November 28, 2018

Cold Cases: the major advances in the freezing of eggs and embryos

Boston Place’s Dr Erik Hauzman spoke to Clare Finney of the Marylebone Journal on major advances in freezing of eggs and embryos.

“What do you think of when you hear the term social egg freezing?” Dr Erik Hauzman, deputy medical director at Boston Place Clinic, enquires. And for a moment, I hesitate. I know what springs immediately to mind—a group of girlfriends meeting up to get their eggs frozen, just as they got their ears pierced together a decade ago. “I think it’s a bit of a misleading term,” he says, encouragingly—so I confess my vision, and he laughs. “Exactly! It can cause confusion. What the term references is the widespread changes in society, which have given more and more opportunities for women to have leadership positions and diverse careers and with that, increasing autotomy over when to have children.”

In short, the social part of social egg freezing is more for anthropologists’ reference books than it is you and me. All we need concern ourselves with is the fact that it is simpler and more effective than it’s ever been. Equally, it is not the only form of fertility preservation out there: “Alternatively, couples can freeze embryos—that is, eggs fertilised with the sperm of the partner.”
The freezing of eggs is nothing new. However, the technology and procedures by which eggs and embryos are frozen have advanced dramatically. “Ten years ago, during the era of ‘slow freezing’, the survival rate for eggs was 50 to 60 per cent. Now it’s around 80 to 90,” says Dr Hauzman.

Embryologists now use a method called vitrification, or ‘flash freezing’, which takes the eggs to the necessary -196C in a fraction of a second, meaning there’s no time for the formation of ice crystals, which can destroy mechanisms responsible for cell division. Embryos always had a better survival rate than eggs, “in fact, this rate is now between 95 and 100 per cent.”

Reassuring results

Survival rates alone are not the most dramatic part of the story. “This may sound unbelievable, but recent data is showing very reassuring results in terms of further developmental capacity. Embryos derived from frozen eggs can contribute to healthy pregnancies similarly to those from fresh eggs, and they can be perfectly frozen again,” says Dr Hauzman. For example, a patient can have 10 eggs frozen, return for them some years later with a partner or donor, “and we may achieve three or four embryos: one of which goes into the uterus, and the others we’ll refreeze” to be used if the pregnancy doesn’t come to term, or if she wants another child later.

What’s more, an implanted embryo now has a better chance of making it to term. “In the early days of IVF, the notion was that the best incubator for an embryo was the uterus and that the earlier the embryo was replaced into the womb, the less risky it was. With the improvement of lab methods, however, it became clear that the more time the embryos spent in the lab, the more opportunity we had to evaluate them and select the best one for embryo transfer.”

Today, most embryos will spend five days in the incubator, “so they’re in blastocyst stage when they are placed in the uterus,” says Dr Hauzman. By that time, the embryologist should have sufficient information about their development to know which will fare best. This reduces the chances of transplanting into the uterus an embryo that will struggle to develop properly. “If an embryo didn’t survive until day five under perfect lab conditions, it would have a very limited chance of doing so in the uterus.”

Another benefit is the extra information the embryologist can infer. “The male genome only starts kicking in after day three, so in the past if there was a problem with the male factor we would have much less information about it. The embryos could have been dividing happily up until we transferred them, thanks to the genetic programming of the mother.” In short, the mother could have had a succession of failed embryo transfers without the specialists ever realising the problem lay not with the egg or fertility process, but with the sperm.

Read, scrutinise, compare

One of the most recent advances in lab technology has been the creation of an embryo incubator with an in-built camera that takes photos every 10 minutes—“so, after five days, you have several hundreds of those photos through which the embryologist can rewind and fast-forward,” says Dr Hauzman. They can read these images, scrutinise them, compare them—all without opening the incubator.

In the past, the classic way of evaluating each embryo was “to look at it under a microscope for two minutes, once a day”, thus affecting the atmospheric conditions of all the embryos, as the incubator door was frequently opened and closed. The significance of this development cannot be underestimated: potential problems can be more regularly highlighted, and potential misery allayed.

