmow; grade of disease and use of effective chemotJ1erapy in the fonn of paclitaxel.Carboplatin.

VULVAR CANCER T he aim of integra ted multimodali ty the rapy including surgery, rad iation a nd possibl)' chemo radiation tl1 erapy is to reduce the risks of loco regio na l fai lure in patientS with adva nced primary o r nodal d isease, and to obvia te the need for exenterati on opera lions in women in whom tl1e a nus or lower ure thra wi ll be involved. The dose of rad iation given is 4500-5000 cGy to women with microscopic disease and 6000-6400 cGy to women witJ1 macroscop ic d isease. Preoperative radium needles (60 Gy in 6 days) shrink me tumour and facilitate extirpation oflhe tumo tu· at a later elate. Postoperative pelvic 1-adiotherapy is preferred to pelvic l)"llphaclenectomy as it reduces the surgical morbidit)'· Pelvic radiotJ1erap) is administered only if tJ1e inguinal lymph nodes prove histologicall) positive.

VAGINA Radiotherapy is often chosen in place of 1-adical surgery, especially in children. If the tumour is locatecl in tl1e upper

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SHAW'S TEXTBOOK OF GYNAECOLOGY

one-third of vagina, radiotherapy is similar to that of the cervix. Lf it is locaLed in the middle one-third, interstitial needles (iridium-192) are placed in the vaginal tissue.

r

TUMOUR CELL KINETICS A fundamental characteristic of malignant tumo urs is the rapid proliferation of malignant cells. These rapidly proliferating cells keep repeaLing a cycle of biochemical eventS continuous!) which culminate in cell division (Fig. 39.5). Each proliferative cell gives rise to two daughter cells that continue the proliferative process, so the cell population increases geomeu·icall). A tumour is described as consisting of four t) pes of cells (Figs 39.5 and :l9.6). Dividing tumour ctliJ: This is the only compartment that adds to me cell population. Cells in this compan.ment are most sensitive to cytotoxic agentS. Rellingcells: These are nondividing cells resting tempor:uily (cells in Go phase). They are •-efractOI)' to chemotherapeutic agents. Differeutiated celiJ: T hese cells have lost tl1eir dividing potemial and are awaiting natural deatJ1. T hey do not h ave malignant potential, so they are of little co ncern to the chemo tl1erapist. Dying cell~: T hese arc tc m1ina l cells. Sma ll rap id ly growing w mours have many mo re rapid!)' dividi ng and grow ing cells; he nce, th e do ub ling time is short. However, these arc the same LU mo urs which have a

Postsynthetlc gap

DNA synthetic period Go (Resting cells or out of cell cycle) Presynthetic gap Figure 39.5 Scheme representing cell cycle: G1 ..... S ..... G2 ..... M phase.

Insensitive to cycle-dependent agents

~

Choriocarcinoma responds exu·emely well to chemotherapy which has replaced surge•) and radiotherapy in yow1g women. Radiotherapy is applicable in the distal metastasis in a few cases.

The use of drugs to u·eatdisseminated cancer has developed imo a speciali:ted discipline. The first successful effort LO control cancer wi th the help of d rugs is atuibuted tO Mm Chiu Li et al. ( 1956), who demonstra ted pe rma ne nt remission in trop hoblasti c disease. T he understa nd ing of the mode of action of th e drugs at DNA level has brought out newer effective drugs witl1 less LOxic it)' and has imp roved and p rolonged tl1e survival of women with gen ita l cancers.

~

Sensitive to cycledependent agents

CHORIOCARCINOMA

CANCER CHEMOTHERAPY FOR GYNAECOLOGICAL CANCERS

Chemotherapy response

->

Figure 39.6

I

~

Of no concern to chemotherapy

c~

Resting (G0 phase)

D Cell types constituting tumour mass.

high number of cells sensitive LO cell cycle-specific cytotoxic drugs. As tl1e w mour mass enlarges, the growth rate progressive ly s lows down, do ub ling tim e beco mes lo nge r a nd the cell inp ut may eq ual loss; hence, a statio na ry size may be reac hed, and tJ1e se ns itiv ity LO cell-specific drugs dimi n ishes. Another factor to be considered d uring cance r chemotherap)' is me wmo ur load present at tJ1e commencement of therapy. Reduction in tJ1e b urden of tumour cell load wi ll bring an apparent remission, but d uring the interva l between successive courses of cancer chemotherapy, the tLUUOLU' growth recurs. This results in stepwise decrease in tLUUOLLr cell mass. To attain maximlUn tumour cell kill, tl1e following principles must be considered: • The chemotl1erapist must be well aware of the 'total tumour cell kill concept'. • Tumour cell kill by C)lOtoxic drugs follows tl1e paLLern demonstrated by Skipper H ~ and Perry S (1970) tl1at the killing of tumour cells by cytotoxic agents occurs in an exponential fashion, so mat a given close kills a constam fraction oftl1e population, i•Tespective of its initial size. • There is a clear close-1-esponse relationship. • Prolonged u·eaU11ent may be necessary to reduce the malignant cell population to a low numbe•· which will tl1en be dealt with by tl1e host immune mec hanism. • Che motherapy is most effective whe n it is Sta rted ea rly beca use tl1e number of wm our cell pop ulati o n is low and the rap idly growing and d ivid ing cells are se nsitive to ca ncer che motherap)'· • Chemotherap)' must a im at d ifferen t cell kill. T he close must be so aclj usted tJ1at max imum desu·uction of tumo ur cell is achieved with minima l damage to norma l cells. • Many cytotoxic dmgs in present use show some degree of tissue selectivity. • Combination drug regimens and/ or sequemial drug regimens achieve superior tumour cell conU'ol with lowered side effects. Drugs with different actions yield better response and reduce drug resistance. • The problem of drug resistance must be constantly bome in mind. This often happens with a single-drug therapy. Drug resistance ma> be temporal)' because of poor vascularity not allowing ch-ugs to •·each me tumour cells caused by fibrosis or bulky tumour, or pennanem when it is eimer spontaneous or drug-induced mutation.

CHAPTER 39- RADIATION THERAPY, CHEMOTHERAPY AND PALLIATIVE CARE FOR GYNAECOLOGICAL CANCERS

Chemotherapy has advanced tremendously in recent years, and is being increasingly used in the management of gynaecological malignancies. The drugs by virtue of prolongation of life and prolonged remission period allow a woman to li'e a near!) normal life.

CHEMORADIATION It is now recogniJ.ed that some chemotherapy chugs act also as mdiosensitiJ.enl and lead to superadded cell kiU prior to or preferably along with radiotherapy and p•·ior LO surgery. They are thus used as 'neoadju,oanLS' in a bulky tumow· and locally achoanced cancer in the pelvis. The most common drug used for this purpose is cisplatin either singly or as in combination. Cisplatin 40 mg2 weekly is given 1 h our before radiothempy. The renal functions should be normal before instituting this regi me. Other chemoradiation drugs in use are 5-FU, gemcitabine and cisplatin combined with gemcitabine 40 mff in 200 mL saline 2 hours before radiation- it takes 1 hour to admin ister. Postrtuiif!litm clumwtherapy is 1Wt e.ffoctive rmd fJoor resfxmse o•cin-D, b leo m>•cin, Adriamyc in, mitomyc in (nonspec ific) and doxorubicin. T hese inhibit RNA and DNA S)•nthesis and hence a rrest mitosis. Plant alkaloid:.: These inc lude vino·istine, vinb lastine, Taxol, docetaxel and etoposide (cell specific) -antimitotic. Homwne~:Th ese include high close preparations in endometrial cancer and Tamoxifene in treated cases of carcinoma breast. Mi~celltmeou~: These include cisplatin, carboplatin, hydroxyurea and topotecan. Biologiatl: IF improves host immune defence and maintains remission.

NEWER ANTICANCER DRUGS The development of new chemotherapy drugs has improved the disease-free ime1"\oal and prolongs sunri,oal. They are as follows: l. Vascular targeting agentS (VII\)

a. Angiogenesis inhibito•-s b. VEGF ligand bevacizumab (Avasti n , GeneTech) c. Receptor ta1·geting Vl!:GF Recep tor tyrosine kinase inhi bitor, cedirani b, nintedanib and anti -Vl!:GF a ntibody T he form er primaril )' prevent deve lopment of new vessels in tl1e uun ou1: The latter damage the established vessels in tl1e tumo ur with cediran ib 30 mg daily orall)'; 30% benefit is repon ed in recurrem epithelial ovarian wmo w·s and fallopian tube cance.: Complication includes hypertension. Bowe l perforation is seen in intraperitoneal tumours involving tl1e bowel. Vascular disrupting agents (VDA) fosbretabulin, olaparib (oral I00-600 mg daily). 2. Farletuzumab- a monoclonal antibody against ovarian cancer. 3. ovel C) totoxic agents (a) Trabectedin (b) Epotl1ilone analogues (c) Topoisomerase I inhibitors (d) Pemetrexed (e) Aurora kinase inhibito•-s

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SHAW'S TEXTBOOK OF GYNAECOLOGY

VULVA 5-FU is effective in cancer involving the anus. It shrinks the tt.tmour which may even disappear. Local excision of the residual tumour is then successful. VAGINA The metastasis of choriocarcinoma responds to methotrexate and aCLinOm)Cin-0. CERVIX The use of cisplatin concomitant with radiotherapy and prior to surgery in endocervical growth is mentioned in Chapter 33. It also •·educes the incidence of lymph node metastasis in bulky cervical tumour in Stages IB and llB and improves the smgical outcome, ahJ1ough the survival rate has not shown improvement. The drugs most effective are as follows: • Doxon.tb icin 120 mg/m2 + cispla tin 50 mg/m2 i.v. over 24 ho urs weekl y for six C)•Cies (th ree cycles as radiosensiti zers) • PVB: • Cisplati n 100 mg/m 2 i.v. o n day I • Vinblas ti ne 6-12 mg/ m2 bolus on da)' I • Bleomycin 15-30 mg i.m. on days I, 8 and 15 given 3-weekly for not more than eight cycles Cisplatin requires adequate hydration. Response rate of 50%-70% is seen. Chemoradiation also improves survival in distal metastasis.

ENOOMETRIAL CANCER Chemotherap) drugs are less commonly LLSed becaLLSe of poor response in endometrial cancer and surgety and radiotherapy being the comerswne in itS managemenL Metastatic wmours respond better to progeswgens. Medrox)p•·ogesterone acetate (MDPA) I g i.m. weekly or 400 mg orally dail)\ I g norethisterone i.m. weekly or 17-alphah)droxyprogesterone i.m. are effective in well- and Gynaecology Vol20 1998. ' ~laggino J, et al. Gp1ecol Oncol Vol 68: 274-279. 1998. Studd J. Progres. in Ob>tetric> ,md Gmaecology Vol 16. 2005.

IMAGING MODALITIES, ENDOSCOPIC PROCEDURES AND MAJOR AND MINOR OPERATIONS IN GYNAECOLOGY 40 Imaging Modalities in Gynaecology 41 Endoscopy in Gynaecology 42 Major and Minor Operations in Gynaecology

506

43 Obesity and its Significance in Gynaecology 44 Instruments Used in Gynaecology

Imaging Modalities in Gynaecology

Plain Radiography 507 Hysterosalpingography 507 Ultrasonography 511 Computed Tomography Scan 515 Mogne~c Resonance Imaging 51 6

Rodionuclide Imaging 517 Duoi-Photon Densitometry 517 Key Points 518 Self-Assessment 518

PLAIN RADIOGRAPHY Advances in imaging modalities have revolutionized the practice of gynaecology in recent times. Plain radiograph was the first modality used in older times but has limited place in current gynaecological practice. Advem of ultrasonography, CT and MRJ has made virtual real time imaging possible in ID naecolom•. Sonography especially, uansvaginal sonograph)' provides excellent ' 'iew of anatomy of pelvic organs. In mnaecological practice 80..90% need for imaging IS met by ulu-asonograph). More advanced teclmiques such as Cr scan, MRJ imaging having added newer dimensions in the management of g)11aecological conditions specially malignancies. The latest addition to imaging techniques is PET scan which is of immense value in managing cancers. An abdominal radiograph is not used in t11e diagnosis of pelvic pathology. However, an incidental radiograph taken for other med ical or surgical conditions may reveal unsuspect.ed pelvic pathology suc h as the presence of a tooth in a dermoid cyst or a calcified fibro id (Fig.10.1). A plain radiograp h of t11e pelvis in ameroposterior (AP) and lateral views ta ken after placi ng a uterine sound in t11e uterine cavity help to locate an inu·auterine contraceptive device (lUC D; comm on!)' a CoppeP·T in present times) (JregnartC)'· The patient is requ ired to have a full bladder. The patient is given 600--800 mL of a dilute oral contrast medium about I hour before th e commencement of the procedure. Just before starting, a vaginal tampon is inserted to he lp delineate the position of the vaginal vault and cen ix. a nd a rectal co ntraSt medium given. The oral and rectal co ntrast media he lp to differentiate bowel loops from other pehic o rgans. The patient is scanned in a supine position. In g)llaecologic malignancies, inu·avenous injection of iodinated conu·ast medium is recommended to improve wmour delineation, characterization, assess vascula.-ity and lymph node identification. Advantages of Cr are as follows: • It is useful in th e diagnosis ofintraabdominal abscess. • It is useful to diagnose pelvic vein thromboph lebitis.

