Podcast: Elective egg freezing to preserve fertility
Transcript
Kirsten Patrick: Many women may consider freezing their eggs as a way to increase their chances of successful pregnancy later in life. But it's important to be aware of the risks, the costs and the process in order to make an informed decision. I'm Dr. Kirsten Patrick, deputy editor for the Canadian Medical Association Journal. Today I'm speaking with the authors of a short informative practice article on elective egg freezing that's published in CMAJ. Dr. Jenna Gale and Dr. Paul Claman are joining me today to discuss. Hello.
Jenna Gale: Hello. Thank you for having us.
Paul Claman: Thank you.
Kirsten Patrick: Let's start with each of you telling listeners a bit about who you are. Dr. Claman, what's your background?
Paul Claman: I started in the field of reproductive technology pretty early on in the mid 1980s. I am now professor emeritus at the University of Ottawa after 32 years of practice. I'm a trained obstetrician gynecologist, but my entire medical practice has been focused on trying to help people with difficulties getting pregnant or who have a reason to consider reproductive technology as part of their life experience. I left Ottawa and moved to Jerusalem last summer. I have now started to work in an academic medical center the Hadassah Hospital Medical Center and medical school here in Jerusalem in the same field. So although I retired in Ontario, I've started an academic work here in Jerusalem.
Kirsten Patrick: Dr. Gale, how about you?
Jenna Gale: I'm a newer recruit to the field of fertility, having just completed my specialty training here in Ottawa in 2018. And I'm working as a fertility specialist at the Ottawa Fertility Center here in Ottawa, Ontario, and I'm also completing my master's degree in clinical epidemiology.
Kirsten Patrick: Okay, so let's get to the subject at hand what is elective egg freezing?
Jenna Gale: So it's great to start off with a definition of that. Elective egg freezing, also referred to as oocyte cryopreservation refers to the treatment where a patient elects to go through with ovarian stimulations, followed by an egg retrieval procedure and freezing her eggs. These eggs are then kept as a backup in the event of difficulty in achieving a healthy pregnancy in the future. And so reasons why women can decide to delay their childbearing are a number of reasons, including personal, educational, professional financial, and we are seeing a lot more delay in childbearing and a higher number of women who are considering doing these this egg freezing treatment.
Paul Claman: Well, I just want to somehow give the audience appreciation with the issue is in is a very brief physiology intro. Although it may not sound fair, Ben, really, at any age, even a man who is 70-80 years old could father a child, because men make sperm de novo throughout their life. The issue here is that women unlike men, don't make any new eggs after birth, they're born with every egg they're ever going to have. And as women get older, particularly into their mid 30s and afterwards, two very important phenomena occur. One and that's often only what other physicians and women are aware of. There's a profound reduction in the reserve of eggs left in their ovaries, which is, indeed a very important reasons why women as they get older, have lower chances of getting pregnant. But the other, which not as many people realize, is that the proportion of eggs that women have that have a normal set of chromosomes, falls quite profoundly, I would say, in the average 29 year old woman, the eggs that they release, at that age, maybe almost 80% have a normal set of chromosomes. Whereas at the age of 39, or 40, about 80% of the eggs that are released have an abnormal set of chromosomes. It's for these two reasons why delaying childbearing can make it very, very difficult to have a healthy pregnancy A because of the profound loss of ovarian reserve and the profound increase in oocyte aneuploidy as women get into their mid and late 30s. And it's for that reason that this technology has become such a hot topic and why it is that women as again, you don't really think of a woman through 35 as being all that old. But getting older than that really reduces the chances even of a healthy fit women at having a healthy pregnancy. So if they have to delay their childbearing into that age group, this technology offers somewhat of an insurance policy.
Kirsten Patrick: So Dr. Gale, you said that women for many reasons are delaying childbearing. Is egg freezing therefore becoming more popular and has its popularity increased as we've seen a delay in women's childbearing?
Jenna Gale: So we are indeed seeing a delay in the childbearing over the past 30 years. Interestingly, the average age of a mother at first birth has increased from the age of 26 to what it currently is that at the age of 29, in Canada, and we are continuing even over the past five years to see an ongoing gradual increase. And in association with that increase, we are seeing that the popularity of this treatment is on the rise as well, and it is likely to continue and gain in popularity over time. However, overall, this is still not a very common treatment. Over the past five years, we have seen by more than quintuple number of egg freezing cycles in Canada. In 2013, there were 94 cycles and the last data that we have from 2018, there were a total of 504 cycles in Canada. And this is data from the Canadian assisted reproductive technologies register the annual report that was published this year.
