Test Tube Revolution : The Early History of IVF 9781922235077, 9781922235060

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Test Tube Revolution

Test Tube

Revolution The Early History of IVF John Leeton

© Copyright 2013 John Leeton All rights reserved. Apart from any uses permitted by Australia’s Copyright Act 1968, no part of this book may be reproduced by any process without prior written permission from the copyright owners. Inquiries should be directed to the publisher. Published by Monash University Publishing on behalf of Monash University. Monash University Publishing Building 4, Monash University Clayton, Victoria 3800, Australia www.publishing.monash.edu www.publishing.monash.edu/books/ttr-9781922235060.html Design: Les Thomas  National Library of Australia Cataloguing-in-Publication entry: Author:

Leeton, John, author.

Title:

Test Tube Revolution: The early history of IVF/ John Leeton

ISBN: (pb)

9781922235060 (paperback)

Subjects:

Wood, Carl, 1929–2011. Fertilization in vitro, Human--Australia--History Fertilization in vitro, Human--United Kingdom--History Human reproductive technology--Australia--History. Human reproductive technology--United Kingdom--History. Human embryo--Transplantation--Australia--History. Human embryo--Transplantation--United Kingdom--History.

Dewey Number: 618.178059 Printed in Australia by Griffin Press an Accredited ISO AS/NZS 14001:2004 Environmental Management System printer. The paper this book is printed on is certified against the Forest Stewardship Council ® Standards. Griffin Press holds FSC chain of custody certification SGS-COC-005088. FSC promotes environmentally responsible, socially beneficial and economically viable management of the world’s forests.

C on t en t s Foreword . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ix Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi Abbreviations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .xii Note on Sources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xiii Chapter 1 The Rival Teams . . . . . . . . . . . . . . . . . . . . . . . 1 Chapter 2 Alternative Treatments: Artificial Tubes . . . . . . . . . . 7 Chapter 3 Nine Frustrating Years . . . . . . . . . . . . . . . . . . . 11 Chapter 4 The Boy from Jerilderie . . . . . . . . . . . . . . . . . . .21 Chapter 5 Success at Last . . . . . . . . . . . . . . . . . . . . . . . 25 Chapter 6 Nine Normal Pregnancies . . . . . . . . . . . . . . . . . .31 Chapter 7 The Legislators’ Dilemma . . . . . . . . . . . . . . . . . .35 Chapter 8 Ethics and Frozen Embryos . . . . . . . . . . . . . . . . 44 Chapter 9 Opposition and Guidelines . . . . . . . . . . . . . . . . .50 Chapter 10 The Problems of Ambiguous Legislation . . . . . . . . . .56 Chapter 11 The GIFT of Life . . . . . . . . . . . . . . . . . . . . . .65 Chapter 12 The Struggle for Surrogacy . . . . . . . . . . . . . . . . .68 Chapter 13 The End of the Beginning . . . . . . . . . . . . . . . . . 75 Afterword: Where Are They Now? . . . . . . . . . . . . . . . . . . . . . .79

In memory of Professor Carl Wood AC, an inspiring leader in medical research and champion of women’s health.

F oreword

F oreword I remember first meeting Carl Wood at the inaugural meeting of the Australian Society for Reproductive Biology in the late 1960s. To me as a graduate student he was already an awesome man of medicine, interesting and interested in the ideas of those around him and surprising in his interest in basic biology. When he came to Jerilderie in western New South Wales to visit Neil Moore, my PhD supervisor in 1971, I got to know a little better the extraordinary character that was to have an indelible influence on my career and personal life. He was the genuine model for creativity – he thought outside the perimeters of his discipline and encouraged us to explore his vision with whatever expertise we had. He had a problem that he could not resolve for infertile patients: the failure of sperm and eggs to intermingle because of tubal blockage and other reasons meant that such couples could rarely form a family. The availability of babies for adoption had literally evaporated with the advent of the ‘pill’ and legalisation of abortion. He turned to engineering (CSIRO) and biology for a resolution. It was my good fortune that I happened to bump into him on one of his wanderings as he innovatively explored the options. It is true that he co-opted colleagues and students like me to his cause through an infectious spirit of inquiry that challenged their intellect. Giants of endocrinology – Jim Brown, Bryan Hudson, Henry Burger, David de Kretser – were all involved in one way or another, although a number of these thought Wood was over-optimistic about the medical application of IVF. Wood did win a Ford Foundation research grant that primed the pump to bring me back from Cambridge in the UK, to join his team in 1977. John Leeton and Mac Talbot were the clinical front line of Carl’s IVF interest and Alex Lopata was trying to develop viable human embryos in the lab. Carl and John persuaded me to join them because they thought a basic scientist, who was unafraid to innovate, might make a difference. I returned to an adventure that shook the world. There are some moments that have extraordinary meaning. Perhaps the most significant was when I asked Carl if I could work with John on a few patients where we controlled superovulation with the synthetic drug clomiphene and the timing of ovulation with hCG (human chorionic gonadotropin). The idea of using fertility drugs had been dismissed by Bob – vii –

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Edwards and Patrick Steptoe, leaders of the British team involved in the development of IVF, who had had success in the natural ovulatory cycle (1978), and by the Melbourne teams, due to persistent failures. I believed the animal data for IVF success, that I was familiar with, would translate to the human. Carl agreed to the study and John and I set about making this work with the help of the hospital Obstetrics and Gynaecology resident Dr Paul Sheckelton and our incredibly motivated and professional nurse coordinator, Sr Jillian Wood. My students and technical staff – particularly Janice Webb – were backing me up, together with the patients’ enthusiastic support and advocacy. In 1979 we began a revolution in medicine using fertility drugs to enable IVF to treat infertility. It worked! A raft of IVF pregnancies in 1980 caught the world’s attention and we never looked back. Carl was the inspiration and energy behind our work. He cajoled us, he intellectually stimulated us, pushed us, lauded us, and he found ways to enable us to work in the face of considerable opposition. His legacy is this story, told through the eyes of a true believer – Carl Wood’s close colleague John Leeton – who survived the onslaught of the press, other colleagues and some personal disappointments to be the scribe for the events of a medical revolution. The story of Carl Wood – the enigmatic genius who crafted diamonds from the rough stones around him, with his charismatic personality and astonishing intellect, to enable the world to enjoy the ability to form their own families by assisted reproduction techniques – should never be forgotten. The numbers now exceed five million IVF children. They are born in almost every country of the world, using variations of the method he oversaw. Thank you Carl for all that joy. Alan Trounson, San Francisco, October 2012

– viii –

P reface

Preface The writing of this book began ten years ago when journalist Robyn Riley embarked with IVF pioneer Carl Wood on a project to chronicle his life’s work. After only a few interviews, however, it sadly became evident that the disease that would eventually take his life in 2011 – Alzheimer’s – was progressing, and would soon preclude further discussions. The important story of Australia’s leading clinical scientist was, therefore, suspended. In 2005 it was suggested that his role in one of the great medical stories of the 20th century could be carried on and completed with my assistance, as a colleague and long-time friend of Carl’s, who had worked closely with him throughout most of his professional life. Robyn Riley and I began to continue the work to highlight Wood’s involvement and leadership in the early development of IVF, the crowning glory of his illustrious career, and when she needed to step back from the project, I brought it to completion. As far as I am concerned, IVF and Carl Wood should be forever linked. You can’t mention one without the other. It was for good reasons that Wood was recognised throughout Australia as a father of IVF. In the pioneering days of IVF, during the 1970s, there developed a close but largely unknown rivalry between the British team, led by Bob Edwards, and the Australian team led by Carl Wood. Although rarely in direct contact, they experienced remarkably similar challenges and adversities on their respective journeys. Those early trials and tribulations, and the competitive aspect of the research, are part of the early history of IVF and help to make it such a remarkable and inspiring story – a story yet to be told in regard to events in the 70s and beyond, which led to the first IVF pregnancy in the world in 1973 and the first IVF birth in Australia in 1980. This pioneering work was carried out in a climate of ongoing opposition and hostility from many influential quarters of the community where emotionalism was running high, particularly in relation to the moral and ethical aspects of the research. Although there have been many detailed accounts of the numerous successful research projects and outcomes in IVF published in both national and international journals, as well as a plethora of reports of ‘world firsts’ in the mass media, there has been little of the human side recorded and there is a lack of public understanding and appreciation of many of the difficulties and obstacles confronting the early researchers. The challenges of obtaining funding, the politics at hospital, university and government levels, and the – ix –

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legal impediments to various IVF procedures have never been fully reported. Many of the shortcomings of the 1984 Victorian state legislation, which was passed in haste without understanding its possible adverse implications on further IVF developments, have never been fully exposed. They are discussed here in the context of such events as the 1983 government moratorium on the DE program and the total prohibition of the 1984 Act on the development of both the micro-injection and embryo biopsy techniques, pioneered in Victoria but clinically developed overseas. This is a story of endeavour by a large number of dedicated researchers working in an uncharted field, under the inspirational leadership of Carl Wood, that has eventually led to the successful developments of IVF treatments today. John Leeton, Melbourne, October 2012.

–x–

Acknowledgemen t s

Acknowledgemen t s The author wishes to gratefully acknowledge the valuable contribution of Robyn Riley, who began the writing of this book as Carl Wood’s biographer, when she made extensive interviews with Wood and his family, and later with Alan Trounson. She was the prime mover in the original proposal to record this history and was further involved in the writing, drafting and photo acquisitions for the book. Alan Trounson has also given helpful advice on the contents of the book as well as supplying added data in the scientific discussions. The author wishes to acknowledge the fortitude and frustrations of the women participants in the early IVF programs. Very few women in the early days of IVF treatment succeeded in taking home a baby but their deter­ mination, belief and courage paved the way for the successful IVF programs of today. Finally I wish to thank my publisher, Monash University Publishing, and its Director, Nathan Hollier, for their support, helpful advice and tolerance in finally bringing this story to print.

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T E S T T U BE R E VOL U T IO N

A bbreviat ions CJD

Creutzfeldt-Jacob Disease

CSIRO

Commonwealth Scientific and Industrial Research Organisation

DE

donor egg

DI

donor insemination

EPU

egg pick-up

GIFT

gamete intra-fallopian transfer

hCG

human chorionic gonadotropin

ICSI

Intra-Cyptoplasmic Sperm Injection

IEC

Infertility Ethics Committee

NHMRC

National Health and Medical Research Council

O&E

obstetrics and gynaecology

PGD

Preimplantation Genetic Diagnosis

QVH

Queen Victoria Hospital

RTAC

Reproductive Technology Accreditation Committee

RWH

Royal Women’s Hospital

SRACI

Standing Review and Advisory Committee on Infertility

SUZI

Sub-Zona Injection

– xii –

N o t e on S ources

No t e on S ources This book has been written for a general readership and, as such, detailed references have not been included. Graphs, diagrams and tables have been avoided for the same reason. All statements, comments and reports have come from interviews, discussions, meetings, scientific papers, mass media reports and personal communications, all of which, except the last, are in possession of the author or can be readily confirmed from the public record.

– xiii –

The R ival Teams

Cha pte r 1

The R ival Teams On 25 July 1978 the world’s first test tube or in-vitro fertilised baby, Louise Brown, was born in Oldham, England. For scientist Dr Bob Edwards and gynaecologist Patrick Steptoe the birth of this baby girl was the culmination of ten years of endeavour. Their stunning achievement was acclaimed throughout the world, yet few people were aware of the close rivalry during this decade between the British group and a similar IVF group in Melbourne, Australia, led by Professor Carl Wood. The Australian group achieved its first IVF birth in 1980 (the world’s third IVF baby) with the delivery of Candice Reed in Melbourne, but quickly became the international leaders in further IVF developments. The achievements of this Australian group would later include the first frozen embryo pregnancy in the world, the first donor egg baby in the world, and the world’s first pregnancy and birth from a sperm retrieval operation. They would also make possible Australia’s first surrogate birth. Infertility had remained in the backwater of gynaecology for many years, but the early 70s saw a rise in the demand for its treatment. There were several reasons for this. The first, and most important for Australia, was the passage of the Births and Deaths Registration Act (1960), that removed the blight of ‘illegitimate’ pregnancy and allowed single women to keep their babies with full legal and financial support. This legislation, though commendable, drastically reduced the number of babies for adoption, that until then had represented the main means of managing infertility – a medical condition that still affects around one in ten couples worldwide. The legalisation of abortion in Victoria in 1969 also affected the availability of babies for adoption, albeit to a lesser extent. Another factor was the amazing advances in other branches of medicine, including open-heart and heart-transplant surgery, joint replacements and cancer cures. Why not in the treatment of infertility? The British and Australian teams exploring IVF were not at all, then, engaging in an exercise that was either purely academic or on the other –1–

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hand simply commercial, as various critics suggested. Rather, they were responding to meet a social and human need as couples demanded effective treatment for infertility. The early history of these groups followed a similar pattern, despite their working independently at opposite ends of the world. Acting in isolation they faced remarkably similar, stressful circumstances of frustration, failure, criticism and condemnation.

The Australian Team Carl Wood was appointed in 1964 to the Foundation Chair in Obstetrics and Gynaecology at Monash University, at just 34 years of age. He had a brilliant medical mind, graduating from the University of Melbourne with the Honours Prize in Medicine in 1952 and winning a Fulbright scholarship to London in 1961 to research uterine action. He also worked as a research associate at the Rockefeller Institute in New York, before returning to Melbourne with wife Judith to accept the position at Monash and raise their three children, Gavin, Caroline and Simon. Wood originally considered a career in cardiology but like Bob Edwards, who switched from agriculture to embryology early in his career, he changed his mind to take up obstetrics and gynaecology. He obtained wide surgical experience in Melbourne and later in London. Character and destiny are said to be determined to a large extent by genes. If this is so environment clearly also plays a role. Carl’s father, Carlyle, was a respected gynaecologist still operating from his Melbourne practice at the age of 70. Carl was born in Melbourne in 1929 and educated at Wesley College where he excelled in, among other things, sport and debating. In a series of interviews with Robyn Riley he remembered: ‘We had a wonderful English teacher called A.A. Phillips. Mr Phillips was an exceptional teacher and it was many years before I appreciated his contribution to students such as myself. He taught us to think for ourselves and be analytical in our thinking.’ That same class of 1946 would produce a Queen’s Council, in S.E.K. Hulme, and Australia’s leading historian, in Geoffrey Blainey. Five years after graduating from Melbourne University, Wood became a Senior Lecturer at London University. ‘I liked London, and thought of staying,’ he said. ‘I had also been invited to be a professor at London University, but in the end accepted the offer at Monash University because I knew it would allow me more freedom for my research.’ –2–

The R ival Teams

Wood was a flamboyant lateral thinker with diverse medical interests. In the first five years of his professorship at Monash his team became leaders in several fields including birth control, abortion reform, foetal physiology and monitoring in labour. Writing his obituary for the Australian Medical Journal in 2011, colleagues Gab Kovacs and I wrote: He had many endearing features. He very generously shared the credit for his achievements with his team, was inclusive of colleagues who had skills to offer, and could ignore someone’s negative characteristics while encouraging their positive contribution. He successfully managed the egos of the IVF team, and kept us working together for the common good. But most of all, he was fun to work with. Carl often entertained us with his anecdotes, and was very open and analytical when speaking about himself.

Wood was described in interviews by Judith as a workaholic. In 1964, when Wood took up his Chair at Monash, I was a part-time Sen­ ior Lecturer in the department. In those early years infertility was a minor specialty; not due to a low patient demand – that was increasing – but because of the absence of successful treatments. Male infertility was recognised, but had no proven cures; donor sperm was not yet available and success in surgery for blocked fallopian tubes was less than 20 percent. The only encouraging treatment of infertility in the 1960s lay in the development and clinical application of fertility drugs to stimulate ovulation. Wood became interested in IVF in 1969 following a report in Nature by Edwards and Steptoe describing early fertilisation of human eggs in vitro. He sent one of his department members, Dr Mac Talbot, to visit the Oldham program in London. Further encouragement in 1970 came from Professor Neil Moore, an auth­ ority on culture of sheep embryos whom Wood had visited at his laboratory at Jerilderie, New South Wales. Moore encouraged him to try IVF treat­ment in humans. At this time, however, Wood was busy directing at least ten diverse research projects and had neither the time nor the inclination to personally undertake an IVF program. Instead, he turned to me to organise and manage a clinical IVF program. I was an obvious candidate as I had recently been elected Honorary Director of the Infertility Clinic at the Queen Victoria Hospital (QVH), that was the teaching hospital for Carl’s university department. I was experienced in laparoscopy and also had a public and private practice in –3–

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obstetrics and gynaecology. These avenues offered a steady supply of infertile patients to the program. With the assistance of Dr Talbot I carried out the required clinical egg collections and embryo transfers for the next seven years. Talbot had been told earlier by Wood to ‘bring back a gimmick’ from his visit to London, so he brought back the laparoscopy technique that would revolutionise man­ agement in gynaecology. Wood and I had already done significant research on contraception. We were both Foundation Members of the Family Planning Association of Australia, and we’d established the first comprehensive family planning clinic in Australia, at the Brotherhood of St Laurence in 1967. While our initial projects involved sex without pregnancy, these became superseded in the next decade by our research into pregnancy without sex. But while the goalposts shifted, clearly the results showed that the medical developments in birth control in the late 70s were relatively successful, whereas the treatments of infertility were not. It could be said that the idea of the ‘test tube baby’ was conceived in the laboratory in England but at the bedside in Australia. Dr Alex Lopata, a medical graduate with a research background, was a full-time Senior Lecturer in Wood’s department and became the scientific director of the program. He had spent the five years before this in the Department of Physiology at Melbourne University. The team was completed by the inclusion of Sister Jillian Wood, unrelated to Carl, to manage the nursing duties. In later years Alan Trounson recalled Jillian’s efforts to do pretty much everything, down to organising the occasional chook raffle to raise money for research. Monash IVF began in early 1971 at the QVH, a 400-bed general hospital in the heart of Melbourne.

The British Team

The prime movers in the British team came from very different backgrounds to Carl, although their long-term aims of overcoming infertility were identical. Edwards was a scientist working in a laboratory, trying to transfer his research on animals into the clinical sphere, whereas Wood was a clinician working at the bed-side striving to overcome infertility in his patients. Edwards was the driving force behind the inception and development of the British IVF program and in 2010 he was awarded the Nobel Prize in Medicine for the development of human IVF therapy. –4–

The R ival Teams

Born in Batley, England, in 1925, by the early 1950s, when he was exten­ sively researching mouse embryos, he was regarded as a brilliant scientist. He began studying agricultural science at Bangor University in North Wales but in 1951 changed to the Department of Zoology. In 1952 Edwards was accepted into the Department of Animal Genetics at Edinburgh University where he began his research in mice embryos and in 1958 he moved to the National Institute of Medical Research at Mill Hill in London. Here Edwards extended his research on embryos into the human species where he attempted unsuccessfully to fertilise eggs recovered from surgical specimens of ovarian tissue. In his final year at the Institute the Director ordered him to stop all further attempts at fertilising human eggs, as this was considered unethical. Finally in 1963 Edwards entered the Physiological Laboratory at Cam­ bridge University where his groundbreaking work would begin. Still, more attempts at fertilising human eggs from ovarian tissue failed until 1968 when Barry Bavister, a PhD student, successfully fertilised hamster eggs with a special ‘magic fluid’. Edwards tried this medium with eggs extracted from ovarian tissue and was delighted to see human fertilisation for the first time. This was certainly a significant milestone in his quest to create a human pregnancy. All further attempts at fertilising human eggs from ovarian tissue failed and Edwards realised that the only chance of successful fertilisation lay in collecting pre-ovulatory eggs from ovarian follicles prior to their rupture and then fertilising the eggs with prepared sperm in the laboratory. The question was how to collect human eggs without resorting to the major surgery of opening the abdomen. The answer lay in a new instrument called the laparoscope that was a modified telescope that could be passed into the abdomen through a small 2 cm incision, allowing the patient to leave hospital within 24 hours. Dr Raoul Palmer pioneered the procedure in Paris in 1958. Two years later, Patrick Steptoe began using this new technique in England at Oldham in 1960. Steptoe, the son of a church organist, was born in 1913 and ed­ucated at King’s College, London. He graduated from St George Hospital Medical School in London in 1939, and in 1941 volunteered to become a surgeon in the Royal Navy. Later that year his ship was sunk off Crete. Steptoe spent three years in a prisoner of war camp in Italy, including a long stint in solitary confinement –5–

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for helping prisoners escape, before he was released in a prisoner exchange in 1943. After the war Steptoe concentrated his studies on obstetrics and gynae­ cology and in 1948 became a member of the Royal College of Obstetricians and Gynaecologists. That year he moved to Manchester to a post in Oldham and set up a private practice. He pioneered laparo­scopy in England and wrote a book about the technique in 1967. In Edwards’ Nobel Prize citation in 2010, Steptoe was described as the clinician who developed IVF from experimental to practical medicine. Edwards needed a surgeon experienced in this method to collect eggs for his fertilisation experiments and in 1968 he met Steptoe at a meeting of the Royal Society of Medicine in London. This was the start of a partnership between scientist and doctor that would eventually achieve the world’s first test tube baby, Louise Brown. The big problem in the organisation of this project was that the work had to be carried out at the patient source, requiring Edwards to set up a makeshift laboratory in Oldham and travel to Oldham from Cambridge – a return journey of 580 kilometres – on a regular basis. In 1969 the team began laparoscopic egg collection with attempted IVF, not realising success would elude them for almost ten years. This did, however, give them a two-year head start over the Australian team.

