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Egg freezing and fertility preservation – patient’s guide

Alpesh Doshi
Consultant Embryologist & Founder at IVF London, IVF London

Category:
Egg Freezing

Egg freezing and fertility preservation - patient's guide #OnlinePatientMeeting
From this video you will find out:
  • What is the optimum age to consider egg freezing?
  • How long does the process take?
  • How many cycles of egg freezing will I need?
  • How many eggs are required for me to have a baby?
  • What is the pregnancy rate with frozen eggs?
  • What is the survival rate of frozen eggs?
 

Patient's guide to freezing eggs and preserving fertility

Alpesh Doshi, Consultant Embryologist & Founder of IVF London, is talking about the role of the embryologist in egg freezing and the outcome of the whole IVF treatment.

Egg freezing – definition

Alpesh Doshi started his presentation by explaining what egg freezing means and how it is done. Egg freezing is retrieving the eggs from the ovaries and then cryopreserving them. Cryopreservation means storing the biological cells at a very low temperature, as low as minus 196 degrees in liquid nitrogen, and at this temperature, all the activity in the cells, and all biological function stops. Hence, you can preserve them without deteriorating the quality of the eggs themselves. It is one way for fertile women to preserve their fertility so they can have a family in the future.

Women choose to freeze their eggs if there is a medical condition which can potentially make them infertile, such as cancer. The cancer cure, chemotherapy, or radiotherapy, are the treatments offered to women who may want to consider some cancer treatment, and as a result, women may lose their fertility because the drugs that they’re given are very harsh, and that can also make them infertile. Before women consider any kind of chemotherapy or radiotherapy, they may have an option to freeze their eggs to preserve their fertility for the future.
At the same time, there’s a huge number of women are now considering fertility preservation purely because they’re not ready to have a child for various reasons. Either it’s the career, it may be because they want to get a fair education, or they didn’t find the right partner. Another reason can be if a woman is a member of the Armed Forces and is deployed to a war zone, also a lot of men freeze their sperm before they are deployed to Afghanistan or Iraq in the event they do not have the potential of having their child or naturally producing sperm. Another reason can be a transitioning female to a male may want to consider freezing their eggs.

Today, a social trend toward delaying childbearing has been observed in women of reproductive age. This delay is due to different factors such as:

  • academic education
  • careers
  • income
  • other self-fulfilling activities

There are common dilemmas women face these days in terms of trying to balance the pressures of modern-day limits versus a reproduction. Seeking a long-term relationship, getting pregnant, considering maternity or taking care of the child during the first years of life. If they take maternity leave, that could potentially affect their careers, and they are opposed to trying to balance the amount of time they want to spend at home once the baby is born in the early years.

Fertility & woman’s age

What role does age play? A woman’s chances of conceiving naturally fall as she gets older because the quality and the number of eggs drop with age. Egg freezing is a process which allows patients to preserve their fertility by freezing their eggs when a woman is young, and the eggs are of the highest quality. The graph presented demonstrates what is the decline in fertility as women age, after 35 years old, there is a very rapid decline in a woman’s fertility potential, and the quality and the number of eggs in their ovaries do drop. In the 40s, the drop is o high that the chances of conception are very slim, and at the same time, the risks of genetic abnormalities in the babies can be very high as well. The quality of and the number of eggs goes down with age, but at the same time, the risk of miscarriage goes higher. With age, live birth rate drops while the rate of miscarriage goes up. There are more chromosomal errors in the embryos as there is an increased risk of genetic abnormalities, and the risk of having an ongoing pregnancy with a genetically abnormal embryo also increases with age, such pregnancies potentially can be terminated or result in a live birth of children with some major disabilities. The age-related increase in genetic abnormalities is not linear. Rather, the rate sharply increases when women reach their mid-30s. Typically, after 37 or 38 years of age, there is a very rapid decline in the quantity and quality of the eggs.

