The amazing story of IVF: 35 years and five million babies later There's an old bell jar that sits on top of a cupboard at a Cambridgeshire fertility clinic where history was made; it was in a dish inside this jar that the world's first IVF baby spent the hours after her conception. With the success of in vitro fertilisation (IVF), scientist Robert Edwards and his gynaecologist colleague Patrick Steptoe had changed the future for infertile couples around the world. Louise Brown, that first IVF baby, is 35 this month and what was then a revolutionary scientific advance has become a routine medical treatment. More than five million IVF babies have been born, and it's easy to forget quite how controversial the idea of fertilising human eggs in a laboratory was at the time of Louise's birth. "It was viewed with absolute suspicion," says Professor Peter Braude, head of the Department of Women's Heath at King's College London. If you talk to people today about human reproductive cloning, the feeling you get that it is playing God is just how it was in 1978 with IVF. Steptoe and Edwards started to work together in the 1960s. Scientists had been experimenting with fertilising animal eggs outside the body, but few believed it would ever be possible to create human embryos this way. Steptoe and Edwards thought that they could help couples with fertility problems if they could take eggs directly from the ovaries and return them to the womb once they had been fertilised. Many, even within the scientific community, felt that their research using human eggs and sperm was unethical and immoral. They were refused a grant by the Medical Research Council, but set up base in Oldham, where they had no shortage of infertile women volunteering for the experimental treatment. Grace MacDonald, whose son Alastair was the world's second IVF baby, had read an article in the Lancet about the research Steptoe and Edwards were doing, and her overwhelming desire for a child led her to volunteer. "It was all very new so when we started in Oldham we were sworn to secrecy - I think for our own protection," she explains. There had been so much controversy. I never looked on going there as being anything to do with courage though, it was just determination. MacDonald discovered she was pregnant after her second attempt at IVF, and gave birth to Alastair, the first IVF boy to be born, in January 1979. Across the world, other scientists were attempting to replicate the British achievement, and Australia's first success came in 1980. A year later, the first IVF baby in the US was born, but the total number of children across the world conceived using the process still only stood at 15. Steptoe and Edwards had originally hoped to carry on their work within the NHS, but it was clear that there was no appetite for this so they eventually set up their own private clinic at Bourn, just outside Cambridge. Treatment was expensive with each cycle of IVF costing £3,000, at a time when the average annual income was around £6,000. Fertility treatment was restricted to those who could pay, and were willing to undergo this radical new technique. The media fascination with IVF was intense, and the literature given to patients included advice about publicity; women were warned not to talk to the media, to "beware of telephone enquiries" and to avoid mentioning the names of any other women they'd met at the clinic. Many people, even within the medical profession, knew little about the treatment, as Ro Facer, who went on to have three children using IVF, discovered. She had been trying to conceive for some years when she heard Steptoe interviewed on the radio. "I'd never heard of IVF, I'd never heard of Louise Brown, and when I went to my doctor, she had never heard of IVF either so I had to do the research myself," she explains. Eventually I got a referral. We saw Patrick Steptoe and I felt in very safe and caring hands. It didn't ever feel as if you were being taken advantage of or experimented on. With success rates in the early years averaging 12%, most women who went to Steptoe and Edwards did not end up with a baby, but that didn't deter couples from around the world joining the waiting list. Lucy Daniel Raby had eight cycles of treatment in the 1980s before she finally got pregnant with her daughter Izzy. "It was all new and a bit sci-fi," she says. We were the early pioneers, and part of this exciting experimental process. I didn't have a second thought about it once I knew it was the only way I could get pregnant. We were lucky that it was available. Gynaecologist Dr Thomas Mathews moved down from Scotland to learn about IVF from Steptoe and Edwards and he says patients were often very secretive about the fact that they were trying IVF, not telling their friends or families what they were doing. "The term test-tube baby had a stigma attached to it and it wasn't seen as natural," he explains. I was passionate about it, but many people didn't understand. The embryos created during IVF are stored in small dishes rather than test tubes, but the term "test-tube baby" has stuck and, as Mathews suggests, does have negative connotations. There were wild rumours about what went on inside the clinic and the hostility and suspicion took a while to die down, as Vivien Collins discovered when she went to work for Steptoe and Edwards as a receptionist in the 1980s. It was all very new and there were people who were critical. I had somebody who was disgusted that I worked at what she called a test centre where they made babies. IVF was far more demanding for patients than it is today. Women were required to spend two to three weeks as inpatients, staying in Portakabins in the grounds of their clinic. They had to collect all their urine during treatment as this was the only way doctors could monitor their hormone levels. If they weren't at the clinic, this meant carrying large plastic containers around with them at all times, and inpatients had to give samples every three hours, even during the night, as Daniel Raby recalls. We were in beds in ranks, six