By fertility experts from Spain.
When it comes to fertility, women’s age matters the most. As women get older, their eggs diminish in numbers and in quality which results in problems conceiving. From this perspective, egg freezing seems to be a good way of pausing one’s biological clock. In this webinar, Dr Malini Uppal, Fertility Specialist at GENNET City Fertility in the UK, explains egg freezing and fertility preservation options for patients.
Infertility is a significant health issue that affects 11.8% of all reproductive age women. Much of this often publicised ‘infertility epidemic’ has long been contributed to the phenomenon of delayed childbearing. For women who are not ready to conceive but wish to try to preserve fertility for the future, freezing their eggs in their late 20s and early 30s allows them to take advantage of the time when their eggs are at their healthiest.
According to Dr Malini Uppal, egg freezing is broadly categorised into two groups: either as done for medical reasons or for social reasons. The first one refers to women who have been diagnosed with any medical condition or need treatment that can affect their fertility status. We also talk about medical reasons when there is a family history of early menopause – if there are women whose mothers, sisters or aunts have had early menopause, they should definitely consider egg freezing.
It may also happen that a woman, who is at her peak of fertility, is simply not ready for motherhood and she wants to pursue other things in her life. However, she still wants to have children in the future and is worried about her declining fertility – so in her case, egg freezing is a good option. Similarly, women working in armed forces and being at risk of injury can protect their fertility in such a way to be able to conceive later on in life. Finally, egg freezing is also a good solution for women who are planning gender reassignment. Before taking medications and going through necessary changes, they should consider freezing of their gametes.
Dr Uppal admits that there is an age-related drop in women’s fertility. Women are born with a finite number of eggs which they start using when they attain puberty. With the advancing age, this pot of eggs decreases and, as a result, fertility decreases as well. The chances of conception are significantly reduced once women attain their mid 30s – it is the time when an accelerated decline in female fertility is observed.
Another important thing that we have to understand is a higher risk of miscarriages associated with increasing age. Dr Uppal does not say it is impossible to get pregnant at the age of 35 or even 40 – however, it is much more difficult. Once a woman crosses a certain age, she is more likely to have miscarriages and less likely to give a birth to a healthy child. This is a solid fact that 90% of all early miscarriages are attributed to genetic abnormalities – and the risk of an ongoing pregnancy with a genetically abnormal embryo increases with age. Such pregnancies are usually terminated or result in the live birth of children with major disabilities. However, according to Dr. Uppal, the age-related increase in genetic abnormalities is not linear in nature. Rather, the rate increases sharply when women reach their mid-30s.
Today, one in five women has her first child after the age of 35 – which is an 8-fold increase compared to previous generations. More and more women delay childbirth to pursue career or education goals. Although this is entirely a woman’s choice and all women should have the right to do that, they should also be aware of the consequences of such decisions.
Dr Uppal says there is a misconception that many women take for granted – namely, they think that if they have delayed fertility, they can probably have IVF later on. However, it is not so simple and IVF at a later age is not always the solution. Assisted reproductive technologies do not address the issue of age-related drop in fertility effectively. In fact, the highest live birth rate per IVF cycle started (41.5%) is observed in women younger than 35 years old. Then it goes down as low as to 1% for women older than 44 years old. In their case, the only way to get pregnant successfully and give birth is through egg donation.
According to Dr Uppal, most non-infertility specialist physicians do not appreciate the extent of this fertility decline. The same goes for the general public or men and women who delay childbearing. That’s why it is so important to make people aware of the fact that an increased rate of infertility, miscarriages and genetic abnormalities during pregnancy as well as a reduced rate of live births through IVF treatment originate from one and the same problem: age-related drop in the quality of women’s eggs.
Taking everything into account, one has to understand the difficult situation women find themselves in in the today’s world. Having all the possibilities at hand, they want to, first of all, focus on their careers and other self-fulfilling activities. What is even more important, they want to be financially independent and not to worry about their income, mortgages or financial resources while on maternity leave and during the first year of their child’s life. It is also true that they choose their life partners more consciously nowadays and often find the right person only in their mid-30s – or not at all.