The American data has been published that 1 in 5 American women has chosen to have her child much later. One of the studies showed that from 2000 to 2012, there was a 24% increase in women having their first child between the age of 35 and 39. Around 35% of women decided to have their first child in their 40s. This translates into a 50-fold increase in the annual number of IVF procedures performed in the US since 1985, half of which are currently performed on women over age 35.

Age has an adverse effect on IVF outcomes. The chances of live birth after a cycle of IVF plummets from 41% at the age of 35 to 4% after the age of 40. The extent of this fertility decline is not appreciated by most non-infertility physicians, the public, or men and women who are delaying childbearing. Hence, it’s very important to make yourself aware of fertility education. The live birth rate at 35 years old is around 41.5%, and at the age of 44, it is less than 1%.

Egg freezing process

There are 3 main steps of the whole egg freezing process. The first step is the workup, which includes an initial consultation to discuss medical history and suitability for egg freezing. Some basic tests to check the woman’s hormones, such as AMH (Anti-Müllerian hormone), a good predictor of women’s fertility, and AFC (Antral follicle count) to check how many tiny follicles are present in each ovary. This could give your consultant an indication in terms of how the fertility hormones will reflect when stimulation is given. The combination of the antral follicle count and the AMH gives a very tailored stimulation regime and helps determine the right dose to give for hormonal stimulation to mature or grow those follicles in the ovary. You will be asked to do virology screening, full blood count, HIV, chlamydia, rubella, and gonorrhoea tests. The second step is the preparation, whereby you will have a nurse consultation, you will do all your consent forms, all the paperwork, all your injections are going to be taught, and your medication can be purchased as well. Step 3 is the actual treatment itself, where you would start injecting yourself with fertility hormones and then over 10 to 12 days, you’d be monitored in terms of the scans to see how those follicles are growing, and then there is an egg collection. Finally, freezing of those eggs. From the time a woman has her period, and if we’re using a short protocol, the whole process can be finished in 2 to 3 weeks from start to finish. A woman only needs around 5 to 6 visits to the clinic to complete the whole egg freezing cycle.

Once the eggs are collected they are stripped of all the cells around the egg because when egg freezing is performed we do not need any of those external cells as its role is to nurture the egg within the ovary, but once the eggs are already out of the array all the peripheral cells can be removed to maximize the survival rate of the eggs. To freeze the eggs, they need to be dehydrated, meaning the water content has to be removed because having water in the eggs can make them very susceptible to being damaged during the freezing and thawing procedures. Therefore, removing the water is crucial, and if this procedure is not done properly or it’s not done with skill, the eggs will not survive the freezing procedure. Finally, once the eggs are dehydrated through various solutions, they’re frozen in liquid nitrogen, the straws containing the eggs can then be stored in tanks containing liquid nitrogen for many years.

Fresh vs. vitrified oocytes – comparison

Is there a difference in outcomes between fresh eggs and frozen eggs, and that would be a very good question to ask and then mean some studies that have shown that there is no difference in various parameters or various embryology beliefs parameters between fresh and frozen eggs? One of the studies has shown that there is no difference in fertilization rate, embryo development rate, and most importantly, there is no difference in blastocyst formation rates. Frozen eggs can have the same potential as fresh eggs.

Egg freezing & law

In the UK, there is a law governing egg freezing, so the regulatory body called the Human Fertilisation and Embryology Authority (HFEA) ensures that all patients receive the best level of care by monitoring and inspecting clinics. They have set a 10-year storage limit for frozen eggs which is currently under review. This limit can only be increased to 55 years if a woman is diagnosed with premature infertility.
If you’re a single woman or you’re in a same-sex relationship you may want to use donor sperm, and there are very well-established UK and European banks to give you a wide selection of donors to choose from. The selection begins by reviewing donor profiles, and the staff assists you through that process.