Earlier attempts at IVF in animals

Before discussing this intense but friendly Anglo-Australian rivalry further, it should be remembered that the earliest attempts at IVF – in animals – were made in America. As early as the 1930s Gregory Pincus at Harvard was attempting IVF in rabbits, and in 1934 reported successful fertilisation and pregnancy. This claim was refuted, however, as the fertilisation appeared to have occurred in vivo (‘within the living’) from naturally ovulated eggs. In the 1940s John Rock tried IVF with 138 human eggs – but again without success. But in 1959 M.C. Chang, working at the Worcester Foundation in Massa­ chusetts, successfully achieved IVF fertilisation and live births in rabbits with donor eggs, that irrefutably proved the IVF conception. It is interesting to note that Chang viewed his success with only academic interest, seeing no reason to apply it to humans. He believed there were already too many people populating the planet. –6–

A lt ernat ive Treat men t s

Cha pte r 2

A lt ernat ive Treat men t s Artificial Tubes Carl Wood had been interested in infertility long before beginning work on the IVF program. The main problem of infertility during the 70s was due to blocked fallopian tubes that had been caused through either infection related to illegitimate ‘backyard’ abortions or previous failed surgery. He wanted to investigate using an artificial plastic tube to bypass this tubal blockage. This was an innovative idea, but had unresolved problems concerning embryo culture and timing. In 1970 Wood and I attempted such a procedure on an infertile woman who had lost both her fallopian tubes in previous surgery. The aim was to syringe the husband’s sperm into a plastic bag encasing the ovary at ovulation and then flush the hopefully fertilised egg into the uterus via a plastic tube. The plastic material was constituted of silastic, a biologically inert substance specially provided by the Dow Corning Institute in America. This idea originated from a previous ambitious operation devised in 1969, where Wood and I wrapped plastic bags around both ovaries to achieve a reversible form of sterilisation. This operation was given the imaginative title of Ovariotexy. No woman became pregnant in this series of twenty cases, but surgical difficulties, including a bag ending up in a bladder, curtailed its future development. When the anxious urologist phoned Wood to announce finding a plastic bag in the patient’s bladder, and asked ‘What will I tell her?’, Wood replied ‘Tell her the truth,’ to which the urologist then responded, ‘She demands it can’t be replaced until I get your permission.’ Such divine faith in a doctor would be hard to find today. The plastic tube flushing technique was repeated over two-monthly cycles without success and it had to be abandoned. A curious postscript –7–

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to this failed procedure occurred when a Senior Registrar in the Monash department, who had assisted at the operation, became enthusiastic about its prospects. He flew to Geneva without the knowledge of any member of the team to arrange a possible patent for the procedure. Not surprisingly, his mission was not successful. This procedure, though ultimately unsuccessful, did demonstrate the Monash team’s determination to try and overcome tubal infertility.

Tubal Transplants

In 1972 a further example of this determination to solve the problem of infertility in women occurred through two attempts at transplanting donor fallopian tubes. These attempts entailed using the newly developed tech­ niques in microsurgery combined with immunosuppressive therapy to pre­ vent the tubal rejection. The idea underpinning the attempts was credible, as a human heart trans­ plant had already been successfully achieved and kidney transplants were developing. A microsurgical team headed by Professor Bernie O’Brian, a world leader in microsurgical technology, and including Dr Peter Paterson and Dr Bruce Downing, both members of Wood’s department, attempted this procedure in two infertile women. The surgical transplants in both cases were successfully achieved, after mara­thon operations, each taking more than twelve hours. But once more, the ultimate goal was not achieved as both women failed to conceive. The cause of failure behind all these early surgical procedures lay in the inadequacy of the function of the fallopian tubes, or their substitutes. This function involved the collection of the ovulated egg, with its fertilisation, followed by nourishment and transport of the developing embryo into the uterus. The delicate mechanism required strictly controlled conditions in the laboratory that had to exactly mimic the situation in nature. The procedure of IVF and embryo transfer presented the only alternative way to achieve this and therefore offered the only means of successful infertility treatment.

Microsurgery

Another serious breakthrough in the treatment of tubal infertility arrived in the early 70s through the development of microsurgery. This technology –8–

A lt ernat ive Treat men t s

enabled surgeons to operate more precisely, using binocular microscopes that magnified structures five to twenty times. It had previously been used successfully in joining up small structures such as blood vessels and nerves. Microsurgical tuboplasty operations cer­ tainly increased the overall pregnancy success rates over traditional surgery. Skilled micro-surgeons reporting selective clinical trials could claim succ­ ess rates of up to 70 percent. Pregnancy was limited, however, to those cases with relatively minimal overall tubal damage, which were classically seen in conditions of a singular block at either end or, more particularly, with blockage in the mid-length from a sterilisation procedure. This latter group could achieve pregnancy rates at up to 90 percent. Nonetheless, because of the supplanting of microsurgical operations by the development of successful IVF, sterilisation reversal remains the only form of tubal microsurgery that is practised today. A further example of the supersession of microsurgery by IVF can be found in the stellar medical career of Dr Robert Winston, who was recognised in the late 70s as the leading tubal micro-surgeon in Europe. In 1982, with some encouragement from Alan Trounson, Winston switched his interests to start an IVF program at the Hammersmith Hospital in London and within a few years became a world leader in its further developments. Unfortunately a large number of clinical cases of tubal infertility were due to severe pelvic disease where often the organs were stuck together, forming a so-called ‘frozen pelvis’. Surgery in such cases was hopeless and these patients, combined with women who had already undergone unsuccessful surgery, formed the main group of IVF treatment in the early days of the Monash program.

Donor sperm

Although donor sperm is not an integral part of IVF technology it is relevant to briefly consider its development, as it was often used by couples undergo­ ing IVF with a co-existing male infertility factor. In fact donor sperm offered the only successful treatment for male infertility for over twenty years, until the later advancement in IVF of micro-injecting (intracytoplasmic sperm injection: ICSI) a single sperm into an egg. Sperm donation was predictably a highly controversial subject. The sperm donor, being the biological father, was considered by Australian statute law to be the legal father until the Status of Children (Amendment) Act was passed –9–

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in Victoria in 1984, which recognised the infertile husband as the legal father and excluded the donor from any legal right or responsibility toward the child. A further clinical problem in the early donor sperm program lay in the timing of treatment. The sperm originally used was fresh, meaning it was inseminated within a few hours of its collection. The timing between the sperm donation and the recipient’s time of ovulation presented obvious difficulties in clinical management. In the late 70s this problem began to be overcome by the use of deep frozen sperm, as part of a technique finalised at the Monash Department by Trounson, with co-worker Maha Mahadevan. This allowed a more flexible schedule for timing the insemination with the recipients’ day of ovulation. Trounson reported the first successful use of stored sperm in an IVF program in 1983. I had tentatively begun the first donor sperm service in Melbourne at the Monash Department at QVH in 1975, where donors were recruited from resident medical students. Dr June Backwell managed the clinical treatment. This service survived on a shoestring budget. It was next located at my private rooms and later at Epworth Hospital. No payments were made to either doctors or donors. The AID Trust, designed to charge and pay expenses involving donor sperm treatment, was established by Wood on behalf of Monash and in 1977 began trading at QVH. Wood formed two further trusts: the MFMC (Monash Family Medical Centre), for paying for the donor insemination (DI) program, and the IMC ( Infertility Medical Clinic ), for paying for the IVF program. Without them the two programs could not have continued. I became the first Director (unpaid) in 1977. Gab Kovacs followed in 1983. A revealing side story to the funding of this service occurred when Wood requested a grant from Monash University soon after the DI clinic was established. He was refused on the grounds that donor insemination was immoral, a similar rebuff to that experienced by Bob Edwards at the Mill Hill Institute in London in 1962, and again in 1971 when the Medical Research Centre refused funding for his work because it believed there were serious doubts about its ethical aspects. The service demonstrated, however, the Monash team’s determination to tackle the overall problems of human infertility and not only the tubal factor in isolation.

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N ine F rus t rat ing Y ears

Cha pte r 3

N ine F rus t rat ing Y ears

A Combined Melbourne Team

It is a curious fact that it took both the British and Australian teams, individually, over nine years of failure to achieve a successful pregnancy. Certainly in the early years the going was slow for the Monash group; in 1973 only thirty-two patients were treated. Wood realised that a larger supp­ly of infertile women treated on the IVF program would increase the chances of success, and in 1972 he invited Dr Ian Johnston of the Royal Women’s Hospital (RWH) to join the Monash team and form a collaborative group. Johnston was the Honorary Director of the Infertility Clinic at the RWH and had been keenly interested in all aspects of infertility since attending an international meeting on these areas in Tokyo in 1969. He had visited Patrick Steptoe at Oldham in the same year. His clinic actually treated more patients than those at the newly formed QVH: in 1979 the RWH clinic treated sixty-nine patients compared to the twenty-seven at the QVH. Johnston was an experienced laparoscopist and keen to work on the IVF program. Now a combined Melbourne team existed between the RWH under Ian Johnston and the QVH team under me. Dr Alex Lopata remained a fulltime Senior Lecturer at Monash University but was also the scientific direc­ tor for both groups. Because of the greater number of patients treated at the RWH he naturally spent more time with the RWH group.

Difficulties

Treatments in the early years, with both the British and Australian programs, were often frustrating, and progress was slow. In many cases the egg pick-up (EPU) by laparoscopy was difficult because of severe tubal disease that had resulted in multiple adhesions, or hidden ovaries forming a so-called ‘frozen – 11 –

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pelvis’. Sometimes this condition necessitated blind stabs at collection be­ cause no operating laparoscopic instruments were then available. Egg collection was always a major achievement with less than 50 percent recovery of oocytes (eggs) from each follicle. The IVF program was dubbed the Egg Project, in its early days. In 1976 the Monash team developed the operation of ‘ovariopexy’ to free and relocate buried ovaries to allow access to subsequent laparoscopy. Technological advancements inevitably change approaches to problems. This was demonstrated again ten years later when the vaginal approach to EPU, through the use of ultrasound, superseded the laparoscopic method. The ‘frozen pelvis’ was ideally suitable to EPU and the ovariopexy cases were not. It is important to stress that despite the surgical difficulties no serious operative complications occurred during this time. To collect more eggs for IVF treatment required not only more patients, but also more eggs from each patient. In the natural reproductive cycle only one egg finally develops within a mature pre-ovulatory follicle. This number was increased by the use of hormonally stimulated cycles. Hormones had previously been successfully developed to stimulate ovu­ lation and comprised either human pituitary injections (HPG and HMG) or clomid tablets with a final injection (hCG) to trigger ovulation. This stimulation treatment was not without its dangers and discomforts and required strict control with early daily blood and urine tests to monitor the development of the egg follicles. This would lead to the eventual accurate timing of the EPU. The regimen always entailed much inconvenience and discomfort for the patient. Doctors and others were surprised and cheered by the willingness of these women to undergo a difficult treatment that continued to register a success rate of zero. These patients wanted to be the first success and most IVF workers considered these early women, who endured so much, the true pioneers of IVF. An addendum to the use of HPG (derived from pituitary glands of human cadavers) occurred in 1993 following five reported deaths from its use in ovulation induction programs. A federal inquiry was established into the use of pituitary hormones and their association with Creutzfeldt-Jacob Disease (CJD), a rare but fatal brain disease of delayed onset. About twenty patients on the IVF program had received HPG injections from 1972–1978. The Monash IVF team, however, only used HPG prepared personally by Dr Jim Brown, a brilliant biochemist working from the RWH, who used a special method of preparation that would almost certainly have circumven­ – 12 –

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ted any risk of CJD. After almost forty years it is safe to say that no deaths from CJD occurred in any IVF programs in Australia.

Improving the Embryo Transfer Technique

In the early days of IVF, with low or negative pregnancy rates, several in­ novative measures were applied to the embryo transfer procedure in the desperate hope of improving results by enhancing the positioning and im­ plantation of the embryo. One addition was placing the patient precariously on a pile of pillows in the ‘doggie’ (knee-chest) position – as the uterus usually lies forwards – so that the embryo fluid would move downhill towards the top of the uterus. This position was both uncomfortable and unstable, and particularly so for one patient who almost toppled off the operating table. Another supplement to the embryo transfer procedure was the enforced absolute rest (breathing only allowed) for two hours following the transfer. This ruling was soon challenged after an impatient embryo recipient jumped from the table and hurriedly left to keep another appointment, only to return two weeks later, pregnant. Neither of these two measures was based on any scientific data, as con­ trolled trials were impossible and there obviously existed no corresponding data in bovine embryo technology. It was known that the walls of the uterus were normally in apposition, suggesting the above procedures were unlikely to be helpful. After less than twelve months the ‘doggie’ position was replaced by the conventional litho­ tomy (lying on back) position used today, with the required resting time after transfer gradually diminishing until today it rarely exceeds thirty minutes in most clinics. Although unsuccessful, both these measures demonstrated again the des­ peration of the IVF workers to improve a frustratingly poor success rate. Time would tell, however – several years later with improved embryo culture techniques – that the most significant factor determining success lay in the quality of the embryos being transferred.

A Glimmer of Hope

In 1973 I operated in a private hospital on a farmer’s wife, Marie Dawes, from central Victoria, for infertility due to severely damaged tubes. Her reproductive cycle had been stimulated with fertility injections to allow the operation to be deliberately timed with ovulation. – 13 –

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Dr Talbot assisted and Dr Lopata dealt with the IVF laboratory procedure. Five eggs were collected, all eggs fertilised in the laboratory and two were transferred two days later. A tubal repair operation was performed at the same time. Surprisingly, an early positive pregnancy test was recorded, just over two weeks later. Unfortunately the pregnancy lasted only eight days, which roughly co­ incided with the rupture of the abdominal wound, requiring immediate surgery. It is remotely possible that this pregnancy could have produced the world’s first IVF baby, though this is unlikely as it would take another eight years of intense international endeavor for the first IVF baby to be born, in Baltimore, USA, using a similar stimulation program. If it had succeeded this pregnancy would certainly have curtailed the many later attempts using an unstimulated cycle. This 1973 pregnancy, however, proved beyond doubt that an embryo created in the laboratory could implant in the womb and create a pregnancy. The news of a world first IVF pregnancy, albeit only a short ‘chemical’ one, was reported in the Lancet on 29 September 1973, and immediately re­ ceived worldwide attention. Here I broke the cardinal rule of scientific publication by listing the research personnel involved in alphabetical order – rather than via the main contributors – in an altruistic attempt to emphasise the team nature of the event. Dr David de Kretser, who would become a leading world authority on research in endocrinology and male infertility and, in 2006, Governor of Victoria, but who at that stage had little involvement in the IVF program, was therefore placed first, while Wood was listed last. I came to consider this a mistake, though some members did support me in the decision. Lopata was naturally upset and I made a public apology to him at an international meeting at Perth in 2003. When the Lancet article was released, reporters from across the world descended upon Melbourne for the full story, though I was able to hide the patient back on her farm to avoid unwanted publicity. Steptoe was sceptical of the report by the Australian team, stating in the press: ‘We have published several papers about pregnancy outside the body. It seems the team in Melbourne have been guided by what we have re­ported. But the problems are about implanting the embryo back into the woman. We have not succeeded yet. I don’t think anybody has been successful so far in implanting the embryo.’ He apparently missed the significance of the positive pregnancy tests. – 14 –

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Professor Brian Carey, head of Obstetrics and Gynaecology at the Uni­ versity of New South Wales, was also apparently dismissive of the reported pregnancy, being quoted in a Sydney newspaper declaring ‘that there were more important things to do’. An important follow up to this story was the timed visit of several mem­ bers of the Ford Foundation to Melbourne in October 1973 to consider an application for funding. Wood had already applied for funding in the same year, after meeting Trounson and naming him as the possible scientist in the grant. Much to everyone’s surprise the Foundation awarded a $750,000 research grant to the IVF program in 1976, provided that Trounson did be­come involved. Trounson had already met me in theatre in 1973, as well as Wood on several occasions. In 1977 he became an active member of the Monash IVF team. It is interesting to note that the British team suffered similar failures in 1975 as the Australians had in 1973. Their two reports of an IVF pregnancy in a fallopian tube, and an early miscarriage, also attracted wide publicity. These ‘failures’ gave the British fresh hope, as a final successful pregnancy could surely not be far away. Marie Dawes returned to the farm and became pregnant naturally five months after the IVF operation and later delivered a healthy baby girl. She therefore became the first woman in the world to achieve an IVF pregnancy and the first to achieve a natural pregnancy after its failure. Many similar such pregnancies would follow in women who became pregnant naturally after fertility treatment.

Visitors

From 1975 onwards a growing number of people visited the group in Mel­ bourne. The working environment became a virtual ‘open house’. Visitors were interested in the new concept of IVF and were attracted to the conjoint pro­gram by a growing output of international publications contributed by all mem­bers of the group. Many more papers would follow after the 1980–81 successes. One was a young Swiss doctor, Angelo, who had invited himself to join the Monash team. Wood recalled: ‘He was young, charming, good-looking and enthusiastic [and] involved himself in many of our experiments. Unbeknown to us, he was at the same time using much of our data to promote himself.’ – 15 –

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He attended some important overseas conferences, including meetings in Italy and Cambridge, presenting himself as a member of the Monash team. Trounson, now the scientific director of the Monash program, was not happy about this and became so fed up with his irresponsible attitude to important research work that he finally barred him, at a meeting in South America, from using any further Monash IVF research data. Another was a young Italian medical graduate, Dr Luca Gianaroli, who joined the Monash team from Bologna. He spent three years from 1980–83 working with Trounson and his Monash colleagues. Gianaroli became the most significant IVF clinician in Italy and eventually the President of the influential European Society for Human Reproduction and Embryology (2010–11). He continued to collaborate effectively with the Monash team over three decades. Another medical graduate arrived from Brussels after winning an international award in science. Dr Michel Camus was keen to learn about the new IVF technology and was involved in several projects under the direction of Trounson. Like most of those involved in the early Egg Project, Dr Camus was working long hours with little reward. ‘Unfortunately he was forced to return home for health reasons,’ Wood recalled. Money was always short and Dr Camus moved to my home for several weeks to recover. He eventually became a respected leader in IVF in Belgium. Another visitor of distinction was Pierre Soupart, the Professor of Ob­ stetrics & Gynaecology at Nashville University in Tennessee, whose grant application to the US National Institutes of Health (NIH) was rejected by the US Health Ethics Committee. This then prevented all US scientists from receiving NIH funding and from being involved in human embryo research, including IVF, effectively handicapping the US research teams who then had to rely on private financing. Soupart was invited by Trounson to participate in the work of the Monash team, having already published widely on IVF research in humans (particularly the ultrastructure of fertilisation in vitro) and animals. The Brussels-born scientist, with his wife Simone, arrived in Melbourne in 1979. There was no available funding for their stay in Melbourne, which em­ barrassed Wood. ‘To cover living expenses Pierre and Simone stayed with my family for six weeks and then with John Leeton’s family for six weeks,’ he recalled. Soupart was a leading scientist in America and was able to collaborate helpfully with Trounson in his early projects. He stayed on in Melbourne for six months before returning to America where, sadly, he died in 1981. – 16 –

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The US research team led by Howard and Georgeanna Jones also sent their senior embryologist Dr Ed Wortham to work with Trounson in 1981 and learn the critical embryology for IVF success. These and many other visitors from the UK, America, France, Spain, Germany and Sweden, encouraged by Wood and Trouson, enabled the IVF procedures to translate into effective treatments worldwide.