Rgure 40.19

MRI is ~he well-established cross-seCLional imaging modality. It prov1des multiplanar imaging capability with high soft tissue conu·ast resolution witho ut inte rference from air or bone. There is no need for administration of oral contraSt or for injection of intravenous dye for vascular contraSt. MRI, LLnlike CT. has no adverse effecLS on pregnancy, embryo, fetLLS or fuwre reproductive potential of the ovary as it has no radiation effect. The major limitations are availability, ume taken for procedure and cost It cannot be done in women with prosthetic vahe and other prosthetic u-ansplant

INDICATIONS • To assess pelvic anatomy in women with endomeu·iosis and adenom)osis. • To evaluate Mullerian anomalies. • Localize the position and si~e of the fibroids (Fig. 40.19A and B) and sarcomatous change.

(A) Mirror image of fibroid seen on MRI. (B) MRI showing fibroid uterus.

CHAPTER 40 - IMAGING MODALITIES IN GYNAECOLOGY

517

Table 40.2 Indications of CT and MRI in Gynaecology CT

MRI

Diagnostic Endometrial cancer staging, lymph node assessment, recurrence Cancer cervix extension, lymph node Involvement recurrence Ovarian cancer staging , lymph node involvement, recurrence Pitu~ary tumour Hyperprolactlnaem ia Amenorrhoea Cerebral metastasis • Abdominal abscess • Pelv ic vein thrombosis Contraindicated In pregnancy due to radiation

Endometrial cancer myometrial invasion and endocervical extension MOIIerian anomalies Endometriosis Fi broid , sarcoma Cancer of the cervix involvement of pa-ametria and lymph nodes Ovarian cancer In obstetrics - to detect fetal anomali es THERAPEUTIC MRI-gulded procedures In uterine fibrolds and adenomyosis

• Staging and assessment of pelvic neoplastic diseases such as cancer cervix, e ndo me trial carcinoma and o ther cancers. • Assess adnexal pathology, endomeu·iosis and chocolate cyst • To assess depth o f myo meltial invasion and endocervical extens io n in a case o f e ndome u·ial carcinoma. • Staging o f cervical ca ncer and detec tio n of recurrence. • Assess rec urre nt pelvic d isease and metastasis. • ln o bsteu·ics, it can pick up fe tal anomalies. • Detection of l)ln ph nodes metastasis. • MRI-guided therapeutic procedures used in leio myomas and ade nOm)OSis.

CONTRAINDICATIONS • • • • •

Pati ents with a pacema ker o r cochl ea r implant. Metallic foreign body in th e e) e. Paramagneti c anetu)sm clips. Overan xious patients need pri or sedation. Those who suffer from clausu·ophobia may not tOler·ate the procedure well. However, newer open machines ru·e now available whi ch overcome this disadvantage. • Epileptic and wo me n with atria l fibrillation, because electroco nvu lsio ns ca n occ ur. indica ti ons of C l' and MRI are listed in Table 40.2

RADIONUCUDE IMAGING This fo rm o f imaging in gynaeco logy is used for specific clinical situations . Bone scans us ing tPc/mPtiwn-99 m diph osphonate are used to detect bone metastasis in patie nts witl1 maligna ncies. Ventilation fJeifusion swns are used fo r de tecting pulmo nal') emboli. Radhrktbelled wltite cell scan s can be used for locating abscesses.

DUAL-PHOTON DENSITOMETRY The use of this new imagi ng techni que is becoming increasingly popular in d etermining the r·isk of osteoporosis in postmenopausal women. It is recommended in women who

Figure 40.20 PET scan showing Increased FOG uptake in uterus, bilateral kidneys and brain.

suffer from earl)' me no pause or who undergo oophorectom)'· The lu mba r spines and hip are scanned with a d ualpho to n de nsitomete r; which produces co mp ute rized graphs and measureme nts of bo ne de nsity and rela tes the m to agere lated normal values. Positron emission tomography (PEl) is a functional diagnostic imagi ng tec hnique, ta kin g advan tage of t11e fact t11 at mal ignant cells have a greate r glycolysis co mpared to no nnal tissue. It helps in initial staging, management and fo iiO\N rp of cancer growths (Fig. 10.20). PET-Cr combines me meta bolic stattlS with the anatomical details o f the patie nt, respecti,·el). [F-18)-fluoro-2 d eoxr-0-glucose (FOG) is used as a .-adiopha nnacological agen t whi ch is an analogue o f glucose. Glucose uptake by ma lignant cells is higher than tl1at of normal cells. PET maps the tissue spread. It also helps to distinguish cell death following radi oilierapy from tumour r·ecurrence, and helps in posur-eaunent management. PET scru1 is a nuclear biological modality and functional diagnostic image techn ology using ra dioactive material given orall y, injected into the body or inhaled. It is now used in t11e di agnosis of ca ncer in its ea rly s tage, detect its extent and severity a nd a lso assess the pa ti ent's response to therapeutic ime rve nti o ns by Stttd)'ing the mo lecul ar ac ti vity in the tissues . It is no ninvasive. P~T scan measures the blood flow to t.he organ, oxyge n consump ti on and glucose metabolism, wh ich is high in the ca nce r cells. Combining with CT, which provides anatOmical details and PET showin g metabolic sta tus, it improves the acc uracy of the tes ts. ' Ho t-spo ts ' ru·e de tected wh ere large amo unts of radiotracer have acc wnulated, and these spots are mapped in planning tl1e rapy. Preparation:

The womru1 should not eat food for a few hours ~ iliis caLLSes misinterpretation of th e test, but take plenty of oral flu· icls. PET takes 30 minutes to perform, and Cf about 2 minutes. PET is contraindicated in the following: • Pregnancy and lactati on , because o f the use of radi ou acer. • Diabetes- one sh ould be careful , as tissue blood sugru· is usually high .

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• An obese woman as she ma> not fit imo Lhe nan·ow machine. • All metals, i.e. hait·pi ns, jewellery and metal implanLS should be removed. Sensitivity of PET is 80%-90%. Currently PET scan is used to detect rec urrences in wome n treated for cancer cervix, endome u·ial cancer and ova ri an ca ncers. Some peo· p ie are exploring useful ness of PET sca n in pre-opera tive worku p of cases of carcino ma cervix, endometrial cancer and other gen ital tract cancers.

KEY POINTS • Se'eral newer imaging m'mp h nodes. These have a great ro le to p lay in staging of genital cancers.

• A Doppler examination helps to determine the pattem of blood flow in the organ, ide mil) an ectopic pregnancy and detect suspicious malignant tumours. • Sonosalpingography is indicated in suspected cases of endomeu·ial polyp an d submucous fibroid. • PET is the la test technology whi ch swdies the metabo lic sta tus of the tumo w·, a nd whe n co mb ined witl1 CT wh ich gives ana to mical details also.

SElf ·ASSESSMENT I. What is the ro le of hysterosalpingography in Ll1e practice

of ID naecology? 2. Discuss Lhe impon.ance of ulu-asonography as an imaging modali ty in obsteuic practice. 3. What is L11e role ofTAS and TVS in g)11aecological practi ce? 1. Wri te short notes o n (a) colo ur Doppler and (b) role of CT and MRI sca ns in ID'naecology. 5. What is the ro le of dual-pho to n bone dcnsito me ll)' in ID'naecological prac tice?

SUGGESTED READINGS Guiddino for diagnostic Imaging during pr~-gnanc). American College of Ob>tetricians and Gp1ecologiscs Commiuee. Opinion :Xo. 299, Sept 2004. Kamel li S. Dan\'ish A~I et al. Comparison of ll".ltb\"aj,~na l ultr.;sound and :.onohp.terO),...-;tphy in the detection of endometrial polyp$. Acta Obsttl Cynrrol Srand, 2000, 79 (I): 60. Rosen CJ. Postmenopausal osteoporosis. N E11g j Mtd, 200!5; 363(6) : 59!>-GOG. Repon on Ullm"ound Screening - Supplemcnc to Ullrasoun d Screening for Fetal Abnorm alicies London. 1l1c Royal College of Obscetricians and GynaecologistS Working Parc y. RCOG, !WOO. S~anford E. Prevention and ~nagement of O>tt'porosis. OB/ G\'N 6th Edition. 2006: 3 1.

Endoscopy in Gynaecology

Laporoscopy 51 9 Solpingoscopy and Folloscopy 530

Key Points 531 Self-Assessment 531

Endoscopes are telescopes designed to view the interior of body spaces or viscera. AlLho ugh attemptS at e ndoscopy ela te back to over 100 )'CCII'S, th e po te ntial of this method as a diagnosti c and therape uti c too l was apprec iated and came to the forefront on ly in the past t11ree decades. When used appropriate I)'• endoscopic surgery offers t11e advantages of a more acc urate diagnosis, less invasiveness, red uced pain, faster recovery and shortened hospital stay or a clay care. Advances in instrumentation and techniques now enable t11e endoscopist to accomplish several operative procedttres hit11erto performed on I) b) open surgery, including cancer surgery. Some of t11e advances are harmonic scalpel, suture mate rials and laser. Minimal invasive surge•) (MIS) implies avoiding an abdominal scar, minimal handling of peh~c and abdominal organs, less pain and thereby fast recove•)'· Advantages of laparoscopy: (i) lesser pain, (ii) few analgesics, (iii) sho•·t hospital stay, (iv) quick return to daily work, (v) no scar- no scar site hernia, (vi) good cosmetic and (vii) less pelvic adhesions. Disadvantages of laparoscopy: (i) longer procedure lime, (ii) more anaest11esia, (iii) expensi\e and (iv) expen.ise required

LAPAROSCOPY Laparoscopy was deve loped in late 1970s, and operative laparoscopy has started gaining ground in t11 e past two decades. Advances in tec hno logy led LO the development of high-resolution cameras, video laparoscopy, the development of safe instrumentS permitting t11 e use of electrical and laser energy and harmonic scalpel for cutting and caute•izing tissues or ach ieving haemostasis. LLS role in the management of infertili ty stands twdisputed, so also the benefi LS of laparoscopy over laparotomy of being minimall) invasive and having a lower incidence of adhesion fom1ation. Low incidence of infection render endoscop) to be an attractive alternative procedure in many gynaecological diseases. Despite t11ese advantages, t11ere are potential limitations. For example, tlle exposw·e to tlle operative field may be reducecl, manipulation of the pelvic ,-iscera often 1-esu·icted and tissue apposition during suwring is as accw-ate. Moreover,

t11 e feel of tissues experienced b)' the surgeon durin g open surgery lacks during endoscopic surgery. The endoscopic sw·geon in t11e making has to go t11rough supervised u-aining and acq uires the skills over a period of Lime. There is a longer learning curve d Uiing wh ich t11e endoscopist in u·aining tmderstancls t11e li mitations of t11e procedure and knows when to stop. Thereafter, t11e incidence of complications dLUing endoscopy begins to decline and prog•-essively more complex procedw·es can be successfully tmdertaken. Laparoscope (Fig. 11.1 ). Laparoscope is a rigid telescope varying in diameter between 4 and LO mm and it is 30 em long, incorporating an optical S)'Stem as a means ofillwnination. The light is transmiued from an external source to the distal lens b) means of fi breglass cables. L.iglu source of 300 W is usee) for illumination of abdominal ca,•ity. Photography requires light source of 1000 W. Other insuumenLS include Ve•·ess neeclle, u·ocar- cannula and accesso•·ies to perform tllerapeutic procedUI-eS (Fig. 11.1 ). A long Veress needle is a\'•omas from tJ1eir beds, tJ1e caviL)' is obli terated with inte •n•pted apposing e ndosutures to achieve haemostaSis and preve nt ad hesion formation. Large fibro ids may be removed by morcellation or tJ1ro ugh a small suprap ubic incision. Small myomas can be removed piecemeal after shredding ( myelolysis) or by tJ1e vaginal route through tJ1e posterior colpotom> incision (Chapter 29) . • LAVH and TLH are performed in women in need of a h)'Sterectom> for benign conditions (myomas, adenomyosis. menorrhagia and abnorma l ute rine bleeding) in women with in situ cancer of tJ1e cen~x in whom there is no d escem of tJ1 e uterus tO facilitate vaginal surge•)', and in women o lder tJ1an 15 >ea•-s in whom concomitant removal of the O\oaries is desirable. The purpose of LAVH is LO convenan abdominal h)'SterecLOmy to vaginal hysterectOmy or a difficult ' oagi nal h)Sterectomy to an easy surgery. Realizing that LAVH ca•·ries a higher morbidity in terms of prolonged anaestJ1 esia and resui cted view, many lapru·oscopists now pe•·fonn vaginal hysterectOmy even on undescended uterus and are able to remove botJ1 the ovaries from below as well. In T LH the entire procedure is carried out laparoscopicall)' and at tJ1e end of procedure uterus is delive red vaginally. T he vaginal vault is closed laparoscopica ll y.