When you’re ready to use your frozen eggs they would have to be thawed out. Once they’re thawed out, the method to inseminate them with the sperm is using a procedure called Intracytoplasmic Sperm Injection (ICSI), this method helps to initiate fertilization in the frozen eggs. The embryos that are created by inseminating those frozen eggs can then be monitored for 3 to 6 days in the laboratory, and then 1 or 2 embryos can be transferred into the uterus to establish a pregnancy.

The main factor influencing the chance of success is the age at which your eggs are frozen. The earlier you freeze them, the higher the success rates. In terms of pregnancy rates, vitrification is a very successful freezing technology, which is between 90 to 95% survival rate.

There is a study that has shown that typically the survival rate of the eggs can also go down with age, but even after 40, we expect survival rates above around 85%, it’s important to understand that the pregnancy rate or clinical pregnancy rate per egg thawed is 6%. If there is a 35-year-old woman who’s frozen 10 eggs and has 10 surviving eggs, her chance of getting pregnant is around 60% of all those 10 eggs have been thought out.

Egg freezing – risks

  • ovarian hyperstimulation syndrome (OHSS), which means that ovaries over-react to fertility drugs, it’s very rare, and it’s more precipitating in patients who have PCOS (less than 3%)
  • surgical complications of egg collection (less than 1 in 2000)
  • eggs surviving the freezing and thawing process (over 95%)
  • there is no evidence that the stimulation hormones increase the risk of ovarian cancer
  • there is no evidence to suggest that stimulation causes early menopause

Patient's guide to freezing eggs and preserving fertility - Questions and Answers

What is the optimum age to consider egg freezing?

Global data has suggested that the best time to consider egg freezing is anytime from 32 to 37. This is a very prime age to consider egg freezing because after 38 the decline in fertility is very sharp and very rapid.

How long does the egg freezing process take?

The process is very fast nowadays, so there have been so many developments in the IVF sector or at least even in the stimulation regimes that has enabled us to use very short stimulation protocols. We do appreciate that when women are working or when they’re busy with education, the whole process needs to be very well thought through and most importantly it needs to be non-invasive in their day-to-day life. So the whole process of egg freezing can be finished in around two weeks so hypothetically a patient can come and see us for a consultation, and as soon as they have their period, they can start on the stimulation and from two weeks from then, they would have their eggs frozen. It can take anything from two to three weeks depending on where you are in your cycle, but the short protocol gives us amazing amounts of flexibility now, and the whole process can be very fast.

How many cycles of egg freezing?

There is no set answer for this. The way we assess and advise on this concept is by getting women to check their fertility potential. If you remember in my first couple of slides, I mentioned that we would recommend women to test ovarian hormone called AMH and also look at their antral follicle count. We know that a lot of women nowadays have got a declining ovarian reserve so for example if a woman has polycystic ovaries, she may only need one cycle of egg freezing because she’s likely to produce a lot of eggs, but if you have a woman who has got a very low AMH and a very low ovarian reserve such as an AMH of 1 or 2, then they may not produce that many eggs as a result of stimulation and such patients may need multiple cycles of egg freezing. Typically, as a lower average, we get women who would consider at least two cycles of egg freezing to give themselves a good chance in preserving their fertility, and because the whole gross plus is quite fast now it just takes two weeks as I said, it can fit in quite nicely in the whole scheme of things.

How many eggs are required for me to have a baby?

In essence, this is what women are asking that how many eggs do I need to have a baby, and again I think there’s no kind of magical answer to this because the factors that govern the answer to this question are age, ovarian reserve. If patients have got a very good ovarian reserve and if they have quite a lot of eggs produced and they’re young then all the eggs that they have from one cycle will be enough to potentially have a baby but if we keep this figure of 6% in our mind, so 6% clinical pregnancy rate, so typically I would say that in order to get a 60% chance of being pregnant you are looking for at least 10 to 15 eggs in storage. As a ballpark figure, if you are a woman in your 40s or early 40s, you may want to consider freezing more eggs because we know that after 40 it’s not necessarily about the number of eggs, it’s more about the quality of the eggs that give you a better chance of getting pregnant.