All of the latter could be the reason modern women delay starting their families. From this perspective, freezing their eggs while they are young will give them more freedom to decide when to become a mother.
Dr Uppal describes egg freezing as an IVF cycle with a pause. It means that a woman undergoes a controlled ovarian stimulation and egg collection procedure when she is young and likely to produce good quality eggs. Then the pause comes – and it means the time she needs to e.g. complete her education, develop her professional career or find the right person to start a family with. Then, when she is ready, she literally pushes the ‘PLAY’ button again. Her frozen eggs are thawed, they undergo fertilisation and the patient has the embryo transfer done. The latter may even be done when the patient is late into her 40s.
Dr Uppal says that the main benefit of the whole egg freezing process is that eggs are suspended in time at the age they are frozen. So women who freeze their gametes in their early mid-thirties can effectively reduce the age-related risks. Then, when faced with difficulty in conceiving at a later age, they may opt to use their frozen eggs to give them the same chance of a live birth that they had at the point of egg freezing. In this way, a woman in her 40s may have the same chance of a live birth as she had when she had her eggs frozen. This literally translates into an approximate 10-fold improved chance of giving birth to a healthy baby.
Dr Uppal admits that the whole egg freezing revolution has happened after the invention of the new technique of freezing called vitrification. Vitrification is the process of the so-called ‘fast-freezing’ – it means that the water molecules don’t have time to form ice crystals, and instead solidify into a glass-like structure right away. Diminishing the risk of ice crystal formation helps to overcome meiosis spindle damage and does not interfere with the quality of eggs. This is a great improvement when compared to the previous method of gametes freezing called ‘slow freezing’. The latter carried with it a risk of cell loss of approximately 30%.
The other possible risk associated with egg freezing is ovarian hyperstimulation syndrome (OHSS), being an excessive response to the medicines responsible for stimulating the egg growth. Fortunately, it is overcome by using Antagonist short protocol and Agonist trigger which minimises the chances of hyper stimulation to less than 1%.
Dr Uppal says that every day she gets a patient who comes in for treatment and wishes that somebody had told her about the egg freezing option at the right time in the past. The truth is that such knowledge can save a lot of time, money and emotions invested into IVF treatment at a later age. That’s why it is so important to make women aware of the choice they have. The possibility of freezing one’s own eggs does not only allow them to preserve their fertility but also gives them invaluable peace of mind to take their time and do whatever they want in their life before deciding on motherhood. What is important is the whole process is neither bothersome nor very complex. The most important thing for a woman to do is to undergo fertility assessment or ovarian reserve assessment by age, AMH (Anti-Müllerian Hormone) blood test and ultrasound scans of the ovaries (AFC, antral follicle count). The assessment is followed by a consultation to discuss the results and plan the next steps.
When it comes to the best age for egg freezing, Dr Uppal suggests 35 years or less. It gives 50% chance of live birth and 60-85% chances with 10-15 frozen eggs. Of course, it has to be stressed that even egg freezing does not offer 100% guarantee of becoming a mother – as there are no guarantees in life. Nonetheless, it gives every woman a very good chance of having own biological children at the chosen time of her life. To support her claims, Dr Uppal recollects the survey of a cohort of women who chose to freeze their embryos for the purpose of fertility preservation (Stoop et al., 2011) – according to its results, none of the women regretted having the procedure and 95.4% said that they would do it again.