Kirsten Patrick: Now, is that a function of demand or a function of wider availability of services, do you think?
Jenna Gale: I really do think that this is a function of demand, we haven't seen a huge increase in the number of fertility centers over that same period of time. But I think it's a function of women's education, becoming more aware that this is a treatment that is readily available to them, and that they are seeking out and a lot of women that I see for this purpose, they really say that they've had to push together in consult with the Fertility Center to consider this treatment. So they really are sticking it out.
Paul Claman: Here in Jerusalem, we're seeing an increased demand for this treatment. I think part of the reason there is less demand for the treatment it is, particularly in Canada, US and Europe have very expensive treatment. And generally younger people don't have a lot of money. And the paradox as you get older, you usually have maybe God forbid trouble getting pregnant, but you have more money, it's very difficult to come up with the kind of funds as an insurance policy when you're 28-30 years old for this kind of treatment.
Kirsten Patrick: So I think that's what talking about at this point. What sort of cost are we looking at for this treatment? In your article, you lay it out very carefully in terms of the initial egg harvesting, and then the freezing storage and later use of the eggs. Perhaps you could do that for us here.
Jenna Gale: Absolutely. So the cost of egg freezing a treatment cycle does vary from clinic to clinic. Typical cost per cycle for the procedures ranges between about six and $9,000. And the medications are an additional three to $8,000. And this is per cycle. We will get into it. But occasionally some women be it may be recommended that more than one cycle would be appropriate. And if that is the case, these costs are incurred per cycle. In addition to these fees, the clinics also have a storage fee that range between $300-$500 per year to keep the eggs frozen.
Kirsten Patrick: Now in your article, you indicate that this is not covered by government medical insurance. Is there another way that women can pay for it by private coverage?
Jenna Gale: The private coverage does not would not cover the cost of the egg freezing procedures, but it could potentially cover part of the medication costs. So typical insurance policies if they can't cover fertility medications can often cover room percent or 100% medication costs. Now, this is in contrast to cycles where egg freezing is undertaken for a medical indication. And that's not what we're talking about in this piece or in this podcast today. But it's worth a mention because there are patients who do pursue egg freezing for medical indication, for example, before going through chemotherapy if they have a recent cancer diagnosis, or they proceed with gender affirming surgeries, and those can be provincially insured but that does vary by province.
Kirsten Patrick: Can you guide us through the typical process for freezing eggs? So you have a woman who's thinking she's getting older and wants to find out more about freezing her eggs. What would you tell her and what would happen next?
Jenna Gale: So the first step in considering this treatment would be a referral to a fertility specialist for a full evaluation to undergo ovarian reserve testing and counseling about the risks, the benefits and alternative options to egg freezing. When the patient is seen by the fertility specialists, they will undergo assessment and evaluation of markers of ovarian reserve. And the two most reliable marker in the ovarian reserve being the serum blood level of AMH which stands for Anti-Müllerian hormone and a transvaginal ultrasound for antral follicle count. And these are important to know because they're important tool for counseling a woman who's considering proceeding with egg freezing. Now these markers of ovarian reserve or you know number of eggs that a woman has left as is commonly kind of referred to by patients are it's important to know that these are not these don't predict woman's fertility or her chance of achieving a pregnancy independent of fertility treatments. But they are important when we're trying to figure out how many potential eggs could be frozen from a single cycle of ovarian stimulation and and egg retrieval. So they're important for that reason. And so after all of the that those investigations and counseling if a patient elects to proceed with egg freezing, a typical protocol starts with daily ovarian stimulation injections within a few days after the start of her period. And then these injections continue for about eight to 12 days after which an ultrasound guided egg retrieval procedure is performed by needle aspiration of the ovarian follicles. And often this procedure is done under constant conscious sedation and takes about 5 to 10 minutes and typically is done at the same site as the fertility center. At the time of the procedure, the eggs are taken to the lab, they're stripped of the surrounding cells, and then they are the ones that are determined to be mature then vitrified, which is process of fast raising the eggs. As far as what the patient can expect time being off work typically just the day of the egg retrieval and the following day are needed off work and from the initial referral to the fertility center to the time of the egg retrieval, that could be really as little as two to three months depending on how motivated a patient is to pursue the treatment.
Okay, so I'm curious about some pain and bleeding, any side effects of the procedure that you are aware of?
Any procedure has associated side effects, I would say that this procedure is a pretty well-tolerated procedure, there is discomfort which every clinic is a bit different how they manage. Most clinics will provide conscious sedation for the procedure. Some clinics elect to do local freezing at the top of the vagina for the procedure. The actual time of the procedures is quite short to 5 to 10 minutes and and most women do quite well with it. As far as bleeding complications, you know, the risk of major complications is very low less than less than 1%.
