Academy of Clinical Embryologists

NEWS

Robert Edwards is awarded the 2010 Nobel Prize for the development of human in vitro fertilization (IVF) therapy. His achievements have made it possible to treat infertility, a medical condition afflicting a large proportion of humanity including more than 10% of all couples worldwide. .



Professor Robert Geoffrey Edwards, CBE, FRS was born on September 27, 1925 and grew up in Batley, Yorkshire, and in Manchester. After finishing Manchester Central High School, he served in the British Army, and then completed his undergraduate studies in Biological Sciences at the University of Wales, Bangor. Initially, he decided to study agriculture at the University College of North Wales (UCNW) in Bamgor, but he soon realized that he was interested not so much in plants but rather in animal reproduction. Thus, he transferred to the Department of Zoology and received his B.Sc. in 1951 from UCNW; in 1962 the same institution offered him the degree of DSc. After working for 1 year at the California Institute of Technology, in Pasadena, with a grant from the Population Council, on the immunology of reproduction, he returned to the UK and got a 5-year position at the National Institute for Medical Research in Mill Hill, London. There, he continued his research on oocyte maturation in a variety of animal species.

In vivo and in vitro experiments showed that rabbit, hamster and rat oocytes matured within 12 hours of administering hCG. However, oocytes from cows,sheep and monkeys showed no signs of maturity when inseminated at 12 hours. Similarly, human oocyte maturation was also thought to be impossible in vitro. Molly Rose, the gynecologist who had delivered two of Edwards’ daughters, agreed to provide him with human ovarian tissue. He worked with oocytes harvested from slithers or wedges of human ovaries removed from patients with Stein-Leventhal syndrome. The results from the first two years of his work were disappointing. Having worn out a number of options such as changing culture media, adding higher doses of hormones and sera, Edwards decided that there might be some difference in mammalian species regarding the time to oocyte maturation. This was a vital breakthrough and he was finally able to demonstrate meiosis between 24 and 48 hours. This was further refined and the time of ovulation for human eggs was identified as 36 hours. Pig oocytes were closest to humans, requiring 37 hours.

When his contract with the National Institute expired, Professor Edwards was appointed to the Physiological Laboratory in Cambridge. There, he continued his basic research but did not have access to human oocytes. Thus, he went for 6 weeks to the John Hopkins Hospital in Baltimore, Md., USA, where he collaborated with Howard and Georgeanna Jones in trying to mature and fertilize human oocytes in vitro, but with limited success.

The most important moment in the evolution of human in vitro fertilization was when he attended a lecture at the Royal Society of Medicine in London given by Patrick Streptoe, a gynecologist, describing laparoscopy, a surgical technique that could give access to the ovaries, enabling the retrieval of eggs in order to be fertilized in vitro. The historic collaboration began with a phone call from Edwards to Steptoe and flourished at the Oldham and District General Hospital and later at the Kershaw’s Hospital. Their collaboration started in 1968, but since Patrick Sreptoe was working in the Oldham General Hospital, Professor Edwards had to travel 4 hours from Cambridge to Oldham whenever there were oocytes available. These difficulties did not deter them, and in 1969 they achieved normal fertilization and cleavage of human oocytes in vitro, using freshly ejaculated spermatozoa.

Women were stimulated with purified urinary hMG and ovulation triggered with hCG. Oocytes were aspirated 36 hours later via laparoscopy. Human embryo formation was routinely achieved. Once again, there were disappointing results in the first three years with no pregnancies. One of the mistakes that was identified was the use of Primolut depot as a form of luteal support. It was later found to be a luteolytic and abortifacient. They switched to hCG and progesterone thereafter. The pressures from critics, ethicists and colleagues were mounting. The patients, however, remained loyal and a steady stream ensured that work progressed. Much of the early work was funded by Edwards and Steptoe themselves. More bad news was in store. Though a clinical pregnancy was established in 1976, it turned out to be an ectopic which had to be removed at about 10 weeks.

Working against the odds, Steptoe and Edwards experimented with various stimulation protocols and natural cycle IVF. Lesley and John Brown were the second entrants in the natural IVF group. Lesley had no oviducts, having lost them to ectopic pregnancies earlier. This proved to be a valuable discouragement to critics who would later claim that the pregnancy was a fraud. After seven years of work at Oldham, the positive pregnancy test in a natural cycle was a major milestone. Louise Brown was born at 11:47pm on July 25th 1978 at Oldham, through a planned caesarean section delivered by registrar John Webster. She weighed 5 pounds, 12 ounces (2.608 kg) at birth. Among the letters to the editor of the Lancet on 12 August, 1978 was a report of the world’s first infant conceived outside the mother’s body. The birth of Louise Joy Brown by caesarean section, just before midnight on 25 July, 1978, represented the culmination of ten years’ collaborative research between Patrick Steptoe and Robert Edwards. As Steptoe later recalled when he first handed Mrs Lesley Brown her baby: ‘She cradled the infant, then managed to whisper: “Thank you for my baby. Thank you.� Louise Joy had arrived, a whole new person to make this family complete at last. I doubt if I shall ever share such a moment in my life again.’ The world of human reproductive medicine and infertility would never be the same. Louise’ younger sister, Natalie Brown, was also conceived through IVF, four years later, and became the world’s fortieth IVF baby, and the first one to give birth herself—naturally—in 1999. Louise Brown also has a son, conceived naturally and born in 2006, with Professor Edwards in attendance. Steptoe and Edwards published their early results in 1980 with four pregnancies out of 32 embryo transfers.

Acknowledgement:
Life Invitro

UPCOMING EVENTS

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ACE Family salutes the pioneer of IVF

Professor. Robert Geoffrey Edwards (M.S, PhD)

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