Desperate Measures

Fertilisation rates remained low (10–15 percent) in the early 1970s. Because of this poor outcome, a radical attempt to improve fertilisation was carried out by the Monash group in 1974. They placed human eggs and sperm into a sheep’s oviduct. Wood had a veterinarian friend, Dr R.A.S. Lawson, ‘a bit of a wild guy’, he recalled, who brought in two sheep at night for the experiment. Wood continued: ‘We didn’t know where to put them, I hadn’t thought of that, so I put them in the lab with all the chemistry and stuff and, of course, they were a bit bloody noisy. Patients at the Queen Victoria Hospital had a sleepless night.’ The experiment was unsuccessful; the sperm actually sur­ vived for 48 hours, but all eggs were lost. Interestingly, Bob Edwards had tried the same procedure earlier with similar results. In 1965 he received a Ford Foundation grant and spent six weeks researching IVF in animals with Howard and Georgeanna Jones at Johns Hopkins Hospital in Baltimore. There they tried fertilising human eggs with human sperm in the oviducts of rabbits and later in rhesus monkeys, but all attempts failed. The ideal situation for human fertilisation, nature’s own fallopian tube, could never be considered because of the overwhelming technical and ethical problems (although it did become the site of fertilisation in later gamete intra-fallopian transfer [GIFT] procedures, as discussed in chapter 11). It had to occur in the right fluid media in a laboratory – nothing else. Essentially it required the ‘magic fluid’ – as dubbed by Edwards – to achieve successful fertilisation.

The Melbourne Teams Expand

In contrast to the British program that consisted essentially of the dedicated trio of Edwards, Steptoe and Jean Purdy, the two Melbourne teams, under Wood’s guidance, increased dramatically in size after 1980. – 17 –

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The attempts at IVF involved the cooperation and advice of a large num­ ber of scientists and clinicians. Dr Brian Hudson of the Howard Florey Research Institute, Professor Henry Burger of Prince Henry’s Hospital Research Centre, Professor James Brown of the University of Melbourne, Professor David de Kretser, Department of Anatomy at Monash University, Professor Pincus Taft and Dr Jim Evans of the Royal Women’s Hospital and Dr Peter Dennis of Prince Henry’s Hospital all gave useful advice on hormonal stimulation and sperm manipulation. Dr R.A.S. Lawson of the S.S. Cameron Research Laboratories advised on egg fertilisation and embryo transfer as he had considerable experience in animals. Dr Ian Hoult, senior registrar in the Reproductive Biology Unit at the Royal Women’s Hospital, organised the treatment cycle and carried out many of the hormone tests. Other recruits at the Royal Women’s hospital were Dr John McBain, Dr Andrew Speirs, and Dr Hugh Robinson, Dr Lachlan de Crespigny and Dr Colm O’Herlihy of the ultrasound team. Dr A.H. Sathananthan, an electron microscopist, joined the group in 1978. The Monash team was joined by Dr Gab Kovacs in 1978 and Dr Nick Lolatgis in 1979. The clinical team was later complemented with the addition of Drs Bruce Downing and brothers Mark and Tony Lawrence. Dr David Healy, who in 1990 became Professor, joined in 1985. All clinicians, including Wood to a lesser extent, had busy obstetric and gynaecological practices, as did Patrick Steptoe. On the scientific side Trounson had initially received valuable help from Janice Webb, but soon increased his staff to include Postdoctoral Fellows Dr Penny Nayudu, Dr Peter Rogers, Dr Jill Shaw, Dr David Gardner, Dr Leeanda Wilton, Dr Andrea Laws-King, Dr Gayle Jones and Dr David Cram; PhD students Maha Mahadevan, Linda Mohr, Denny Sakkas, Orly Lacham and Peter Lutjen; and technical staff Lesley Freeman, David Jessop, Trina Caro and Donna Howlett, all of whom would later develop highly successful careers. Wood had certainly cast a wide academic net to achieve his goals. The practical work at both the Royal Women’s Hospital and the Queen Victoria Medical Centre involved over fifty people. The better facilities at the Royal Women’s Hospital best enabled the clinical procedures to be done, whereas most of the scientific studies were being carried out in the Monash University Department of Obstetrics and Gynaecology. – 18 –

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Cost and Financial Support

A Publicity Report by Carl Wood in 1980 costed the combined project at about $150,000 each year. This may be an inflated figure as Monash University alone was contributing $68,000 in salaries that were obviously funding other activities separate to IVF, including teaching and other disciplinary programs. Nonetheless, considerable costs needed to be met. Most doctors and scientists in both IVF groups in Melbourne worked many extra hours for which they were not paid, as did Edwards and Steptoe in the UK. The Monash group was strapped for cash. Early on Talbot and I began donating 25 percent of our surgical payments towards laboratory expenses, a policy that all doctors continued for many years. In 1980, two months before the highly publicised birth of Australia’s first IVF baby, Candice Reed, Dr Ian Johnston, the Director of the Reproduc­ tive Biology Unit at the Royal Women’s Hospital, appealed to the Prime Minister, Malcolm Fraser, to consider providing a grant for the IVF program. He warned that his program would have to stop soon unless about $100,000 could be found from outside the hospital, adding: ‘I don’t know what the politicians expect of doctors and scientists. They bask in the glory of our achievements, yet it seems impossible to get funds to keep research going.’ Johnston’s statement regarding the federal government’s self-congratulatory attitude to IVF achievements in Victoria, was pertinent: the Government was soon to identify IVF technology as second only to Sir Howard Florey’s contribution to the development of penicillin (work carried out entirely in England), in a list of internationally recognised Australian achievements. Funds from the federal government were given to and allocated by the states. The Victorian State Health Commission found ‘cost containment measures and the present policy of “zero” growth prevents the allocation of funds for new services’. Most large grant-giving bodies preferred not to be involved, in the early years. The National Health and Medical Research Council (NHMRC) initially considered the work should be done on monkeys (although no one in the world had achieved a successful pregnancy in this animal at the time). The UK Medical Research Council rejected Bob Edwards’ application for human IVF studies for similar reasons in 1971, though it said it ‘would be prepared to consider an application for support of an experimental program of work of the type you have already proposed to be carried out in primates’. During this time Steptoe and Edwards received no government funding, while in the US, as noted, Federal funding for research in this area were – 19 –

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frozen in 1978, probably contributing to the delay in the development of IVF in that country. Fortunately the flexibility of the Medicare system in Australia was able to help towards IVF development, as Medicare benefits were payable for medical services associated with IVF, including charges for hormone assays, ultrasound scans and clinical procedures. The Royal Women’s Hospital supported the project by providing improved laboratory and operating facilities as well as essential funding from several trusts. Funds were obtained from university sources directed towards research or from other bodies specifically responsible for granting research funds, such as the Ford Foundation. As mentioned, the most important grant, of $750,000, came from the Ford Foundation in 1976, enabling Trounson to join the Monash program the following year. It is now time to have a look at this remarkable character.

– 20 –

The B oy from J erilderie

Cha pte r 4

The Boy from J erilderie Alan Trounson first met Carl Wood and his wife Judy at the McCaughey Memorial Institute in Jerilderie in 1971, when he was studying animal embryology with Professor Neil Moore. Trounson said he was impressed by Wood and liked the notion that a high-profile clinician would be prepared to support such basic research. Wood was a debonair 43-year-old Professor of Obstetrics and Gynaecology at Monash University and Trounson, 26, an eager science student about to ob­tain his PhD from Sydney University for studies in sheep embryology. ‘I was a master PhD student and only interested in reproductive biology and phys­iology in large farm animals. That had been my background for some time and I was particularly interested in sheep and cows,’ Trounson recalls. As it happened, this interest was shared by Wood, as he had heard about IVF being tried on sheep at the animal research station at Jerilderie and was keen to learn more about the technique. On that weekend early in 1971 Wood took his wife Judy with him, but it was no romantic get-away. It was, as always, about IVF. ‘Carl was intrigued by it,’ Judy said. ‘He used to do these drawings all the time and would ask me how he could get the egg down to mix with the sperm. He had an extraordinarily imaginative mind, he always thought laterally and I think the reason he was able to do what he did was that he could focus on the big picture and forget the minor details.’ On that drive to New South Wales Carl Wood was looking for practical solutions to infertility. He was familiar with Dr Moore’s work experimenting with IVF in sheep and keeping fertilised eggs alive in a Petri dish until the eight-cell stage. He now wanted to know if it would work in humans. ‘I was fascinated,’ Carl said. ‘I knew that Chang in America had pioneered this work in rabbits in the 1950s and was confident I had the scientific expertise here in Australia at least to try this on humans. We had to do something.’ Trounson was working with Moore on a property in Jerilderie with 30,000 sheep that they could access for research. The weekend that Carl and Judy arrived, the group talked about IVF in humans over several glasses – 21 –

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of wine. ‘I’d never thought about that possibility,’ Trounson says. ‘Here I was, a student, and it was a remarkable opportunity to be exposed to those ideas and to think that some of the techniques that we were exploring could be used in human medicine. It made me realise that Carl had one of those incredibly open minds in respect to working out a problem and he would not necessarily take the most obvious view.’ Trounson saw in Carl Wood a radical man willing to find answers outside the square; Carl saw in Alan Trounson, potential. Wood had tried to talk Neil Moore into working with him in Melbourne but Moore had refused. He was well and truly ensconced as a leader in animal husbandry. And so Wood turned his attention to the young scientist eagerly offering opinions and suggestions. At Wood’s invitation Trounson then came to Melbourne in 1973 where he met me in the operating theatre and saw the tiny research laboratory that had been established at the QVH. Trounson was told Wood and I were looking for a scientist to complement the team. He turned the offer down. It was not vanity stopping the young man from accepting, but the fact he had a chance to do a post-doctoral fellowship in Cambridge in the UK. Wood encouraged him to accept the offer, telling Trounson it was a great opportunity and the Cambridge Unit of Reproductive Physiology and Biochemistry was a Mecca for promising scientists. In truth, however, Carl also could not afford to hire Trounson at the time and had been hatching a scheme to find money to employ the brilliant young scientist full-time. Trounson has said he found out later that Wood, Talbot and I were spend­ ing a percentage of the money we earned from medical procedures to prop up research. This, and the fact that no-one ever got paid overtime, stood out: ‘Looking back it was an unusual arrangement, but it worked; it was a partnership.’ In Trounson’s memory: ‘I wanted to do a post-doctoral fellowship and I told Carl. He told me he was putting in an application to the Ford Foundation.’ The application would involve Dr Brian Hudson from the Howard Florey Institute, Professor Henry Burger from Prince Henry’s Hospital Research Unit, and Dr Jock Finlay from the Animal Research Unit in Werribee. ‘They were really looking to integrate someone in reproductive research through a major grant and Carl asked if he could nominate me as the embryologist in the application, and I said “sure”.’ After joining the Monash team as Senior Research Fellow in 1977, Troun­ son quickly began several controlled experiments involving different aspects – 22 –

The B oy from J erilderie

of the IVF program, all of which would lead to outstanding success rates three years later. His improvements in IVF culture included simplifying culture media, eradicating oil from culture, because of its toxicity, and introducing quality control by checks with mouse embryo culture. He also found increased fertilisation rates occurred after delaying in­semination, which allowed eggs to complete their development. And he experimented with several types of catheters to replace the embryos. To control these experiments scientifically and eliminate possible bias on clinical skill, he arranged for me to carry out all embryo transfers during 1979–81, and we both worked on stimulated cycles using clomid tablets. Trounson’s great contribution to the IVF program was the re-introduction of stimulated cycles, that had been abandoned in 1978 after the successful IVF pregnancy and birth involving Louise Brown, using a natural, nonstimulated cycle, by Edwards and Steptoe. On many nights, especially during trials with unstimulated cycles, I drove Trounson home at around 3 a.m. Trounson didn’t have a car but, like Ed­ wards, worked all hours of the day and night.

Beautiful Blastocysts

When the phone rang I grabbed it before the third ring. I saw it was 11.30 p.m. and did not wish to disturb my wife Audrey, sleeping beside me. It was a technique I had mastered after twenty years of obstetric practice. Down the line an excited Alan Trounson was describing what he considered a most wonderful sight. ‘It is beautiful, John, it looks like a chandelier.’ Trounson, oblivious of the time, was explaining with his usual enthusiasm a blastocyst, a 100-cell human embryo that had been collected from the uterus before being implanted. I had fluked finding this structure earlier that day in a patient undergoing laparoscopic sterilisation. The operation had been planned, with daily hormone tests and temperature charts, to occur five to six days after ovulation. The woman and her husband had given informed consent to the procedure, including timed coitus on the suspected day of ovulation. The operation was planned primarily to check the timing of human ovulation and embryo implantation. Trounson was understandably excited because, although he had seen many animal blastocysts, he was now looking for the first time at a human one. Some years previously Edwards had experienced a similar emotion on seeing his first blastocysts in the laboratory. In his delightful book A Matter of Life he exclaims: ‘[T]here they were. Four excellent blastocysts. The intrinsic beauty of it!’ – 23 –

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The blastocyst could be considered the Holy Grail of reproductive science and it is no coincidence that these two scientists reacted with awe and admir­ ation to seeing them. The fact that one was conceived naturally and the other in the laboratory was irrelevant. They were absolutely indistinguishable from each other.

Trounson and Lopata

The first three years at QVH were difficult for Trounson as he found himself sharing the workload with Alex Lopata, although the latter was now spend­ ing more time at the RWH. Both were dedicated scientists but did not get on well, largely due to a clash of personalities and ideas. Trounson was an affable, gregarious char­ acter whereas Lopata was more studious and reserved. This confrontation was finally resolved in 1980 when Lopata moved to a full-time Melbourne University position at the RWH, leaving Trounson as senior scientist with the Monash group. The promotion gave Trounson full rein to put his ideas and expertise into practice. Within only a few months his scientific expertise resulted in the world’s next fourteen successful IVF pregnancies.

– 24 –

S uccess at L as t

Cha pte r 5

S uccess at L as t By 1977 both the Australian and British teams were experiencing increas­ ing frustration. Carl Wood was considering abandoning the IVF program if success did not occur within the next two years. The teams had a common dilemma: why had all the apparently normal-looking embryos that were carefully transferred back into the uterus failed to produce a normal pregnancy? All reproductive cycles in both teams had been stimulated with hormone injections so possibly the artificially stimulated wombs were acting as a barrier to implantation and subsequent development of the embryo.

The British Team Wins the Race

Edwards then decided to attempt an IVF cycle without using stimulating drugs. This natural cycle would require careful monitoring to accurately predict the time close to ovulation. About thirty-six hours before ovulation, a surge in the LH hormone occurs (this can be identified from serial coll­ ections of urine). This allows accurate forward timing of the laparoscopy to collect a ripening egg before it is lost at ovulation. The British team also implanted an embryo into a non-stimulated womb by freezing all embryos collected from a stimulated cycle and subsequently replacing them, freeze-thawed, in a natural cycle. Maybe the transfer of an embryo into a non-stimulated womb could be the answer? It was. The history of Lesley Brown’s IVF pregnancy is now well documented. Within a natural cycle a single egg was collected, fertilised with the hus­ band’s sperm in the laboratory and replaced two days later as an eight-cell embryo. On 25 July 1978 the couple’s daughter Louise was safely delivered by Patrick Steptoe by a caesarean section. She was perfectly normal. The future development of IVF was now assured. Following their first success with Lesley Brown’s pregnancy, Edwards and Steptoe understandably continued their IVF treatments on natural cycles. – 25 –

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Their early success was regarded with suspicion by some agencies in both the UK and the US. In 1978 the Barren Foundation, a research organisation in Chicago, withdrew their award to Steptoe on the grounds that no scientific work had been published. Steptoe was incensed, describing the Foundation’s action as the most disgraceful exhibition of bad manners he had come across in the scientific world. Scepticism regarding the pregnancy was finally laid to rest following its full report in the Lancet. A second successful IVF pregnancy and birth was achieved at Oldham Hospital the following year when Grace MacDonald gave birth to a son, Alastair. This second success suggested the natural unstimulated cycle was the way forward for IVF treatments.

The Australians Follow On

On the other side of the world the Melbourne teams received the news of the English success with mixed feelings; elation and relief that IVF could at last produce a live and healthy baby, but also some regret that they had been beaten. Both teams, however, took up the bait and began routine natural cycles in most cases, although Trounson was trying stimulated cycles with clomid tablets again, because of his belief that this method could be successful in humans as it had been in animal research. The timing of the egg pick-up again directly depended on the detection of the LH surge, which had been so successfully demonstrated in the case of Lesley Brown. Timing and management of the natural cycles therefore became difficult, due to the necessary scheduling of the surgery at any hour of the day or night. This often interfered with other operating lists, particularly at the QVH. The setup for the laboratory and clinical procedures at this hospital were very basic, mainly through a shortage of available space. At one stage a small opening, dubbed the ‘oviduct’, was cut in the wall between the ‘laboratory’ (a corner in a theatre) and the clinical room (a store room) to allow the passage of the embryos. At another time Trounson, carrying embryos loaded in a catheter and rushing from one room to another, tripped and fell sprawling at the outstretched legs of a surprised patient. During 1979 general support for the IVF program at this hospital was cool, indeed hostile in some areas. Finally the hospital management summoned me and accused me of ‘wasting valuable hospital and residents’ time with IVF experiments’. By 1980 the Monash group had been forced to move from – 26 –

S uccess at L as t

the QVH to nearby St Andrews Hospital. Trounson was made to relocate his laboratory equipment ‘from one broom cupboard to another’. This forced move from the QVH at least demonstrated the impracticality of running an IVF program within a busy general hospital surgical schedule, instead of as a separate independent unit. In 1982 the Monash group moved to the Epworth Hospital in Melbourne where such an independent situation was finally made available. In 1980 the conditions at the RWH, however, were more promising. Because more IVF treatment cycles were being carried out, operating and laboratory facilities were better. Conditions improved further after the team broke through, in June 1980, with the birth of Candice Read, the first IVF baby born in Australia and the third in the world. Dr Ian Johnston was the clinical leader of the team and delivered the baby by caesarean section, assisted by Dr Andrew Speirs. Dr Lopata was using an improved culture media that allowed 90 percent of ripe eggs to be fertilised in the laboratory, and was mainly responsible for the successful outcome. The treatment cycle used was natural and unstimulated, similar to the two previous successful IVF pregnancies in England. This again required precise timing of the egg collection that was determined by three-hourly hormone tests carried out by Dr Ian Hoult and Julie Mitchell. This timing of the operative procedure was further refined by the ultrasonic scanning of the ovaries that was performed by Drs Robinson, O’Herlihy and de Crespigny. It was indeed a well-organised team effort that culminated in this successful outcome. Both Johnston and Lopata now became recognised on the world stage as authorities on IVF developments.

