Human Fertility, September 2009; 12(3): 137–143 THIRTY YEARS OF IVF Thirty years of IVF: The legacy of Patrick Steptoe and Robert Edwards PETER R. BRINSDEN Consultant Medical Director, Bourn Hall Clinic, Cambridge, UK Abstract In this article, the author presents a review of the early collaboration between Patrick Steptoe and Robert Edwards, gynecologist and scientist, which ultimately led to the birth of Louise Brown in 1978, the first baby to be born as a result of in-vitro fertilisation. Following this momentous event, the author shows how Steptoe and Edwards continued to influence further developments in the treatment of infertile couples, both in the United Kingdom and Worldwide. Keywords: In-vitro fertilisation (IVF), IVF treatment ‘To understand science it is necessary to know its of Louise Brown, the world’s first ‘Test-tube baby’, history’ in July 1978. In 2008, we celebrated the 30th anniversary of this Auguste Compte, 1798–1857 momentous event and we also marked the 20th anniversary of the death of Patrick Steptoe. In this ‘A thorough comprehension of the history of IVF will article, the early history of in vitro fertilisation (IVF) improve the depth of appreciation of challenges we are For personal use only. facing today, hopefully resulting in improved outcomes is reviewed from the perspective of Patrick Steptoe of future treatments’. and Robert Edwards, who together ‘created’ Louise Brown. An understanding and knowledge of the Editorial. Human Reproduction, 2005 early history of IVF is important to our under- standing of the practice of IVF today. Although ‘This is not the beginning of the end, but only the end of others had been involved in the early development of the beginning’ animal, and later human IVF, it was through the determination and dedication of Steptoe and Patrick C Steptoe, Quote from the Press Conference following Edwards, together with Jean Purdy, that they the birth of Louise Brown, 25 July 1978 achieved the first birth. This was some 2 years before workers in Australia, and later still in the United The very close working relationships between physi- States, achieved their first births. The story of the Hum Fertil (Camb) Downloaded from informahealthcare.com by Universitaetsbibliothek Heidelberg on 10/04/10 cians, scientists, nurses, counsellors, administrators Steptoe and Edwards’ collaboration, their early years and ethicists that exist in Assisted Reproductive of disappointment and failure, culminating in their Technology (ART) programmes is almost unique in eventual success with the birth of Louise Brown is a the field of medicine and science. The embodiment fascinating story (Edwards & Steptoe, 1980). Their of this collaborative effort can be discovered in the influence on today’s practice of assisted reproductive close working relationship which existed between the technology (ART), and even on our future practice, ‘founding fathers’ of ART – Patrick Steptoe and is still relevant. Robert Edwards. The coming together of Steptoe Patrick Christopher Steptoe was born on 9 June and Edwards in 1968 and their subsequent work 1913, the seventh of a family of 10 children. He came together, assisted by Jean Purdy, their nursing and from a musical family, studied music as a child and laboratory colleague, finally culminated in the birth nearly took it up as a career; however, he chose Correspondence: Peter R. Brinsden, Bourn Hall Clinic, Bourn, Cambridge CB23 2TN, UK. E-mail: [email protected] This paper is based upon The Patrick Steptoe Memorial Lecture given by Peter Brinsden at The British Fertility Society Annual meeting, Liverpool, on the 4 September 2008. ISSN 1464-7273 print/ISSN 1742-8149 online Ó British Fertility Society DOI: 10.1080/14647270903176773 138 P. R. Brinsden medicine and qualified as a doctor from St George’s embryos, which he further developed during a year Hospital, University of London, in 1939. At the spent at Glasgow University (Cole et al., 1965). outbreak of the Second World War, he joined the However, Edwards then moved to The University Royal Navy Volunteer Reserve as a Surgeon. While of Cambridge in 1963 to join two of the ‘greats’ in serving in the Mediterranean, his ship was sunk and animal reproductive physiology; Professors Alan he became a prisoner of war in Italy. It is said that, Parkes and ‘Bunny’ Austin, where he continued to because of his unique position as a Medical Officer, work on immunology and oocyte maturation. In he was able to help fellow prisoners to escape; 1965, Edwards spent some time in the Unites States however, he was found out and put into solitary at The Johns Hopkins University, where he confinement. He was released in 1943. On returning collaborated with two other ‘greats’ in the field of to the United Kingdom he specialised in obstetrics human ART: Drs. Howard and Georgeanna Jones. and gynecology, with a special interest in infertility, He again worked on human oocytes (Edwards and in 1951 became a Consultant at Oldham et al., 1966), and