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Let me answer the fist question: should you think of doing egg freezing? I would say: yes. If syringomyelia is a mutation that can be carried on to offsprings, then, at the time when you are doing the fertilisation of the eggs, we will need to do PGD – the genetic testing of the embryos. But if it is de-novo and it is something that’s just affecting you physically at the moment, then yes, you can do egg freezing, even if you are not having your period. The first thing that we need to do is to assess your ovarian reserve. You said you’ve had a scan and there are some follicles – so we can regulate your period and we can bring on bleeding and stimulate you. If there are some follicles there, we can always freeze them. You’ve said that you’re in a relationship so I also want to mention that embryo freezing is much stronger than egg freezing and gives us a much greater chance later on. An egg is a single cell and obviously it’s more vulnerable to damage as compared to an embryo which is hundreds of cells. When they’re frozen, it gives you better chances as they can withstand the processes of thawing and freezing much more easily when compared to an egg. So if you are in a stable long-term relationship, my suggestion would be to freeze embryos. Or you could freeze both – you can freeze eggs and embryos and see which of those you can use in the future. When it comes to chances of having a baby with an autoimmune disease: yes, you can have a baby with an autoimmune disease. There’ll obviously be a consultant whose care you’ll be under and we’ll have to see what medication you’re using, if you can use it in pregnancy and if you can have the transfer when using it. Maybe we can use some alternative medication, too. But yes, we do have patients with autoimmune diseases and they do have successful pregnancies. You’ve also asked about the nuclear and spindle transfer. If we are talking about any mitochondrial transfers, these are still in experimental stages. Yes, there are some centres that are doing it but there’s not enough data out there for me to tell you that something like this can be done in your case and that it will be successful. And when it comes to using donor eggs: you were saying that your sister can donate it for you. It can be done and it is called a known egg donor. You can have anonymous egg donation as well – that is also an option.
Unfortunately, this level of FSH is not very reassuring. It is telling me that your ovarian reserve is very low. This is why you’re missing your periods and you’re having just an occasional bleeding – it is because it’s almost a menopausal level of FSH. In fact, it is actually menopausal. So these results of low estrogen, high LH and high FSH are actually saying that having your own cycle of egg freezing might not be an option now. Maybe looking into egg donation is more realistic for you.
I would still say egg donation. Even if there are any leftover follicles, I’m afraid that they’re not likely to give us any good eggs – with the FSH level that we’ve got and because you are hitting menopause. We might not be able to stimulate the ovary with such high FSH. And even if we do stimulate it and there is a follicle that grows, we might not get an egg which is worth freezing or which will give us any results later on. And that would mean going through unnecessary procedures without any results. So my strong advice would be to start looking into egg donation.
I don’t think that women should start thinking about egg freezing in their 20s because it is still very young age and they might just conceive naturally. But once they hit 30, I think it’s time to think about that. So late 20s and early 30s is a good time to do egg freezing – if they are not planning to start their families at that time. However, it will always be good for them to be aware of the fact that there’s an option like that and that they should get their fertility status checked. The latter is very easy – it is just getting a scan done once they are 26/27/28 years old. It gives them the idea if it is a good time, if they are okay for the next 2-3 years and if they should wait till the age of 30 and then do egg freezing. I think every young girl at the age of 30 should get the ‘egg freezing’ birthday present from her parents.
Thank you for acknowledging it. We need to be the ambassadors and we need to be out there telling as many young women as possible about it – whether this is a workplace or your family or the cycle of your friends. Women need to be aware that there is an option and that they should use it. If I’m given an opportunity, I’ll be happy to go to every university or a school and give a talk and make all these young women aware of it.
Using egg donor and having ICSI is no indication for you to have a hospital birth. Anybody can have an egg donation and fertilisation with ICSI. You would be indicated to have a hospital birth only if there are any medical conditions associated. We would have to assess whether your pregnancy is going as well as we expect it to go and whether the baby is growing well. So if I tell you today that you can have a home birth and then it will turn out that the pregnancy is not going well or you develop any complications – then I will have to take back what I said. Please remember that after certain age, we are more likely to get some complications during pregnancy as well. So you would need proper monitoring and the results we would get could be the indication for a hospital birth – rather than it having anything to do with egg donation and ICSI.