The Fall-Out

Following the successful pregnancy and birth of Candice Read, Dr Lopata transferred to a full-time position with Melbourne University and the RWH, that offered him improved laboratory conditions and research facilities. There was an irony to this appointment as Professor Lance Townsend, the Emeritus Professor of Obstetrics and Gynaecology at that university, had been strongly opposed to IVF research, considering it immoral. The full description of this successful IVF pregnancy was soon published in the prestigious international journal Fertility and Sterility. There had been an unofficial agreement between the two Melbourne teams that a publication emanating from any successful pregnancy would include Wood, Trounson – 27 –

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and myself in the authorship. This did not occur. Media coverage certainly involved both teams, but some resentment was felt in the Monash group at its exclusion from the important scientific publication. Wood was sum­ moned to see the Vice Chancellor of Monash University and was severely reprimanded for this omission, particularly as Alex Lopata had been a fully funded employee of Monash during the period of research that led to the publication. As Trounson replaced Lopata as Director of the Monash IVF scientific program, the two teams officially went their own way. Within a few months Trounson helped produce several successful IVF pregnancies from stimu­ lated cycles. On the other hand, the RWH team continued its IVF program mainly using natural cycles, but without further success for over two years. In 1982, in consideration of the RWH’s continued lack of successful IVF treatments, Wood privately offered the team help by providing them with Monash IVF scientific data. Trounson strongly disapproved, as he had painstakingly developed this research over the past four years. Edwards and Steptoe also experienced a similar fate of long-term failure with natural cycles after their second successful IVF pregnancy and birth in 1979. Alastair MacDonald was born six months after Louise Brown, to less fan­ fare. His mother, Grace, was one of the many women recruited for Steptoe and Edwards’ trials at Oldham General Hospital and she became pregnant on only her second cycle. Edwards and Steptoe moved their IVF program to a private situation at Bourn Hall and Steptoe retired in 1982. Maybe the natural cycle for IVF was not the best method for producing persistently successful pregnancies after all?

What happened in America?

There was a curious lack of world interest in IVF prior to 1980, with only the British and Australian teams actively involved. Certainly earlier claims in IVF treatment had been made by Dr Subhas Mukherjee in India, and the two leaders in infertility research in America, Drs Howard and Georgina Jones, had shown great interest when collaborating with Bob Edwards’ research in Baltimore in 1974. Successful results in IVF had already been achieved in mice, so why wasn’t there more research going on around the world? There was reluctance by many doctors to recognise infertility as a sig­ nificant human ailment as it was not life threatening. Some doctors thought – 28 –

S uccess at L as t

IVF could never succeed in humans, and if it did would create such difficult moral and legal problems, including the risk of severe foetal abnormalities, that it couldn’t actually become a practical form of treatment. Clinical IVF treatment in America suffered a shaky start in 1978 through the highly publicised legal case involving the prestigious Columbia Presbyterian Hospital in New York. Dr Langdon Shettles had begun IVF research at this hospital and in 1977 had successfully fertilised a batch of human eggs in vitro. The Director of the hospital, Dr Raymond Van de Wiele, disapproved of this new and contentious research and secretly raided the laboratory and discarded the embryos. The unfortunate couple associated with these embryos sued both the Director and the Hospital for damages (‘drowning my babies’). In July 1978 a highly publicised court case took place that found in favour of the litigants, who were awarded $50,000 damages. The Hospital Director was discredited, as was the entire IVF program to some extent, and the US President , Ronald Reagan, later refused any federal funding for its development. Interest in IVF in America then languished for the next few years. Reports of the successful IVF births in England turned things around, however, and several infertile patients of Drs Howard and Jones approached them requesting the same treatment. Although considering retirement, this remarkable couple in 1979 resigned from Johns Hopkins Medical Center to change course and set up an IVF clinic with private funding at The Jones Institute at Eastern Virginia Medical School, Norfolk, Virginia. Using a stimulated cycle based on instruction from Wood’s group at Monash, they produced America’s first successful IVF pregnancy and birth when a baby was born in December 1981. A further seven babies were born by the end of 1982, the same year that France, Austria and Sweden reported their first IVF births. (In an ironic twist of fate, the same Dr Van de Wiele who had tried to derail IVF research in the US, was appointed a Director of a large IVF clinic in 1985, the same year that America recorded 115 births from IVF procedures.) America quickly developed IVF procedures and research to become a world leader, and by the end of 2006 had recorded 400,000 births through IVF. A revealing postscript to the early history of IVF in America is the story of what occurred at the annual conference of the American Association of – 29 –

T E S T T U BE R E VOL U T IO N

Gynecological Laparoscopists at New Orleans in November 1980, where Professor Pierre Soupart was to chair the fledgling IVF discussion meet­ ing. Soupart, whose pioneering studies in human IVF were prematurely halted by policies of the NIH, had recently returned from working with the Monash team, and Wood and Trounson both thought it a fitting gesture to allow him to report their five early, ongoing pregnancies, at the meeting. Dr Talbot, who was attending the meeting, brought him the data for presentation. On the morning before the session on IVF, however, Professor Soupart, after reviewing these astonishing results, reluctantly refused this generous offer. Reportedly, he thought it would demonstrate to the Americans how far ahead the Australian group had progressed and contradict the widely held view in that country that the Australian success was only associated with Ian Johnston and the RWH group. ‘America is not ready to hear this at present,’ he commented. America may not have been ready but it would soon hear more in any case, when news of nine successful pregnancies was presented to the world by Trounson at the Berlin International Congress of Human Reproduction in March 1981.

– 30 –

N ine N ormal P regnancies

Cha pte r 6

N ine Normal Pregnancies In barely six months, between June and December 1980, after so many years of failures, the Monash team produced an astonishing nine normal preg­ nancies. This successful outcome was mainly due to Alan Trounson’s ex­ pertise in devel­oping new culture media, together with the re-use of the stimulated cycle. That magic moment of their first successful pregnancy was recalled by Wood over twenty years later: ‘I remember the day because Alan came run­ ning down the corridor and said: “We’ve got a pregnancy, Carl!” I said, “That’s great, congratulations. It’s wonderful”. And it was.’ Eight more pregnancies soon followed. At the Third World Congress on Human Reproduction in Berlin in March 1981, where these results were presented, there were over 600 delegates, including Trounson and myself. Interest in IVF had recently been boosted by reports of the birth of the three babies conceived through IVF – two in Oldham in 1978 and 1979 and one in Melbourne in 1980. Fresh hope and expectation were brought to the Berlin conference. The delegates were not to be disappointed. Dr Bob Edwards was naturally the keynote speaker at the conference but, at breakfast with Trounson, and learning of his successes, remarked that his opening address now needed drastic changes. The conception of these nine pregnancies coincided with Trounson’s first six months’ tenure as Scientific Director of the Monash program and, as noted earlier, the achievement was largely due to his scientific skill and innovation in using stimulated cycles. I carried out all the embryo transfers together with most of the laparos­ copic egg collections, and described these procedures at the conference. They included the manufacture of a new Teflon-lined aspiration needle that diminished turbulence and thereby minimised damage to the collecting eggs. This needle, together with a foot-operated suction pump for aspirating eggs from the ovarian follicles, was the brainchild of Dr Peter Renou, a – 31 –

T E S T T U BE R E VOL U T IO N

remarkable doctor with an impressive set of skills. Not only was he an exper­ ienced obstetrician who delivered many of the early IVF babies, but also an accomplished mechanical engineer. Trounson then discussed in detail the total production of sixteen preg­ nancies from 112 treatment cycles ending in four ‘chemical’ pregnancies without foetal development, three miscarriages, but nine normal on-going pregnancies. One of these required donor sperm and two were twins where one twin had been absorbed during pregnancy; all these characteristic developments would soon be found in increasing numbers in IVF programs all over the world. Most cycles were mildly stimulated with clomiphene tablets and were monitored with daily urine hormone tests and several ultra-sound scans. Timing of the laparoscopy was made in most cases thirty-six hours after the injection of hCG, the hormone stimulating ovulation. As Trounson concluded his address a brief hush fell over the audience, broken by a prolonged, standing ovation. Trounson received the ovation, on behalf of the entire team, as well as the personal congratulations of Edwards. These results proved that the judicious use of hormone stimulation and careful monitoring could now create successful pregnancies; moreover, the use of the hormone hCG allowed the timing of the laparoscopy to be made several days in advance. Unlike with the natural program, IVF could now be scheduled into a workable formula resulting in less patient anxiety and the more efficient employment of staff. The conference delegates now had concrete data to take home and try to use in emulating these outstanding results that, although then giving a modest success-rate of only 8 percent per treatment cycle, would take most clinics several more years to reach. Three normal baby girls were delivered within the two months following the Berlin conference, and the twins – the first IVF multiple birth in the world – were born three months later. By the end of 1981 the Monash IVF team had achieved forty-three pregnancies with ten live births. Trounson was the first to report the increasing pregnancy rate with an increasing number of embryos transferred, and this practice would become more prevalent with the re-introduction of pituitary hormone injections by Trounson and Dr John McBain of the RWH, to hyper-stimulate multiple ovulation. This eventually led not only to a steady rise in pregnancy rates but also to a concomitant increase in multiple pregnancies, which would soon become a contentious legacy of all IVF programs. – 32 –

N ine N ormal P regnancies

The Bourn Hall Workshop: August 1981 Following the Berlin meeting, Edwards and Steptoe arranged a small con­ ference for international IVF workers at Bourn Hall, Cambridgeshire, which had now become their principal location for IVF treatment. This move coincided with Steptoe’s retirement from the National Health Service at Oldham at the age of 65. Attendance was by invitation only and twentyfive delegates attended from different countries including France, Germany, Austria, Switzerland, Italy, Sweden, the United States and Australia. Australia was represented by Drs Trounson, Lopata, Johnston, Speirs and myself. In the delightful setting of an old English Georgian manor house, a busy week was spent informally discussing all aspects of IVF management around a large conference table. Edwards and Trounson were the unofficial leaders in the discussions, but most delegates contributed useful information. Edwards was also adamant that, although freeze thawing of human embryos had not yet resulted in pregnancy, such treatment would not cause any intrinsic damage to the embryo. This was useful information for Trounson who had been involved in the successful freezing of bovine embryos at Cambridge five years previously. Two aspects of the meeting surprised the Australians. One was the absence of other British teams outside the Bourn Hall group, which included members from the Royal Free Hospital and Kings College Hospital. The second was the proposal that all IVF pregnancy results be pooled and coll­ ated at Bourn Hall. This was not favourably received, particularly by the Australian group who argued it seemed inequitable, as the majority of IVF pregnancies had come out of Melbourne. This idea was soon dropped. The meeting was, however, a success, and was the first international IVF conference to be held. Many more were about to follow. Six months after the Berlin meeting, Wood decided to make an official reporting of the births of the babies from the early IVF pregnancies. He chose the strange arrangement of a dual announcement, one in Sydney by himself and one in Melbourne with myself and Trounson. Wood was also to be the guest speaker at the opening of the IVF clinic at the Royal North Shore Hospital in Sydney at the time of his announcement. As the Sydney reporting was scheduled one hour ahead of Melbourne, over twenty national and international reporters gathered in Sydney, leaving one lone cub reporter to cover the Melbourne meeting. – 33 –

T E S T T U BE R E VOL U T IO N

Trounson and I felt somewhat chagrined with this arrangement as between us we had done all the scientific work and most of the clinical pro­cedures. In fairness to Wood, however, it must be conceded that the final accolade for these births belonged to his original idea and organisation of the IVF program exactly twelve years earlier. His contribution to the develop­ment of IVF was acknowledged in 1982 when he was made a Com­ panion of the British Empire. In the wake of the Bourn Hall meeting, in April 1982 Trounson and I were invited by Dr Vincenzo Abate, a flamboyant Italian gynaecologist specialising in infertility, and who had been a close friend and supporter of Pierre Soupart, to establish an IVF clinic in Naples. Abate’s clients came from all walks of life, and included a mafia don’s wife. Three weeks were spent arranging an IVF program and about twenty treatments were made. Unfortunately no successful pregnancies occurred, but the clinic was established and soon became a leading IVF unit in Italy. The prominence of press coverage of early IVF developments had an unexpected benefit one afternoon in Naples, when Trounson and I were arrested at gunpoint. The police had mistaken Trounson for Carlos, the notorious international terrorist. A tense standoff followed, mainly because no-one understood what the other person was saying, and it was only resolved when a magazine was produced, revealing an article depicting the two Australians’ IVF work. On the final leg of their flight back to Melbourne, Trounson and I found ourselves delayed for five hours at Frankfurt airport. During this time the idea of donating an embryo from one woman to a recipient was discussed, along with the ‘priming’ of the recipient’s uterus to accept and nurture the ‘foreign’ donated embryo. An attempt at this new frontier was planned for our return.

– 34 –

A young Carl Wood prior to his work with IVF. Reproduced courtesy Judy Wood.

Carl Wood and John Leeton during the plastic tube operation in 1970. Photographer unknown.

John Leeton, Alex Lopata and Carl Wood in 1972. Photographer Richard Crompton. Reproduced courtesy Monash University.

John Leeton and Carl Wood describing the first IVF pregnancy in 1973. Photographer unknown. Reproduced with permission of News Ltd.

Carl Wood at microsurgery. Fairfax syndication.

Alex Lopata. Photographer Richard Crompton. Reproduced courtesy Monash University.

Bourn Hall meeting 1981. Alan Trounson, standing second from left; John Leeton pictured back row right, behind Alex Lopata, Andrew Speirs and Ian Johnstone. Bob Edwards, Jean Purdy and Patrick Steptoe are seated in the front row, closest to the left’. Photographer unknown.

Herald headline, 3rd June 1983.

Top left: Mrs. Marie Dawes (with her daughter) – the first woman to become pregnant through IVF. Bottom left: Maggie Kirkman and daughter Alice in 1996. Photographer Craig Borrow. Reproduced with permission of News Ltd. Above: Carl Wood in lighter mood. Fairfax syndication. Right: Alan Trounson. Photographer Todd Dubnicoff (CIRM).

Monash IVF workshop 1985: Carl Wood centre front row, flanked by John Leeton and Bill Walters; David de Kretser centre row far right. Photo courtesy Monash University.

The L egislat ors ’ D ilemma

Cha pte r 7

The L egislat ors ’ Dilemma As an ‘event’, the establishment of the first donor egg (DE) pregnancy, where an infertile recipient conceived following the donation of another woman’s egg, was not so much a medical ‘breakthrough’ as an example of the difficulties of instituting good legislation on a new and controversial topic. DE pregnancies, where eggs from a donor were fertilised in the laboratory with sperm from the recipient’s husband, with the resulting embryo trans­ ferred back into the recipient’s uterus, were an expected and inevitable corollary of successful IVF technology. Women requiring donor eggs in 1981 had either no ovaries (these being congenitally absent or surgically re­ moved) or inaccessible ovaries at laparoscopy. But where do donor eggs come from? Where normal sperm were un­ available donor sperm had been successfully used in an IVF program, as was reported at the Berlin meeting. However, the clinical situation where normal eggs were unavailable for IVF could only be overcome by using donor eggs, which is obviously the reciprocal concept to using donor sperm. The eggs were initially donated by patients on the IVF program who, foll­ owing ovarian stimulation, had excess eggs recovered at laparoscopy. Only two or three embryos were subsequently transferred, because of the risk of multiple pregnancy. Eggs in excess of three could be fertilised with the husband’s sperm and the embryos frozen, or could be donated to a matched recipient. This may appear a difficult choice for parents, seeking to have a baby, to make. But as there was a world-wide waiting list of over two years for couples seeking assistance from Monash IVF, those pursuing this path were able to have several interviews discussing the issues, more than a year in advance of the procedure itself. Anonymity between donors and recipients was guaranteed and transfer procedures were made at different locations.

– 43 –

T E S T T U BE R E VOL U T IO N

The simple consent form devised for the DE program by Monash IVF, prior to the legal machinations regarding DE pregnancy that preceded the passage of the Status of Children (Amendment) Act 1984, read: We (full name of husband and wife) being lawfully married and desirous of having a child and having been advised that this is unlikely to be achieved by normal sexual intercourse between us, hereby request and authorise you and your assistants to inseminate artificially the egg supplied by a donor selected by the Centre with semen of the Husband and implant the resulting embryo in the Wife. We have had fully explained to us and understand and consent to the various steps that are required to be taken to achieve insemination and implantation. We understand that a successful pregnancy cannot be guaranteed and there may be a risk of foetal anomalies. We agree never to claim any right to have the identity of the donor disclosed to us, and we have been counselled regarding the fact that the resulting child may be illegitimate under the present law.

This consenting document might sound relatively simplistic today, but it deliberately circumvented any obscure legal wording cherished by the legal profession and outlined simply the three main concerns in the DE program, namely, the chance of success, the risk of a foetal anomaly and the legal status of the child.

The First Donor Egg Pregnancy

The first DE pregnancy in the world was achieved by the Monash group in 1982 but, inauspiciously, spontaneously aborted at eleven weeks; an out­ come similar to that of the first IVF pregnancy nine years earlier. The pregnancy was achieved by using synchrony between the natural cycle of a 38-year-old recipient with donor sperm and egg donation from a 42-year-old infertile woman undergoing IVF treatment. Pregnancy occurred in the recipient, but not in the donor. This sensitive situation was readily accepted by the donor, but posed a problem to be faced by all future egg donors on an IVF program. On chromosomal ex­amination, the aborted foetus from this pregnancy was found to be abnormal. – 44 –

The L egislat ors ’ D ilemma

The reporting of the pregnancy in the British Medical Journal in 1983 prompted a hostile response in the same journal from Edwards and Steptoe, who criticised the use of a 42-year-old’s eggs, with their known risk of higher abnormality rates. This reasonable critique was responded to in the following issue of the same journal by the Monash team, who described the counselling that had taken place, where all risks were openly discussed. Furthermore, the Monash team explained how the organisation of such a rostered clinical service for matching donor and recipient cycles did not allow any ideal selection from these cycles to achieve the most likely success­ ful outcome, but had to follow whatever limited clinical choice was available. Additional problems followed this ill-fated pregnancy: the ethics com­ mittee of the QVH accused the team of breaching its resolution to restrict the sperm for DE patients to that of the husband, although the ethics committee at the Epworth Hospital had already accepted the double donor principle. Wood was incensed with me over this shift in policy. He had recently appointed me director of the DE program. Trounson strongly defended the procedure. This unfortunate episode served to highlight the difficulties of super­ vision when more than one ethics committee was involved. However more serious disruptions to the DE program, from the Victorian Government, were about to occur. This first DE pregnancy was not only unsuccessful; it also resulted in a spate of conflicting regulations, restrictions and moratoria from both the Victorian Government and two hospital ethics committees over a short span of only eighteen months.