forged a lifetime friendship with General Hospital, in the North of England. There, the Joneses. he had a large National Health Service (NHS) On returning to Cambridge, Edwards continued practice and it was there that he pursued and to have difficulty in finding human oocytes, not only developed his interest in laparoscopy, which he had for his research, but also to pursue his research on studied under both Frangenheim and Palmer in the treatment of human infertility. At that time he Europe. He further developed the technique, and became aware of the work of Patrick Steptoe, who, finally published his seminal textbook ‘Laparoscopy by use of the laparoscope, was able to view a in Gynecology’ in 1967 (Steptoe, 1967). During the woman’s ovaries and who had developed a technique early years of laparoscopy in the United Kingdom, to aspirate oocytes from ovarian follicles. Edwards this was the ‘bible’ from which all young gynecolo- therefore contacted Steptoe in 1968 and expressed gists, including the Author of this article, learned the his interest in working together. They subsequently technique of laparoscopy. It was because of his ability met at the Royal Society of Medicine in London, to visualise the female pelvic organs during laparo- where Patrick Steptoe was giving a lecture on scopy that he wrote his first major paper – ‘Laparo- laparoscopy, during which he showed the first scopy and ovulation’, published in The Lancet in laparoscopic photographs of ovaries in the female 1968 (Steptoe, 1968). He also discovered that it was pelvis. This early pioneering work on laparoscopy possible to aspirate oocytes from follicles under caused much criticism and even hostility among For personal use only. direct vision using a laparoscope, the experience of Steptoe’s peers, who branded it as an unsafe which he later published in 1970 (Steptoe & procedure which would never ‘catch on’! Edwards Edwards, 1970). approached Steptoe at the end of this meeting, Robert (‘Bob’) Geoffrey Edwards was born in introduced himself and suggested that they should 1925 and educated at Manchester Central High collaborate; a suggestion which was readily accepted School. After doing his National Service in the by Steptoe. Army, serving in Palestine, Syria, Jordan and Iraq, he From 1968 until 1978, Steptoe and Edwards’ early went to the University of Wales at Bangor in 1948. pioneering work on human in vitro fertilisation was There, he gained his BSc degree, and then moved on done in Dr Kershaw’s Cottage Hospital at Royton, to The Institute of Animal Genetics at Edinburgh near Oldham. They very soon started to produce University in 1951, where he worked on mouse important papers on early human IVF, including: oocytes and embryos, gaining his PhD in 1955. ‘Identification of the mid-piece and tail of the Hum Fertil (Camb) Downloaded from informahealthcare.com by Universitaetsbibliothek Heidelberg on 10/04/10 While he was there he met and later married another spermatozoon during fertilisation of human eggs young scientist, Ruth Fowler, with whom he in vitro’ (Bavister et al., 1969), and ‘Laparoscopic published several papers. From Edinburgh he went recovery of pre-ovulatory human oocytes after to California for a year and then, in 1958, moved on priming of ovaries with gonadotrophins’ (Steptoe & to The National Institute of Medical Research, Edwards, 1970). They also carried out the first London, where his interests changed from animal treatment cycles of oocyte recovery with tubal to biomedical research. It was during this time that insemination (ORTI) which was much later devel- he became interested in human oocyte development oped by others, becoming known as gamete intra- and the possibility of achieving in vitro fertilisation of fallopian transfer (GIFT). Other important papers human gametes. At the Institute he did some of the included: ‘Control of human ovulation, fertilisa- very earliest work on in vitro maturation of human tion and implantation’ (Edwards & Steptoe, 1974) oocytes from small slices of human ovaries, provided and ‘Induction of follicular growth, ovulation and by a gynecologist in London (Edwards, 1965). He luteinisation of the human ovary’ (Edwards & also at this time further pursued his interest in Steptoe, 1975). All of these papers and others were embryonic stem cells derived from mammalian produced during a time of intense activity in History, in-vitro fertilisation, Steptoe, Edwards 139 Oldham, with Edwards and Jean Purdy travelling hundreds of miles from Cambridge to Oldham on a regular basis. During these early years there was much con- troversy and criticism of their work, especially when they started their first human embryo transfers in 1972 (Edwards & Steptoe, 1980). Difficult years followed, in which none of their first 40 patients became pregnant until, in 1976 they did achieve their first IVF pregnancy. There was huge disappoint- ment, however, when it was discovered that this was an ectopic pregnancy (Steptoe & Edwards, 1976).