What is the pregnancy rate with frozen eggs?

The pregnancy rate with frozen eggs is around 6% for egg thawed-out, so if a patient has got 10 eggs, then she’s got about 60% chance of getting pregnant, and usually, most women do have around 10 to 15 eggs per cycle. I would say that the pregnancy rates between fresh and frozen eggs are the same. Whether you are 34 right now and were considering fresh egg collection via IVF and wanting to get pregnant versus freezing your eggs and using them later, your chances of pregnancy are the same whether you use frozen eggs or whether you use them fresh.

What is the survival rate of frozen eggs?

The survival rate of frozen eggs depends on age. We know that in women who are in their thirties, early thirties the survival rate of the eggs can be very good, this is because the quality of the eggs is a lot more robust and the eggs can take a certain level of trauma during the freezing. Whereas women who are in their 40s have got very fragile eggs and they may not be able to take the pressure of egg freezing per se. Typically what we expect in women in the thirties is a survival rate in excess of 90 to 95% whereas in the 40s we expect a survival rate of around 80 to 85%, still very good but there is definitely a decline in survival rate with age.

Are 18-20 eggs from a donor considered a good result? Also, how many times should I an egg donor donate without diminishing the quality of her eggs and what would be the ideal time she would wait between each donation?

18 to 20 eggs is plenty from a donor, one also needs to be very cautious that we do not over stimulate donors because donors also can risk ovarian hyperstimulation. There are two things here about the number of eggs. In my opinion, 18 to 20 eggs are quite a lot. What we’re aiming to get in a cycle of egg donation is between 10 and 15 eggs at the most. Whenever it goes from 18 to 20 or even more than potentially these two aspects that can be compromised and I’m not saying it is compromised but can be compromised. Firstly, the risk of ovarian hyperstimulation. Apart from that, many studies have shown that the higher number of eggs you retrieve, the quality of those eggs starts going down. We know that there are some clinics out there that will stimulate a donor quite heavily, maybe to get quite a lot of eggs sometimes even 30 eggs and what they will do is then they will divide those 30 eggs between 3 recipients and give them ten eggs each. In my opinion, this is not the right thing to do because the quality of those eggs is then going to be compromised.

You’re better of keeping to only one or two recipients but at the same time giving a couple of the recipients a very good chance of establishing a pregnancy. When it comes to waiting between each donation, I would say definitely a couple of clear periods before you go on to your next cycle. I would not advise a back-to-back cycle, you need to wash those hormones out of the body before you consider another cycle of egg donation, so at least 2 to 3 months is my suggestion.

My last donor accidentally gave herself the trigger injection, and my doctor advised us to cancel retrieval as the eggs would’ve been too tiny to retrieve and would’ve been a waste of money and cycle. What is your opinion on having possibly had retrieved those eggs and trying to make them into viable embryos?

I think what your doctor advised was correct. It all depends on what stage was that accidental trigger injection taken. If the donor has just started injecting herself and was only at about day 6 or day 7 of simulation and then in the accidental trigger injection was taken, in that case, it’s the correct thing to do, is to cancel the cycle because the eggs will have not been mature enough with such little stimulation. If it was about 10 days or 11 days of stimulation trigger, if the follicles were over 16 millimetres in diameter, then it would it could have been performed. Sometimes, it’s not only just about the day of stimulation, sometimes even on day 12 of stimulation, but the follicles also could not be very big. Because some women stimulate for a bit longer even up to 14 days. I think it’s more about the size of the follicles. If your follicles were all above 14 millimetres and you accidentally took the trigger injection, and egg collection could have been attempted.

I am 50-year-old working currently with a donor of 30 years old that has 3 boys. The donor has had few successful donations so far. The average donation count was about 18-20 eggs. How many blastocysts shall I expect given that I have had a DNA fragmentation test done recently, and the results came out quite good?