525

Edopic Pregnancy

An early unruptured ec topic pregna ncy can be treated ef-

fectively laparoscopically. The surgeo n may attempt milking out the gestationa l sac, particularly so if it is close to tJ1e fimbria! end. An ampullar> ectopic pregnancy can be treated b) linear salpingostOm) and enucleating the tubal gestational sac. An earl> unrupwred ectopic pregnancy catl be treated b) local injection of metJ1otrexate into tJ1e gestational sac. All these procedLU·es are conse rvative measures aimed at preserving tJ1e woman ·s reproductive potential. H) drosalpinx of the tube can be treated by lateral salpingostomy and fimbli oplasty with eversion of the inverted fimbl'iae by fashioning a cuff. In blocked LUbes, segmental resection and anastomosis h as been successfully performed lapa•·oscopicall y. Hyd•·osalpinx is also removed prior to fVF to improve th e pregnancy l'l\te (Ch apter 16).

OTHER INDICATIONS Amongst the othe r opera tive proced ures accomplis hed laparoscopicall y, tJ1ose given in tJ1 e s ubseq ue nt text deserve to be noted. Genital Prolapse

Conservative procedures for seco nd-degree uterine prolapse such as abdo m inoce rvicopex>' and uterine sling ope raLion have been successfully performed laparoscop ically. Vaginal vault prolapse is correc ted by sao·opexy. Stress Urinary Incontinence

The operation of colposuspe nsio n has been successfully performed laparoscopicall). Both the Marshall-MarchettiKranu procedure a nd the Burd1 operation can be undertaken laparoscopicall). Pelvic Floor Repair

This has been perfonned laparoscopically to restore tJ1e at1atomy of the peh•ic floor (lapa roscopic colposacropexy). Dysmenorrhoea

Other uterine surge ries done unde r laparoscopic guidance are excision of ute rine septum and S)•nechiae in Asherman S)'ndrome . A rud ime ntary no ncomm unicating horn may be the site of a haematome u·a, ec topic pregnancy or to •sion. Laparoscopic re mova l is feasib le in s uch cases.

Laparoscopic ULerosacral nerve ablati on ( LUNA) aims at cautel')' and cutting of botJ1 tJ1 c uterosacral ligaments close LO their uteline auachme nt. The uterine pain-carrying nerve fi. bres travel along tJ1e uterosacral ligaments to reach tJ1e pelvic auto nomi c ganglia. Di visio n of tJ1ese liga mentS interrupts the pain pathway and provides relief. However, tJ1e re is risk of damaging tJ1e ure ters, and in d ue course of time, tJ1 e nerves regenerate, so tJ1at dysm eno n·hoea ofte n re turns. T he presacral nerve lies in front of tJ1e sac ral promomory. Exposing the nerve b uncU es laparoscopicall y and d ivid ing the same is possible. Howeve•; witJ1 tJ1e availab ilit)' of efficie nt analgesic drugs, tJ1e 1-e is seldom an)' need to have •-ecotu se to such drastic surgical proced u1-es except in endome u·iosis.

Laparoscopic Radical Hysteredomy

Others

Oncologists now perform We rtJ1 eim's hysterectomy lapru·oscopicall) (radical abdo minal hyste rectomy and bilateral extrape•·itoneal dissection a nd excisio n of tJ1e iliac atld pelvic I) mph nodes for ca ncer of the ce rvix).

Procedures such as repair of he rniae, a ppendicectomy and pelvic lpnph node biopsies are being performed laparoscopically.

Fallopian Tube

TECHNIQUE OF LAPAROSCOPY

The most comm on ope ration perfonned on the tube is sterililatio n for family planning. The tubal occlusion is achieved through occlttsion "itJ1 ' Falope rings' or ' Filshie clips'.

Lapat'Oscopy has become a safe MIS; tJ1erefore, it is employed more liberally than before, both for diagnoStic and for cen.ain therapeutic procedures. Howe,er, bearing in mind tJ1at a l'al'e

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SHAW'S TEXTBOOK OF GYNAECOLOGY

but a serious complication may develop d t.u·ing therapeutic procedures such as myomectomy, hysterectomy and ablation of endometriosis, certain preoperative preparations are reqt.Lired These are: •

• • • •

Fibroic~

It is desirable to sh 1ink a huge fibroid to reduce bleeding and make it easier to perform m)omectomy. This is done b) gonadou·opin-releasing honnone (GnRH) injection administered monthly for 3 months (Chapter I3). Bowel preparation and intestinal antibiotics (metrogyl) are safe precautions in case bowel injury occurs. Bladder should remain empty throughout the procedure using a catheter. Systemic antibiotics should be staned a day before surge•y Signawre for open suq~ery should be obtained in the case of complication or inabili ty to complete the proced ure laparoscopicall y.

Major complications are as follows: • Cardiopulmonary an·est and gas embolism • Acidosis. arrh)tltmia and cardiac arrest caused becat.LSe of C02 • Haemon·hage • Caute•') burns to \'al'iotLS viscera • Sepsis • Injury to tJ1e bowel, small intestine, blood vessels, bladder and ureter with the sharp instrumentS and bum i•'\iuries • Failure to complete the procedure Cardiopulmonary arrest is an anaesthetic complication. Embolism occurs witJ1 the use of air, but excess C02 and accidental insei'Lion of Veress needle imo a blood vessel can also cause embolism. T his mishap is avoidable if pneumoperitoneum is checked by Palmer test.

PROCEDURE

Haemorrhage

• Whereas d iagnosti c proced ure may be ca n·ied o ut under sedati on and local anaesthesia, the therape utic procedure always requi res general anaesthesia because of prolonged ti me taken and intra-abdom ina l ma ni pulatio ns required. • Position: The patient is placed in sem ilithoto my and slight Trendelenburg position. • Pneumoperitoneum is created with a Veress need le using carbon dioxide (CO!) gas through a small infrawnb ilical incision. Air and niu·ous oxide (N 20) should not be employed, because oftJte risk of air embolism in tJte former and combustion witJ1 lO if electrocautery is used. llte proper pneumopetitoneLUn is confirmed by noting the t.mifonn distension of tJ1e abdomen and Palmer test, which consistS of i11iecting 5 rnL of saline tJwough Veress neeclle. Failure to aspirate saline indicates proper placememoftJte neepic excision of uterine septum.

• Genital tract infection present. • Pregnane) • Dming menstnaation, as view is obscured and infection rate increases. • Scan·ed uterus and enlarged utent.s more than 12 weeks' siLe fonn relati'e conu-ainclications. • Cenical stenosis can calt.se cen·ical tear and uter·ine perforation. • Cardiopulmonary disorders: These include anaesthesia risks, fluid over blood and pulmonary oedema.

DISTENSION MEDIA IN HYSTEROSCOPY Several distension media arc in current usage for hysteroscopy. T he choice of medium depends o n iLS ava ilabil ity, safety, effec ti veness and cost as well as whethe r cautery and laser are to be used . T he media in comm o n usage include

Table 41.2 lndlcati ons of Hysteroscopy Diagnostic

Therapeutic

• En docervical study In suspected endocervical malignancy, preinvasive cancer and biopsy uterus - malformations, endometrial TB, Asherman syndrome, misplaced IUCO, menorrhagia, intermenstrual bleeding, submucous fibroid, polyp Falloposcopy

• Endometrial polypectomy Submuoous fibroid Septate uterus Asherman syndrome Removal of IUCD Tubal sterilization Balloonoplasty IVF intrafallopian insemi· nat ion

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SHAW'S TEXTBOOK OF GYNAECOLOGY

carbon dioxide gas de livered through the Hysteroflator at a maximum rate of 70 mL/ minute and pressure less than 100 mm Hg. This gives a clear panoramic view of the imerior of the uterine caviL), but flattens soft pedunculated poi>'P against the uterine lining as against those seen as floating objects when liquid media are used The popular liquid media used in practice indude no•mal saline, 5% dextrose and Ringer's laCLate solutions. To provide adequate uterine distension, the inu-auterine pressure needs to be 10-50 mm Hg. More sophisticated pressure S)'Stems are a' and if indicated for bacteriological examinat.ion. Previous!), a r-igid metal cannula was used for the same purpose. Procedure is a short OP[).based test and can be done without an> anaesthesia. Howeve r; for an apprehensive patient, local anaesthesia with mild sedation given by intramuscular or intra,enous route suffices. Complicatio11s:

Figure 42.3 Karman's cannula.

Rarely, there may be difficul t)' in nego ti at.ing interval cervical os, while introd ucing ute rin e so und o r Ka rm an 's ca nnula . Suspected perforat.i o n of the uterus sho uld be managed by immediate!)' s topping th e procedure, ca refu l obse rva tion of patients for possible intraabdom ina l bleeding and by giving antibiot.ics to prevent infections.

DilATATION Of THE CERVIX AND ENDOMETRIAL CURETTAGE (DilATATION AND CURffiAGE) Dilatation and Curettage (O&C) remains one of the most often can·ied OUt procedure in g)naecology. O&...C is a minor ID naecological procedure of dilating the cervix and cur·ett.ing (scraping) the endomeu·ial tissue from the uter·ine ca,•ity.

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SHAW'S TEXTBOOK OF GYNAECOLOGY

It is mainly a diagnostic proced ure; howevet~ can be t11erapeutic in cettain obsteu·ic co nditions. Dilatation of the cervix alone is required in the following conditions: • Before curettage (commonest). • For cervical stenosis. • To prevent cet'l ical stenosis following Manchestet· operation for prolapse of the uterus. • To prevent postoperative cen·ical stenosis in cauterization of cet'l•ical erosion and conir.ation. • To drain haematometra. • To drain p)Omeua. • Befot·e insertion of radium into tlle utet·ine cavity in cancer oftl1e cervix and endometrial cancer. • Before removal of embedded inu-autet·ine conu-aceptive device (IUCD). • Before breaking ute tine adhesions in Asherman syndrome. • Before endoce t'l•ical cureuage (ECC) for endocervical cance t: • Before hysterosco p)'· • To di agnose inco mpe te nt os. If No. 8 d il atO r goes in easily, tl1e inte rnal os of t11e ce n•ix is co nsidered as an incompe te nt os witl1 the risk of hab itual abortion and preterm !abo ut:

Figure 42.4

Hawkln's single-ended dilator.

N

Figure 42.5 Fenton's dilator.

c= Figure 42.6 Metal Curette.

Obstetric indicaLions a re as follows: • Before evacuation in missed abortio n, inco mplete abortion. evacuation of a h)datidifonn mole. It is also necessary for medical termination of pregnancy. Curettage of endomeu·ium is mainl)' diagnostic. This is indicated for following:

Rgure 42.7 Blunt and sharp curettage.

• AUB to obtain endomeuium to stud)• tlle honnonal pauem

causing abnormal bleeding. • S«inulary tWU?IIOrriiO«I to detect tubercular endomeu·itis. • Postmf!lwJxmMII bleeding to rule out endomeu·ial cancer.