The Government Steps In

By late 1982 the IVF and DE programs were both gaining momentum due to the reported successes of the IVF program creating pressure for treatment from prospective clients, including many now from overseas. The Monash team, led by Wood and Trounson, was now extending its research into deep-freezing human embryos, as well as continuing the use of both donor sperm and eggs in the IVF program. Opposition against the IVF program, that had simmered intermittently since the program began ten years earlier, now bubbled to the surface and became more forthright in the media and lay press. The main opposition came from the Roman Catholic church whose leaders argued that IVF contravened God’s natural law of human reproduction, a similar tenet to its – 45 –

T E S T T U BE R E VOL U T IO N

earlier stance against oral contraception. The Anglican Church also suppor­ ted this disapproval to some degree. It too was concerned about the freezing and research on abnormal embryos. These attitudes were further reinforced by the fact that outcomes of both DE and frozen human embryo pregnancies were totally unknown, and pressure was now being applied on the state gov­ ernment from several quarters to oversee these new developments. At the same time Wood, who had vigorously and publicly promoted the program and defended it in the media, had become more aware of the potential ethical, social and legal implications of IVF and was now also calling for an inquiry to explore society’s attitude to this new area of medical ethics. His call for social debates about IVF was extremely prescient. As the public face of the program in Australia Wood also became the target of death threats and abuse by detractors. This disappointed, but never deterred him. In August 1982 the Attorney General of Victoria requested that all work involving donor eggs and sperm in the IVF program be halted to allow time for deliberations by a state government-appointed Committee of Enquiry under the chairmanship of Professor Louis Waller. At the end of 1982 donor eggs and sperm were reintroduced into the IVF programs, which again prompted protests from the some radical feminists and conservative religious minority groups, causing a further backflip by the Victorian Government, which reapplied its ban in March 1983. The reprieve of the ban for a few months fortuitously allowed an egg donation to a certain Italian woman who would become the world’s first mother with a donor egg and delivered a healthy baby by caesarean section in November. The timing of her treatment was so obviously close to the ban that Professor Waller phoned me to check these dates, following the birth. It was clear that Big Brother was now watching and monitoring every new development by the Monash IVF team. The state government continued its ban on the use of donor eggs and sperm in the IVF program despite its acceptance by the Waller Committee Report in August, 1983. It was unclear how the Government could hope to improve upon the detailed enquiries of the expert Waller Committee. Further enquiries by a less expert group within the Government had the danger of confusing rather clarifying the issue, while also allowing minority groups more time to exert undue influence on the Government. A Morgan Gallup Poll in April 1983 showed significant public acceptance of the DE program (57 percent), closely comparable to acceptance of donor sperm (56 percent). – 46 –

The L egislat ors ’ D ilemma

Protests against the ban now began appearing in the media and Trounson, as an incendiary gesture, publically threatened his resignation from the IVF program. Mounting support for the donor gamete program forced the Government into another backflip in June when it lifted its ban on donor sperm, but maintained the ban on donor egg procedures. A remarkable person championing the DE program now entered the fray: Dr Barbara Burton, of Sydney, organised seventy patients on the DE program into a cohesive action group. They raised over $50,000 towards the program, a sum which included the salary of Peter Lutjen, a newly appointed junior research officer to the program. A letter of protest from patients then appeared in the media, bringing further pressure to bear against the Government’s moratorium.

A Successful Legal Challenge

Dr Burton next took her crusade to revive the DE program further by planning a direct legal challenge against the Government’s moratorium. With my connivance, a plot was hatched with twelve couples on the DE waiting list, including two from Sydney, to sue both myself (as the Director of both the DE and DI programs) and the state government (who initiated the moratorium). It was on the grounds of discrimination, as donor sperm on an IVF program was still allowed despite the Gallup Poll showing equal public acceptance between the two donor groups, a short time earlier. The couples forced a preliminary hearing at the Equal Opportunities Board on 11 November 1983 on the grounds of obvious discrimination. The patients were represented by Ron Meldrum QC while I represented myself and the Government was represented by Elizabeth Curtain. The state government and I were both found guilty of discrimination as charged. The Government duly lifted its moratorium against the program on 15 December 1983, and the program was cleared to recommence in early 1984. Several more successful DE pregnancies quickly followed.

First Donor Egg Pregnancy and Birth

The first donor egg pregnancy and birth in the world was achieved by Monash IVF in November 1983 following the mother’s treatment four weeks before the treatment being banned. The patient suffered from a congenital absence of her ovaries and required hormone replacement therapy to support the early stages of the pregnancy. – 47 –

T E S T T U BE R E VOL U T IO N

The background for steroid treatment for a receptive uterus came from Trounson’s earlier work on pregnancy induction in ovariectomised sheep, using embryo transfer. Dr Peter Lutjen, now a promising young scientist, was given senior authorship of this important paper in view of his managing the hormone replacement in early pregnancy, and to help his scientific career. (He soon switched to medicine and twenty years later would become clinical director of Monash IVF.) The interesting issue, from a scientific point of view, was whether patients who had no functioning ovaries could deliver the pregnancy, or whether the absence of an ovarian corpus luteum prevented the start of labour. Wood thought it likely from his previous research that such patients could deliver, because the placenta effectively took over control of gestation, from the steroids, early in pregnancy. He was right. The patients delivered their babies without undue problems. A dozen members of the local media gathered in the hospital for a story on the birth, but were kept out of the operating theatre by Wood, who gave them an impromptu lecture on DE in the changing room. Wood always enjoyed talking to the media. Former wife Judy has said that Carl adored being in the spotlight. (Judy and Carl divorced but she became his carer as, towards the end of his life, he suffered from Alzheimer’s.) ‘I enjoy life,’ he told journalist George Negus in 2004. ‘I enjoy trying to change things.’ Carl being a colorful character with plenty to say, annoyed some. Others worried his public profile could overshadow his pioneering professional achievements, especially in IVF. But he used the media’s attention to leverage coverage and debate about the social, legal and moral implications of IVF. In a scene reminiscent of the media melee experienced by Edwards and Steptoe in Oldham at the birth of Louise Brown five years earlier, in the early hours after the birth of the world’s first donor egg baby members of the media chased Wood and myself, unsuccessfully as it turned out, three blocks down Swanston Street at 3 a.m.

The Rapid Rise in the Development of Donor Egg Pregnancies

Despite these chaotic beginnings the DE program was to become an increasingly large and important component of IVF treatment throughout the world. After the first pregnancies were achieved in women whose ovar­ ies were either absent or inaccessible to laparoscopy, a waiting list of 220 – 48 –

The L egislat ors ’ D ilemma

patients quickly developed, of which 180 had ‘buried’ ovaries (inaccessible to laparoscopic visualisation). This demand would soon be swamped, however, by a much larger and growing group of older women failing in their IVF treatments, which pushed the waiting list for DE treatment to well over two years. Women with inaccessible ovaries to laparoscopic retrieval would, by 1986, be able to undergo egg collection through the relatively new technique of ultrasound, whereby ovarian follicles, being fluid-filled sacs, could be readily identified. Initially follicles were aspirated by passing a needle abdominally through the bladder, but soon a more accessible and safer approach, through the upper end of the vagina, was developed by Dr Matts Wikland and colleagues in Sweden, who included nurse coordinator Karin Hammarberg, later to become Alan Trounson’s wife. These new techniques were pioneered by Dr Suzan Lenz, who was a respected leader in ultrasonography from Denmark. Dr Lenz was head­ hunted by Wood to stay in Melbourne for three months and train the eight Monash IVF laparoscopists in this new technique. She proved to be an excellent teacher and the technique quickly caught on. Today ultrasound egg collection is the only method used in IVF procedures. Laparoscopy remains an important diagnostic procedure in the investigation of infertility and pelvic pain. It soon became evident, however, in the early successful IVF treatments, that women over 35 had a significantly lower chance of taking home a baby, due to reduced pregnancy rates and increased risks of spontaneous abortion. Female fertility peaks at approximately 18 to 25 years before slowly declining and then more rapidly declining after 35 years, due to reducing egg quality with age. Women over 38 years, following failed attempts at IVF, were now turning to donor eggs from younger women to achieve a pregnancy rate of over 30 percent per treatment cycle. As with the initial demand for fertility treatment, several outside factors also contributed to this development of DE pregnancies. In Victoria, the Family Law Act 1975 had soon made divorce a more acceptable and easier recourse to a failed marriage, increasing the demand for fertility treatment in older women in their new marriages and partnerships. The contraceptive pill also gave women the chance to control their fertility by postponing pregnancy and pursuing a career free from the burden of childbearing, but would reduce their chance of natural or IVF-assisted pregnancy in later years. There is no doubt that many women were also unaware of this reduction in fertility with age. Finally, legal acceptance of donor pregnancies came – 49 –

T E S T T U BE R E VOL U T IO N

through the passage of the Status of Children (Amendment) Act of 1984, the first such legislation in the world, by the Victorian State Parliament. This Act conferred legal status to children conceived from donor eggs (and donor sperm). It also importantly withdrew all rights and responsibilities from the donor towards the existing child. This commendable legislation had actually been pre-empted as early as July 1980 by the Standing Committee of Commonwealth and State Attor­ neys General, who decided that uniform legislation on the status of children born from DI treatment should be enacted in all Australian jurisdictions. All these factors in varying degrees have contributed to the large and growing demand and acceptance of DE treatment throughout the world today.

Flushing the Donor Embryo

A further possible method of donating eggs by fertilising them in vivo was reported in the Lancet on 9 April 1984 by Dr John Buster, from California. He claimed two successful pregnancies through DI using sperm from the recipient’s husband followed several days later with uterine flushing and retrieval of the donor embryo. This method was relatively simple compared to the more invasive IVF procedure, but carried a risk of an unacceptable pregnancy in the donor should the flushing procedure fail to recover the potential embryo. Wood discussed the method with the Ethics Committee of the Epworth Hospital, where it was rejected on the grounds of the risk of an unwanted pregnancy in the donor. The method was never attempted in Australia and soon fell into disrepute internationally.

Dissent in the Ranks

In November 1983 a disagreement in management occurred when Wood summoned me to an unplanned meeting that also included Drs William Walters (Wood’s deputy in the Department of O&G) and Mac Talbot, but without Trounson, who supported me on the issue about to be raised. Wood criticised the management of a case where a 44 year-old woman who had undergone IVF injection treatment without stimulating was ad­ vised by me to refrain from further attempts and to seek counselling. She had sought a second opinion from Wood who had supported her right to further attempts. The outcome of her further management is unknown although she certainly did not become pregnant. – 50 –

The L egislat ors ’ D ilemma

Wood further criticised my failures to delegate. There was some truth in this reprimand as I usually did most of the clinical procedures myself and was at that time directing the DI, DE and IVF clinical programs. Years later Wood confessed he was under pressure at that time. I relinquished control of the DI and IVF clinical programs, maintaining the DE program and becoming the clinical research director. But the damage had been done and the previously warm relationship between Wood and I, friends of many years, cooled. In retrospect it seems amazing that, despite the egos and ambitions of members in both the clinical and scientific staff, and the highly emotive area of medical research they were in, few serious altercations or acrimonious resignations occurred. This was unlike experiences in many IVF clinics elsewhere.

– 51 –

T E S T T U BE R E VOL U T IO N

Cha pte r 8

E t hics and F rozen E mbryos Ethics can be broadly defined as a system of principles or rules regulating human behaviour. The rules of medical ethics had largely been controlled by the medical profession itself until the middle of the 20th century, but since then the ethics of medical practice in general and IVF programs in particular have rightly attracted, and reflected, a wide community debate. The main problem concerning the regulation of IVF was related to the question of who makes the rules. Two basic but opposed ethical approaches to the control of IVF are the metaphysical approach of an authoritative society, and the empirical concept associated with liberal democracy. The former is usually absolute and dogmatic and is well represented by the attitude of the Vatican to all areas of IVF. The type of ethics consistent with empiricism is situational specific, recognises that all effective medical treatments have risks and holds that, in order to be acceptable, the proportional good of the treatment must outweigh any proportional harm. Armed with knowledge of the relevant risks and benefits of a medical procedure, a patient then has a choice to either reject or accept the offer. In a liberal society the principle of personal autonomy represents a most important value, but one which must be diluted or compromised when applied to practice. This respect of personal autonomy can be suppressed by paternalistic (government) or authoritative (religious) groups so that pure autonomy rarely exists. The ideal of free choice is difficult to realise perfectly in a pluralistic society such as Australia because of the great diversity of opinions, where no overriding consensus on moral issues can be achieved. The implication of this is that the wishes of the majority of different groups of people are or should be met, provided that the interests of no particular group becomes paramount. The Infertility Medical (Procedures) Act of 1984, placing a ban on embryo research, despite the majority of Australians supporting it, exemplified the potential dominance of a minority view within legislation. – 52 –

E t hics and F rozen E mbryos

A further ethical issue concerning IVF related to its effect on the ‘common good’ in society. Would the development of IVF research on human embryos affect society’s values in relation to human life? Would the acceptance of surrogacy arrangements threaten society’s attitude to childbearing? They were two of the hot topics intensely debated. Finally the basic medical principle of ‘do no harm’ outlined by Hippocrates was particularly relevant to the outcome of the offspring conceived through IVF. Would there be a greater risk of foetal abnormalities at birth or of psychological or social problems in later life? All of these ethical issues were discussed at length by many groups. The Monash team, led by Carl Wood, never shied from being available and involved in these debates and Carl Wood, Alan Trounson and I would personally, collectively, author hundreds of scientific papers and write a number of books on related subjects. Possible risks related to IVF were considered unlikely, but were nevertheless still possible, and the fears of an adverse outcome from IVF were finally laid to rest only after several decades of successful IVF pregnancies and followup outcomes. Thus, any imagining that IVF technology had been developing rapidly, particularly after 1981, without any consideration for the moral and ethical issues involved, would be very mistaken. As early as 1972 the Monash IVF team submitted a proposal to the Hos­ pital Research Sub-Committee of the Queen Victoria Hospital ‘to pursue a regime of ovulation stimulation using gonadotrophins (pituitary hormones) and subsequently fertilise the maturing oocytes with spermatozoa in vitro. The ultimate clinical goal would be the in vivo implantation of an in-vitro cultured oocyte fertilised by spermatozoa of the husband.’ Furthermore, ‘we agree this work lies in a difficult arena with moral and ethical problems and would be most willing to discuss this project with you further.’ Understandably, there was no interest in IVF from the legal profession until after the first births. It was at this stage that lawyers and law-makers could become active in influencing IVF procedures and developments. In the prestigious American Year Book of Obstetrics and Gynaecology, in 1975, the Monash team, by invitation, presented a 20-page description of their IVF program, including a large section on its ethical aspects. In 1982, Professor William Walters, a senior member in Wood’s department and a member of the QVH Ethics Committee, and Professor Peter Singer from the Department of Philosophy at Monash University, edited Test Tube – 53 –

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Babies: A guide to moral questions, present techniques and future possibilities. Around the same time, due to public concern regarding possible risks to the embryo, Trounson published ‘Freezing of human embryos: an ethical obligation’. Back in England, however, Bob Edwards had already claimed the first publication of this debate on ethics with his 1971 Nature article ‘Social Values and Human Fertilisation’. Mary Warnock, an Oxford philosopher who would later head the British national inquiry into the ethics of IVF, strongly disagreed with Edwards’ views. Edwards recalled of the IVF debate, in 2003, ‘it didn’t need a philosopher, and you still don’t need a philosopher to look up the ethics of IVF.’ Warnock strongly disagreed and, in support of her view, the Queen Vict­ oria Hospital had convened a meeting of its Ethics in Research Committee, in 1980, inviting both Professor Singer from the Department of Philosophy and Professor Louis Waller from the Faculty of Law to attend. Edwards’ attitude to IVF ethics, in the article in Nature, was short-sighted to the extent that it possibly covered IVF procedures until about 1980, when all normal embryos were transferred back into the uterus. The production of surplus embryos for possible donation, freeze-storage or research that followed successful stimulated cycles, ushered in much broader ethical issues. The main topic in the debate centred on the moral acceptability of using human embryos for research, and thereby destroying them. A later, similar problem concerned the fate of freeze-stored embryos that were no longer needed for either research or uterine transfer. The freeze-storage of human embryo research had begun at Monash IVF in 1981 under the direction of Trounson, who had already been involved in the development of techniques for deep-freezing cow embryos at Cambridge. Interestingly, Trounson argued for the use of embryo freezing to the Queen Victoria Medical Centre (QVMC) Research and Ethics Committee in 1982 and won the approval of the Committee, which included two priests, one Roman Catholic. They considered it more ethical to freeze the embryos for the patients than to either discard them or transfer an excessive number to the patients – risking multiple births and foetal morbidity and mortality. The Church itself was unimpressed with such arguments. Before starting a clinical program a ‘Consent to Freezing and Disposition of Embryos’ form was devised by Monash IVF: We (the Husband and Wife) certify that we both understand the reasons for and the concept of deep-freezing of one or more of our – 54 –

E t hics and F rozen E mbryos embryos following successful in-vitro fertilisation and consent to the undertaking of the appropriate procedures. We understand that uncertainty exists concerning the status of the frozen embryo. We understand it is not practicable to keep a frozen embryo indefinitely and accordingly consent to the lawful disposition of any of our frozen embryos as and when those responsible for keeping the embryo consider it appropriate. We understand that there is no certainty of a normal pregnancy following this procedure and that there may be a risk of foetal anomalies. Again this document was devoid of ‘legalese’ and addressed clearly the three main concerns in the frozen embryo program, namely the chance of success, the status of the embryo and the risk of foetal anomalies.

In 1983, the first frozen-thawed human embryo pregnancy in the world was reported by Trounson and his co-worker Linda Mohr in the journal Nature. Trounson attributed this success to both meticulous care in all steps involved in the procedure and to changing the timing of embryo freezing from the 100-cell blastocyst (as successfully done in cows) to the earlier 4–8 cell embryo. Unfortunately, the pregnancy aborted spontaneously at twenty-two weeks, for obstetric reasons. The foetus was found to be entirely normal (as Bob Edwards had confidently predicted at the Bourn Hall meeting in 1981). The first frozen embryo birth (baby Zoe) in Australia was achieved by Trounson in 1984. Baby Zoe was also normal at birth. The media immediately pounced upon this new spectacular development. Comedians and cartoonists had a field day depicting frozen embryos. Years later Wood recalled thinking, after seeing the sensational headlines, ‘Oh my God, I’m going to be in terrible trouble now.’ After the announcement of the birth by the media it was revealed that the baby had actually been born two weeks earlier; furthermore, the parents had sold exclusive rights of their story to a popular women’s magazine. At a packed news conference Wood certainly had a difficult time fielding questions from irate reporters regarding the reason behind this delay in announcing the birth, and was accused of holding back information. This was unfair as Wood had always been open in discussing all new aspects of the IVF program with the media, and had been appearing at – 55 –

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almost weekly intervals on national television describing current IVF prac­ tices. Furthermore, in relation to the availability of information, the first international workshop on IVF had been convened in 1982 by Dr Gab Kovacs, a young and enthusiastic member of the Monash team, and was attended by twenty international doctors and scientists. All current aspects of the IVF program were presented, irrespective of their publication. This was in direct contrast to the attitude taken by Patrick Steptoe as an invited visitor to Melbourne in 1978, when he refused to discuss any unpublished data. In Britain, the news of the world’s first frozen embryo pregnancy was received less favourably than in Australia. Dr Clive Froggart, president of the Royal College of General Practitioners, thought it impossible to guarantee the safety of such an experiment: ‘even if this pregnancy is safely brought to term, there is still no way to ensure that another one would be’. The Royal College told Mary Warnock, heading the enquiry into the ethics of IVF in Britain, that the freezing of human embryos was unethical. The Royal College of Nursing took a similar position, finding the freezing of eggs and embryos to be unethical. The Waller Committee in Victoria, however, opposed these views and in its final report in September 1984 recommended that embryo freezing be permitted under certain conditions. It is certainly the case that the successful freeze-storage of human embryos was a significant milestone in the development of IVF treatment. Since the birth of Louise Brown in 1978 from an unstimulated cycle, the two most important developments in IVF technology have been the production of multiple embryos from stimulated cycles and their subsequent freeze-storage. Trounson was the main person responsible for both these new achievements, which were quickly followed by all IVF clinics throughout the world and remain the basic procedures in all IVF treatments today. It is now estimated that hundreds of thousands of babies worldwide have been born from frozen embryos. The freeze-storage of excess embryos, with their subsequent thawing and transfer in a natural cycle, significantly improved the overall success-rate of a treated cycle, although not all thawed embryos were suitable for transfer and not all transferred embryos produced a pregnancy. Freezing also promoted the development of the DE program because the stored donor embryo could be thawed and transferred at the appropriate time in the recipient’s cycle. Although the successful freeze-thawing of human embryos proved a rad­ ical advancement in IVF treatment, it also presented, as noted, the difficult – 56 –

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ethical problem concerning the disposal of unwanted stored embryos. This was highlighted in 1984 by the untimely death of the Rios couple, a wealthy American husband and wife from New York who had travelled in their private plane to Melbourne for IVF treatment. They returned home leaving two frozen embryos in storage, but were killed in a plane crash in South America. The question was then raised of who had legal custody of embryos in such situations. Pre-treatment legal documentation, in case of death or, much more commonly, divorce, was, necessarily, then developed. Again, this situation was addressed by the Waller Committee Report of 1984, which recommended that all couples with stored embryos must state in writing their intended disposition of their embryos, or failing this the stored embryos ‘shall be removed from storage’. Obviously this would result in the death of the embryo. The Committee further advised that ‘the embryo, after removal, should not be destroyed in any deliberate fashion, but the ampoule be set aside in the laboratory’. As Professor Peter Singer wryly observed: ‘[O]ne could be forgiven for wondering whether there was a more deliberate way of destroying a frozen embryo than leaving it in the laboratory to thaw.’ Another special case that tested the legal boundaries in Victoria in 2001 concerned a young widow, Joanne Bandel-Caccamo. Her husband died from cancer after the couple had produced frozen embryos. Under Victoria’s strict IVF laws, his death meant she was being denied access to the embryos. After much media attention, the then Victorian Health Minister, John Thwaites, said the Victorian Government would amend the laws in order to allow the young widow to be implanted with embryos created from the sperm of her late husband.