of us in each of the Portakabins. They'd come round and wake us up in the middle of the night and we'd all troop off and we had to wee in a bottle so they could monitor our hormones. It did help us all to bond with one another. When these checks showed the hormone surge that indicated ovulation, the eggs had to be collected exactly 26 hours later. This meant that the medical team would often have to get up in the middle of the night to carry out operations to harvest women's eggs. It was felt that gravity might increase the chances of embryos implanting, so women were required to crouch forward with their bottoms in the air for an hour or two after embryos had been transferred. Despite all this, former patient Ro Facer says that it was a very supportive environment, which made the emotional strain of infertility and treatment more bearable. "The collaborative, team atmosphere helped with the stress and pressure," she explains. We felt that we were all in it together, the staff and the patients. Today, IVF is a far more streamlined process. Women are treated as day patients, and there are no three-hourly urine collections, no hours of crouching after egg collection. Although moral and ethical questions still surround new advances, for the most part it has become an everyday treatment. Freezing allows spare embryos to be stored for future use and the advent of intra-cytoplasmic sperm injection (ICSI), where sperm are injected directly into the egg, has meant that male fertility problems can be treated too. Donor eggs, sperm and embryos can all be used to help couples with more complex fertility problems, and the multiple birth rate, which has been the biggest health risk from IVF, is coming down. The advances continue. This week it was reported that the first IVF baby to be screened using a procedure that can read every letter of the human genome had been born in the US. The birth of Connor Levy in Philadephia in May suggests next-generation sequencing (NGS), which was developed to read whole genomes quickly and cheaply, is poised to transform the selection of embryos in IVF clinics. In another significant development, it was reported this week that the cost of IVF could be cut dramatically from thousands of pounds to around £170 in what could mark the start of a "new era" in IVF. Fertility doctors from Belgium told a London conference that 12 children had already been born through the technique, which replaces expensive medical equipment with "kitchen cupboard" ingredients, like bicarbonate of soda and citric acid, with a success rate similar to conventional IVF. In the 35 years since Louise Brown's birth, IVF has become a global money-making business producing very healthy profits, and there are hundreds of centres offering treatment around the world. Labour peer Lord Winston, who was head of the IVF unit at Hammersmith, has been highly critical of the charges patients face in many clinics. "The biggest change has been the increasingly commercial market which has driven IVF," he says. I think that the inequalities in treatment are scandalous, and I do feel very angry that the NHS has used IVF as a moneyspinner. Susan Seenan is deputy chief executive of Infertility Network UK, a charity that supports patients and campaigns for changes to the postcode lottery for NHS treatment. "Infertility is a devastating medical condition, and the emotional impact is exacerbated when people cannot access treatment," she says. Thirty-five years after IVF started in the UK, we have a situation where your chances of having NHS-funded fertility treatment depend entirely on where you live, leaving many people unable to get the help that they need. Despite that, the most recent figures show an annual IVF birth rate of more than 17,000 babies in the UK, and average success rates have risen to around 25%. Professor Braude worries that women may put too much faith in fertility treatment, believing that it can override the biological clock. There is a huge expectation, and people think that if they stave off motherhood for whatever reason then IVF will be their salvation, but that's not true. If one is realistic, it isn't that successful. So where will we be in another 35 years? Yacoub Khalaf, director of the IVF unit at Guy's and St Thomas's, suggests that ongoing stem cell research is the area to watch. "IVF has evolved significantly, but I think it is almost near the limits of biology now unless we find a way of creating eggs," he explains. We do see patients who are struggling at 40 to 45, and the only thing which would change the face of treatment would be if we could make gametes from stem cells; if we could make sperm from men's skin cells, or eggs from women's hair cells. If that all sounds rather "brave new world," it is worth remembering that's just what many people thought about IVF itself 35 years ago. Whatever the future holds, it is clear that Steptoe and Edwards, who are now both dead, have left an extraordinary legacy. Mike Macnamee worked with them in the early days and is now chief executive at Bourn Hall. "They inspired incredible loyalty, but what came through most from both of them was that they understood the pain of infertility," he explains. We forget that until Louise was born there was no hope for many couples. Louise Brown may have grown up in the media spotlight, but is keen to stress that today she leads an ordinary life. She is married and has a son, Cameron, who was conceived naturally. She says she tries not to think too much about being the first IVF baby, which is to her "just a normal thing because I have never known anything else." However, she is clearly proud of what Steptoe and Edwards achieved. "They helped thousands of people, people they hadn't even ever met, to have babies," she says. Without them, these children wouldn't have been born. Louise's own birth was the landmark that changed the face of reproductive medicine, but it was the tenacity of Steptoe and Edwards, and the courage of their early patients, that so many parents today have to thank for their families.