•

JindometriJ:~l amcerto

study t11e endocervical tissue and the extent of spread. This helps in staging and deciding on treaunent. • lufertilit:y. Now a days, ulu-asound is used for monitoting ovulation. H owe1pentium is a double-ended specullUn which reu-acLS me posterior 'oaginal wall, in dorsal and left lateral positions (Fig. 12.8). It comes in differentsiLes. Sim-1 ~i~. This includes routine and microscopy urinalysis. CuiLUre examination is requisitioned. if microscopy reveals significant number of pus cells (more than 5) or histO t)' of urinary tract infectio n (UTI), especially in women with C)'Stocele, urin at)' complaints and fistula. • FasLing and postprandial b lood suga r es tim ati ons. • Kid11ey function tests. Blood urea, sentm creatinin e and uric ac id. • Liverfuuclion tests. Pan.icula.-ly in women witl1 a history of jaundice and in all women undergoing cancer surge•)'· • 13/Qod ltsllfor VDRL, Ausu-alia antigen and HlV-l and ll. • Serum electroi:J•t.es. Na, K, Cl and HCO,. • R(u/iograph of the chest, preoperatively or in genital cancer for metastasis. • 1\CG and ~twss test whenever indicated. • lntr(ll)triOu~ fJJelogmplry (IVP) in case of cancer cervix and urin at)' fistulae. • Blood group and Rh factor. • BIPediug time arui clotting time.

PREOPERATIVE WORKUP PURPOSE OF PREOPERATIVE WORKUP It is the comers tone for successful surgical outcome.

• To make the correct diagnosis. • To decide on the need for Stu-ge•)' and its correct selection. • InvesLiga Lions to: • con firm the diagnosis. • fitness for anaesthesia and surgeq•. ldentil)' the risk factors, any abnorma l condition and rectify tl1is before undertaking sw·ge•)'.

CORRECT DIAGNOSIS Detailed histOf) and clinical examination can lead to correct diagnosis in most cases. History includes the presenting symptoms, drugs taken, any allergy and previous blood transfusion and surgery. CUNICAL EXAMINATION Apan from abdom inal, speculu m and biman ual examination, general exa mination rules o ut hitheno undetected anaemia, tl1y•-oid enlargement, breast disease and cardiovascular examination besides blood pressure. Pap smear is taken as required. INVESTIGATIONS These include the following: • Confirmation of clinical diagnosis b) ultrasound, CT and MRI. • To assess tl1e extent of the disease, any anatomical disto•tion of b ladder; ure ter b)' the pelvic tumour and malignancy. • St.aging a nd feasibility of s r11-ge•y In case of uterine fibroids, tJ1 e number, size and loca ti on of fibro ids decide the t)•pe of surgery appropriate to tJ1 e case. • Decide on tl1e type and route of surge•)'.

FITNESS FOR SURGERY It is necessary to ens w-e that the woman is fit for surgery, by perfonning the following investigations: BP check-up. Hb% white cell coLrnt, differential count, blood group-Rh. Ro utine urine examination for pus cells, sugar and p•-otein. Kidn ey function tests. Li ver function tests in cancer surgery and in previous liver disease. • Blood sugar. ln a known d iabetes patient, to check on sugar control. • X-ray of the chest, routine and for secondat)' malignancy. • • • • •

• ECG. • Th) roid function tests if required. If an) abnormality is deteCLed, the woman is refen·ed w the appropriate specialist for treaunent and t11e operation is postponed until the woman is considered fh. To protect the surgical staff regarding hepatitis B virus, HI V in high-risk patients. Patient test such as HBsAg, H[V s houl d be done. In an e me rgency and life-saving condition, minimal essential in vestigations are done, blood arranged and the risks of ope•-ation explained. In a planned surgery, some g)•naecologists prefer autotransfusion, and blood of tl1e woman is withdrawn 2 da)S before su•-ge•·y and preserved. Altemately, a relative donor is a•·ranged. This avoids t11e •·isk of HIV and other sexually transmitted diseases, hepatitis B vint.S. B) assessing the fitness in this way, sudden cancellation and prolonged postoperative hospitalization due to complications are avoided.

DRUGS Woman on a ny drug needs counsell ing, rega rding temporary stoppage or addition of alternative drugs or a new drug. Any alle•·gy to a particular drug should be noted. HistOt) ' of

CHAPTER 42 - MAJOR AND MINOR OPERATIONS IN GYNAECOLOGY

previous blood transfusion, t.h e reason for transfusion and any adverse reaction is noted. Oral comracepuve pills should be stopped 4 weeks before surgery. These can cause thromboembolism. Warfarin should be stopped and replaced b) heparin with good monitoring. Aspir·in is also best a' oided as it can cause bleeding. Anaemia should be treated and Hb% should be at least 10 g%. Any infecuon should be cleared with anubiotics. Smoking and alcohol should be stopped for a few days befor·e surger)'· Lithium andUiC)clic anti-tetrics and C) necology 2010.

Obesity and its Significance in Gynaecology

Prevalence 542 De~ni~on 542 Aetiology 542 Pathophysiology 543 Clinicol Features 543

Complications and Sequelae 543 Management 544 Key Points 545 Self-Assessment 545

Obesit)' is on an increase the world ove t: In Ind ia, the incidence is reported to be 10%- 15%. Obesicy affects menstrual functions, reproductive functions and other organ systems in tl1e bod)' with a profound effect on tl1e incidence of PCOD, infertilit), pregnancy outcome, endometrial cancers (increased) and a variety of mensu·ual irregularities. WitJ1 an ever-increasing incidence of obesity, it looks like a major factor which will influence healtJ1 of the people in the next few decades. Obesit) until recentJy,,'as considered a cosmetic nuisance, personal issue and social problem, blll now it is realized tl1at it also poses a major health haard in later >ears, causing morbid conditions and, at Limes, early death. Now considered a metabolic disorder, its prevalence has increased globally and threatens the health of the individual. Once acquired, it is difficult to get rid of, despite dietary comrol and exercise. It is therefore important to d1eck the growtl1 and weight of adolescents and adults before it creates healtl1 problems.

PREVALENCE Increased prevalence ove r Ll1 e previous )'ears is because of several factors: Life~tyle clu~~tge: Better social and economic environ· mem has changed the li festyle of people; overeating and overindulgence in wrong foods has led tO obesity (fatty food) • Lack of exercise because of heavy and prolonged hours at work, ph)sical disability and sedentary life, causing less utilit:ation of calories and accumulation of bod) fat o Genetic o Increased birthweight and maintenance of increasing weight Lllrough childhood and adolescence

•

542

DEFINITION Obesity is defined in terms of bod)' weight over heighL Body mass index (BMI) is expressed as follows: BMI

= weight(kg) height(m: )

o o o o o o

onnal BMI is between 18 and 25. Below 18 is considered underweighL Between 25 and 29.9 is overweight. Between 30 and 35 is obese. BMl over 35 is considered morbidly obese. ·waist-to-hip ratio should not exceed 0.8.

AETIOLOGY Apart from the above-mentioned fuctOt'S well known for gain in weight, obesity is considered a metabolic disorder originating in the fellts itse lf, part!)' conu·ibuted by mother's environmen t dwin g p regnane>'· Materna l conditions during pregnancy are ove rnuu·iuon, glucose intOlerance and diabetes, leading to mac rosomi c fetus. The metabo lic changes in tl1is fetus persist Ll1rough chi ldhood, ado lescence and adu ltl1ood leading to overweight and obesicy. Other factors are as fo llows: o

Genetic Family history reveals obesity.

o

Prepregrumc;• weight: Overweight mothers gain more weight

o

than nonnal women during pregnancy. They also retain increased weight gain postpartum, and put on some extra pounds or so following each delivery; multiparae therefore tend to be overweight compared to pt·imis and those \\~Lh lesser pregnancies. Menopause: Low metabolic rate and inacti\·ity add tO tl1e woman's weight after the menopause.

CHAPTER 43 - OBESilY AND ITS SIGNIFICANCE IN GYNAECOLOGY

• Overeating and eati ng wrong food also lead to obesity. • Lack of exercise and seclen Lary lifestyle lead tO an increase in the woman's weight. • Di~litt~e~ Thyroid (h)'J)Oth)TOiclism) and oedema occur because of hepatorenal disorders. • Dru(Jl: Corticosteroids over a prolonged period, androgens and oral hormonal conu-aceptives tend to increase the woman's weight.

PATHOPHYSIOLOGY Bones make up 12% of the total body weight, muscles 35% and body fat 27%. The rest comes from other organs and blood and body fluid. Of the tota l fat, abdom inal and visceral fat (waist circumference) is linked to diseases in the adult life. Women tend to accumulate more fat over the abdomen than over the hips, as compared to men, th ey te nd to suffer from obesity more tl1anmen. Lep tin ( 167-am ino ac id prote in ) is a ho rm one secreted by adipocytes in the fat that influences hypo tha la mus regard ing appe tite. Increased leptin increases fat acc umu lation. Lep tin secretion is also regulated b)' insulin which stim ulates lep tin secretion. In pregnancy, some wo men develop insulin resistance, a nd hype rinsulinaemia may be responsible for excessive weight gain thro ugh fat depos ition and retention of weight gai n postpartum.

CLINICAL FEATURES • Agrr. Pregnane> and menopause are linked to obesity in women.

• Parit)' Multiparous women tend to be more overweight than less parous women. • Farllily history (genetic) also leads to obesity. • Many obese women are born overweight.

COMPUCAnONS AND SEQUELAE (Fig. 43. l ) • O bese adolescents tend to have precocious puberty which in turn reduces their height over-all (see Chapter 6). • There may be mensu·ual d)Sfunction because of horm onal and metabolic cl)Sfunction. • Pol yc)stic ovarian syndrome ( PCOS) is nowadays seen in young women who are over·weight. They also demonstrate insulin resistance. • Anovulatory infertility may occur beca use of anovul ation and PCOS. • T he success of in vi tro ferti lizatio n (IVF) in infertile obese women is repo rted to be low. • Breast, uteri ne and colonic ca ncer are repo n ed to be higher in obese women than in lean women. • Stress incon tine nce of urin e is more prevalem amongst overweight women. • Fungal and uri nat")' infection are mo re common in obese women. • Disea~~: Obese women tend to suffer more from tl1e following medical problems tJ1an lean women: • Gall bladder stones • Cardiovascular disease, especially myocardial infarct • Su·oke and osteoanhritis • Thromboembolism and pulmonary embolism • Respiratoq problems such as asthma • Sleeping disor'(lers

( Complications of obesity )

!

I

Adolescents

! ( Childbearing period )

• Precocious puberty • PCOD

~

• Anovulatory infertility • Poor IVF outcome

1

Pregnancy

• PIH insulin resistance • Macrosomia • i Caesarean delivery • i Anaesthesia risk • i Surgery difficulty • i Postoperative sepsis • Thromboembolism • Scar site hernia • Postpartum depression

543

CVD

• • • • • • •

l

Myocardial infarct Diabetes Hypertension Stroke Arthritis Thromboembolism Hyperlipidaemia

Figure 43.1 Complications of obesity.

l

l • • • • •

Breast Cancer Uterine Cancer Ovarian Cancer Colonic Cancer Stress incontinence

544

•

•

•

•

•

SHAW'S TEXTBOOK OF GYNAECOLOGY

• Diabetes II • 1-lyperlipidaemia S111gery•: lt is cUfficult to procure a vein for intravenous drip during surgeq. • Intubation during general anaesthesia and getting into an epidural space for spinal anaesthesia could be a problem. • Laparoscopic surge•1 is technica lly difficult. • Dlll·ing laparotomy, inadequate space and exposure of organs may make surgery difficult. Trauma to organs occurs more in obese women, so also bleeding during surgery. • Postoperati,·e per·iod may be complicated b)' infection, poor wow1d healing, thromboembolism and scar hemia. Pregu an cy • Pregnanc)'-inclucecl h ypertension • Insulin resistance and gestatio nal diabetes • Macrosomic baby • Increased incidence of caesarea n sec ti o n li kely because of abnorma l position ca used by macrosom ia, cephalopelvic disproportion and feta l d istress PuJtjJartum complication$; Reten lio n of we ight gain, postpartum depression, thromboembolism a nd poor lactation. Poor lactation is see n in obese women. T his, in turn, causes overweight infants th rough boule feeding. Contraceptive$: Hormona l conu·aceptives are contraindicated in obese women. Functional limitations because of overweight are well known.

MANAGEMENT Management comprises: • Prophylaxis (pre\'ention) • Treatment

PROPHYLAXIS DIET Proper balanced diet is the essential step in maintammg normal weight. A bala nced diet sh ould co ntain 60% carbohydrate, 20% protein and 15%-20% fat. Intake of diet with 1800-2000 cal cla il)' is adeq uate, but also depends on body weight (body weight [kg) X 35). A diet containing fibres delays abso rpti o n and lowers the glucose level. Carboh)•drates sho uld be main ly of low gl)•caemic index. Animal proteins with amino ac ids a re preferred. EXERCISES Yoga, mecUtation and regular exercises help in red ucing weight. Rapid weight loss is not recommended, but! lb/ week is safe. Walking for half an hour daily for 5 days is sufficient to maintain weight. PREGNANCY • Prepregnancy "eightshould be nonnal. Overweight women should be asked to reduce weight before conception. • 'v\'eight gain should be monitored regularly.

