Friday 20 September 2019

'In terms of life's most stressful events - fertility is up there' - IVF expert

This month marks the 40th anniversary of the first 'test-tube baby' and it comes as financial aid is mooted in Ireland for the first time for couples who need assisted reproduction. Professor Alison Murdoch, a specialist who has been at the forefront of IVF and fertility medicine for almost 30 years, speaks to our reporter about early IVF programmes, the ongoing stigma about fertility problems, and the industry's latest invention: Three-Person Babies

Advocate of early fertility checks: Professor Murdoch. Photo: John Millard
Advocate of early fertility checks: Professor Murdoch. Photo: John Millard
The world's first 'test-tube baby' Louise Brown, who was born at Oldham General Hospital, England, in 1978. Photo: Getty Images
Humble beginnings: The International Centre for Life in the heart of Newcastle, England.

Jessie Collins

Professor Alison Murdoch became the first person in Europe to be granted a licence to clone human embryos for research in 2004. "We knew it was going to be a big event, we set up a press office to deal with it, but Reuters leaked it too soon. It was that moment of being in the room and all the phones go off at once. It was a classic media moment. Suddenly you are everywhere, and you think I've done nothing. They've just given me permission to do something. That was all in retrospect a pretty horrible experience."

Notoriety has never been a priority of Murdoch's, who holds one of the most trusted positions in her field. Born in 1950 in Manchester, the daughter of a doctor, she studied medicine at Edinburgh University (her mother is Scottish), and after qualifying decided to specialise in obstetrics and gynaecology.

It was not an easy area to get into, however, and very competitive; most trainees at the time were expected to put in 120-hour weeks. Murdoch was already the mother of a young child so she found a "part-time" position requiring 70 hours per week and managed to raise three more children while continuing to grow her expertise.

A chance to take on some research work looking at the hormone condition of polycystic ovary syndrome fired her interest in that area of gynaecology. Then it became clear that there was a need to set up a fertility clinic.

The world's first 'test-tube baby' Louise Brown, who was born at Oldham General Hospital, England, in 1978. Photo: Getty Images
The world's first 'test-tube baby' Louise Brown, who was born at Oldham General Hospital, England, in 1978. Photo: Getty Images

Pioneering programme

At that time, in the early 90s, there was no service, there was no funding, since infertility was considered to be a social problem rather than a medical one. Already attached to the Royal Victoria Infirmary in Newcastle, England, she went about creating a pioneering programme. "We set it up by doing a bit of lateral thinking," creating a pseudo trial comparing different fertility treatments, the cover under which they smuggled in the actual system itself. So the department of reproductive medicine at Royal Victoria Infirmary in the city in 1991 was founded, starting with just two paying patients a week.

Conditions were basic at best. Their first IVF lab was a converted toilet on the gynaecology ward, the second was a converted sluice room, the third was an abandoned operating theatre, "it was better then the converted sluice", she recalls.

They were out on a limb. "It was a case of doing it and then just dropping a line to the hospital going, by the way I've done this, you don't mind, do you?". Furniture was curated from discarded chairs in wards, resources begged and borrowed. "Eventually I just lost patience entirely and that's why I moved to the Centre for Life. There is a point when you've done that for eight years, it just felt like it was going nowhere," the five-year waiting lists making a particular mockery of a desire to treat those in need.

So the department moved and became the Newcastle Fertility Centre at The International Centre for Life. The Centre for Life is a remarkable place, a science village that boasts a mix of both cutting-edge research as well as temporary and permanent exhibitions, a science theatre, a planetarium and a 4D-motion ride. Its placement at the heart of the city's bustling life normalises it, according to Murdoch. "If you had it out in the middle of nowhere surrounded by barbed wire, you'd create all this suspicion, where it is now, it doesn't make it something to be afraid of. People in Newcastle are quite proud of it."

As soon as the fertility centre was established it was met again with phenomenal, though now private demand, something that was challenging the science as well as the resources. The simple fact is, she says, we still know so little about what happens in early human development. "We are really very different to even our closest mammalian relatives. If you take a baboon, the chance that it will achieve a pregnancy with the first mating is about 80pc, with a human it's about 15pc."

Humble beginnings: The International Centre for Life in the heart of Newcastle, England.
Humble beginnings: The International Centre for Life in the heart of Newcastle, England.

Thus, the research, particularly spearheaded by others at the centre, including the Professor of Reproductive Biology Mary Herbert, became a vital part of the work, and also where they ran quickly into legislative, as well as moral issues.

"It has not been easy," explains Murdoch from her home in Newcastle, "but we've had a licence to conduct the research right from beginning. And it was for very simple stuff, how do we handle the embryos when you are doing IVF but the more you do it, the more complex you got. The main areas of research is into where embryos go wrong, why we have miscarriages, Down syndrome, all those are things you think are not infertility but it is, but those problems all occur in the early stages of development." The research required working on discarded embryos from IVF procedures, something that required the parents' consent first and foremost.

When they became the first in Europe to be given the go-ahead to clone embryos for research in 2004, it was to go further and potentially look at creating embryonic stem cells, which can be extracted from cloned embryos, as a way of potentially curing some of the most challenging medical conditions, including Parkinson's, Alzheimer's disease and even paralysis.

"The research is about understanding conditions babies are going to have before they are born, so you only put back embryos that don't have the disease, and that takes us to stem cells, and then to mitochondria. All these processes are using the science of IVF, but the fertility side is almost going parallel to that, the research is going on all the time."

