IVF is mainstream medicine – an established procedure that has provided the means of realising the dream of parenthood for millions worldwide.
But 40 years ago, plenty viewed the method of fertilising an egg with sperm in a laboratory with the deepest suspicion, voicing their opposition with pronouncements that were positively medieval.
Professor Simon Fishel – the founder and president of CARE Fertility, Britain's biggest chain of IVF centres which has a facility in Sheffield - had just gained a PhD in embryology at Cambridge University when the first 'test tube baby', Louise Brown, was born in Oldham near Manchester in 1978, following 450 failed attempts by the pioneering team led by doctors Patrick Steptoe and Robert Edwards.
Two years later he was asked by Steptoe and Edwards, his study supervisor and a future Nobel Prize winner, to join them as deputy scientific director for the opening of Bourn Hall, the inaugural private IVF clinic in Cambridgeshire.
Before he began his new job, a senior member of his university's staff stopped him in a corridor with a word of advice: 'Do not give up what could be a brilliant research career to work with the devil'.
"IVF has become almost a commodity now," says Fishel, who recalls the foreboding incident in his new memoir, Breakthrough Babies, which tells the tale of decades spent 'creating life against all odds' and features a special foreword by Brown, now a mother-of-two. "It's moved from my day, where it was demonised by almost everybody, to conventional medical practice."
It's a book with drama. He once had a gun held to his head by a colleague, was sued and nearly bankrupted in a bitter dispute with Nottingham University over his consultation work abroad, and escaped with minor injuries when he was on board the train that derailed in the Hatfield rail crash of 2000 that killed four people and injured over 70.
"I've had a few very pleasant comments saying 'It's open, it's honest'," says Fishel. "It has stories that are very testing to our morality and ethics. Some people have been really quite shocked at some elements of it."
Fishel grew up in Liverpool, the son of Joseph, a tailor, and Jane, one of 12 siblings from a family of Ukrainian refugees. His was a 'traditional Jewish family', he writes, although he admits to not having been particularly academic - so much so that his school wouldn't allow him to study for three A-levels, ruling out university. He eventually gained the necessary qualifications by taking evening classes while, by day, working as a teacher's aide at a primary school in tough Speke.
"I've always felt that most children are born with a brain that is used to a very small amount of its capacity," says Fishel, who graduated from Salford with degrees in physiology and biochemistry. "We are so conditioned from the moment of our birth by our parents, and our environment, that we become constrained. It was only when I was faced with a very stark choice - 'What is the rest of my life going to hold for me?' - that I decided to have one final crack at using my brain and things seemed to click. I sometimes despair of the tragic loss of opportunity for every human being to explore themselves."
His PhD was in mammalian embryo development and implantation - IVF for animals, essentially - so Edwards and Steptoe were keen to bring him on board. "The excitement of the intellectual challenge was enormous," says Fishel. "Even though all around us was hostility, I didn't care."
He says this visceral reaction came from 'several quarters'.
"People were either thoughtless, religiously defined or just unkind. Nobody ever saw infertility as a big issue. Next door neighbours would pontificate and have a view as to what people should do with their lives if they can't have children. Most thought 'Just get on with it'."
Today the World Health Organisation defines infertility as a physical and mental disorder that requires intervention, but Fishel says the problem has implications beyond the personal. "If society can't reproduce, that becomes the number one political agenda, not climate change or anything else. If we are going to die as a species that becomes pretty important to us."
Early techniques at Bourn Hall were 'rudimentary'.
"If anybody looked back at the lab I first worked in... it's definitely a museum piece, but it's a wonder anything actually worked. We didn't even have the proper incubators that we have today, let alone the highly-sophisticated time-lapse imaging. We had to make everything ourselves - when I designed technology to try to inject sperm into eggs, to make the tools to do that was incredibly difficult. Now you'd buy it all off the shelf. We really have come through an amazing revolution. For me the mind just boggles at what the next four decades are going to bring."
Fishel later worked in Italy, developing a technique called SUZI - sub-zonal insemination - which involves injecting sperm into the tiny area between the outer shell of a woman's egg and its inner material. On the continent he worked with Severino Antinori, a maverick who became increasingly violent as he began to believe in his 'untouchable genius', according to Breakthrough Babies. When Fishel decided to sever their partnership, Antinori coerced him into signing a bizarre, unenforceable contract stating that he'd never offer his services to anyone else in IVF.
"He took out a gun and put it to my temple: 'Otherwise, I kill you'," Fishel writes.