A couple who are looking to preserve fertility could consider freezing embryos, “because they will be in a much better position to predict their chances of achieving pregnancy,” says Dr Hauzman. “If I am freezing eggs, then I will have limited information about the capacity of these eggs to be fertilised and develop into usable embryos, whereas fertilised eggs cultured for five days have passed some of these obstacles.” It’s no guarantee of success, but with a couple of embryos in the freezer you do have a much better idea of where you stand.

Still, that’s an ideal scenario. The reality is that many women who are looking to preserve their fertility either haven’t met the right person yet or are facing medical treatments that risk depleting their ovarian reserve. Chemotherapy in particular poses a risk to the ovarian tissue and the quality of the eggs, so collaboration between oncologists and gynaecologists is “one of the most welcome changes we’ve seen recently,” says Dr Hauzman. “The more oncologists are aware this is an issue, the greater the chances of us being able to perform at least one round of egg harvesting before the start of chemotherapy.”

Available to all

Even just a few years ago the prevailing belief was that egg retrieval could only take place at a specific moment in the menstrual cycle, thus reducing this already limited window of opportunity from several weeks to almost nothing for a woman whose period fell at the ‘wrong’ time. “More recent theories have suggested a random approach is just as effective,” says Dr Hauzman, “so one round of treatment is available to almost all patients, regardless of where they are in their menstrual cycle.”

So far, so reassuring. But there are, as with all seemingly miracle solutions, serious caveats. The most significant and most sensitive is a woman’s age. “We know that egg quality is enormously correlated to the age of the woman; that her best chances of pregnancy, whether it’s through freezing, IVF, or natural conception, is in her twenties and early thirties. Yet there is still a conflict between what we think is the ideal age for egg freezing, and the age of the patients we tend to see coming in,” says Dr Hauzman. “We’ve observed some trends in the reduction of the age of women opting to freeze their eggs, but it is very slow.”

The decline in egg quality is “particularly upsetting” he continues, “because there aren’t any signs.” You can be menstruating as normal, right up until the menopause. There are no visible indicators of egg quality inside the body, and very few even when they have been extracted. “Until you use them, you have very limited information about whether the eggs can be fertilised, whether the embryo will reach blastocyst stage, and the risk of chromosomal abnormalities in the embryos, of which there is an ever-growing percentage as the parents’ age increases.” It’s these chromosomal abnormalities that can lead to miscarriages and genetic conditions such as Down’s Syndrome.

It is vital that women understand all the risks involved. “It’s so important to counsel women before they decide to undergo fertility preservation, and ensure they know they are only preserving the fertility that is specific to them at that time in their lives. If they freeze their eggs at 38, they have the same chances of achieving pregnancy later with fertility preservation as they would have had in natural conception at 38. It does not increase their chances.”

Surrogacy and donation

Counselling is key—not just to advise and reassure new patients, but to guide current ones through the process. “It is extremely important that patients are well informed about what fertility treatment means for them,” says Dr Hauzman. The counsellors at Boston Place “help us by prompting patients to come up with questions that might not necessarily be raised through clinician or nurse-patient meetings.”

 

This is particularly pertinent where surrogacy and donation are concerned. “When I worked in other countries, I was sometimes faced with a scenario where a patient who had expressed her wish to undergo egg donation started getting more and more anxious about whether she’d made the right decision. Having witnessed that, I am so glad we are blessed with such fantastic fertility counsellors in the UK.”
In short, the story of social egg freezing is a long one, and quite complicated. But if you’re at a time in your life when, either as a single woman or a couple, it seems sensible—go for it. In terms of your own physical health and your potential to get pregnant naturally, you’ve nothing to lose. “You don’t want to hyper-stimulate the patient when harvesting eggs—but modern stimulation methods and drugs have almost completely eliminated the risk of that,” Dr Hauzman explains.

The gleaming lab is purpose built to the highest specifications and led by consultants who are all fertility specialists. Sedation for egg extraction is carried out by a consultant anaesthetist “which is not the case elsewhere”. There is always a helpline to nurses and a consultant, even after hours, “so there is always the possibility of talking to someone”—a source of some relief at a time of high emotion. It makes me think of another interpretation of the word ‘social’: fertility treatment that is delivered with care, consideration and humanity.