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The History of IVF, a chronology

Professor Gab Kovacs AM

Fertility Specialist
MB BS Hons (Monash), MD, FRCOG, FRANZCOG, CREI, FAICD, Cert Mgt (Macquarie)

View Professor Kovacs’s biography here

Adapted from a document written by Carl Wood.

The In Vitro Fertilisation research program commenced through a joint effort between Melbourne and Monash Universities at the Queen Victoria Hospital (Figure 1) and the Royal Women’s Hospital (Figure 2) in 1970, under the guidance of a committee chaired by Carl Wood.

The team included Carl Wood, John Leeton and Alex Lopata from Monash University, and Ian Johnston and James Brown from Melbourne University – RWH.

Reynolds and May accountants were appointed to run the financial side of the program.

Figure 1. Queen Victoria Hospital_later QV Medical Centre                        Figure 2. The Royal Womens Hospital Carlton
Figure 1. Queen Victoria Hospital, later QV Medical Centre       Figure 2. Royal Women’s Hospital, Carlton

The research undertaken by the team resulted in the world’s first human IVF pregnancy in 1973.

Nicknamed the “test-tube baby”, the team took an egg from a 36-year-old-woman and fertilised it in a test tube, three days later the embryo was implanted in her womb. The pregnancy lasted nine days after the implantation, reaching the biochemical pregnancy phase.

This revolutionary research was publishing in the Lancet (Figure 4), one of the most prestigious medical journals in the world.

Figure 3. Front Page Daily Telegraph 1973                Figure 4. The Lancet Paper, DeKretzer et all
Figure 3. Front Page Daily Telegraph 1973   Figure 4. The Lancet, DeKretzer et all

Despite continuing attempts for several years, no further pregnancies were obtained. However, these early works sparked excitement in fertility science and spurred on other research teams particularly in the United Kingdom where Bob Edwards had been working on the collection and maturation of human eggs in vitro (Figure 5).

Figure 5. Excerpt_The Lancet_Maturation in Vitro of Human Ovarian Oocytes_1965
Figure 5. Excerpt, The Lancet, Maturation of In Vitro of Human Ovarian Oocytes

 

At the time, there was no treatment for male infertility or fallopian tube blockages, and men and women who were unable to fall pregnant naturally lived their lives childless.

By 1977, The Melbourne Family Medical Centre Trust was established to run Donor Insemination and IVF research and in 1979 a separate Infertility Medical Centre Trust was established to run the IVF program. This was on advice from Monash University, both Trusts were granted tax exempt status by the ATO, with trust deeds stating any profit would be spent on research or education in infertility or related areas.

Direct funding occurred from NHMRC (National Health and Medical Research Council) and other grants, as well as from Monash University, however these were nominal. The doctors contributed a third of their operative fee for egg collection to subsidise the program.

In 1977, a substantial grant was received from the Ford Foundation; who were keen to support the project as they thought the basic scientific information obtained, may help in the development of new contraceptives. However, they did not want to be acknowledged if an IVF birth occurred. This financial grant allowed Alan Trounson, a scientist with experience in animal IVF in both Australia and the UK, to be recruited and employed.

At the time, IVF caused significant controversy in the media and with political and religious groups, including concerns that the research could result in abnormal children. This negative attention highlighted the difficulties that organisations such as Monash University and the Ford Foundation had in openly supporting such unusual research in the 1970s.

The structure of the trusts for the IVF research and program enabled the university to appear at arm’s length if the system failed, so that criticism could be leveled at the clinical research team rather than the University.

In 1976, Steptoe and Edwards achieved a pregnancy in the UK, albeit an ectopic tubal pregnancy where the embryo implanted in the fallopian tube (Figure 6).

Figure 7. Excerpt_The Lancet_Reimplantation Human Embryo wSubsequent Tubal Pregnancy_1976
Figure 6. Excerpt, The Lancet, Reimplantation of a Human Embryo with Subsequent Tubal Pregnancy

Finally in 1978, the first human IVF birth of Louise Brown was reported by Steptoe and Edwards in the UK after 102 attempts at embryo transfer, and a second birth, Alastair McDonald, was achieved in January 1979.

Following this, the Melbourne based team approached IVF with new vigour. Even before there was any real success, Trounson commenced publishing articles on the new knowledge achieved, such as the application of IVF to unexplained subfertility. (Trounson AO, Leeton JF, Wood C, Webb J, Kovacs G. The investigation of idiopathic infertility by in vitro fertilization. Fertil Steril. 1980 Nov;34:431-8).

The combined team led by Carl Wood achieved the third IVF birth in the world and first IVF birth in Australia in June 1980 (Figure 7).

Figure 8. Report of the First Australian Pregnancy
Figure 7. Report of the first Australian IVF Pregnancy

Only the Royal Women’s Hospital team members (Johnston, Spiers, Holt) and Alex Lopata were named as authors on the scientific report of the first Australia IVF Pregnancy. Monash University was mentioned as Lopata was full time employee of Monash University at the time. The pregnancy was created at the Royal Women’s Hospital; the clinician was Ian Johnston, the embryologist Alex Lopata.

The teams then split, RWH with Johnston, Lopata, Spiers and McBain, and the Monash team with Carl Wood, John Leeton, Alan Trounson and Gab Kovacs. Mac Talbot who had an appointment in the Infertility Clinic QVH, later rejoined the team. The only two full time Monash University employees were Trounson and Wood.