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Cha pte r 9

Opposi t ion and G uidelines There was growing opposition from various groups within Victoria to new IVF developments. The strongest offensive was mounted by the Roman Catholic Church – that not only represented approximately 30 percent of the Victorian population (according to religious self-identification figures recorded by the Australian Bureau of Statistics) – but also carried considerable political clout. At the outset the Catholic Church condemned the practice of IVF, as it separated the conjugal act in marriage from its procreative function. Vatican teaching also stated that human life begins at the moment of fertilisation (when the sperm enters the egg) and deserves full sanctity and protection from that moment. The possible adverse effects of freezing and the definite destructive outcome of research on human embryos were therefore totally unacceptable. B.A. Santamaria, a prominent Catholic theologian and right-wing political activist, called on the legislatures to enforce a total prohibition against all IVF practices. The Anglican Church also voiced concern on these issues. The majority of Australians, however, supported IVF. A Morgan Gallup Poll in July 1981 reported 77 percent approved of the test-tube baby method, 11 percent disapproved and 11 percent were undecided. Ninetynine percent were aware of this method, a similar finding to that from UK surveys. Of all Australians surveyed only 1 percent stated they opposed IVF on religious grounds. Morgan Gallup Poll surveys in 1982 found Australians slightly more tolerant of IVF and its developments than the population of the UK. In addition to the Catholic Church’s intransigent stance against IVF there now appeared opposition from other quarters, especially following the 1981 announcements of the early IVF births. One came, surprisingly, from a strong radical feminist lobby at the School of Humanities at Deakin University. – 58 –

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In November 1981 Dr Robyn Rowland, a lecturer in Social Psychology at Deakin University, approached Wood with a request to carry out psycho­ logical research in selected areas within the infertility program. I assisted in the research and for the next two years Rowland undertook some useful research in the DI program. In May 1984 Wood – always trying to improve the overall standards of the infertility programs – offered her a role directing research into the psychological aspects of the IVF program. Within two weeks of this, however, before Rowland had any direct contact with the IVF program, she suddenly and publically resigned in protest at what she described as ‘morally reprehensible’ reproductive techniques. These included, she said, ‘donor embryo womb flushing’, which was never attempted in Australia. She also complained of an attempt to ‘muzzle’ her research publications: all publications emanating from the IVF team were to be recorded as jointly authored. Years later, Wood reflected: ‘I think her conclusions concerning this brief meeting demonstrates [sic] her ability to draw conclusions from misunder­ standing or not hearing information and from an incomplete exploration of the topic under discussion. Her continuation to oppose the group must be for other reasons.’ Dr Rowland was a founding member of the Feminist International Resistance to Reproductive and Genetic Engineering and remained an outspoken critic of IVF. She called for the closure of all programs and spoke in the House of Lords and on British and Australian television against women being used as ‘living laboratories’. She also spoke of the threat of male domination in female reproduction, in spite of the fact that the great majority of IVF scientists in most IVF laboratories were female. Although her stance against IVF now appears extreme and misguided, Rowland’s criticisms added to the general debate concerning the control of IVF that raged in Victoria during the early 80s. Opposition to the Monash IVF team also came from members of the medical profession. Several senior doctors advised Wood and I to ‘stop wasting time on IVF’. Dr Peter Paterson, a highly respected gynaecologist in Wood’s university department and a leader in microsurgical tubal repair operations, opposed IVF. In 1982 at a meeting of 200 doctors in Victoria he claimed ‘IVF would have no therapeutic role in infertility treatment but could be a useful diagnostic tool’; and at an international meeting later in Ireland was reported to claim that IVF successes were a hoax. – 59 –

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This attitude closely paralleled the opposition experienced by Edwards and Steptoe from some doctors following the birth of Louise Brown in 1978. Edwards recalled in 2003: ‘The worst were the doctors, the British gynaecologists. They said it was a fake. When we got to lecture in the Royal College of Obstetricians six months after Lou was born, they told people, “Don’t go, it’s all a fake.”’ The media in Australia was generally supportive of the IVF programs although new developments were always sensationalised in ‘world-first’ headlines, and mistakes were made. Following the birth of the first donor egg baby, one newspaper mistakenly concluded that the treatment transfer had ignored the moratorium placed on the DE program by the Victorian Government. The pregnancy treatment had actually pre-dated the moratorium. In 1982, the report that six of the first seven IVF babies born worldwide were girls led to claims of possibly flawed IVF laboratory techniques. These fears were soon debunked following the births of further IVF babies, confirming a sex ratio equivalent to the natural ratio of approx­ imately 50/50. Some early television programs, however, were deliberately misleading. In the 1970s Edwards related the story of a request from a BBC producer ‘to do a program about fertilisation and other matters’. When he learnt that the program was to focus on such subjects as cloning and hybrids between species, he wisely withdrew but was horrified to view the program later maliciously comparing his work with Ernest Rutherford’s nearby laboratory where the atom was split, that resulted in the devastation of Hiroshima! Wood and his group suffered a similar experience in 1982 when they naively agreed to a BBC television documentary, to be made in Melbourne. The final production was both scandalous and libellous, comparing IVF procedures with the inhuman experiments of the infamous Dr Mengele in Nazi concentration camps. Such disingenuous programs deliberately misrepresented IVF procedures and added to the scaremongering tactics of these procedures’ opponents.

National Guidelines

In 1983 Australia was the first country in the world to publish ethical guidelines on IVF procedures and research at a national level. This followed a review of the working party on ethical issues connected to programs in medical research receiving NHMRC grants, and particularly – 60 –

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those in IVF research, established by the NHMRC in 1981. These guide­ lines stated: 1. Every centre offering an IVF or ET program should have all aspects of this program approved by an Infertility Ethics Committee (IEC).

2. Research with ova, sperm or embryos has been and remains inseparable from the development of safe and effective IVF.

3. Continuation of embryonic development beyond the stage of implantation is not acceptable. It is interesting to note here that these three factors were adopted in Eng­ land in 1990 with the passage of the Human Fertilisation and Embryonic Act. The American Fertility Society published its guidelines in 1986. Enlight­ ened and perceptive as these national Australian guidelines were, it was un­ fortunate for Wood and the two IVF teams in Melbourne that health matters, including all IVF procedures, were essentially under state jurisdiction.

State Guidelines: The Waller Committee

In response to the increasing number of IVF births and reported attempts at egg donation and embryo freezing, the Victorian Government in March 1982 appointed a Committee of Enquiry to consider the ‘social, ethical and legal issues arising from in-vitro fertilisation’, with a view to establishing legislation to control them. The Chairman of the Committee was Professor Louis Waller, a professor of law at Monash University since 1965. He was a good choice as he already had a wide experience in both national and international law reform and also held a deep regard for the welfare of couples undergoing infertility treatments. His Committee of eight members consisted of doctors, lawyers, theolog­ ians, a social worker and a layperson but unlike the sixteen-member Warnock Committee in Britain, no philosopher. None of the members were directly involved in an IVF program. The Committee published an Interim Report in September 1982, a Report on Donor Gametes in August 1983, and finally, after more than two years of research and discussion, its final document in September 1984: the Report on the Disposition of Embryos Produced by In Vitro Fertilization. The Committee’s task was onerous, entailing interviewing scores of people and reviewing hundreds of submissions. Although not all decisions – 61 –

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were unanimous – which is understandable in view of its membership – the Committee overall did a good job. It recommended that donating eggs and embryos be allowed to continue under regulation, and the freezing of embryos be permitted under certain conditions. The basic implication of the Waller Report was that the human embryo is not a human person in the full sense, and cannot achieve human status until the early development of the brain and nervous system that begins fourteen days after fertilisation. This timeframe represented the pre-implantation stage of embryo development. The Committee therefore recommended that excess ‘spare’ embryos be allowed for research, but no later than fourteen days after fertilisation. This recommendation was in close agreement with both a similar re­ commendation of the Warnock Committee in Britain made in the same year, and the guidelines presented by the NHMRC in 1983. The significant difference between the Waller and Warnock recom­ mendations lay in the latter allowing the deliberate creation of em­bryos for research rather than restricting the carrying out of research on embryos to those ‘left over’. The Committee’s final recommendation called for the establishment of a ‘standing review and advisory body’ to continue to examine and report on all developments in the IVF program. This was an important proposal. The proposed body would become the Standing Review and Advisory Committee on Infertility (SRACI), con­ sisting of eight members, including a philosopher, but without any member of an IVF program. Professor Waller was elected Chairman and remained in this role from 1985 to 2001. It was envisaged that the Committee would be able to deal with both rapid new developments in IVF procedures and the changing attitude of society towards them. This important recommendation was similar to one made by the Warnock Committee, which called for the establishment of a statutory authority with strong lay and scientific representation to regulate IVF research. A lone dissenting voice against the impending Victorian legislation came from Sir Gustav Nossal, Australia’s leading scientist, who considered that IVF technology was moving too rapidly for legislation to cope with. ‘The genie is out of the bottle, and cannot be put back,’ he said in 1982. ‘It is much better to use soft-edged measures, depending on human judgement and decency, such as strong ethics committees, including outside lay mem­ bers, to monitor research and treatment in laboratories and hospitals.’ A similar view, opposing legislative control, was also held by the Reverend – 62 –

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Davis McCaughey, the Victorian Governor. Their pleas fell on deaf ears, but within a few years history would prove these pleas remarkably prescient. Despite the reasonable recommendations of the Waller Committee in 1984, in close agreement with the Warnock Report of the same year, the Government of Victoria was about to pass, in haste, not only the world’s first legislation relating to IVF, but also one of the most restrictive and punitive forms of this legislation to be proclaimed anywhere in the world. .

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Cha pte r 10

The Problems of A mbiguous L egislat ion In November 1984 the Victorian State Parliament passed the Infertility (Medical Procedures) Act, regulating certain procedures in the IVF program. The passage of this Act followed just three months or so after the release of the third and final report of the Waller Committee at the begin­ ning of September. The Waller Committee had spent two and a half years considering the private comments and views from various community groups before giving its final recommendations to the state government. The state government, in turn, considered these recommendations, along with countless private and community views, before presenting a Bill to the State Parliament, that then hastily passed the above legislation. The Infertility (Medical Procedures) Act not only rejected some of the Waller Committee’s recommendations, especially those related to em­ bryo research, but also generated many administrative tasks of questionable usefulness. It has remained a constant source of controversy and been the subject of numerous reviews and inquiries since its passage in 1984 and its amendment in 1987. The Act stipulated that all IVF procedures could only be performed at an ‘approved’ hospital which was required to have a ‘designated officer’ responsible for recording the use of sperm, eggs and embryos. These records were to be kept in a central register held by the Health Commission that could be inspected by the Government at any time. While the disposal of embryos and the use of donor gametes should be recorded, for several practical reasons, the reason why couples using their own sperm and eggs needed to keep records beyond those essential for proper standards of clinical care, were not clear. As no equivalent data is recorded when fertile couples conceive naturally, the information recorded about – 64 –

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couples using their own gametes in an IVF program could be considered both intrusive and discriminatory. The access to IVF treatment was limited to married couples, excluding those in de facto relationships. This requirement was it seems reliant on the unproven premise that legally married couples make better parents. It would take thirteen years for this section of the Act to be altered to allow de facto couples to have access to IVF treatment, following an amendment in 1997. Admission of single women for IVF treatment was allowed, finally, when Dr John McBain, a leading IVF pioneer from the Royal Women’s Hospital, successfully challenged the law on the grounds of discrimination in the Federal Court in 2000. Mandatory counselling by an ‘approved’ counsellor was also demanded in the Act. Although counselling is important in donor gamete treatments, its mandatory role in routine IVF treatment was questionable. Many well-informed couples found it unnecessary and insulting; in the state of Victoria the only other patients requiring compulsory counselling were the insane. Another section of the 1984 Act stated: ‘[C]ouples must have at least 12 months’ investigation and treatment before carrying out the procedure’. This was clinically unnecessary and presented a legal conundrum in the case of those couples where the wife had blocked tubes or the husband had no sperm. The most contentious section of the 1984 Act, however, lay in its total prohibition of research on human embryos. The legislation was primarily based on the definition of human life as beginning at the moment of fertilisation. This reflected a strong religious bias. Here it differed dramatically from the very recent recommendations of the Waller Committee. All experimental procedures were prohibited that involved ‘carrying out research on an embryo of a kind that would cause damage to the em­ bryo, would make the embryo unfit for implantation or would reduce the prospects of a pregnancy’. Any abuse of this section carried a punishment of 100 penalty units or imprisonment for four years. Penalties for infringement of any section of the Act were all strictly defined while, in stark contrast, no definition was given of an embryo itself. This oversight led to some misunderstanding in relation to later amendments to the 1984 Act and was finally rectified in the 1995 Infertility Treatment Act, where an embryo was defined to mean ‘any stage of human embryonic development at and from syngamy – the stage of development of a fertilised – 65 –

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egg where the chromosomes from the male and female pronuclei align on the mitotic spindle’. The 1995 Act, however, continued the ban on embryo research. The prohibitions of the 1984 Act created an impassable obstruction to all em­ bryonic research by the Melbourne teams. Particularly unfortunate was its blocking of Trounson’s pioneering work in microinjecting a single sperm into an egg in clinical cases of male infertility, codenamed Sub-Zona Injection (SUZI). SUZI was an outstanding example of the inadequacy of legislation en­ acted quickly with little consultation with the scientific community about the implications of the prohibitions in the Act.

The Difficulties for SUZI

In 1987 Trounson and his team reported the fertilisation of human eggs by the microinjection of a single sperm under the zona pellucida (the egg’s soft glycoprotein shell). This technique had profound implications for the possible treatment of severe male infertility. However, before embarking on a clinical program, Wood and Trounson realised that the technique held possible risks, including the production of major chromosomal abnormalities in the resulting embryos. A request was therefore made to SRACI to approve a research exper­ iment to examine the chromosomal normality of embryos produced from the microinjection of eggs with sperm from severely infertile men. The Committee was unable to grant permission for this study as the embryos would be deliberately created for research – and destruction. As a compromise the Monash team proposed that the analysis could be made before the completion of fertilisation i.e. at the early pre-syngamy stage before the mixing of the maternal and paternal chromosomes. After much discussion SRACI recommended an amendment to the 1984 Act to allow the fertilisation of eggs, but limited it to no more than twenty-two hours after sperm penetration (pre-syngamy). The Victorian Parliament passed the Infertility Medical Procedures (Amendment) Bill in 1987, allowing this important research project to start provided it was carried out in the pre-syngamy stage. This compromised research project showed no increase in chromosomal abnormalities, allowing the Monash workers to finally start a clinical trial. Before the 1987 Victorian Bill was passed, however, Trounson, unable to carry out his SUZI research program in Victoria, relocated this program – 66 –

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to Sydney, where he continued his work with the helpful cooperation of Dr Rob Jansen, the Director of Sydney IVF. Although Trounson had pioneered the microinjection technique, the first SUZI pregnancy and birth in the world occurred in Singapore in 1988, and the next few successful pregnancies were from Sydney IVF. SUZI pregnancies from Melbourne were not achieved until 1991. Within a few years the SUZI technique was replaced by IntraCyptoplasmic Sperm Injection (ICSI) where the sperm is injected into the centre of the egg. This method was pioneered in 1993 by Gianpiero Palermo in Brussels and soon showed superior pregnancy results to SUZI. Although sperm microinjection was originally developed to overcome male infertility its high fertilisation rates have led many clinics to adopt its use routinely in all IVF procedures. Microinjection was promoted further following the development of needle testicular biopsy in men suffering from azospermia – a complete absence of sperm – whereby a few sperm could be extracted from the testis and injected via ICSI to give comparable pregnancy results. The legislative restriction on embryo research in Victoria in the mid-80s was the main reason behind Melbourne losing its position as the world leader in scientific research to overseas programs working under more supportive regulations.

Human Embryo Biopsy Research

In 1985, Monash IVF scientists received a research grant with funding from the NHMRC to explore the possibility of diagnosing genetic and chromosomal abnormalities in pre-implantation (4–8 cell) embryos. The study aimed to explore the effects of removing one or two cells, from 8-cell embryos, on their continuing development. Leander Wilton, a brilliant young researcher working with Trounson, was able to demonstrate the feasibility of such techniques in mice embryos. A request was therefore made to SRACI to study ‘spare’ human embryos for chromosomal abnormalities. These embryos had delayed fertilisation and many were considered abnormal and were to be discarded. Despite an initial approval by the Committee for this study, the Victorian Minister for Health, responding to the outcry from the anti-IVF lobby groups, stepped in and announced a moratorium on testing embryos after syngamy. – 67 –

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The Victorian Premier also stated that IVF should be used to help childless people have babies but: ‘It should not be used for scientists to conduct brave new world experiments.’ Two SRACI members resigned over this government intervention and Wilton left Australia to continue her work in London. Monash IVF scientists were unable to obtain the preliminary data required and had to abandon this important IVF procedure that was then taken up and successfully developed and reported in London in 1989. Known as Pre­ implantation Genetic Diagnosis (PGD), it soon became a selective mand­ atory procedure in all leading IVF clinics throughout the world and has significantly reduced the possibility of embryo loss, miscarriage and severe birth defects. Infertile women in Victoria, however, who were at risk of having a severe genetic disease or a chromosomal abnormality in their offspring, were denied this technology for many years and could only access prenatal diagnosis using amniocentesis or chorionic villus sampling, carried out between eight and sixteen weeks of pregnancy. The irony, arising from the Act, was that the destruction of such afflicted foetuses, usually by late term abortion, was legal, whereas the diagnosis and destruction of this same embryo at two to three days old, was illegal. As noted previously, the Morgan Gallup poll of 1984 had found that 66.7 percent of Australians approved of embryo biopsy and 58.1 percent approved of research on human embryos aimed at preventing genetic disease. The Government’s continuing ban on embryo biopsy, contrary to the principles of democracy and pluralism, was not consistent with comm­ unity values.