• Postpartum weight should be carefully mon itored. Most women reduce weight and return to prepregnancy weight by tl1e end of 3 months postpartum; othenvise, diet control and exercises are recommended. Breastfeeding prevents obesit) in infants. Obese infants tend to remain obese throughout life, exposing themselves tO diabetes, h) pertension, h) perlipidaemia and certain cancers.

MANAGEMENT OF OBESITY • Diet • Exercises • Drugs -lipase, inhibitors • Orlistat • Rimonabant • Sibutramine • Surgery- bariauic li pectomy • Gene therapy DRUGS Li pase inhi bitors are p resc ribed for obese women. T hese are as follows: • Orlistat (Reshape) is an a ntiabso rbe nt of fat and 120 mg dail)' red uces 30% of fat abso rption from imestinal tract. It also prevents absorption offaL-solub le vi Lam ins which is a rusadvantage. lt a lso causes fatigue a nd depression. • Rimonank reduces food intake. • Sibutramine en hances safet) and is thermogenic b)' inhibiting serotonin and noradrenaline reuptake. lt acts centrally.

FETAL OBESITY Apart from changing lifest) le, diet and exercise, the important cause of adult obesity and its sequelae is fetal obesity or what is also known as macrosomia. It is now realiLed that fetal macrosomia is because of a disorder in the matemal environment causes fat deposition in the newbom and infant. Metabolic disorder thus sets in and continues through adolescence and adulthood. Pregna ncy adds LO this metabolic disorder and incr·easing weight gain during pregnancy worsens the situation. Once obesity sets in, it is extremely difficult to shed it off. Valious seq uelae of diseases follow, impairing life and eve n ca using early dea th (Table 43.1). Prevention th e refo re lies in managing pregnancy, co ntro ll ing weight ga in and blinging back th e o riginal prepregnancy we ight in the postpartum peliod. Con u·olli ng

Table 43.1

Classification of Disorder s of Obesity

BMI

Classification

< 18.5

Underweight

18.5-24.9

Normal weight

25.~29.9

Overweight

30.Q-34.9

Class I obesity Class II obesity

>40.0

Class 111 obesity

CHAPTER 43 - OBESITY AND ITS SIGNIFICANCE IN GYNAECOLOGY

preconceptional weight and avoiding obesity before pregnane>• are also very important for optimal outcome for the individual and long-ter·m health benefiL

TREATMENT SURGERY When medicines fai l, stu·get) is resonedto as follows: • Sleeve gastrectOm) and gastric b)pass Sttrgery are two common!) done procedures for morbid obesity. • Gastric Bypass surge f) t."lkes 3 hours to perfonn, but is a one-time procedure. • Li pectOmy may be helpful. • Lapa roscopic ac!justable gasu-ic band (Lap Band) takes half an hour LO perform, but the band needs periodic adjustments, so follow-up is necessat)'· • Gas u·ointestin al im planLab le electrical s timula tion of nerves is be ing tried. • Gene the rapy tn tl)' prevent obesity.

545

• Gynaecological problems 1·elated to obesit)' are menstrual d)Sfuncr.ion, anovulatOI)' infertility, PCOS and certain malignancies. IVF also )ields poor resultS. • Obsteu·ic problems to obesity are considerable. Apan from maternal complications, fetal macrosomia is now considered a ve11 impo 1tant cause of adult obesity. • Surge!") increases morbidities in obese women in the form of infection , respiratOI) problems and thrombo em bolism. • Medical problems in ad ults impair qualit) of life and ma> even catLSe earl) death. • Prevent u·eau11enl, treau11enr. of obesit) often fails and can be fntstrating.

SELF-ASSESSMENT I. Disc uss th e haza rds of obesit)' in reproductive fun ctions. 2. Disc uss th e seque lae of obesity.

KEY POINTS

SUGGESTED READING

• BMI is used to rate a pe1'So n as overweight or obese. • Obesity poses many health h azards in adult life and some can be life-threatening. • Common causes of obesity are well known and can be rectified.

Green BB, Weiss NS, lf~ling.JR. Rhk ofO\~Jiawry inf~rtilil)' in relation Ieri :.can the >)lllbol or log in 546

Advtmtagtr. It does not require the help of an assistanL

DistulvtmUtge It covers anterior and posterior vaginal walls; hence, conditions such as fistula in anterior or posterior vaginal wall can be missed. Metlwd of sterilizatio11: It is clone through autocla,1ng/ heat boiling/ Cidex.

INSTRUMENTS USED TO CATCH ANTERIOR UP OF CERVIX Whi le performing any procedure on endocervi.x and endomeu·ium, one n eeds to hold the anteri or li p of cervi.x to stabilize the uterus. Some of these procedures are endometrial biopsy, endomeu·ial aspiration for histology/cytOlogy, endocervical biopsy, di latation and curettage, hysteroscopy, HSG and those during laparoscopy. Commonly used insu·ume nts for this purpose are tenac ulu m, vu lsellu m, long Al lis forceps or a sponge-hold ing forceps in pregnancy.

TENACULUM It has a single pair of teelh to grasp the anterior lip of cervix (Fig. II. I ). It is useful to catch the amerior lip of cervix for procedures where dilatation of cervix is not needed such as EB, £A, ECC, Copper-T insertion and HSG. DistulvtmUtge lfa force is used to pull on cen1x, it can cut through substance of cen ix. Metluxl of~terilizatioll: It is done through auLOclaving/ heat boiling/ Cidex.

I() rour account on ""'-~1, 174-185 in pchic tuberculosis, 3, 248 in PIO, 337-343 in puberty, 75-86 Abdominal sling operations, 297-298 in genital prolapse, 28!>-30 I Abdominocervicopcxy in genital prolapse, 28!>-30 I Abnormal IH~rinc bleeding, 2, 123t, 128-140. 130f, 147, 192,218,241, 263,463.510,514,525,528-529 Abon ion. 303 Acne. 120 Acquir~'CI sten)mpto•m of. I 78-179 treatment, 18&-187 AdcnOill)O>b uteri, I 86f, 248-249 Adherent placenta, 284 Adnexal rna.., !>-6, 179,351,510 Adol e.ccncc su puberty Adolescent conU"dccption, 84-85 Adolescent gynaecologic problem>, 75-86 Adolescents, 82, 275,457 contrdception for, 275 hormonal contrdceptive>, 275 I CCO, 275 Adrcnogcnital syndrome, I 14-116 tre.umcmof.ll6 AID$.255.346.365-366 Aldo>terone. 114-1 I 5 in .idrenogenital S)ndrome, 114-115 in P~IS. 126 Alii>' forcep•. 26(}...261, 281 Alpha·aclrcnc~ic dru!,'S, 390 in ~tn.:~ incontinence. 388 Alpr.ttolam, 127 in PMS, 127 Alpn>stadil (prostaglandin), 212 in male infertility, 203-212 Altheimer disease, 89

86, 90, 94-95, 233,275 cugonadotropic, 141-142 imestig.ttions in, 149-154 managementof, 144-146 primary, 141- 146 classification of, 141-142 secondary, 14&-154 aetiolog); 14&-149 iiH'('Stigations in, 149-154 treatment of, 150 Ampicillin, 333 in urct hrit.is, 376 Anaesth, 320 in pruritus vulva, 320-321 Anti-M1illerian hormone (AM II), 54, 86 Anti-o used for, 210 Artificial urinary sphincter (AUS), 390t Artificial vagina, I 16 Ascites, 162 Ash~rrnan >yndrome, 350 Aspirdtion of pouch of Dou1,>1as se culdocentesis As.ist~'CI reproducti\-e technique> (ART). 203 in female infertility, 212 in male infertility, 203-212 Atheru.clcrO>i.s, 89 Atrc.ia recti, 73 At)pical squamous cell ofundctcrminignificance (ASCUS), 9t Augmentation 'clam' cystoplasty, 394 Autosorn of, 330 treatment, 331 Bactericidal cre-ams, 334 in vaginitis, 334 Baldy-Webster opemtion, 304 Ball's operation, 321 Barium enema, 510 Barium meal follow through. 510 in o'arian ntet"Qtatic dbcaM"". 510 Barr bodies, 109-110 Bartholin's absce», 320, 362-363 Bartholin's cyst, 319 Bartholin's gland, 15 Bartholin's gland tumour. 478 Behcet;yndromc, 321 Benign ovarian cysts, 444, 452-456 differential diagnosis, 454-455 invesligalions in,

455

ph}sical signs, 453-454 symptoms, 452-453 tre-.ument, 45.~-456 Beta-hCC, 483 Bethesda dassif1Cation, 409 in dysplasias, 409-410 Bicornuate uten1>, 70. 163 Bilateral salpingo-oophorectOill) (BSO). 470 Billings or o\'ulation method, 253-254 Birth control, 252-263 need of, 2:52 Bladder anatomy, 24 fist.ula, 3 79-395 injury, 380 stress incontinence, 374 Blocked fallopian tubes, 210 Blood sugar e>timations, 538 B. melaninogenicus, 338 Boari-Oap operation, 384 in ureteric llstula, 384 Boer-~leisel S)"Slem, 345 of prognostic ""'ltouion. 34:5 in PlD, 345 Bone mineral den,ity >tudy. 90f Bonney's test, 388 in stress incont,i ncncc, 388 Bowen's dise-.a.se, 475 B. proteus, 375 Br.tchytherapy, 495-497 Br...tin met.astas.t:.-s, 491 Bmxton Hick$ contractions, 4

553

554

INDEX

Brea.>t cancer, 91, I 02-105 in' c-stig.ttion~, I 0~ I 04 progn of, 9~100 examination. 99 Breastfecding. 99, 459 Brenner tumour, 96, 444 Broad ligament, 21, 308 haernatoma of, 309 Broad lig-.unent cyst>, 308-311 par.to\arian cysa., 308-309 Bromocriptinc , 99, 199,209 in ano"Jlatory infcnility, 199 in cyclical mastalgia, 199 in PMS, 126 in supprc.,ion of lactation , 199 Burch colposuspcnsion, 39 1 Buscrclin, 198

c

Cae.arean >tar e-ctopic pregnancy, 243 Cae.arean >L'Ction, 402. 405 Cakarc'Oll> degener.1tion, 159,449 Calendar method, 253 Call-Exner bodic">, 38 Cutter

of the \'uh·.t, 472-480 actiolog). 473 das:.ifJCation. 4 73 clinical feature.. 473 incidence of. 473 imcstigation>. 473-474 management. 4 74 preim'aShe. 4 73-475 staging, 475 Cancer cervix. 420-429 clinical ft:'.tlllrc'>. 421-422 diagnosis. 424-425 pat holo)O'· 4 20 st..ging. 422 lre-.uuH::ru, 426 Candida! \".tgi nit is, 365 clinical feature">, 36.~ diagnosis, 36.~ risk factotll, 365 treauncnt, 3f.J.:j Candidiasis, 1-2, 7 Capsular haemorrhage, I() I Carcinoma, 4721' of cervix, 378, 480 aetiology, 473 clinical features, 479 differential diagno>b. 422 epidemiology. 475 rnanage::n'lcnt, 474 >taging of, 475 of corpu.~ uteri, kt ~ndomctrial cancer, 437t of endometrium, ~1-48

Ctntnculae m}Ttiforme>, 21 !l, !l96 Cauterization tcdlnique, 27!1-274 failure r-.tte. 27!1 Ca\'aterm balloon thcr.tp), 136 CD, count. !l66 Ccfotetan. !l44t Ccfoxidn. !l63 in !,'Onococcal \-.tginiti>. !l62-!l63

Ceftria.xone, 361 in chancroid, 361 Centduornan, 26~270 contraindications of, 270 in emergenq,. contr.tception. 270 pregnancy rate, 269 side effectS, 268 Central nervous system {C:\S). 141 Cephalosporins, 376 in urethritis, 376 Cerazeue, 266 Cenical cap, 399 Cenical d)osplasia, 409 Cenical d)'Stocia, 396 Cenicalllbroid, 157-1 61 Cenical glands, 19 Cenical intraepithelial neoplasia (GIN). 9t Cenical mucus, 46 fern test, 46 Cenical pr(:!,'llan(.y, 242 treatment, 242 Cervidt is, 256 Cervix, I:>- I 6 descent of, 287 dong.u.ion of, 290 Chassar Moir technique, 383 Chemotherapy, 494 for gynaecologic cancer, 500-505 classification of dru!,>S, 501-503 t.umur cell kinetics, 500-50 I Chlamydia trachomatis, 363 Chlamydia, 36~364 diagnosis, 364 treatment, 364