From what you’re telling me, the donor is young, she’s had proven fertility 18 to 20 eggs which is great. I would expect at least 8 to 10 blastocysts from this donor. This is obviously bearing in mind that we’re just talking about the eggs, of course, there’s an impact of sperm as well, but you’re saying that the DNA fragmentation test was normal, so I would expect around 10 blastocysts from those eggs. The donor is young, proven fertility, a good number of eggs hopefully good fertilization should be expected about 80%, and I will definitely say 8 to 10 plus.

Can you share the difference in success rates if the eggs are frozen before fertilization versus freezing embryos?

We often get asked that should I freeze eggs or should I freeze embryos and our responsible answer should always be that embryo freezing gives you better outcomes than egg freezing. But it’s comparing chalk and cheese. It’s got to be understood that when you’re freezing eggs these are eggs, and when you’re freezing embryos they have undergone quite a lot of barriers of development. An egg so hypothetically if you have fine eggs, you may get to 2 or 3 embryos, so one has to take that into account that there is a funnel, egg start off at the top end of the funnel and embryos are the bottom end of the funnel, so comparing eggs and embryos could be comparing apples and oranges. But a frozen embryo gives you a much higher success rate than a frozen egg if that makes sense.

I’ve read that the sperm sample is best taken early in the morning. If we’re doing ICSI do you have an opinion on this as we have male factor issues as well as low AMH and ovarian reserve?

I believe that it is important to more than the timing of sperm production. It is more important than abstinence is there. We generally recommend 2 to 3 days abstinence period in the men, and usually at IVF London, the sperm sample is always taken in the morning. Once the patient has had the egg collection, the male partner will be asked to produce a sperm sample, and the sperm sample will be processed in the laboratory. But there is nothing to say that if the egg collection is in the afternoon, the sperm sample cannot be produced in the afternoon, so there is no evidence to suggest that a sperm sample produced in the morning is better than a sperm sample produced in the afternoon. What is more important is making sure that we have the abstinence period that is required which is at least 2 days.

Have you seen a difference in women who take the DHEA and the number of quality eggs they produce?

DHEA is mainly recommended to be taken in women with a very low ovarian reserve. It also must be said that the evidence around DHEA is quite average. The Americans used DHEA a lot because again DHA is available over-the-counter in the US and the UK it’s not. But with all the papers that I have seen or read, DHEA benefit is only if it is taken for a period of at least 3 months, so it’s a slow-acting benefiting drug or an androgen drug. I would suggest that if you have a low ovarian reserve, then one has to take a very calculated approach then, do we want to wait for three months and risk that ovarian reserve goes down further just because we’re trying to see if DHEA improves the outcome. Usually, women with low ovarian reserve or poor ovarian reserve would not want to wait those three months. At the same time I have seen women who will say that well I’m gonna have my IVF next month, is there any harm if I started in the DHEA now, I’ll say no it may not benefit, but it will certainly not do any harm, try it but again it’s got to understand that you’ve got to take it 3 times a day as well, so it’s pretty much a protocol when one has to really follow. In the UK clinics are not so pro DHEA, I find the American clinics very pro DHEA, especially with poor ovarian reserve.

Are there any side effects of the DHEA?

I mean certainly, the DHEA should not be given without consultant prescription, in my opinion. Some women who have a high androgen level can have quite bad side effects with DHEA. So DHEA is nothing but an androgen as well so what we want to make sure that in women where it’s contraindicated, we should not be giving them DHEA. Again, I say that you need to take DHEA under supervision of your consultant and you shouldn’t just take it because your friend from the US has given you a bottle of it.

I am 35 and have endometriosis. Should I look into booking a fertility assessment? 

The answer is yes because most importantly, what you want to know is what your ovarian reserve is. I have seen quite a few women who are in their thirties with a very very low ovarian reserve. Sometimes they’re 33-34, but when they come for an ovarian reserve test or fertility assessment, we find out that their ovarian reserve is very low and they are at high risk of premature menopause and again you’d rather know this information early than later because if you do know it in good time, then you can at least freeze the eggs or even consider starting your family earlier because you have a real-time check on your fertility potential. I think it’s very important to get a fertility assessment done. Every woman as she turns 30 should have fertility checked to see what the ovarian reserve is so that they can plan their future. They can plan when to have kids, they know exactly how much time potentially they have to be juggling a family career, education etc.

