FEATURE - 28TH JUNE 2017
The Harley Street Medical Area is home to three clinics working at the cutting edge of fertility medicine. We take a tour of some of the innovations that are transforming the field of IVF.
“This is an egg which has been fertilised by conventional IVF. See the sperm attached to the outside there...” says laboratory director Eve Glage, pointing at the illuminated screen in front of us. I peer closer, and sure enough, a wiggling, long-tailed tadpole is clinging to a blueish sphere as if life depended on it—which, I suppose, it does. She clicks through the series of images, thrown up on a monitor above the EmbryoScope+: an incubation machine in which growing embryos are nurtured and closely monitored until they are ready to be implanted back into the womb of a woman who, all being well, will be a mother nine months hence. “Now we can see the embryo divide: this is day one.” The embryo has cleaved into two blobby cells. “On day two, you will see four cells there; day three, eight,” Eve explains.
At that moment, my attention is distracted, momentarily, by the name glimmering at the side of the screen. “Santa Claus?” I exclaim, not quite able to believe what I’m reading, but longing for it to be true. Eve laughs. “These are stored images which are de-identified to protect patients’ privacy. With their consent, we use these images for teaching and training purposes.”
Here at the IVI fertility clinic on Wimpole Street, there’s a belief that the IVF process should be as open and transparent as possible, that clients and visitors should be given the knowledge they need to understand the ins and outs of fertility treatments that for many remain cloaked in mystery and doubt. That is why I’m here. It’s why I’ve been to two similarly respected fertility clinics in the Harley Street Medical Area in the past week: The London Women’s Clinic and Harley Street Fertility Clinic. And it’s why, after a typical reproductive health education that was for the most part conveyed via a series of cryptic videos by whatever poor, blushing teacher had drawn the short straw, I find myself inspired and dumbfounded by the IVF innovations the country’s leading embryologists and gynaecologists have brought about.
At IVI, I am constantly reminded that innovation alone is not enough. “I think that in some places, there are exciting, innovative techniques that have been brought into clinical practice before they have been properly evaluated,” says Professor Charles Kingsland, a consultant in gynaecology and reproductive medicine with IVI. He talks of the importance of “randomised studies carried out in more than one centre”. At the moment, IVI is working with the University of Oxford on a study looking into natural killer cell populations in the womb and blood stream, but until the results have been reviewed and evaluated, IVI’s practices will remain unchanged.
Once a woman passes the age of 35, the majority of embryos produced from her eggs are chromosomally abnormal, and a chromosomally abnormal embryo will not result in a normal pregnancy
The EmbryoScope is an innovation whose benefits have been thoroughly reviewed. Pioneered by scientists employed by the IVI clinic in Spain, it has now been widely adopted by clinics across Europe. As well as nurturing the embryos, with a pH and temperature that mimics the environment of the womb as closely as possible, its imaging software and sophisticated monitoring tools allow the embryologists to closely study the developing embryos without disturbing them. “Until recently, no one could improve on the fact that morphology—the way the embryo looks—is the clearest indicator of a healthy baby,” says Professor Kingsland simply. “But in order to look at an embryo, you needed to take it out, cool it down and put it under a microscope. With EmbryoScope, you put the embryo in the incubator, close the lid, and every 10 minutes it provides us with in-depth data.” Analysis of the data and imagery generated by the machine allows the team to predict the likelihood of the embryo turning into a baby, based on its growth and development.
How does it divide? At what rate? Do bits “fly off” or is the divide disorderly? Professor Kingsland continues: “Two embryos could look the same at the end—even at 24 hour intervals—but their journey might be completely different in between.” The speed and smoothness of cell division offer clues to the viability of the embryo. “It is critical that division occurs within a certain time period, because if it divides too quickly or too slowly, it has a negative impact.” With an average of five to choose from per patient, IVI aims to ensure that the embryo restored to the womb is the one with the best chances of a healthy birth.
By inserting only the embryo considered most likely to be successful, IVI avoids as far as possible a scenario commonly associated with IVF: the twins and triplets that result from the multiple embryo implantations favoured by some other clinics. “One in 12 twin pregnancies result in miscarriage, still birth or disability,” Professor Kingsland points out. “That’s a high statistic; we want to practice safe medicine.” Occasionally it is okay to put more than one embryo back, “for example, in someone who is 41 or 42, we know that 72-75% of their embryos will be abnormal and will be unsuccessful, so there’s still a low multiple pregnancy rate if we transfer two,” he continues.
The London Women’s Clinic also aims for one healthy baby per pregnancy, by making use of pre-implantation genetics and its One by One programme: an approach to IVF that moves away from the usual method of collecting the egg and returning the embryo to the uterus within the same cycle. “There is good evidence that you cannot simultaneously optimise egg collection and optimise the uterus environment into which you transfer the embryos: the two are sort of conflicting,” says Dr Christian Ottolini, a senior embryologist at The London Women’s Clinic. “What we have done is disjoin the cycles so that we carry out the egg collection, create the embryos and then freeze them. Then, in a subsequent cycle, we can optimise the environment into which the embryo goes before we do the transfer.”