Chlarnydial infection, 7, 363 diagnosis, 330 treatment, 331 Chocolate LJSt, 130 Cholecystitis, 34 2 Choriocarcinoma, 481 'cannon hair metastases in lungs. 490 differendal diagno.is of, 490-491 inddence, 489 signs of, 490 symptOms of, 490 treatment of, 491-492 chemotherapy, 491-492 surgery, 492 Chorionioillus biop;y (CVB), 109-110 Chromosomal sex, 10~110 Chronic interstitial salpingitis, 340 Chronic pelvic pain ;;yndrorne (CPPS), 249 Chronic pelvic pain (CPP), 247-251 aet iology, 247-248 history, 249-250 investigations, 250 management, 250-251 Chronic pyosalpinx, 340 Cicatricial stenosis, 373 Cimetidine, 120 in acne, 120 Cipn:>Ooxacin, 361 in chan(.Toid, 361 Clear cell cardnoma, 444 Climacteric, 86-87 Clindam ydn, 331,344 in dllarnydial infeL'lion, 363 Clitoris, 398 Clitoroplasty, 115 Clomiphene citrate, 192-194. 222 in ano\'ulation, 223 in ano\'ulawry inferulity, 222 in female infertility, 212 in male infertility, 203- 212 in pol)'C)'SliC o''arian disease (PCOO). 35

Clomiphene citrate (Cqlltillu,d) in ~pcrmatogcnt.o.sis, 192 in 'itro fcrtilir..alion, 192 Clue cclh, 330 Coelomic metaplasia theory, I 74 Coincident rurcinoma of uterus and 0\~ry, •1&1-'165 Coittl>, 212 Coittl> intcrrup~t.l>, 206, 2.?:lf Coll.ttcr.tl ancrial ciratlation, 3 It Colour flow Doppler, 208, 455 Colpocente.b, I 7 Colpocleisb, 299 Colpoperineorrhaphy, 294 Colpo;ropy, 10, 479 Colpo>ttSpCnsion, 391 Combined oral pill, 263-26.~ bide dfccts of, 264-26.~ Complem ent fixation test, 360 Comput cl'assistcd sem en ana lysis (CASA),

22:; Conception, 11 2, 203 Condom s, 252, 254-255 advancagcs, 255 dis.advanlagcs, 255 Con dylomata acuminata, 357-358 diagnosis of, 358 trcauncn 1, 358

Cone biop>)', 414 Congenital adrenal hyperplasia, 76 Contact \'uhitis, !l20 examination, !l20 Contiform. !l90 Contmception, 252, 257 a woman hith medical disease, 276 for women O\Cr the age of35 )ears, 276 l.lctdtional amenorrhoC"a, 27:>-276 method. of, 276 po>tcoital contracep1ion, 270 >uppre..ion of O\'\tlation, 26~270 >pennatogenesis, 277 >uJl.,.;Cal >terili1.ation, 271 Con1if1Cation index, 327 Conntal re.ection, 272 Corpu> luteal haematoma, 235 Corpus luteum, 313 hy.tlin i1.a1 ion, 40-4 I of pregnanty, 40 of the menstrual ~ycle, 41 rc trogn:ssion of, 40-41 (.orticostcroid thcmpy, 95 in autoilmllll llC disease. 95

(,ortisol thcmpy, 11 !>-116 in postnatal adrcn ogenital syndrom e,

11 5- llfl Coue 's ope rat ion, 12fi Cracked nippk-s, 99 Cn:acti\'C protein, 343 Crimin al abort ion, 284, 338 Crohn's dise>t.SC, 321 Cryptomenorrhoea, 142 CT .can, II. 151 Cubittl> mlgus, 112-113 in 1\1mer's >}11drorne, 112-1 13 Curnulu> oophortl> s" !,CO'> >pL'CUIUtn, 4

Ctl>hing'• >)11drome, I 15-1 16 C)clO>porin, 209 in male infcrtilit), 210 Cyproterone acctue, 118, 196 in hir>utism, 191,315 Cyl>l ic ~,otandular h)perplasia, 133

INDEX C}'>tOCch:, 287-290, 291 C}'Stadcnocarcinoma, 442 Cj-'>tO>Copy, 374 C}-stOu n:thrography, !l89, 510 C}tOhormonal cmlu:uion, 10 C)-•tolog)'. 328 of \'agina, 328

D Danazol. 90. 99. 191 in AIDS. 36~366 in bre-..st disc aM.'>. 99 in decre-..sed libido. 191 in dysmenonilOc.t, 124-126 in t:ndumcuio~h, 192 in fibrocp.tic di>c:~>e of brc:-.ts, 192 in gynaecoma>tia, 192 in mak infertility, 192 in PMS, 126 l}drifct>acin , 394t in ~tre:;.s inc.:ontincncc, 384 Decubitus ulcer, 290 Dchydrocpiand rosten e dion c ( 0 I I £A), 116 Delayed puberty, 82 causes of, 82 Denver •Y•tcm, 109f Dcrm uid cy.t of ovary, 44 6f Dctruwr in•tability (0 1), 393-395 in \'L';)tig.Jtion~, 393 •Y"' ptom>, 393 treatment, 393-395 Dcxametha>ne, 209 in hir.uthm, 116-120 in male infertility, 203-212 Dcxarnetha>onc ACfll lC>l>, 118 Oiabcto. 1-2 Diagnostic laparO>COp) m laparO>COp) Oiathcrn>) cxci>ion. 376 Oiqclominc, 394 in stress incontinence. 384

Dienoestrol cream. 189 in senile vaginiti>. 87-88 Difficult coitw.. 214 Dilatation and curcu.tge (O&C), 96-97 Discus proligcrw. sl'!'gr.tafian follicle Disst:minalt..'"tl in1r.wa~ular coagulation

( DI C), 246 Di,·cniculitis, 342 DNA study. 474 DNA virus, 368 Dodcrlcin 's bacilli, 7, IG, 326 DonoV'.tn bodic:; stt 1-,rranlalom a ing,ainale

Doppler uhr.JM>und , 237, 249 for pelvic congestion, 250 Dox y~yclitH: in chronic PIO, 343 in lymp hogranuloma venereum, 360 Dro1avcrinc, 125 Dry day., 253-254 Dry vagina, 89, 333 Dual-energy X-ray ab>orptiomctry ( DEXA), 89 Dual photOn den>itometry. 517-5 18 Duma. cap, 256 Dupha.ton, 92 conu·..indication>. 25~256 failure r".tle of. 2~256 in>ertion of. 255 D)drogcstcronc. 151 D)e tesL 22 D)ing cells. 500 D)-saesthetic \'\thodynia D)'>gemtinoma. 463

Dysm enorrhoea, 34, 124-126 aetiology, 124 clinical fe-auues, 124-125 investigations, 125 treatment, 12~126 Dyspareunia, 2, 212, 376 causes of, 213 due 10 male partner, 213 due 10 female partner, 213-214 investigations, 214 treatment, 21 4-220 Dysp la.ias, ce nix, 409-4 18 diagnosis, 411-412 !,'l":tded as, 409-410 treatment of, 414-418 Dystrophies •ulva, 319, 322- 325, 323t Dysuria, 89, 376

E E. coU, 333, 337,375 Econazole, 321 in pruritus vulva, 320-321 Ectopic gestation, 228-244, 342 aetiok>!,'Y of, 229 caesarean scar, 243 differential diagnosis, 234-235 incidence, 228-229 investigations in, 236-237 ovarian pregnancy, 230-232 tubal prct,'ltancy, 230 persistent ecwpic, 243 physical signs of, 234-235 •ymptorns of, 233 treatment of, 23 7-240 !)pes of, 23~240 un ruptured, 240 treatment, 241 Ectopic pregnancy S« ectOpic gc.tation Ectopic ureter, 73 Ectropion, 326, 329 Electromyelography, 403 Elephantiasis \Uha, 325 Embolization of uterine artery. 168-169 Emergency contraception, 275 preparations a'ailable for, 270 End-t-OC:I, 2, 123 Epoophoron, 23f Erogenic are-.t>, 202-203 El')1hroc)1C .edimentation rate (ESR), 351 El')throm)cin, 361, 362, 364 in !,'T.tnuloma in!,'ltinale, 3.?~360 in lpnpho;,rr.muloma """"ettm, 360 U.ure de,ic.e, 274 Ethacridine lactate, 283 in MTP, 283-284 Et hinyloc>tr.uliol (EE1), 263-265 Evening primrose oil, 99 in breast diseases, 100 Extern al iliac glands, 32f Extern al urin ary meatu s, 14- 15, 24

F Faecal incontinen ce, !18 Fallopian tube, 2 1-!13 ftmbtial end of, 2!/f layers of, !12 lymph atics of, 2 1 methods of testing paten cy of, 22-23 normal, 20 parts of, 2 1-!1!1 ampullary, 22 intc~titial,

22

patency of, 22 Fallopian tube cancer, 469-471 clinical fc•llure., 470 >Urgical >Ulging, 470 Faiians, 6 1--64 De\clopment, C. I extental genitalia, 107, 110 b'Onad, 65-66 M Ctllerian duets, 66--6 7 dc,elopmental defects, 66 h ermaphroditism, 66 MCtllerian duct anomalies, 66 rectum and an al can al, 73 renal tract anomalil$, 5 10 Wolffian duct anomali)'ndromc, 112- 113 Fcm;hicld, 256 :~eh-,uuagt-s of, 25 7 failu n: r.ttc, 256 F~nton ':,operation, 213

Fent lC>l, of. 162 secondal') chango in. 158-160 atroph)'· 158 calcareous degcncnuion, 159 red degencr.uion. 159-160 sarcom.uous dungc, 160 sym p10ms of, I 62 lrt:'dln>clll, 164-171 FlCO scaging, 4301, 4661, 49 II Filshie clips, 273-274, 52.? Firnbrieccomy. 272 Finasceride, 119, 196 in hirsucism. 116-120 Fine-ne~-dle a>pir'dlion ~yiOIO!,'Y (FNAC), 100, 514 ' Firsl pa,s· l>. 312-!ll!) Follicular haem atom a>. !ll!) Folliculostatin stt: inhibin Forbcs-Aibrighc >)1ldrome, 142 Forceps delhel'). 40!) Fossa na,icularis. 13 Fothergill's repair opcnuion, 146 in genic.dl prolapoc. !lOO Frankenhauscr plcxu.. 29 Frei 1es1. 360 Frohlich S)'lldromc, 142, 145 Fro>.c n pchis. 343

G Galac10rrhoca. 100 U'laJ'Iagcmcnt of, J{)()

Game1e incmfallopian 1ransfcr {C IF'T) cechniqur, 210 Gamma benzene hexachloride, 35f>-357 in pcdiculo>i> pubis, 356-357 Gamma-linoleic acid (CLA), 99 in PMS, 126 Garcnerc)'>t, 73 Ca. ernboli>tn, 526 Ccner'dti\'e organ>, 61-64 rnalforntation~ of, 73 Gene therapy, 503 Genetic "'"• 106 Genital cancer. 402 Genital fistulae. 379-!l84 classification of. !lSO clinical feature> of. !)8~!)82 causes of. 380 imestig.uions in. !l82-!l8!l rnanagemenc of. !l8!l-!l84 poscoperati\ e managcmcm, !lS!l