Leaving it too late

IVF treatments, Murdoch admits, haven't changed massively since they were first introduced. Improvements in egg collection have helped, but there are greater challenges all the time, and it is mostly that people are leaving it too late. "There isn't that much that we can do about it, except to help people understand the choices they are making. A lot of people we are seeing in their late 30s didn't realise they were making that choice. The family planning system ought to be giving more information about not only how not to get pregnant, but when we do need to get pregnant. The idea that IVF can put it right is not that good. It can help, but for people who have left it that late, IVF is not going to be the solution."

Even if IVF isn't a solution, it can offer something of a solace. "From my perspective, if you can offer someone quickly three treatments, we would expect that over 70pc would have a baby, those who can't get pregnant are usually those people who've really been through the mill. If we've given them the proper support and proper guidance, that in some ways, it helps them to move on. For most people who complete their three treatments, although you've not got a baby for them, you've got some kind of resolution."

"It's not the IVF that's the stressful bit," she continues, "it's the infertility. In terms of life's most stressful events - fertility is up with it. When you are trying to conceive, you've probably got an image in your mind, whether it's going to be a boy or a girl, what it's going to look like; you get the nursery ready, think about what schools they are going to. Then if you can't get pregnant, it's a very real thing that has been taken away from you. If one of your children died, you'd be devastated. That child in your mind has been taken away from you. When you get to the fertility clinic, that is very real. You are only there because there is a problem. It is horrible, really horrible. For people to say it's just a social thing, it isn't."

It is an extremely emotional experience for many too, and she admits to having gotten too close to patients in the past, and realising she was doing them more harm than good. "You have to have a professional bit that allows you to empathise and help your clients but then be able to go home and shut it off, otherwise you'd crack up."

The drive, she says, is the need to offer more hope to potential parents, something certainly furthered in fertility's most-recent breakthrough, the so-called 'Three Person Baby'.

In March this year, the UK government granted Newcastle Fertility Centre permission to use the fertility technique in which babies are created with DNA from three people - the mother, father and a female donor, using mitochondrial replacement therapy, designed to prevent mothers from passing on mutated mitochondrial DNA which can often lead to early or instant death in young babies. The pioneering method replaces the defective mitochondria with healthy ones from the donor while unchanging the DNA makeup of the child, so it still has its defining DNA from both its parents.

"The first time this was suggested was about the year 2000, we were doing stem cell work, doing therapeutic cloning work, so we were a unit that had a good track record of doing ethically-based research. A change in the UK law was required, and sought, and granted in 2015.

"It was important that what was understood was the patient story and that was what its was about," explains Murdoch. There were immediate moral questions, with talk of designer babies, further concerns over the genetic consequences.

A body of experience

Though there hasn't been a baby born in the UK yet with this new treatment, it is only a matter of time. It is not something Murdoch intends to turn into an event. "What the media needs to be aware of is that we are not going to get a blow-by-blow progress report of what's happening.

"There is real concern and effort not to create another Louise Brown (the first IVF baby, who become a focus for much attention). It's not in anybody's interest. We can't say on the basis of one treatment whether it's successful or not successful, you can't make a decision on whether the next one is going to be okay. You need a body of experience because it's a new technique. What's important is that we are allowed to complete that body of experience."

That hasn't stopped others. The first baby with DNA from three parents was born in Mexico in September 2016 to a Jordanian mother with the genetic disorder Leigh syndrome which had already caused her to have four miscarriages as well as the death of two children - one at eight months and the other at six years of age. In January of this year, the second was born in the Ukraine. This, however, was to an infertile couple, not one with a genetic condition, something Murdoch is vehemently against.

"IVF is a big business, but you have to be really careful with these techniques because we don't yet know that it's safe. So using something that has a good chance that it could make things worse, for no good reason, is not ethical."

Given that she is one of just two people with a licence to clone embryos, what are the boundaries? "I would say things like reproductive cloning is a no-no. There is no clinical need that I know of at the moment. Why is a clone going to be of any use to anybody? Because, you can recreate a person's genetic makeup, but you can't recreate them as a person."

She is an advocate of early fertility health checks, and education around the whole area, as well as making IVF as widely available as possible. "If you think logically about the distress that is caused by infertility compared with lots of stuff that is treated routinely then it should be up there, high up there. If I were diagnosed now with a cancer and it would cost me £10,000 to have an extra six months, would I rather have that, or have my children. It's about priorities, what are the priorities?"

With the steady rise in women opting for egg freezing, does Murdoch see this as a viable option for tackling infertility later in life? "In theory I don't have a problem with it. It's not going to benefit a 40 year old, it would just take too long to collect enough eggs. But you have to look at the psychology of it [in younger women], if it is because her boss at Apple said if you have a baby now you can't have a promotion? The solution is not to freeze her eggs, it's to challenge Apple. You need to work through the process and the motivations."

Given that IVF is an option that more and more are going to need to avail of, what is the future down the line? New developments will certainly come, but our attitude to fertility, even more than science is the future challenge.

"There is still a big stigma about infertility," Murdoch states, "the vast majority of people don't talk to anyone about the fact that they are trying to conceive. But if people don't talk, people don't know. You say to people, when are you going to have a family, and they'll say, 'Oh no, we are not ready yet, we are going on holiday', when they might have been trying for two years.

"But until fertility is something that is talked about as part of a normal human event, then we are going to go on denying it."

IVF in Ireland

* First Irish IVF baby: born January 14, 1986

* One in six couples in Ireland now has fertility issues

* The average age of first-time mothers in 2016 was 30.9 years, up 0.2 years from 2015.

* Three percent of all births in Ireland arise out of fertility treatment

*The average cost for a round of IVF is €5,000 rising to €10,000 with donor eggs

* Typically women at 35 are half as fertile as they were at 25. At 40 you’re half as fertile as you were at 35

Indo Review

Editors Choice

Also in Life