The Monash team moved to St Andrews Hospital in 1980, where Kovacs had a regular operating list, and at the instigation of Alan Trounson, started using stimulated cycles using the hormone clomiphene citrate. During 1980 they achieved 15 pregnancies resulting in nine births, all conceived at St Andrews Hospital and delivered at the Queen Victoria Medical Centre. This included the world’s first IVF twins.

In 1982, the team moved to Epworth Hospital, where John Leeton and Gab Kovacs were already operating, as St Andrews could no longer accommodate the increased demand and limited the throughput at 7 patients per week. Clinicians Downing and Lolatgis joined the group with Beresford Buttery, Peter Renou and Paul Shekleton providing ultrasound expertise, Henry Burger and Jock Findlay, endocrinology, and David DeKretser as an andrologist.

In 1983, the team achieved and delivered the world’s first human frozen embryo IVF pregnancy and birth, and in 1984, the first donor egg IVF pregnancy.

The team was visited by many international scientists and clinicians, including Ed Worthem from Norfolk, who was the scientist in the team led by Howard Jones that achieved the first US IVF birth in December 1981. Howard graciously acknowledged the help from Melbourne in his report of their pregnancies (Figure 8).

Figure 9. Norfolk Credits Melbourne team in report of pregnancies
Figure 8. Norfolk Credits Melbourne Team in report of Pregnancies

The Monash team enjoyed significant international requests for experts to visit and learn; an International IVF Workshop was organised in 1982 to cater for this demand (Figure 9). The world’s first IVF Workshop held at Monash IVF and Epworth Hospital included 43 attendees from every continent, and included the subsequently famous Andre van Steirteghem and Paul Devroey from Brussels, David Meldrum and Bud Keye from USA.

Figure 010. The Worlds First IVF Workshop_Monash IVF 1982
Figure 9. International IVF Workshop 1982

The move to Epworth Hospital resulted in the doubling of the capacity of the IVF unit, and by 1984, almost 100 pregnancies were achieved with a pregnancy rate per laparoscopy in the mid teens. (Figure 10).

Figure 011. Monash IVF success rates 1979-1984
Figure 10. Monash IVF Success Rates 1979-1984

Although IVF was originally developed to treat women with blocked tubes, male subfertility became a major part of the program. It became apparent that many men who could not impregnate their wives naturally, had sufficient sperm to fertilise their eggs in vitro. The “Male factor” group was established with David DeKretser, Andrologist, Chris Yates, scientist and PhD student, Jillian McDonald, nurse co-ordinator and Gab Kovacs, IVF clinician co-ordinator.

Various sperm preparations were tried, including percoll and microdrops to get a better sperm sample. Peter Temple-Smith, anatomist and scientist, and Graeme Southwick, plastics microsurgeon, joined and the group achieved the first birth, Baby Joseph, (Figure 11), from surgically recovered sperm from the epididymis of a man who had a previous vasectomy.

Figure 012. Monash IVF Team with Baby Joseph
Figure 11. The Monash IVF team with Baby Joseph

Concurrently, Alan Trounson and Geoff Mann were experimenting with microinjection of sperm under the Zona Pellucida (Subzonal Sperm Injection – SUZI). After attempting the technique on a couple, the Victorian Health Minister at the time Ms Caroline Hogg, instructed the team not to continue with the technique. SC Ng who was working with Monash IVF returned to Singapore, and later achieved the first human pregnancy and birth with SUZI using the Monash Technique in 1988.

Bruce Downing became the co-ordinator for the cryopreservation program and Monash IVF continued the focus on research and development, concentrating on improving embryo freezing. This process evolved to the current practice of vitrification or snap freezing.

Other techniques that were pioneered under Alan Trounson and Carl Wood’s directorships were in vitro maturation of oocytes, and blastocyst culture.

The team made a significant contribution to the technique embryo biopsy and Fluorecent In Situ Hybridsation (FISH) for pre-implantation diagnosis (PGD). Leanda Wilton was part of the team developing the technique, and subsequently was a member of the Hammersmith Group under Robert Winston and Alan Handyside who produced the world’s first PGD pregnancy.

Other developments at Monash IVF included the application of the MIFT (Microinjection Fallopian Transfer) where oocytes were injected with sperm and then replaced laparoscopically into the Fallopian tubes. This technique soon became obsolete.

Monash IVF continue to remain at the forefront of reproductive medicine in Australia and internationally. In 2010, the Monash IVF Group established the Monash IVF Research and Education Foundation (MREF), operating under an Advisory Board of clinical, scientific and educational specialists to continue the work of our visionary pioneers.

MREF have a number of current research projects being undertaken and more information on these can be accessed via our website.

Monash IVF have a unique standing in the industry as through the ongoing research undertaken through MREF, we are able to translate research into patients treatments.

What started as an innovative hypothesis in the 1970s; has now enabled everyday Australians access to fertility treatment so they can realise their dreams of having a family.

Professor Gab Kovacs AM is the Monash IVF International Medical Director. He is a Reproductive Gynaecologist, and Subspecialist in Reproductive Endocrinology and infertility with over 40 years experience in IVF. He is the Director of O & G Institute, Epworth Healthcare, Professor of O & G Monash University, Executive Director Sonoa Health and Honorary Consultant to Family Planning Victoria.

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