Genital organs, 13, 402 Bartholin's gland, 15 bladder, 23 blood \'CSSCis in, 28 developm ent of the lower, 63f fallopian u rbe, 22 parts of, 21 - 22 labia majora, 33 labia minora, 24 l)mphatic dntinage, 33f nene supply, 24 of che child, 18 o'ary, 20f pehic cellular tissue, 2S..29 pehic musculacure, 25-28 urecer, 30 urelhr.t, 2S-24 urogenit.tl diaphr.tgm, 26-28 ucerus, 19 layen; of, 22 posicion of, 28 vagina, 34 relac ions of, 23-24 vuha, 3~34 Ge nital prolapse, 285-301 aec iology of, 287 classification of, 287-291 differential diagnosis in, 292 in\·(."Stigdt.ions in. 292 of JX>$terior vaginal wall, 290 of uterus, 290, 292 •ym pcde of spread, 34 7-348 prognosis. 354 •ym ptuti>m. 50, 116-120 in infcrtilit). 188 in PCOD, I!H-195 Gl)CCI')IIrinicr.ue, 12.? in d)'>~>enorrhoea, 12.? Gl)cinc' 527 Conadocropin-rele-asing hormone (Gn RII), 48,200 acciono of, 197 agoni.c~. 197 analogue•, 197-200 in corpus luceal pha.,;e deficiency, inferrilicy, 190, 199 in CI')'[>IOrchi$m, 197 in d)l>fun clion al ul erin e bleeding, 128 in d)l>m cnorrhoca, 124- 126 in early aborlions, 197 in cnd01nctriosis, 190 in hypothalamic ~unenorrhoca, 197

in hypolhalamic h ypogonadal infcnility, 197 in induction ofnn rhiplc ovulacion, 197 in PMS, 126 in prt-erclin, 50, 197 Cypol, 277 cn.aftan follicle, 39 face of, 39 layers of, 40f shape, 38 Crdln sl~in , 36 1, 363 CrdniiiOm~ in&•trinalc, 32 1 Cr.m11IOStia, 206 C)1landrobla>loma, 449

H ll.tbitt••l aborcion>, 535 ll.tcm.uocolpo>, 68f

INDEX

Haem oglobin pcrccmagc, 488 llaemophilu> ,-,.gin alb, 3!l0 Haemorrhage, 274, 526 Haemorrhoidal 'cin>, 31 llaemo>ta>b, 398 llalban '> dbca.c. I 39 llanging drop prcpar.uion, 7 llcparin, 87. 90 llcpatitis B. 210 llermaphroditbrn. 66 llerpes genitalis (Ccnit.tl herpc>), 359f symptoms of. 36, II llonnollc replacementthcr.tpy (IIR'T) , 91 cardioprotV) infect ion, 10 11-Y antigcll, 106, 109 I Iydatidifonn mole , 481 complicuion> of. 485 diagno>b of, 485 differential d iagno>i> of. 485 illcidence of, 483 itt\e>tigo~tioll> in, 485-486 placental >itc trophobla.tic tumour, 483-488 n'Current mol.tr pregnant). 488 spnptom> of. 484-485 treatment of. 486 ll)drocorthonc, 114-115,319 in folliculiti>. 319-321 in intertri),'O. 319-321 ll)dronephrosi>. I 79

Hydrosalpinx, 340 17-1Iydroxyprogesterone, 114-11 5 in female pseudohennaphroditi>m, 116 in \irilism , 114-116 H}men, 14f imperforate, 67 I Iyperprolactinaernia, 117 lh)TOid tests, 222 treated "ith, 222 ll)perstimulation syndrome, 193 I I)pertension, 89 lltperthecosis, 117 ll)pOmenorrhoea, 2- 3, 123 lltpothalamus, 48 llypospadias, 66, 205 llyskon, 527, 530 llysterecto my, 240 in interstitial pregnan~y. 232 llysterosalpingos;r.tphy ( IISC), 216-217, 507-511 advantage of, 217-218 bicornuate ute rus, 21 if bilate r.il hydrosalpinx, 217f complications of, 217 findings in, 217-218 genital tuberculosis, 509 indications for, 509-510

Interferon. 321 lnter>ex. I 08-109 cht» i lit', 157f lnter.titial pn!gnanrate anus, 73 Im pcrfi:>rate hymen, 142 hnpt:>tence, 205, 212, 213 Infertile couple, 211 inveSt.i),>at.ions in, 206-208 Infertility, 303, 315, 339 female, 212 aetioi!.'Y· 212 itwestigations in, 214 management of, 219-220 incidence of, 203 issu es involved in, 203 male, 203- 212 aetiological classification of. 20:;...206 faults in the male, 205 im·estigations in, 20&-208 management of, 208-209 P>·rchological considerations in. 211-212 treatment, 209 Inguinal glands, 32 lnhibin, 54

557

tech niqu c of insert ion, 260-261 ln tmutcrine growt h retardation ([UCR), 482 lntmvcnous pyelogro~phy ( IVP), 164, 3 10, 538 lntr.t\ cnou s urogmphy (IVU), 509-510 indications, 509-5 10 precaution> and contmindi cations, 5 10 lntroittt>, 212 lm·.~>i\C mole, 483 lmer.ion, !l04-!l06 .!Cute, 30, 304-306 lmitro fenili1.ation (IVF), 2 10-211 ,218,225, 366 coni r.;indicated, 222 in a1oospcrrnia, 2 10 indications for, 211 in female infertility, 212 Iron d clkiency anaemia, 321 Irregular bleeding, 181- 182 Irregular ripening, 138- 139 Irregular sh edding, 139

l.s.aac·s :-.spir. uor, 435 lschaemic h eart disease, 87,89 Isoniazid , 35S in tubcreulosis, genital tract, 353t Isthmu s, 19 IUCD pcrfomtion , 257

J Jon c> dyndrome, 143, 145 Kapo>i'> MII'COilla, 366 Kannan cannula, 281f, 486 KatjOP) knotic index, 10, 52, 53 Kcll) ·, repair, 391 in .)tr~ urimtr) incontinence, 384-395 Kctoron:t7ole, 321, 334, 365 in cmph)'>Cmatous \'ll),, 400 Klincfdtt:r'• ·~ndromc, 114, 205 Kobt:lt> tubule., 308 Koch·, di>c:t>c, 522-523f Kraurosis. 2 I !l Rmkenbt:rg tumour. 464 of the O\"olt). 464 Rulchitsk) cells. 447 R-Yjelly. !158 Kyphosis. 5!1

L Labia majOI"d, 13 consis1 or. 13 Labia minol"d, 13-15 Laparoscopic ch romo1uba1ion, 22-23 adv..nr.agc of. 2 17 indica1ed in, 217-2 18 in •~-sling palcn ty offallopi~n IUbt:, 22-23 Laparoscopic t'Oippcnsion, 39 1 Laparoscopic hy>lcrccwmy (I.AV II), 138 Laparoscopic lymphadcncclom y, 426 Laparoscopic myom celom y, 167-1 f>S Slcps of opcra1ion, I GSf Laparoscopic OV"drian d rilling, 22S Laparu.copic >lcriliJ.alion, 2 7S-274 ad,a•Hag of. 274 Lapart.heopic ulcro~cml ncnc ablation (LL'NA), 525 Laparo.co~. 237 ad,antagc. of. 527 complication> of. 526 diagnostic. 519-524 indication;. 519-525 for genital fhtul.t. 522-523f in ectopic pregnanq. 228 in 0\"olrian and paro,arian pathoiO{..'Y· 52 If in pehic inn.. mm.uory di>ea.e, 524 in u1erine and 1ubal pathology, 522f suspec1tain, 3&4

Lt:trozolt:, 194 in ano\'ulation, 223 in fcmale infertility. 212 in cndon'lctrio.">b. 224

Lt:ucorrhoea, 329 Lc\ator mt..cle>. 25-26 LL')dig cell(>), 65. 205, 208 Lc)dig cell d)'> function. 208 Libido. 5!1. 89. 275 loss or. 150. 196. 277 Lichen sclerosu>. 213. 321 Linea nigl"d. 4 Lipid profile, 90. 93. 190

Liquor folliculi, 39 Lithotomy position, 400, 509 l.i\'er function te;;t (LIT), 353, 492 Loperamide, 403 in faecal incontinence, 403 Low density lipoprotein {LDL). 19 L 192 Lugol's iodine, 328 Luteal phase defect {LPO), 43 Lutein cysts, O\"olt)', 313 Lu teinized unrupwred follicular (Lt:F) syndrome, 224 Luteinizing hormone {LII), 50-51 Lymphaticsyslem, 3 1-33 of !,>en ita! organs, 31 LyrnphO{..'T·illuloma ,·e nereum, 360

M Mackenrodl 's lig-.tmenl, I 7, 24, 28-29 Madl ene r oper.ttion, 272 Magne1ic re;;onance imaging, 516-517 Magnos cope, 412 Malaria, 239 Male inferlilily, 203-212 Malformed fe1us, 203 Malignant melanoma, 478 Mammography, 90, 102-103 in breast, 99-105 Mana1,>eme1ll of azoospermia, 210 ~1anche;;ter operation see Fo1hcrgill'• repair operation ~l ant(>ux

1e;;t, 351 and Bonney's t('St, 388 ~larshall-~larchetti-Krantz opcr.ttion, 391 ~l asculinism, 114 Klinefelter's S}1ldrome, 114 ~lasculinizing o'arian tumoun.. 117 ~lastalgia, I 02f treatment of, 102 ~faturation index S« ka..,X>P)knotic index ~farer-Roki tansl..·y-KUstcr-llauser S)1ldromc. 67-68 ~lcCune-Albright syndrome, 84 ~lebt:ndazole, 320 in lhreadworms, 320 ~fedicallennination ofprq;nancy {~ITP), ~I arsh aii

279-284 grounds for perfonning, 279-280 la1e sequelae of, 284 me1hods of, 280 place for performing, 280 Medroxyproge;;1eron e, 93, 150, 250, 313 in chronic pehic pain, 245-247

in endornecriosis, 24 7 in fi:>llicularq~IS, 312- 313 in ov menstmation, 122 MenMnral rq;ulalion S)linge, 28 If MenMnral.i on, 41-42, 55 nc uroendocrine elponemenl of, 191 S)'IUpiOm>, 179 Ml,.,cs, 465 in opcrfuion scars, 465 in uu.:n as, 465

Mccascatic carcinom:u, 464 MclhOircxalc (mTX), 237-239 in unni(JII~rcd cc10pic gytnpiOIIl S, 133 Metrorrhagia, 2-3, 123 M. hommis, 337 Miconatolc, 32 1 in pruritll> vulm, 320-321 Microa>>i>t~'lone {Rt:, 486), 16.?, 195,270,282- 283 in QJ,hing's >)1>drome, 195 in ~'Ctopic pregnancy, 195 in fibromyomas, 524 in ~rrr, 195 in prcven1.i ng pregnan cy, 270 in ripening of 1he cervix, 195 Millcr-Rul?rok ICSI, 207 Minilap:trolomy, 272-273 Minipiii/ POP, 266-267 :tdvalll~gcs of, 266 drawbacks, 2f>f> side elfeels of, 267 Minoxidil , 117 mlc in hirsulis m, II f>- 120 Mircna, I S6, 182f Mboproslol, 283 in I\'ITI~ 283-284 Mbplau:d IUCD, 261-263 ctu> repair, 298 in genital prolapse, 298

INDEX Mo\'ing.,trip tc..:hniquc. 499 MRI, 69, 72, 97, 517 conLr'd.ind icaLion~, 51 7

idemif}ing brea.>t CilllCCr, 4 28 in adrenal nc"Oplo~.>m, 116 indication;, 516-51 7 in endometri.tl can~"Cr, •I!H--•1!15 in intestinal tract il"!iuric>, 402 of fibroid, 516 technique. 517 ~lucinous C)Motdenoma, 44!1f, 44;;..446, 447.450 ~lucous pol)pi. !129 Mucus method. 25!1-254 Mullerian anonulk~, 66-67 aplasia, 66 h)poplasia, 66 Mounps. 141. 205 M. urc'Qlyticus. 337 Myomatous polypu;,, 305 Myomectomy, 168f com pi icat ion>, 170 preoperative rc", SSS Oestrogen nithdr.m,tl bleeding, 41 Oligospemli.t. 207 Oocpe fusion defect. 225

Pacey's repotir, 391 in stres> incontine nce, 39 1-393 Paediatric f:ynaecological problems, 75-86 Paf,"'t's disease, 3 19, 321, 472f Palliative therapy, 503- 505 PALM-COErN dassifica1ion, 132-133 Pap smear, 4, 46, 86,474-475 Papotnicolaou test, 7-8 for cancer, 7- 8 Par.;colpos, 28, 286 Par.trnetritis, 309- 310 symptoms, 309 treaunent of, 309 Parametrium

S« utenas

Paroophoron, 23 Paro\'arian qst, 308 treatment, 309 Parturition, 328 PCOD/PCOS, 314-318 treatment of, 316--317