The uterus can only viably receive an embryo at a certain point in the menstrual cycle, when it is receptive. “If it was attempted during the first three or four days after the end of a woman’s period, for example, there is no way it would be successful. If you transfer an embryo five days after egg collection, the pregnancy rates are quite high. If you transfer the same embryo on the sixth day the rates begin to drop.” There is a window of opportunity, Dr Ottolini continues. “Disjoining the two processes allows us to realign the age of the embryo with the preparedness of the uterus. This is nothing new, but what we’re doing is putting it at the centre of our programme.” If that embryo doesn’t work, another will be implanted in a subsequent month—and then another. “Once you know the embryos can be frozen, you can suggest transferring them one by one.”
This method would not be workable if not for the huge improvements in freezing technology that have been seen over the past few years. “There was a change about five years ago in embryo freezing,” says Dr Suvir Venkataraman of Harley Street Fertility Clinic. “It used to be done by a method called slow freezing, where the embryo was cooled down very slowly. Now we use a process called ‘vitrification’.” For vitrification, the embryo is dehydrated and the water replaced with a high concentration of cryoprotectant, a chemical that limits the creation of ice crystals. The embryo is then frozen extremely rapidly, reaching close to -200C in just a matter of seconds. The lack of ice crystals means no ruptured cell walls and as a result, the number of embryos surviving the freezing-thawing process has almost doubled, from 48% to 98%.
Eggs can be frozen, too: all three clinics boast egg banks of both donor eggs and eggs belonging to women who want to freeze them for later use, either for medical reasons (before undergoing chemotherapy, for example) or because they feel they may want children later in life. “All too often, women in their early forties come in and say they have been trying for children for the last two years, but have struggled to fall pregnant. We have to tell them there’s a problem,”
Dr Ottolini explains. “We’re not saying all women should freeze their eggs before they’re 35, but we are saying that when you approach your mid-30s you should consider it—as an insurance policy, as it were.”
“Human beings aren’t very good at reproducing,” says Professor Kingsland at IVI, matter-of-factly. “We have only 12 opportunities a year to get pregnant.
When we ovulate, we don’t come on heat like other animals. We have long pregnancies and when our babies are born, they are born very immature and take about 25 years to wean!” he grins. “What we do have in our favour, however, is a big brain and the ability to look after a child.”
One area to which many of these big brains have been applied in recent years is pre-implantation genetics. “The main reason for IVF to fail is a genetic issue linked to increased maternal age. Once a woman passes the age of 35, the majority of embryos produced from her eggs are chromosomally abnormal, and a chromosomally abnormal embryo will not result in a normal pregnancy,” says Dr Ottolini at The London Women’s Clinic. “There is the extreme of Down’s syndrome, which is an extra copy of chromosome 21, as well as other configurations of chromosomes which can cause potentially life-threatening disabilities, or miscarriages—something sadly prevalent among IVF patients. To have that overwhelming joy of discovering you are pregnant only to lose the baby several weeks later is a devastating circumstance.”
Pre-implantation genetic screening of embryos can offer clients reassurance that the embryo transferred will result in a normal pregnancy or, in certain cases, inform them whether they are going to need another cycle of IVF, go down the donor insemination route, or even stop treatment altogether.
“Embryos can look great under the microscope in the lab, but they can be abnormal. We biopsy the embryos in the lab before we freeze them, send them for testing and check if they are genetically normal,” says Dr Venkataraman at Harley Street Fertility Clinic.
“There is evidence to suggest that in certain cases this is beneficial, and in certain cases it isn’t. We don’t insist on it; we advise it only for patients who we think it would benefit.”
Human beings aren’t very good at reproducing. We have only 12 opportunities a year to get pregnant. When we ovulate, we don’t come on heat like other animals. We have long pregnancies and when our babies are born, they take about 25 years to wean!
You might be wondering at this point why innovations have largely been confined to female infertility—abnormal eggs, rather than abnormal sperm. There are several reasons, the most obvious being that chromosomally abnormal sperm is very rare. “Sperm production in males is constantly happening. A sperm ejaculated three months from now is basically being created now,” says Dr Ottolini. Male infertility is reasonably common—more so than the media would have you believe—but it chiefly arises from lack of sperm in the ejaculate, or in the testes. The former has been addressed successfully for years via intra-cytoplasmic sperm injection (ICSI), a process by which a single sperm is, in simple terms, injected into the egg using a needle. The latter is more complicated, demanding surgical sperm retrieval—just the name makes me wince, though it is of course painless, done under anaesthetic—which has only recently been finessed to the extent that it is “almost always” a success.
Both Harley Street Fertility Clinic and The London Women’s Clinic boast world-renowned urologists specialising in this operation. “We put the man on hormones to increase sperm production, then open up the testes and, using an operating microscope, find the areas of spermatogenesis, and biopsy samples of those tubules containing sperm,” says Dr Venkataraman. He talks about one case involving a couple who had been trying for 12 years to have a child. “We managed to find half a dozen sperm in total that were suitable and then managed to ICSI it. They got a baby out of it, which was great.”
Back in the lab at IVI, we’ve reached day five of Santa’s embryonic development: the blastocyst, the final stage before the embryo is returned to the uterus. It’s the last photo I’ll see of this blobby prospective human and I’m awed into silence, but Eve reads my mind. “The implantation was successful,” she says. “This embryo resulted in a pregnancy.” I feel a surge of excitement wash over me as I look back at the screen, and I almost believe in Santa. He may not exist now, boys and girls, but in nine months’ time...
83 Wimpole Street
London W1G 9RQ
0333 015 9774
The London Women’s Clinic
113-115 Harley Street
London W1G 6AP
020 7563 4309
Harley Street Fertility Clinic
134 Harley Street
London W1G 7JY
020 7436 6838