Paul Claman: The other complication too, I think mentioned because physicians listening to this podcast will be interested is a complication which is potentially a severe one known as ovarian hyperstimulation syndrome, which is associated with increased fluid in the abdomen, increase in blood concentration and dangers surrounding that. Using the hormonal manipulations typically is for egg freezing though that particular complication is quite remote, probably no more Jenna probably than one or 2%. And if it does occur, because of the methodology that we submitted the ovary for egg freezing is quite transient in nature as opposed to the prolonged potential situation of danger and women who become pregnant with a fresh transfer of an embryo after a robust stimulation to the ovary.
Kirsten Patrick: Do injectable medications have many side effects?
Jenna Gale: Medications that are used to stimulate the ovaries are subcutaneous injection medications which are taken daily and they do have side effects. The side effects include irritability, moodiness, forgetfulness, occasionally headaches, and as a result of it being a subcutaneous injection, they can cause some local irritation. As a result of their effect on the ovaries, like Dr. Claman mentioned, they cause enlargement overview of the ovaries which does put women at albeit a low risk of this hyperstimulation syndrome. But many women do experience pelvic discomfort and abdominal bloating as a result of the ovaries ovarian enlargement.
Kirsten Patrick: What have you seen is the rate of success in your practice and what factors influence the rate of success?
Jenna Gale: I think to answer this question, it's important just take a step back and talk about what the important contributing factors to the overall success of elective egg freezing are. The two most important factors are one is the patient's age at the time of the egg retrieval and egg freezing, and the second is ovarian reserve. And right now because this is such a new and growing treatment, the rate of success can only really be estimated and data surrounding life birth rates after elective egg freezing are still quite limited. One counseling tool that we have available is a publication in the Journal of Human Reproduction by Goldman et al in 2017, and titled Predicting the likelihood of live birth for elective oocyte cryopreservation: a counseling tool for physicians and patients. And from this publication, it appears that for a woman at or under the age of 35, approximately 14 eggs would be needed to be frozen to achieve an 80% chance of future life birth. We know that there are more eggs required at more advanced maternal ages. For example, at the age of 38, it's predicted that between 25 and 30 eggs would be required to achieve the same 80% chance of future live birth. Now, in keeping with this information, we know that women who have a lower ovarian reserve based on their initial testing would be counseled that it is predicted that more than one cycle of egg freezing would be necessary or recommended to achieve the desired number of frozen eggs.
Paul Claman: What I think is very interesting, personally about this whole field of egg freezing, as Dr. Gale has pointed out, if we read through the lines, it's really only very effective, paradoxically, in younger women who freeze her eggs. By the time you're 38, to freeze 15-20 eggs would require three, four or five treatments of IVF, which for most people is not a practical or tolerable thing to do, where at age 30, you probably could freeze a dozen eggs with one treatment. The thing with it's been noticed is that most women who are in that age group freeze eggs as an insurance policy, although it is new, we don't have more than 10 years of world experience, they're not coming back to use their eggs. These women typically before they get too old, find the person they want to be with to have a family and have a family without needing to use those frozen eggs. So that I think part of the counseling in talking to women about freezing their eggs, is to talk about the likelihood that they may or may not need these eggs. Women that are older, they could try to freeze your eggs. It's not that often that women in their late 30s has a high ovarian reserve that with one or two treatments, you could freeze 15 to 20 eggs in one shot. So that the paradox is it's kind of a little bit late once you're in your late 30s to use egg freezing as an insurance policy. And if you use egg freezing as insurance policy in your 20s or your early 30s, the likelihood that you'll actually use them is pretty low.
Jenna Gale: That's a great point. And studies today are showing that the usage rates are as low as 3 to 10%. So I think that's a really important point when we're counseling these women. And interestingly, there are these cost effectiveness modeling scenarios that suggests that the greatest cost benefit for women to freeze their eggs is closer to the age of 37.
Kirsten Patrick: So say for example, a woman is over the age of 35. And she goes to her doctor and wants to freeze her eggs. How would you advise a physician to go about counseling this woman in a step by step process? So she's 37 what would you discuss first? And then if she still wanted to proceed with it, what would you then discuss in terms of when she might use the eggs?