559

Peak day, 221 f, 253-254 Pearl index. 25S Pediculosb pubis, 35f>-357 dinical features, 356 di.tf,'llOSb, !l56 treatment, S56-S57 Pe hie a~'C», !l6!l Pchic adhesion>. 2, 524 Pchic blood ws.ch, 29--!11 Pchic cellular U..ue, 28-29 Pchic Ooor, 21, 26,28 .ut.~tomy of, 27f l.l)er':> of, 26 Pc hie haematocele, 233 Pchic inOammatO')' disease (PID), chronic, 2,35,162,214,260,337-343, ~?1,356, 399,524 aetiology, S!l7-339 diiTcrcntial diagnosis, 341-342 investigations in, 342-343 prognosis, 345 proph ylaxis against, 346t >yrnptoms and signs, 34 I treat men 1, 343-345 Pelvic inn ervation s, 33

Pelvic kidn ey, lfi3, 310, 5 13f Pelvic muscles, 25 ~upcrficial

1nusck-s, 25

urogenital diaphr.;wn, 25 Pc Ivic oo-gan prolapse, 287f Pelvic pain, 124,245-251 Pchi>, 373 >pact"()CCttpying lt">ions in, 3 73 Penicillin, S!l4 in >yphilb, !l62 Pcrcutan•'Ou> ab>c•~ dr;tinage (PAD), 345 Pcrcutan•'Oll> epidid)mal sperm aspimtion (PESA), 210 Perimetrium sn utcnt; Pcrinc-dllacerations, 400 ~'Ompletc tear, 400 lir':>t d~'TCC, 399-400 old.. runding complete tears, 400-401 S)1nptom>, 401 treatment, 40 I >c-cond d~'Tee, 400 third de~o:ree, 400 Pc ritonc-o~l d isorde~. 224 ther.;py for, 224 Pc riu reth r.;l abscesses, 24 Pcr..istcnt ectopic pregnancy, 243 Pcr..istcnt trophoblastic dise-ase (f'fD), 488 Pcr..onll, 25!l Pc.s>arics, 332 introduction of, 335 Pessary treatmen t ofpmlapse, 293 Ph th:tlyl sulp hat hiazolc, 404 in rcctovagin al fistu Ia, 404-405 Pigmented mole or naevi, 325 Pipcllc aspiration cytOk>f,')', 435 Pipen11in c, 320 in thrcath...·orms, 320

Pituitary gland, 50-51 :ullcrior (adenohypophysis), 5(}...51 honnont'S, 50

posterior (neurohypophysis), 50 honnon~~.

50

Pituiml') infantilbm, 148f Pl.tcenwl alklolinc phosph:uase (PLAP), •(ol •1-•145. 4 55 Pldccnwl pol)pi, 489--490 Pldccnwl >itc trophoblastic tumour, 483-488 acliolog) of, 483-484 imc.ligalion> in, 485-486 trC'o\ltnCnt, 486

560

INDEX

Pla.rna proge>terone, 53, 221-222 Pncumocy~u~

carinii pneumonia, 366

POP-Q>}'>tem, 287f Pol}t}'stic O\'.trian di>ea>.~ge (PPII), S, 18, 150, 215. 49(}...491 Pouch of Douglas, 17, 218f,524 aspirdt ion. II inspection of. 524 Poupart's lig-.tment, 29, 32 Precocious puberty, 83 caus..-s of, 83 Prednisolone, 115, 223 in adrcnog.:nital syn drome, 114-116 in anovulation, 222

in female infert.ility, 212 Pregnancy, 46, 135, 378 Pregnancy-induced hypertension (Pill), 485 Pregnancy lc'l>t, II Premature ejaculaIion. 213 Prernawre menopause. l).l-95 Catt>ement of, 82 neuroendocrinologic control of, 76f physiological changes, 82 Puberty menorrhagia, 85 Puberty, 75-86 anomalies ofgonaddl function, 82--84 precocious puberty, S3 Pubococt.ygeus muscle see pelvic m usck-s Puerperium, 326 Pyelonephritis, 376 treatment, 376 Pyometra, 90 Pyab Stick tL'l>t, 38S

rnanagcrncnt of, 95

Premature mpture of mcmbr.mc (PRO~!), 331 Prcmenstrual>)11dromc (P~IS/ P~IT). 12&-127 aetiolog). 126 clinical feature.. 126 diagnosis. 126 treatment. 126-127 Presacr.tl neurectOlll)'· 250 Primolut, 92 Primordial follicle. 37 Procidcn ti a. 4, 290 Proctitis. 360, 498 Proctoscop)'• 404 Progestascrt, 12.? in dysmenorri1oca, 124f Progesterone, 40, 53, 192 in bredSI malign:mcy, 115-116 in corpus luteal phase deficiency (CLPD), 190 in detecting ovulation, 40 in premenstrual phase, 47 in threatened and recurrent abortions,

190 in uterine 1nalignancy, 116

side effc'Cl> of, 50 ther.tpy, 115-IHi Proge>tcrone challcngc test. 144, 15(}...151, 152t Progcstogen-only pill (POP). I 00, I29t, 26&-267 in benign brea.t tumour., 10(}...102 in irrcgular ripening, ISS-139 Prolactin. 145. 198 Prolactin-inhibiting factor (PI F'), 48 Prolapse. genital Surgicaltcchniques of. 273f male, 271 V'.J>eCtorny, 271 sequelae of, 271 Strangury, 375 Str.Jwberry vagina, 364 "Stre-ak" gonad, 112-113 S trc-ak o\'ary, I I 6 Streptococcus, 310, 332 Stress urinary incondnence, 384-395 in,estigations,382-383 S)mptOm of, 383-384 treatment, 38~393 surgical procedures, 391-393 Stromal endometriosis, 187 Strurna o\'arii, 447

Subdermal implan~.,;, 267-268 ad,ad,·antag of, 269 Sildenafil (Viagra), 209-21 0 in male infertility, 203-212 Silicon tylinder prosthesis, 212 Simmond"; di;ea;.e, 142, 147, 150 Sims·l luhncr test, 303 Sims' vaginal spcyndrome, I 14 in male infertility, 203-212 TeiJ"'dC)'eline, 331, 346, 363 d•lam)dia, 363-364 in chancroid, 361 gonococcal 'aginitis, 362-3()3 in grmuloma inguinale, 35~360 in lpnphogranuloma \enercurn, 360 in PID, 246 in urethritis, 375 Thayer-Martin medium, 363 Theca cell tumour, 448 Threadworrns, 320 ITeallllenl, 319 Threatened abortion, 485 Thyroid function tests, 150

561

ThtToid stimulating homlonc (TSII). 50, 484-485 Tibolone, 93 Tietze ·s S)ndrome, I 00 Tiludronate, 94 Tine-a tTuris, 319-320 treatment, 319 Tinidazolc, 365 in tricho•noniasis, 364-365

Today, 256, 2i'i7f Total abdominal hysterectomy, 345 Total tumour cell kill concept. 500 Toxic shock >yndrome (TSS). 255-256, 334 Tr.msabdominaluhm;,onogr.Jphy (TAS). 511 Transcenica.l resection of endotnccrium

(fCRE), 136t, 405 Trans,aginaluhrasound (fVS). 237 Trachelectom), 426f, 429. 525 Treponema pallidum, 361 Trichomona;. 'aginali;, 320 Trichomonia;.is s"sexually trdn~mitwd diseases (STDs) Trichophyton rubrum, 31~320 Trimethoprim, 361 in chancroid, 361 Tripha;.ic combined pills, 265 Triple X syn drome s~ supcrfemale Trophobla;.tic dise-ases, 481-493 categorized into, 481 WHO prognosis scoring ;,y.tcm for, 4911 Tro>pium chloride, 394 in stress incontinence, 384-395

Tme hermaphrodite, 120 Tubal abortion, 230 Tubal cannulation, 529 Tubal pregnanq, 228, 35sis ofgcnitaltr.oct, 347-355 clinical fCatUrL"li, 350-351 differential diagnosis, 352-353 !,renit.al tract lesions, 34S-350 investi!,r..ttions, 351-352 pathogenesis, 347-348 prognosis, 354 >ur!,>el)', 354 treatment, 353-354 Tuberculous endometriti>. 349f Tuberculous P)OSyndromc, 99, 112-113, 142 deformitiL-. of, 112-113 incidence of, 113 1\vist.ed ovarian cyst, 2S5, 245, 342

u

Ch.rasound, 6, 86, 114-115, 117. 343, 470, 51 I diagnostic indication>, 514 in ectopic pregnane)•, 236 in endometrio.i>, 17•1-185 in g)naecological diagno.i>. 1-11 in hirsutism, 118 in hydatidifonn mole, 485 in measuring bladder \Oiume and n-.idual urine, 389 in PID, 228 therapeutic applications of, 514 Undescended lt"SItation stt ectopic gt.-station Un:apla>ma ttrcalyticum, 2 14 Urett:r. 24-25 rdation. of. 2~24 t:rctcric cathctcri7.ation , 383 Ureteric fistula. !188-!184 im estig.uion>. !182-!18!1 spnptorns of. !188-!184 treatment of. !18~!19!1 Ureteric obstruction. !177-!178 Urethr'.tl caruncle. 21!1 treatc>d by. 376 Urethr-.tl di\erticulum, 377 lre"".tlnlent, 3ii Urethr-.tl prolap.c, 377 Uret hr-.tl steno;,i;, !177 sit e> of narro"ing, !177 lrt:'dUilt:lll,

377

Urethr-dl>yndromc, 89 Urethritis, !164 aetiolo~,ty, 376 symptoms, 376 tre:::-auncnl, 376 Uret hroccle, 287 Urethrocystometry, !189 Urethroscopy, 388 Urethrovaginal fistula, 384 Urge incontinence. SSG Urinalysis, 538 Urinary calculi, 373-374 Urinary r..wlac, 377 cla»ific-. 372-376 L)">titi>. 374 ltt:'.tttnenl, 37~374 incontinence of urinc, 37•1-375 micturition. difficult. 37~37•1 cause of. 374 treatmcnt. 37~374 P)elonephritis (P)cliti>). 376 treatn>ent. 376 retention of urine. 372-!173 causes. 372 urethr-.tl sp>dromc. !17!1 Vrinary rea.enaion srt urinary malfunctions Urinary lr'dCI, !l 77 infection (UTI), !177 injuric>. 396 obstnJCIion in , 291 Urine cu hu re. !182-!18!1 Uri path, 364 Urispa;,, 394 in strt.-ss inconcincncc, 393 Uronowmetry, 389 Urogenital dinCrcntiation , 65 Urogenital system, 62f Uroprofilomctry, !189 Uterine anery embolit.ation , 168-169 Uterine cavity aspimtion. 97 Uterine cramps, 124 Uterine dc-.ccnt, 287 Uterine fibroid, 215, 2!15

U terine i•yury, 402 U terine polyp;,, 172 Uterine prolap;,e, 3 77 Uterine rupture, !196 Uterine sarcomas , 4!18 incidence of, 437 treatment of, 439 types of. 4!19 Uterine S)nechiae, 528 U 1e rosacral ligaments, I 7 U ten•s, 18-20 perforation of, 402 mpture of. 402

v Vacuum evacuation, 281-282 complications of, 280-281 mortality rate, 282 Vagina, 14-15, 52, 397 biolo~:y of, 326-329 chemical and other bums of, 399 diseases of, 323 in fee• ions, 329 in nam mations of, 332-334 d iaf,'11Sis, 332 symptoms and signs, 332 treatment, 330

pll of, 16 radiation, 335 rclati ons of, 16-18 Vaginal bums, 399 Vaginal cancer, 478-480 clinical features, 479 diagnosis, 479 management of, 4 79-480 staging of, 4 79 \ 'aginal cysts, 335 Vaginal discharge, 326, 333, 334 Vaginismus, 212-213 findings, 212-213 treatment, 213 \ 'asec:tomy, 208 \ 'asopressin, 51 in detnJSOr instability, 393- 395 Vault prolapse, 298 VDRL testing, 362, 5!18 Venete'al dis of, !122 ITt:'dllllCnl, !122 Vuh,al \'CStibulitis, !122 Vulvit i>, 2 I !l Vulvov.;gin:tl hacmatoma, 398 Vulvov-.;ginitis, 190, 333, 376 in ch ildrcn , !120

w Wand ering fibroid , 160 Weight bearing cxcrds~-s. 90 Weight change and am enorrhoea, 15~151 Weight gain , 1!151, 18 1- 182 Wcnhcim 's operation, 35, 214, 381 \Vcrthcim 's r,ldical abdo•ninal hysterec1.orny,

525 White leg, !ll 0 Withdrd\\"dl method, 254 \\'olffian duct, 2 11, 73, 308 \\'olffian duct anomalies, 73 \\'uchc!l! ria b•Utcrofti, 325

X X chromo>Ome, 46, 113 X..-d)'· 89, 149f, 494, 509 dl