Donor Eggs

Another example of the inadequacy of legislation on IVF that is written quickly and does not take full account of its possible prohibitive effects on future IVF procedures is to be found in the Act’s section on egg donor recipients. Only those who could not get pregnant any other way could receive treatment. Although the Act did not directly outlaw surrogacy its unnecessary wording inadvertently prohibited the practice of IVF surrogacy in Victoria, as it literally implied that only post-menopausal grandmothers could be clinically considered as surrogates!

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This section in the 1984 Act was finally amended by the Assisted Repro­ ductive Treatment Act (2008) that allowed IVF surrogacy to proceed in 2010 – twenty-six years later.

British versus Victorian legislation

Before comparing the legislation in Britain and Victoria, it is again interest­ ing to note the similarity between bills introduced privately and separately in both the British and Australian Parliaments in the same year to ban research on human embryos. In 1985 British politician Enoch Powell introduced a private member’s bill – the Unborn Children (Protection) Bill – to ‘render it unlawful for the human embryo created by IVF to be used as a subject of an experiment …’ The bill was supported by two million signatures and actually won a majority on its second reading in the British House of Commons before being finally defeated. In the same year Senator Brian Harradine, a staunch Pro-Life independent senator from Tasmania, tabled the Human Embryo Experimentation Bill 1985 in the Australian Senate, aiming at the prohibition of research that involved the destruction of human embryos. This led to the establishment of the Tate Committee to investigate any need for federal legislation to control IVF. Although the majority of Tate Committee members supported the bill a strong dissenting report from two female senators opposed it. Their view primarily ascribed to women the right to decide the fate of their embryos prior to transfer. This bill was also defeated. Although the Waller and Warnock Committees were established in the same year (1982) to explore and advise on similar issues, and both of them submitted their final reports to their respective governments two years later, the resulting legislation, in Victoria and Britain, differed widely. Whereas the British legislation in 1990 has served as a practical and responsible system of overseeing IVF programs and research, the Victorian Acts of 1984 and 1995 have not. The main reason underlying this difference lay in the respective times taken between the submission of these committee report recommendations and their subsequent enactment into legislation. The passing of the Infertility (Medical Procedures) Act in Victoria, less than three months after the receipt of the Waller Committee Report, was

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described by Justice Michael Kirby in 1985 as an example of ‘knee jerk’ legislation. In contrast, the sixteen-member Warnock Committee Report, presented in June 1984, preceded proposals brought forward by the Government in a White Paper – ‘Human Fertilisation and Embryology: A Framework for Legislation’ in 1987. In the following year, the Human Fertilisation and Embryology Bill was drafted, amended and debated at great length in both houses of the British parliament. The Human Fertilisation and Embryology Act was finally drafted from it and passed in 1990. The difference in times taken between the committee reports and the ensuing legislation – of three months in Victoria against six years in Britain – is significant. The British Act established a Statutory Licensing Authority, the Human Fertilisation and Embryology Authority (an executive non-departmental government body) whose principal task was to independently regulate treatment and research involving all IVF procedures. It was composed of a large number of experts and individuals (twentyone) from various fields including six doctors and several eminent scientists and research workers. This Authority stood in stark contrast to the eight-member SRACI Committee established in 1984 in Victoria, that included no doctors, scien­ tists or patients involved in any IVF program. How this committee could be expected to function effectively ‘to advise the Minister in relation to infertility and procedures for alleviating infertil­ ity’ as well as ‘to approve experimental procedures for the purpose of section 6(3)’, as demanded by the Act, is hard to imagine. As Wood noted in a speech to the Australian Institute of Management, the SRACI Committee ‘is not an expert committee, having neither an IVF specialist (provider), a scientist (developer) or a patient.’ Despite these shortcomings, and saddled with the imposition of Section 6(4) of the Act, banning embryo research, it must be conceded that SRACI under difficult circumstances did a good job in attempting to promote IVF developments, and its advice was often ignored by state legislators. The British Authority was clearly much better equipped to understand the changing intricacies of IVF technology as well as to foresee the possible new developments that this technology could achieve. The Victorian Infertility Treatment Act 1995 belatedly tried to overcome the shortcomings of the 1984 SRACI membership by increasing its number – 70 –

The P roblems of A mbiguous L egislat ion

to a maximum of fourteen, including a doctor with clinical experience in IVF, an embryologist and a patient who had undergone IVF treatment. Unfortunately this review of the 1984 Act regarding SRACI came far too late to meaningfully redress the effects of its inadequacy. The 1995 Act also continued its ban on destructive research on embryos. Why did this ban on embryo research persist in Victorian legislation despite the Waller Committee’s recommendation to allow it up to fourteen days after fertilisation? One reason was probably a fear of new technology, as argued by John Funder, Professor of Medicine at Monash University, who queried why a society that allowed the killing of a foetus after as many as twelve weeks of pregnancy should restrict embryo research to within twenty-two hours after fertilisation. He considered that lawmakers in this field, the politicians and lawyers, were ill-equipped. Wood agreed: ‘The alarm concerning new developments, such as embryo experimentation, is partly a fear of the unknown, partly a fear at what might go wrong, partly a fear at what it might lead to (e.g. cloning), partly a fear of change, and partly due to fixed ideologies based on religious views.’ It seems clear that politicians in government, and their associated staff, were not sufficiently trained or knowledgeable to proclaim long-standing legislation in such a difficult and changing field as IVF. One might feel some sympathy for the Victorian lawmakers, as all the new developments in IVF between 1980­–1984 (twelve of the first fifteen pregnancies, the first donor egg and embryo pregnancies, embryo freezing and embryo research) were being pioneered in Melbourne. It must be con­ ceded, however, that British society was well aware of these Australian developments and some of their IVF clinics were already exploring these fields. Edwards had tried donor egg treatment and embryo freezing as early as 1977. The British delay in enacting legislation was crucial in finalising a practical and responsible regulatory system that would not require multiple amendments, as the Victorian legislation has. World leadership in IVF research, including within the new develop­ ments in stem cell technology, now moved to America, England and some European centres. Finally, in this discussion of IVF legislation, it is interesting to compare the official responses to IVF procedures, prior to the existence of legislation in this area, from the two relevant medical institutions involved: the Royal College of Obstetricians and Gynaecologists in England and the corresponding College in Australia. – 71 –

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The Ethics Committee of the Royal College published a detailed report on IVF technology in March 1983, supporting IVF treatment. It purposely defined ‘marriage’ as ‘a hetero-sexual couple cohabitating on a stable basis, whether or not legally married,’ and supported embryo biopsy research to exclude genetic disorders. It also approved the use of donor gametes in IVF procedures, although it opposed the practice of IVF surrogacy arrangements. In contrast to this British report the Australian College offered no official response. Improved legislation followed in South Australia in 1988 and Western Australia in 1991, although both banned destructive research on human embryos. Committees of enquiry into IVF practices occurred in other states without restrictive legislation. In New South Wales the Law reform Com­ mission, under the guidance of Russell Scott, wisely decided in 1986 against legislation relating to IVF. The pioneering Victorian legislation had at least demonstrated to the world the pitfalls to be avoided in any form of legal control. As Associate Professor John McBain, a leading IVF clinician for over thirty years, has concluded, ‘the law has done more harm than good to IVF’. Reflecting on this chapter of Victorian law-making, the words of Alexis de Toqueville, trying in 1845 to conceptualise the nature of threats to freedom within a democratic society, come to mind: ‘Government does not break men’s will, but softens, bends and guides it; it seldom enjoins but often inhibits action. It does not destroy, but prevents much being born. It is not tyrannical, but hinders, restrains, enervates, stifles and stultifies.’

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The G I F T of L ife

Cha pte r 11

The GI F T of L ife A new and alternative treatment to IVF was reported in the prestigious jour­nal Lancet in 1984 by Dr Ricardo Asch from San Antonio, Texas. He described the laparoscopic surgical procedure of Gamete Intra-Fallopian Transfer (abbreviated to GIFT). This technique entailed the traditional laparoscopic collection of eggs, mixing them with prepared sperm in the laboratory and their immediate replacement into the fallopian tubes in the same laparoscopic procedure. Although Asch has been credited with the invention of GIFT it had been reported by Dr Tesaric, from Czechoslovakia, during a tubal repair operation the previous year, and Ian Johnston had actually tried it, unsuccessfully, before 1980. Dr Asch certainly promoted this new procedure that was quickly taken up by many overseas clinics. The main advantage of GIFT over IVF related to the egg fertilisation occurring in the fallopian tube rather than the laboratory; this reduced costs as no detailed microscopy and in-vitro culture techniques were required. GIFT also reduced time spent in hospital as it involved only a one day procedure, as against the double clinical admission required by IVF. To many people it seemed a quite ‘natural’ process, and was approved by the Catholic Church, as it allowed fertilisation to occur in vivo. In Melbourne GIFT was allowed by the Catholic Church provided eggs and sperm were kept strictly separate before being placed into the fallopian tube. This situation was achieved by the tricky but ingenious laboratory technique of inserting a small bubble between the eggs and sperm in the catheter. The traditional collection of sperm also presented a problem to Catholic-run infertility clinics but was overcome through the use of specialised sterile condoms, which had been accepted by the Vatican in 1987 through the Congregation of the Doctrine of the Faith. In 1992 Dr Mac Talbot, a clinical pioneer in the Monash IVF team, established a large GIFT program at the Catholic Mercy Hospital for Women in Melbourne. – 73 –

T E S T T U BE R E VOL U T IO N

Nevertheless GIFT possessed several serious disadvantages. It could only be employed in clinical cases characterised by both normal tubes and ade­ quate sperm, usually referred to as idiopathic infertility. Its applicability in infertility programs varied from 5 to 30 percent depending on the accuracy of the cause of the infertility, identified. GIFT therefore had no place in the treatment of either tubal disease or severe male infertility, the latter being only successfully managed through IVF involving sperm microinjection. Furthermore, as the GIFT procedure precedes fertilisation, the microscopic diagnosis of fertilisation in the laboratory with subsequent normal or abnormal embryo development, including embryo biopsy for genetic and chromosomal abnormalities, was unavailable. Despite these shortcomings GIFT was rapidly accepted into many overseas infertility programs. In 1985 Asch visited Melbourne to demonstrate his GIFT procedure by mini-laparotomy – he was not experienced in laparoscopy – as well as to learn first-hand the IVF techniques. Both Mon­ ash IVF and Melbourne IVF (the RWH group) quickly developed GIFT using laparoscopy and jointly carried out the first large combined series of GIFT procedures. In 1987, Monash IVF reported a controlled clinical trial between IVF and GIFT showing no significant difference in success-rates between them. Large series of successful GIFT treatments followed throughout the world. In 1990, Dr Rob Jansen in Sydney reported another large series of 710 GIFT procedures on 445 infertile couples with a pregnancy rate of 20 percent per cycle and 33 percent per couple entering the program. This important means of expressing treatment success-rates – in terms of the number of IVF attempts instead of the success-rate of a single treat­ ment – had been initially reported by Dr Gab Kovacs in 1986, showing the prospects of an eventual pregnancy after several pregnancy attempts as a cumulative pregnancy rate. After all, life tables of natural human conception had always been presented as the chances of pregnancy after six or twelve months of timed sexual intercourse, rather than as a single month. However, despite its initial popularity, GIFT was to enjoy a life span of less than ten years in most infertility clinics, because of the improving success rates of IVF. By 1993, Professor Robert Winston at Hammersmith Hospital, London, had reported the life table results of a controlled clinical trial between three cycles of both GIFT and IVF showing a cumulative pregnancy rate of 52 percent for GIFT against 84 percent for IVF. – 74 –

The G I F T of L ife

Another important factor contributing to the demise of GIFT lay in the new technique of collecting eggs by vaginal ultrasound under light analgesia, as against the more invasive laparoscopic route, requiring full anaesthesia. The increasing success of IVF combined with its simpler technique of egg collection by ultrasound brought on a decline in the use of GIFT in the late 90s, in most centres. It still survived in those infertility clinics lacking the facilities and expertise of IVF technology, as well as in Catholic hospitals where IVF was unacceptable. It is unlikely that any large GIFT programs are still in use today. Talbot’s GIFT program was finally discontinued in 2010. Dr Asch, the originator of GIFT, received the gratitude of the Catholic Church with the bestowal of a Papal Knighthood by the Vatican, before permanently fleeing the USA after being charged (and later convicted in absentia) with mail fraud, using fertility drugs not approved by the Food and Drug Administration (FDA), and intentionally stealing eggs from patients without their consent.

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T E S T T U BE R E VOL U T IO N

Cha pte r 12

The S t ruggle for S urrogacy In 1987, a new IVF-related procedure in infertility management appeared in Victoria with the initiation of surrogacy, where one woman carries and delivers a baby for another. Surrogacy became, and remains today, the most contentious component of reproductive medicine. The British Report of the Committee of Enquiry into Human Fertilisation and Embryology in 1984 stated that some of the most difficult problems it encountered were those associated with the question of surrogacy, and recommended criminal sanctions against its practice. The early legal and ethical battleground involving surrogacy was waged in Victoria where the legal difficulties surrounding surrogacy were further compounded by the inappropriate legislation in sections of the 1984 Infertility Medical (Procedures) Act. There are two basic types of surrogacy that must be clearly distinguished. Traditional surrogacy refers to a woman who conceives with the com­ missioning husband’s sperm, either by natural or artificial means. This method has been practised by many cultures for centuries and was first reported in the Old Testament. More recently many such surrogate pregnancies have been produced by artificial insemination, mainly in the United States, where over 1000 births had been reported by 1990. The distinguishing feature of this surrogacy arrangement is that the woman provides her own egg that is fertilised naturally in vivo. The surrogacy can therefore be easily carried out, with little if any medical assistance. The concept of IVF surrogacy, however, where the commissioning couple provides their own genetic embryo for implantation in the surrogate, was relatively new, as it relied upon IVF technology. The first IVF surrogate pregnancy in the world was reported from America in 1985. In such cases the surrogate does not provide any genetic material towards the baby and therefore can be expected to have a reduced risk of bonding to the pregnancy. – 76 –

The S t ruggle for S urrogacy

In medical terms, the absolute indication for IVF surrogacy is found in a woman with no uterus, but functioning ovaries. This is an uncommon situation in infertile women under 40 and is usually caused through the operation of hysterectomy with conservation of the ovaries. On the other hand, the absolute indication for traditional surrogacy would be in the case of a woman without a uterus and ovaries, a still less common condition in women under 40 years than the former. It was ironic in Victoria that IVF surrogacy was illegal despite the intense interviewing, counselling and testing it entailed, whereas traditional surrogacy, without any of these prerequisites, was not illegal (although any ostensibly legal contract relating to traditional surrogacy would be null and void). The debate surrounding the ethical and legal issues of IVF surrogacy erupted in Melbourne in 1987 following Australia’s first IVF surrogate pregnancy and birth. This situation was largely brought about through the instigation of two remarkable women, the Kirkman sisters, who lived in country Victoria.

The Kirkman Sisters

Maggie Kirkman had suffered infertility for many years before undergoing a hysterectomy operation in 1978. Her ovaries were conserved. Dr James Evans, the senior endocrinologist at the Royal Women’s Hospital, confirmed through hormone testing that ovulation was still intact, and referred her to me in 1986 for possible further management of her obvious infertility. With her husband, Severn Clarke, she expressed a wish to explore the possibility of a surrogate arrangement using her sister, Linda, as the surrogate mother. Following my initial surprise at this unusual request and after several lengthy conversations with both sisters and their respective husbands, I accepted the idea without further reservation. The foursome presented as a rational, intelligent group and Maggie Kirkman had always held a strong desire for parenthood. Linda Kirkman appeared an ideal surrogate as she had completed her family and her husband, James Ettles, had undergone vasectomy. This difficult scenario was further complicated by the fact that Severn Clarke was sterile and donor sperm was required. An acceptable donor known to the group was found and accepted after routine testing and inter­ viewing for sperm donation. Preliminary laparoscopy revealed accessible ovaries for egg collection and repeat hormone tests confirmed intact ovulation. The two couples next – 77 –

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underwent several counselling sessions and Linda received an independent obstetric opinion to check her suitability for a further pregnancy. The clinical scenario was now a feasible concept, but it needed the usual ethical and legal approval before proceeding. This is where the chaotic discussions, referrals and counter-referrals began. The proposition was first presented to the Ethics and Research Committee of Epworth Hospital, where the procedure would in normal circumstances be carried out. Although the 1984 Act did not state that surrogacy itself was illegal, the Chairman, a lawyer, was quick to point to Section 13 (3) (d) of the Act, relating to embryo donation, that stated it was lawful only if ‘the patient is unlikely to become pregnant as the result of a procedure other than a procedure to which this section applies.’ This unnecessary wording (there was no corresponding statement relat­ ing to sperm donation – another example of sex discrimination) blocked the programming of IVF surrogacy in Victoria for almost thirty years. Section 13, if taken literally (which it was by many in the law), meant that the surrogate must be infertile to the extent that only embryo donation could procure a pregnancy. Only a menopausal grandmother could clinically fit this role. No wonder the Victorian Law Reform Commission branded this legislation irrational, twenty years later. Another Victorian statute imposing an insurmountable legal difficulty to IVF surrogacy, existed. The Status of Children (Amendment) Act was rightfully enacted in 1984 to give legal parentage to recipients in donor gamete programs, so that a woman conceiving from a donor embryo would be recognised as the legal mother. Unfortunately this implied that Linda Kirkman would be declared the legal mother – an unwanted sequel – that could only be overcome through either legal amendment, or adoption. Faced with this conundrum imposed by Section 13, the Epworth Hos­ pital Ethics Committee sought legal advice from Professor Waller and the SRACI. They agreed the situation was extremely difficult and, admitting the Committee was not the source of authoritative legal advice on these matters, suggested obtaining a second opinion from the State Solicitor General. Following this understandable deference an approach was made to the State Minister of Health, who advised seeking a further legal opinion from SRACI. With Carl Wood’s backing I next had a long and helpful interview with Hertog Berkeley, QC, the State Solicitor General, who considered that Linda Kirkman could act as a legal surrogate within the Act as she was – 78 –

The S t ruggle for S urrogacy

socially infertile in view of her husband’s vasectomy. ‘The law should be construed with common sense,’ he explained. The State Attorney General, Jim Kennan, thought otherwise however, and took the opposing view: that Linda Kirkman remained a biologically fertile woman. Because of this obvious ambiguity in the law in relation to the definition of infertility, exemplified in the differing interpretations of the state’s two leading legal authorities, as well as ethical concerns regarding Linda bonding to the baby, Epworth Hospital declined to allow the surrogacy project to be carried out. Wood and I were now left in a quandary as to how to proceed with the Kirkman case in the state of Victoria. Where could we go? Wood rescued the plan by successfully applying to Masada Hospital, a Jewish-affiliated general hospital in outer Melbourne, for permission to carry out the clinical procedures. The Hospital Board agreed after several lengthy interviews with the surrogate foursome, who had previously sought interviews with the Epworth Hospital Ethics Committee and SRACI, but been rejected by both. The procedure of collecting two eggs from Maggie, now aged 40, fertilising them with donor sperm and transferring two embryos back into Linda, took place in September, 1987. A single pregnancy was confirmed two weeks later. The pregnancy was destined to be far from uneventful. Strict secrecy regarding the pregnancy was maintained by all involved until several bleeding episodes at seven months’ gestation required hospital admission to the Monash Medical Centre. Within two days the secret was leaked to the media, members of which promptly besieged the hospital as well as the homes of both sisters. Radio and television networks had a field day following the news of the pregnancy. I was threatened with deregistration by the Monash Medical Centre CEO, although I was supported by the University. Crucially, help was received from an unexpected quarter when the then Premier, John Cain, announced his approval of the pregnancy, on national television, as ‘a first for Victoria’, stating ‘the Government will do anything to support the people involved’. The State Minister for Health, David White, also made public comments of support. The situation was saved. There were, however, a few vocal detractors. Dr Nicholas Tonti–Filippini, an outspoken Catholic bioethicist, branded the Kirkman sisters prostitutes, a most unjust and incorrect statement as neither sexual intercourse nor pay­ ment were involved. – 79 –