Yes, you should have more eggs frozen. 10 eggs would be fine if you were less than 35. But above that age, we should aim to get at least 20 eggs frozen. And yes, embryos are stronger – they have got a bigger cell number so if we lose a couple of cells while thawing, then they can still give a good chance of having a normal baby in a live birth. An egg is a single cell so it is more prone to the effects of the thawing process – it might simply not survive it. So when I have a patient who is a single woman and she is doing egg freezing, I always mention that, apart from doing a couple of cycles of freezing of her own eggs, she should do at least one cycle to create embryos with donor sperm and freeze them. In the future, it gives her a broader option. If you are with the right person, you are in a relationship and you’ve got eggs that you can use, I’d suggest to create some embryos and freeze them as well. Then in the future, you can just simply take a frozen embryo and transfer it and it will give you a very good chance of having a successful pregnancy.
Freezing your eggs is not a waste of time. If you have a reasonable ovarian reserve, you can still freeze your eggs. But you would need a lot more of eggs frozen: maybe 30 or 35 to actually get that reasonable chance of having a live birth later on. As I said, I would always recommend to do a couple of cycles of egg freezing and then do embryo freezing as well so you’ve got both options in the future. You are asking whether frozen eggs are as good as the fresh ones – these days, with the technique of vitrification and with excellent facilities in the labs, frozen eggs can give comparable results. There is a study which actually shows that the clinical pregnancy rate and the live birth rate is very comparable between frozen eggs and the fresh ones. So the answer is: yes, a frozen egg is almost as good as a fresh one.
I don’t quite understand what you mean by ‘naturally’. Basically, when we are doing the ovarian stimulation, we collect the eggs. And instead of freezing them as eggs, we fertilise them. If you have a partner, eggs will be fertilised with your partner’s sperm. If you’re single, you can select donor sperm. Then frozen donor sperm will be used to fertilise your eggs and create embryos. An embryologist observes these embryos in the lab up to day 5 or day 6 and then these embryos, which now have got hundreds of cells, are frozen at the stage of a blastocyst for you.
As I said, there have been studies that have shown that using fresh eggs as donor eggs and using frozen eggs as donor eggs have got statistically almost similar results. The only risk that we have with frozen eggs is that they need to be thawed and we are likely to lose some eggs in this process. But once they are thawed and they are fertilised or injected with the sperm, the chances of them getting fertilised, creating an embryo, implanting and giving a life birth are very comparable to the ones of fresh eggs.
It’s a very good question. It does depend on a lot on factors, including external factors. Of course, age matters the most but there are the conditions and the quality control in the lab that matter a lot as well. But in general, I would expect 4 to 5 good blastocysts from 10 eggs in early 30s.
The only thing that I can add is that there are some new techniques and latest developments, like ovarian rejuvenation, that some clinics are doing. We’re still not doing it in UK at the moment, but there are some clinics in Greece that are doing it. But again, there is not enough literature and not enough research on that – it is still in experimental stages right now. But that could be something to look into and maybe you could try it, if it gives any chances of your ovaries starting to produce any follicles. And then, eventually, we can think about doing the stimulation and freezing those eggs.
Infectious diseases tests cannot be done on frozen sperm. Infectious diseases tests are done to a man who is producing the sperm to make sure he is not carrying any of the infectious diseases, like hepatitis, HIV, syphilis, and that this sperm can be frozen in the lab. Sperm carrying infectious diseases has to be frozen in separate containers so that there is no chance of cross-contamination or cross-infection. And that is the reason of infectious screening. If the sperm is used as donor sperm, then we need to repeat the screening again after a quarantine period. If you’re using a surrogate, then your husband’s sperm becomes donor sperm – and that’s where the difficulty is. If you want to use any sperm as donor sperm, it has to have that post-quarantine blood test as well. But we cannot do the infection screen on the frozen sperm.
Yes, that is the legislation. So wherever you’re having the treatment, the clinics have to follow all the HIV guidance that is available to them. And we have to follow those rules as per country. I think that using fresh sperm will be the best option for you. Yes, there are some studies related to an increased risk of autism with the advances in age of the male partner, but most of them refer to 50 years of age. And there is still a very small chance of it. So I would say fresh sperm is still the best option that we’ve got here.
Even if the sample is not very good, as long as there is some sperm and it is FDA approved, we can have very good results with the techniques that we’ve got in the labs right now – like ICSI.