Jenna Gale: I think the first approach would be to first gather some information from this woman, including whether she's at a point in her life that she wants to start a family or if she has been trying to achieve a pregnancy because we have been approached by some patients where they say they want to proceed with egg freezing but the conversation there's greater depth to that conversation and what they really want, perhaps is a family sooner. And so I think that this is a really good one a good opportunity for pre pregnancy counseling and optimization. So a full review of history of medications, making sure they're on the prenatal vitamin and and to see if perhaps they are at a point where they just want to start a family. Egg freezing certainly does not guarantee a child later in life and the highest likelihood of achieving a baby would be to try for a child in kind of the immediate or near future, either with a partner or for example, donor sperm inseminations. If the woman is indeed in a situation where she is not in a position to start a family in the near future, then elective egg freezing is a reasonable consideration. And we do recommend referrals to a fertility specialist for a full evaluation and counseling of all options and to take it from that point, I think would be best.
Paul Claman: I find it's practical as part of how I would counsel women at age 37. I think the most important information is what Dr. Gale said. But just to help, intelligent thinking women wrap their minds around the technology. At that age, every egg that she freezes, has a potential of somewhere between 3 and 5% of leading to baby later. So that gives them a sense of how many eggs they would need to freeze to really have a reasonable chance of using that as an insurance policy 5 6 7 8 10 years later, just to helpful point that a family doctor can even take that information so that when she sees the fertility doctor, she should speak to the fertility doctor after assessment of egg reserve, how many eggs they think they could probably freeze with one treatment of IVF.
Jenna Gale: And often we use this example of a woman who's 35 years of age. And the reason is that we know that the decline in fertility and the risk of infertility are much greater after that age. And that optimal success with egg freezing occurs before the age of 35. I also think it's important to note that certain women under the age of 35 may also consider egg freezing, especially in the setting of decreased ovarian reserve. Risk factors for decreased ovarian reserve do exist like prior chemotherapy or history of ovarian surgery or family history of early menopause. However, many women have decreased ovarian reserve without any identifiable risk factors. And it's not possible to identify unless ovarian reserve testing is conducted. For this reason, women under the age of 35 may also benefit from a consultation with a specialist to discuss this option of egg freezing. And it may be that she has normal ovarian reserve and this treatment is not recommended until she's closer to the age of 35. But she's still in a position to consider it. But we have seen situations where patients are seen at the age of 35-36. And they are already do have quite low ovarian reserve and are not really candidates for or optimal candidates to pursue this treatment at that point.
Kirsten Patrick: So when you're talking about a 3 to 5% chance from each egg, does that mean that when the woman decides to use her eggs that you use more than one egg?
Paul Claman: Absolutely. When one thaws the egg, not all the eggs survive the thaw. When you then go ahead and put the sperm into the egg to try to fertilize that egg only a certain proportion of those eggs will successfully fertilize. And I think probably mostly because of the problem, which we talked about earlier called aneuploidy, real high proportion, these eggs are not chromosomally normal, only a certain proportion of those eggs that successfully fertilized will grow into an embryo that grows three, five days later, that looks like a healthy enough embryo to try for pregnancy. And for that reason, in my practice, I would recommend to women who have frozen eggs and now they find the partner they want to have them with or they're gonna use donor sperm, that they actually thaw all the eggs try to fertilize them, grow the embryos out and put one maybe two embryos into the uterus and at that point the embryos now that their embryos that is a fertilized and grown for a few days can actually be refrozen with a very high post survival and potential for pregnancy after doing that, later on to have maybe baby number two.
Kirsten Patrick: So let's go on to the aspect of freezing the eggs themselves. Now in your article you point out I think it's point number five that there is no expiry date on frozen eggs. But obviously there is a an expiry date on a woman's ability to bear a child or definitely an increasing risk associated with with carrying a child when you're older. Can you please explain to us how long eggs should be frozen for and what the risks are and the costs and how they are then used later and disposed off.
Jenna Gale: So if a woman comes back in the future and I your point is an important one that we really don't have an expiry date on these frozen eggs and they can be stored for many years. In the future, if a patient who has eggs frozen is in a position where they want to use these eggs, and they return to the fertility center. And you're right there are additional costs related to the thaw of these eggs, the fertilization and the embryo transfers. So at that point, as Dr. Claman mentioned, we do recommend thawing all of the eggs or at least a good proportion of them, because we know that this natural process of attrition occurs from thaw of the eggs through to the stage at which the embryo is transferred. So after they're fertilized the sperm, they're grown in the lab for three to five days before the embryo transfer, and the chance of pregnancy at the time of the embryo transfer is related to the age the woman was when those eggs were frozen. However, as you mentioned, it is important to keep in mind that pregnancy at a more advanced maternal age does increase the risk of complications. And eggs do have an age cutoff after which they will not proceed with an embryo transfer because of too great risks. So in addition to us previously discussing the changes in fertility related to advancing age, there are much higher rates of pregnancy complications associated pregnancy at an advanced maternal age. For example, over the age of 40, women have a greater than 50% chance of requiring cesarean delivery, they have three times greater risk of gestational diabetes and placenta previa, much higher rates of low birth weight, intrauterine growth restriction and preterm birth among a few other complications.