T E S T T U BE R E VOL U T IO N

The tactics of the media covering the story were deplorable, allegedly including reporters masquerading as doctors to gain access to wards. The situation became so intrusive that Linda was smuggled from the hospital late at night to seek care and shelter at another hospital and later at the home of her father, Dr Jack Kirkman. Further bleeding episodes necessitated re-admission to hospital, where a baby girl was eventually delivered at 36 weeks by caesarean section on 23 May 1988. Both husbands were present at the birth with Maggie receiving the baby immediately on delivery. She was normal and healthy and was named Alice. Although Maggie cared for and even partially breastfed the baby, the Status of Children (Amendment) Act denied her legal motherhood. This unsatisfactory situation was eventually circumvented after lengthy and costly legal negotiations that finally allowed Maggie to adopt her own genetic child the following year. The Kirkman sisters kept a diary of the day-to-day events surrounding their extraordinary pregnancy and published them in their revealing book My Sister’s Child, in 1988. Although some lawyers considered the Kirkman surrogacy treatment illegal, as it contravened Section 13 of the Infertility (Medical Treatment) Amendment Act, no charges were laid as the Act had yet to be proclaimed as law. This occurred on 1 July 1988 – five weeks after the birth – another close call reminiscent of the DE pregnancy beating the moratorium by a narrow margin. The issue of surrogacy was next referred to the National Bioethics Cons­ ultative Committee (NBCC) in 1987, an expert committee of thirteen members chaired by Robyn Layton. The NBCC investigated all aspects of surrogacy in great depth throughout Australia and in 1988 published two reports. The Committee concluded that surrogate arrangements should be allowed under strict control with uniform legislation. The Federal Minister for Health and Community Services, along with the corresponding state ministers, unanimously rejected these recommendations of the NBCC and promptly disbanded it. It was a sad situation that the treatment of this group of infertile couples was being denied or made extremely difficult for political and bureaucratic reasons. A successful IVF surrogate birth with triplets was reported in Perth soon after the Kirkman delivery. No more surrogate pregnancies occurred – 80 –

The S t ruggle for S urrogacy

in Victoria, however, despite several proposals to SRACI for approval of genuine clinical cases, as well as letters to both SRACI and the State Government requesting appropriate amendments to the Act. In a frustrated attempt to break this legal deadlock by challenging the law with an appropriate test case, I secretly arranged an IVF surrogacy treat­ ment, camouflaged as a DE procedure. This ruse was eventually detected by the scientific staff, who aborted further proceedings, while I was severely reprimanded by the Monash IVF Board. No further attempts were made in Victoria for almost twenty years. A proposal was made by a senior member of SRACI suggesting the recruitment of women born without ovaries, to act as surrogates, only to be reminded that such women were already on a DE waiting list to achieve their own pregnancy! This was an example of trying to manipulate the clinical situation to fit irrational legislation – rather than the law fitting the clinical situation with appropriate legislation. The uncertainty in relation to the surrogacy legislation was shared by all groups in society, as shown by a social survey of Dr Karen Dawson, a senior Monash researcher. She presented questions to fourteen individuals and agencies relevant to the situation, including SRACI, politicians and the Right To Life, based on the real-life predicament of a couple where the woman had given birth following a successful GIFT procedure, when two embryos were frozen, but required a hysterectomy two days later for uncontrollable bleeding. She had a suitable surrogate in her sister-in-law, who had undergone tubal ligation. In Victoria the only legal options open to them regarding the disposition of their embryos were: donation to another couple, donation to science, or disposal – none of which they could accept. All respondents were sympathetic, none suggested disposal, a few were non-committal, but the majority favored surrogacy – while conceding it was illegal in Victoria. Despite its illegality these stored embryos eventually were covertly trans­ ferred to the surrogate, outside the hospital; unfortunately the treatment was unsuccessful. The case was fully reported in the Australian Journal of Obstetrics and Gynaecology in 1994 under the provocative title: ‘A Case of Attempted IVF Surrogacy in Victoria: Breaking the Law or Breaking the Deadlock’, but no criminal charges were ever laid. The legal authorities supervising procedures relating to the 1984 Act either failed to study or did not understand this publication, or possibly decided to overlook this transgression in view of any subsequent embarrassment to the Act that might – 81 –

T E S T T U BE R E VOL U T IO N

follow a formal public prosecution: an outcome which was in fact hoped for by the Monash perpetrators, so that this would allow them to publically denounce the absurdities in the Act and force a possible amendment. Infertile couples requiring surrogacy arrangements in Victoria were forced to seek treatment interstate, in Sydney and more frequently in Canberra, where law supporting surrogacy had been enacted. Many began travelling to America for treatment, as surrogates were more readily available there, where they were reimbursed. Bill Handel, Director of the Centre for Surrogate Parenting in California, successfully treated more than a dozen Australian couples, mainly from Victoria, over the next few years, and was highly critical of the Victorian legislation. His statement says it all: ‘Some of the best reproductive technology in the world came from Australia but while you were building up the technology, legally you were cutting yourselves off at the knees’. Finally, on 1 January 2010, under the Assisted Reproductive Treatment Act 2008, altruistic surrogacy in the state of Victoria became legal. The practice of surrogacy in this state, however, remains tightly controlled. The Act includes a ban on advertising and directives that there be no direct payment to the surrogate, approval by a Government-appointed patient review panel, and legal and psychological counselling with medical and police checks. The birth mother also has the right to keep the child (which was an unwritten condition in the Kirkman case). In 2011, a total of nineteen children were born through surrogacy arrangements in Australia – a similar figure to that roughly estimated in 1988. Surrogacy remains a difficult issue and demands careful selection and counselling in all its aspects. According to a report from Surrogacy Australia, a Melbourne-based advocacy group, many Australian couples are now seeking surrogacy treat­ ments overseas, in India, Thailand, America and Canada, where, collectively, 296 Australian surrogate babies were born in 2011. This figure is surprisingly high and is not accompanied by more in­ formation regarding the report’s indications, selection, success rates and follow-up of these overseas IVF surrogate pregnancies, which would need to be considered before passing judgement on the strict Australian legislation. In the meantime, members of this group are, regrettably, subjected to ex­ penses often exceeding $100,000 for this treatment.

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The E nd of t he Beginning

Cha pte r 13

The E nd of t he Beginning The primary purpose of this book has been to explore the early, pioneering days of IVF from an Australian perspective. The era of active rivalry between the British and Australian teams ended in the early 1980s, partly due to Patrick Steptoe’s full retirement (following an earlier retirement from the National Health Service in 1978) but mainly due to the rapid development of IVF programs throughout the western world. Success-rates of all IVF procedures have been steadily improving from the late 80s. No new radical scientific developments in IVF programs have occurred since, though of course IVF technology has led directly to the development of stem cell research that is now the new and exciting frontier of medical advancement, and it is not surprising that many of the early leaders in this field, including Alan Trounson, began their careers in IVF programs. Despite this dearth of further ‘breakthroughs’ in IVF, however, certain other aspects of its history are worth discussing in this final chapter.

Deep-freezing Eggs

In 1986 Dr Chris Chen from the Flinders Medical Centre in Adelaide reported the world’s first successful pregnancy following deep-freezing and thawing of human eggs. Much of the early research on frozen eggs had been carried out at both Melbourne and Monash IVF centres. Unfortunately, only very limited success has followed. Results from deep-freezing eggs have been much less impressive than those from freezing embryos and sperm. Because of their relatively huge size (eggs have a diameter of 120 microns compared with 5 microns for sperm), freezing and especially thawing eggs is innately difficult. Despite world-wide attempts at improving its success rate, the pregnancy rate involving frozen-thawed eggs has rarely exceeded 5 percent in most clinics. The advent of vitrification (the formation of glass-like substances during freezing, as opposed to ice crystal formation which damages the egg cell), – 83 –

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again pioneered by Trounson and his colleagues, with the world’s first birth in Luca Gianaroli’s Bologna clinic, enables the very efficient preservation of eggs and ovarian tissue. Some IVF clinics offer banks for egg and ovarian tissue storage, particularly in cases of young women undergoing ovarian ablation for specific cancer treatments. These are now accepted techniques in modern IVF clinics.

Multiple Pregnancies and IVF

The phenomenon of multiple pregnancies associated with IVF began in 1980 when Trounson reintroduced stimulated cycles, leading to multiple embryos available for transfer. He also reported the first study, in 1981, showing a rise in pregnancy rates directly related to an increase in the number of embryos transferred. In the early days of IVF the poor overall success rates demanded the transfer of multiple embryos, but the gradual improvement in technology then began the development of unwanted multiple pregnancies. The first reports of multiple pregnancies with IVF all came from Australia, including twins from Monash IVF (1981), triplets from the Flinders Medical Centre (1982), and quadruplets from the Royal Women’s Hospital (1984). Quintuplets were next reported from London (1986). All these multiples were eventually eclipsed by the remarkable birth of octuplets to ‘Octomom’ Nadya Suleman in the US in 2009. The medical problems associated with multiple pregnancies are legion and include risks of toxaemia and bleeding in the mother with the many severe dangers of prematurity in the neonate. Excessive multiple pregnancies were clearly to be avoided. In many IVF clinics worldwide the increasing number of women with unwanted multiple pregnancies were offered the controversial choice of embryo ablation – a procedure involving the selective destruction of excess embryo sacs under ultrasound control at ten to twelve weeks’ gestation, but leaving intact a remaining single or twin pregnancy. Thankfully this outcome is no longer resorted to in Australia due to the strict reduction in the number of embryos transferred. The Fertility Society reduced this number to two through its stipulated guidelines, which in turn are overseen by the Reproductive Technology Accreditation Committee (RTAC). Indeed, the most efficient IVF clinics now advise a single embryo transfer while still maintaining a good pregnancy rate. – 84 –

The E nd of t he Beginning

The Fertility Society of Australia (FSA)

The Fertility Society of Australia (FSA) was established by leading IVF doctors in 1982. The aims of the FSA were set out by a Steering Committee under the chairmanship of Dr Ian Johnston. The first aim of the Society was ‘to promote the study of science of human reproduction in all its disciplines with particular emphasis on the clinical application of such knowledge’; an aim which in practice did much to promote the early development of IVF throughout Australia. In 1984, Australia was the first country to collate and report on birth out­ comes with IVF and GIFT procedures, beginning with births, as early as 1980. This was a cooperative venture between the FSA and the National Perinatal Statistics Unit where Professor Doug Saunders, of Sydney, was a main player. The Reproductive Technology Accreditation Committee (RTAC) was established in 1987 and funded by the FSA. This Committee supervises compliance of all Australian IVF programs with ethical guidelines through their mandatory Infertility Ethics Committees. These guidelines were stipulated by the FSA and in essence closely follow the federal guidelines laid down by the NHMRC in 1983. RTAC was an innovative example of medical self-regulation that soon gained governmental and international approval. It has proven to be able to provide efficient and effective controls of IVF procedures and research in Australia, in contrast to the effects of the restrictive and irrational 1984 Victorian Act.

IVF Australia in America

A group of Americans working in Melbourne with the support of Alan Trounson, approached Monash University in 1985 with a plan to take Monash IVF technology to the US under the name of ‘IVF Australia’. The group included Vicki Baldwin, who had recently delivered a baby conceived through Monash IVF, Bob Moses, an American-born Australian businessman, and technologist David Beames. At the time, the Monash group was the undisputed world leader in IVF with the highest pregnancy-rate and over 300 successful births – more than the rest of the world combined. In contrast, only six of the sixty IVF programs running in the US had achieved a viable pregnancy. Bob Moses set up and became managing director of IVF Australia (registered in Victoria) and President of its wholly-owned subsidiary IVF – 85 –

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Australia (USA), registered in Delaware. The Federal Minister for Science and Technology, Barry Jones, was enthusiastic about this plan of exporting and commercialising a unique Australian technology: ‘This is an example of the profitable provision of an intensely high-value service, that we – and nobody else – have the know-how in … I am all for the development and commercialisation of this technology.’ The final contracts were signed in November 1985 and in the following March the first IVF Australia clinic was established at the 400-bed United Hospital at Port Chester in the greater New York area. A month later the first treatment cycle began at the clinic, staffed by Monash IVF scientists and clinicians there to help train the American teams. The IVF Australia programs in America were conducted under Victorian legislation and not American, which was largely non-existent. The 1984 Victorian Act was another reason why the American programs, with open and uncontrolled state legislation, were able to further exploit the Monash technology and research. A second Australian IVF clinic was set up in Birmingham, Alabama, and soon further clinics were established in Boston, Long Island and New Jersey. Further clinics were planned, but the overall program of expansion began to falter. The value of the company shares, some of which had been issued unevenly among the eight Monash IVF members involved in the American programs, began to fall, and eventually became worthless. This decline was largely due to American programs quickly catching up with Australian Monash technology so that by about 1986 Monash IVF dominance was lost to several other overseas programs, especially in America, England and Europe, as well as other Australian programs in Melbourne, Sydney, Adelaide, Brisbane, Perth and Hobart.

– 86 –

A f t erword

A f t erword Where Are They Now? Many of the pioneers in the development of IVF have died, but their exploits and their courage should not be forgotten. The practice of IVF is so commonplace today that it is easy to overlook the difficulties and drama of the beginnings of IVF, fifty years ago.

Carl Wood

Carl Wood was forced into retirement in 2002 through the onset of Alzheimer’s Disease. His genius was recognised beyond the IVF environ­ ment, including through his election as President of the International Society of Gynaecological Endoscopy in 1987 and his holding of many other important positions. In 1982 Wood was made Commander of the British Empire and in 1995 was made a companion in the order of Australia. He received the Axel Munthe international award for reproductive science in 1988. This brilliant scientist was also a charming character, as well known for his eccentricity and mischievous nature as for his razor-sharp wit and his ability to think outside the square. It was not unusual, for instance, for Wood to walk around hospital wards in thongs, or to upset some colleagues by arriving at work in a beaten-up Mini Minor rather than something more grandiose. That was Carl. He took up windsurfing in his 60s and had to be rescued when he went out too far. But his exploits never overshadowed his genius and he is fondly remembered as Australia’s father of IVF, who had an incredible deter­ mination and work ethic, exemplified in his writing of twenty-three books, fifty-nine chapters and 400 papers in refereed medical and scientific journals. Wood died in September 2011. At Wood’s memorial service in Melbourne, Sir Gustav Nossal made the supposition that the Nobel Prize Committee erred in not including him as a recipient of the Nobel Prize with Bob Edwards because, although Edwards produced the world’s first IVF baby, from an unstimulated cycle, which is no longer used, it was through Carl’s foresight that stimulated cycles made IVF into the practical reality that it is today. – 87 –

T E S T T U BE R E VOL U T IO N

In his honour, Monash University established the Carl Wood Chair in Obstetrics and Gynaecology, and the Carl Wood Research Fund for research into women’s reproductive health. The university has also established the Carl Wood Foundation, to improve women’s health through research and education.

Alan Trounson

Alan Trounson, the Scientific Director of Monash IVF, was appointed to a personal chair in Obstetrics and Gynaecology/Paediatrics at Monash Uni­ versity in 1991 and awarded the Wellcome Medal for his scientific achieve­ ments in the area of fertilisation and early embryonic development. He became a world leader in stem cell research and in 2001 was appointed CEO of the National Stem Cell Centre in Melbourne. In 2004 he was awarded a personal chair as Professor of Stem Cell Sciences and became President of the California Institute for Regenerative Medicine in 2008. His pioneering achievements in both the early development of IVF technology and stem cell research have been richly rewarded in international honours and degrees. Alan lives in San Francisco, but returns to Melbourne often.

John Leeton

I was publically described by Carl Wood as the ‘linchpin’ of the Monash IVF program – a title that probably best befitted my role in developing and managing the early clinical research programs, which included the world’s first IVF pregnancy, many of the world’s earliest IVF babies, the world’s first donor egg baby and Australia’s first IVF surrogate pregnancy. I retired in 2001 and, for my contribution to women’s health, was awarded a Member of Australia in 2002.

Ian Johnston

Ian Johnston became the first Chairman of the FSA in 1982 and later Chairman of the Australian Reproductive Technology Accreditation Com­ mittee, where he bravely continued despite an incapacitating and eventually fatal illness. He died in Melbourne in 2001, when almost 1000 people attended the funeral service. The award of Officer of Australia was made only months before his death.

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A f t erword

A lecture theatre at the Royal Women’s Hospital was named in his honour as well as the Ian Johnston Memorial Lecture, held yearly by the Fertility Society of Australia.

Robert Edwards

Robert Edwards received numerous international awards including the prestigious Lasker and the Nobel Prize in Medicine in 2010. He remained active in scientific research and continued his role as Chairperson and Keynote Speaker at many international meetings well into the present century. He remained Editor of the prestigious European journal Human Reproduction for many years. With Steptoe he was also made Commander of the British Empire. Sadly, as with Wood, Edwards’ last years were clouded by the onset of Alzheimer’s Disease. He died in April 2013.

Patrick Steptoe

Patrick Steptoe retired from active IVF practice in 1982 after the original program he established in Oldham was transferred to Bourn Hall in Cam­ bridgeshire. His name will always be remembered, alongside that of Robert Edwards, as one of the two workers who finally delivered the world’s first ‘test tube’ baby, Louise Brown. Together with Edwards, Steptoe established the Bourn Hall Clinic in Cambridge, the world’s first centre for IVF therapy, and he remained its Medical Director until his death. In 1987 he was elected a Fellow of the Royal Society and was also made Commander of the British Empire. He died of cancer in 1988 aged 74, one week before he was due to be knighted by the Queen.

Alex Lopata

Alex Lopata was a leading speaker at international meetings following the birth of Australia’s first IVF baby. He became Reader in the Department of Obstetrics and Gynaecology at Melbourne University in 1985, and was a consultant to SRACI in 1988. In 1991 he became Associate Professor at Melbourne University, retiring in 2004. He was the Director of the Cairns Fertility Centre in 2007 and continues to work part-time as a consultant with several research institutions.

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T E S T T U BE R E VOL U T IO N

Louis Waller

Professor Louis Waller has received countless national and overseas awards throughout a distinguished career. As well as Chairman of the Victorian Committee on IVF and Related Issues 1982–1984, he was Chairman of the SRACI 1985–2001, and retired as Professor of Law at Monash University and Chairman of the Victorian Infertility Authority in 2001.

Louise Brown

Louise Brown lives in Bristol and is a postal worker. She is married and has conceived a child by natural means.

Candice Reed

Candice Reed is a journalist living in New Zealand and is writing a biography on Ian Johnston.

Alice Kirkman

Alice Kirkman is well and celebrated her twenty-fourth birthday in 2012. Maggie and Linda Kirkman remain close sisters and have absolutely no regrets about Alice’s conception.

Monash IVF

Monash IVF was to become the most eminent and high-impact academic story of Monash University. It was sold for $100 million and the University used some of the money from the sale to fund the Carl Wood chair in Obstetrics and Gynaecology. Justly or otherwise, neither Carl Wood nor myself, the founders of Monash IVF, received any payment from this sale in 2005, the income of which was distributed among all current IVF clinicians, some scientists, and others.

The Last Word

Over five million children have been conceived in the ‘test tube’. They are well and normal in every possible way – as was confirmed in a recent longitudinal study in Melbourne on adults conceived through IVF. Their numbers are increasing and today 4 percent of Australian births are conceived through IVF. As concluded by Alan Trounson: ‘Carl, we can tick that box.’ – 90 –