I’m looking into egg freezing in both London and Spain, largely due to no 10-year limit and also the shorter waiting times for IVF but also due to donor anonymity. Apart from the obvious convenience of having the treatment closer to home would you say there are many any pros and cons to freezing abroad?

Generally, women who are considering egg freezing for social reasons are usually working women, so for them to take 2 to 3 weeks out of their work just to go and freeze eggs abroad can be quite an inconvenience. I think the biggest inconvenience is being away from your setting whereas if you had egg freezing at a clinic in London or in the UK, then you can continue your lifestyle as usual for example in IVF London we have all of our scan appointments from 7:30 a.m. in the morning, so women come and have their scans, and by 9 o’clock, they’re potentially at work. This is not possible obviously during the pandemic, but if everything was normal, then we get a lot of women coming here for 7:30 scans, they leave the clinic by 8:15 and start work by 9:00 o’clock. They can fit the whole egg freezing or IVF treatment as part of their normal day-to-day routine whereas travelling abroad has its own inconvenience, it may be cheaper, but I think when you try and put everything into perspective including the cost of travel, the loss of income potential in the holiday, then you take the accommodation that you may have to spend on it probably comes to the same thing. I mean in a foreign country the language barriers etc. are all challenges one has to consider.

My consultant thinks there is likely an issue with implantation, so what’s your opinion on having an ERA test?

There is emerging evidence on ERA test. In my opinion, if you had 2 or 3 failed IVF cycles despite having good quality embryos transferred at the blastocyst stage, then I feel it’s worth having an ERA test. Let’s not forget an ERA test is invasive. You have to prepare yourself by taking all the drugs that you would have ideally taken in an embryo replacement cycle, so you have to do a dummy cycle by taking all those injections and drugs, and then you have to perform an ERA test. An ERA test is not cheap, it’s expensive, but also patients have to mimic their body as if they are performing a real transfer which is taking them to a more dummy embryo transfer cycle. It has its value, I believe but not as a first-line approach.

Any advice you can provide on a patient having very low AMH 0.17 ng/ml at the age of 18?

I think if a patient has such a low AMH at such a young age, as long as the patient is 18, of course, they can be legally treated, one really needs to take an expert opinion from a gynaecologist, it may be a case of premature ovarian failure and if at all there is any ovarian reserve still there which indicates there is some there although, the units of measurement of AMH in the UK is picomoles and not nanograms that we can convert that. She really needs to take expert opinion and consider egg freezing or fertility preservation because this definitely a very low AMH.

What is the difference and benefits of ICSI vs IMSI? And does IVF London offer IMSI?

IMSI is a technique whereby you just magnify the sperm and look at it under very high magnification typically 6000 times magnification. What are you trying to identify by magnifying the sperm to that level is to see if you can spot any abnormalities in this firm head which are called vacuoles. This is what IMSI typically looks at, but the data has been very mixed about the benefits of IMSI, and I must say that in the clinical setting we used to use a lot of IMSI about 6-8 years ago and now it’s kind of died its natural death. That is because there are better tests that can now look at the health of sperm, so IMSI used to be done in men with high DNA fragmentation, but now you have better in robust tests in the laboratory that can select sperm with much, much lower DNA fragmentation. IMSI used to be a thing of the past, and nowadays, very few clinics are using IMSI because the real-time benefit can be really questioned.

We don’t offer IMSI, we actually offer high magnification ICSI because with IMSI you have to use what we call oil immersion etc. So we prefer to use what we call high magnification ICSI, and all of our ICSI is done under high magnification. As I said if it is using IMSI purely for high DNA fragmentation, we believe there are more proven methods or better laboratory techniques that can assist in using more viable sperm compared to IMSI, so we don’t use IMSI per se, but we certainly use what we call high magnification ICSI.