The Nottingham University affair, meanwhile, was settled after CARE was launched, and spawned what became known as the 'Fishel effect' in law, defining the parameters for academics doing consultancy work.
Choosing the innovations and cases he is proudest of is 'always very difficult', Fishel says. There are standouts, however - such as twins Robin and Simon Ooi, born in 1987 after their mother used an egg donated from her sister.
"I was pilloried for that because we used a family member as a donor and we were told we would ruin people's lives to know who their parents really are," he remembers. "You wait long enough and society says donors need to be identified. That's the rule in this country now."
On another occasion, his bid to create a 'saviour sibling' for Leeds patient Zain Hashmi, who needed a stem cell donation from a perfect match to treat a life-limiting genetic blood disorder, led to the idea being accepted in the UK.
"Sadly, we couldn't do enough in time for the Hashmis because a pro-life organisation took out an injunction and delayed it too long for them to have their wish, but they were pioneers in enabling us to do it for other children whose lives have been saved," Fishel says. "That technique is now worldwide and used regularly."
He expresses frustration with the regulator - the Human Fertilisation and Embryology Authority - several times throughout the book. Fishel was barred, for instance, from selecting the sex of an embryo for a couple with four sons whose only daughter had died from burns in a horrific accident.
"I think we have been held back to some extent," he says. "The country that gave the world IVF has definitely been slowed down, but maybe it's a good thing from a safety point of view. We certainly have become the has-beens in terms of technological development. Most of it's happened elsewhere."
Last week, official figures were released that showed more than 54,000 patients underwent around 75,000 fertility treatments in the UK in 2017, up by 2.5 per cent on 2016 and resulting in over 20,500 babies being born. Success rates have risen, with the average birth rate for women of all ages using their own eggs reaching 22 per cent, and the technique is now being used by greater numbers of same-sex couples and single people.
However, the HFEA statistics showed that the proportion of IVF treatments funded by the NHS has fallen to the lowest level ever. The health service funded only 35 per cent of IVF cycles in England in 2017, down from a peak of more than 40 per cent in 2010.
Fishel says it would be unaffordable for the NHS to pay for unlimited attempts at successful conception, but brands the so-called 'postcode lottery' - the wide variation in IVF eligibility criteria between different counties - 'morally unacceptable'.
The basic guidelines recommend that women under 40 should be offered three full cycles of IVF, while those between 40 and 42 should be offered one full cycle.
"We need a very plain, universal approach in our country," Fishel argues. "If it's one cycle, or two, it should apply to all, and the conditions set - whether you smoke, have an existing child or are of a certain age. That's the way it is in many countries. If you live in Israel you're very lucky, they will pay as many cycles as it takes to have two children."
CARE is a business, he accepts – its website lists prices of up to £3,500 for a standard IVF cycle – but that aspect has never been his driver. "My only purpose has been to improve people's lives by giving them the children they yearn for, and to do this I've ensured we can do amazing things by being both commercially successful and properly governed," he states in Breakthrough Babies.
Fishel, a father of four, lives in Nottingham when he's not travelling; he gives lectures globally and tours CARE's nine clinics and 13 satellite facilities. Sheffield's is in a converted house in Nether Edge. "It's the only one we've got that is almost akin to having IVF in your lounge," he jokes.
Aged 65, he could retire - but he's putting it off. "I've decided I've got to revisit it when I'm 70. There's too much to do yet."
Breakthrough Babies is published by Practical Inspiration, priced £14.99 in paperback.
‘IVF is going to get smarter’
IVF has a 'very exciting future', says Professor Simon Fishel.
The drugs given to patients, and the understanding and selection of embryos, are expected to improve while robotics are an area of huge development. Incubators already exist that allow embryos to be left untouched for five days as clinicians watch them grow on their smartphones.
"Like other aspects of medicine we're going to get smarter," he says. "We have devices – maybe we can improve on them – that grow embryos inside the womb and then remove them, check them and transfer them properly. The future is going to see change after change. Every time we come up against a problem we're going to find a solution."
Any patient, he contends, can now have a child 'providing we're able to use all the techniques at our disposal'. "So we're going to have to help those that are potentially going to become sterile; for example, preserving fertility is going to improve."
Fishel started the Rachel Foundation, a charity that helps children rendered infertile because of medical treatment, and has set up Profam, a company giving older women the chance to have children and delay the menopause using ovarian tissue.
"More women are living longer in the menopause period. It's a health issue we need to look at."