Kirsten Patrick: That's really valuable information which brings me back to the point that she made that many people might come seeking egg freezing, who actually really just want to have a child. And when you were talking about that being the first step in counseling, I can imagine a scenario where somebody isn't with the partner that they think they would want to be with for the rest of their life. And so they think about egg freezing. And they might actually decide, given the information that we're discussing now, that it would be healthier and more appropriate for themselves to go ahead with having children without the partner that they had hoped to have by that age, or something like that, I expect to see scenarios like that fairly often.
Jenna Gale: Exactly. This is why it's so important to have a detailed conversation with a specialist about all of the options to make sure that those are all very clear, because a woman may not be in a place where she wants to have a baby with her partner. So it is important just to talk about all of the options. Now, elective egg freezing allows a patient who for various reasons, are postponing childbearing until later in life to increase the probability of having a genetically related child later on. But it is important to talk about all options and one of those options may be to do nothing. And know that in the future, if there's difficulty in achieving a pregnancy, for example, over the age of 40, that there's also the option of using donor eggs. So eggs from either a known donor someone known to that person or an anonymous egg donation to improve the chance of achieving a pregnancy.
Paul Claman: What is the most important reasons and why I was so so impressed that Dr. Gale had thought to publish this piece in CMAJ is really to allow primary care doctors to enter into the counseling. I don't want to cast God forbid, cast aspersions on colleagues. But the problem in Canada and for jurisdictions all over the world for patients really to get the truth is that there is a commercial element. And when it comes to having to run a fertility center, and having enough patients coming through that are paying high amounts for these treatments, I'm afraid that it may count color the counseling they get from a fertility specialist. And for that reason, I think it's very helpful that primary care physicians have a little bit of understanding of this technology and its limitations, so that they can sort of help patients make a judgement as to whether or not the counseling they're getting from their fertility specialist it's really a complete and open counselling and not, you know, colored too much by the commercial element of the doctors need to have the patient come through and have treatments, if you understand what I'm saying.
Kirsten Patrick: Absolutely. And that's really useful. I have one more question. It's about what happens to embryos. I mean, ah sorry, what happens to oocytes that are never claimed? What do you do with those eggs?
Paul Claman: I think your error in saying first embryos Oh, I meant eggs is also correct. This is an extremely difficult paradox facing fertility clinics, all across the planet. There are eggs, embryos, and sperm probably from 100s of 1000s of thought maybe even in around a million that are being stored for years and years and years. And everybody's too afraid to discard them. So they're being kept in. Who knows, maybe they even go to the next generation. It's a very difficult problem. And I unless Jenna has heard differently, nobody to my knowledge has come up with a solution. Unless government's mandate that they can only be kept for 10 years or something like that it's going to be very difficult for physicians to go and discard these eggs or even embryos that are left unclaimed. I think it's important for the public to know about it's an extremely difficult problem.
Jenna Gale: I agree which is why we encourage when you know we have there are these storage fees to keep the eggs frozen, and at the point where they do not wish to use these eggs and they know that they will not be proceeding any further pregnancies, typically, the clinics want them to alert them of that and then to sign away to discard the eggs or embryos as it be.
Kirsten Patrick: Well thank you for talking to me today. It's been a wonderful learning experience for me and I hope for lots of our listeners, too. Thanks for joining us.
Paul Claman: Thank you.
Jenna Gale: Thank you.
Kirsten Patrick: I've been speaking with Dr. Jenna Gale and Dr. Paul Claman. Dr. Paul Claman is a professor emeritus of the University of Ottawa, and is currently professor of Obstetrics and Gynecology and Reproductive Medicine at Hadassah University Hospital in Jerusalem. Dr. Jenna Gale is a gynecologist and specialist in reproductive endocrinology and infertility in Ottawa and is lecturer at the University of Ottawa department of Obstetrics and Gynecology. To read the practice article they co-authored, visit cmaj.ca. Also, don't forget to subscribe to CMAJ podcasts on Soundcloud or a podcast app and let us know how we're doing by leaving a rating. I'm Dr. Kirsten Patrick, deputy editor for CMAJ. Thank you for listening.