What’s live birth per cent in frozen eggs at IVF London?

Pregnancy rate is around 6% per egg. I would say the live birth rate is around 5% per egg. So again 10 eggs from a woman who’s 35 years old or less you have a 50% chance of live birth.

I’m thinking of freezing the eggs. How many eggs do I need to freeze? My AMH is 0.739, and follicle count is 6.  

If you’re thinking about egg freezing, I would say you’re looking at a couple of cycles of egg freezing. If your antral follicle count is 6 and your AMH 0.739 presumably nanograms and I think you’re looking at a couple of cycles of egg freezing.

Can I freeze my eggs? FSH/ LH is okay, AFC is 7, AMH is 0.3. I am 40. 

In some women, we have what we call a discrepancy between an AMH and AFC, and in such cases, the AFC is a better predictor. In fact today, I had a patient who’s AMH was 1.3 nmol/l as but she has got about 15 eggs, we stimulate her at the moment, and she’s got about 12 to 15 follicles that are growing simply because her AFC was good, so she had a good antral follicle count but a very low AMH but when you compare AMH and AFC is a better and a stronger predictor especially in cases where you have that discrepancy. I would say the answer to the question is yes, You can certainly attempt to freeze your eggs because your antral follicle count is around 7. What I would expect is around 4 to 6 eggs being retrieved.

Is glutathione beneficial for egg quality?

There is very little evidence for that at all. There is very little that has shown in terms of external supplementation to benefit egg quality. The most important thing to do is to time it right and freeze the eggs whilst your egg quality is better.

Upon egg collection, few eggs were m1 and were not matured farther after donation. Do you recommend freezing those eggs or just discard them? What do you expect upon thawing them? 

Usually, we don’t freeze the metaphase 1 egg. We would only freeze metaphase 2 eggs unless you were a cancer patient then they wouldn’t be an added advantage of freezing metaphase 1 or immature eggs. The common practice is to only freeze metaphase 2 eggs, one has to obviously also make sure that we try and get more mature eggs from you so if you have a lot of immature eggs, then one should be questioning if the stimulation regime applied was correct or not.

Is it safe to refreeze the eggs? All are m2, yet the cycle was cancelled after thawing. What do you recommend in this case?

This is very bizarre because why would the eggs thawed and why were the eggs refrozen because if it is a matter of the sperm not being available, then the eggs should not have been thawed. It’s not easy to give an answer to this because I don’t have enough information here. The answer to your questions is it safe to refreeze the eggs, yes eggs can be refrozen but again as I said in my talk when you freeze eggs you are stressing them out to a certain degree so why would you apply that stress twice unnecessarily. If this was about not finding sperm on the day, then I would have not thawed those eggs, to begin with, and only thawed them once we have sperm.

What is your opinion on a nuclear and spindle transfer with a 50 plus-year-old woman and a 23-year-old donor?

Firstly, I want to say that nuclear and spindle transfer is still under research and development. There’s a lot of validation and clinical information that we need on its safety, so I would not recommend that you look into any of this technology because it is still not validated, it is still not considered to be safe. It’s important to understand that we are creating a life here, we try to create a baby, so we don’t want to be experimenting too early. Technology is moving very fast in reproductive medicine, and I feel it’s my responsibility to say that all this technology including spindle transfer is very much in its infancy, maybe in 10 years time it will be a reality, but at the moment there is not enough known about it. I know there have been some live births from Mexico from China on spindle transfer but what we fail to understand is how many times has it gone wrong. We only see the number of times that it’s gone right, that’s what we hear about, but we don’t hear about how many times it’s gone wrong, so it’s very important to understand, and as a scientist, I would be very sceptical about using technology which is very raw and not ready.

I have Nextplanon in currently to control my endometriosis. I believe I will need this removed for egg freezing? Is this something that a clinic would assist with or do I need to anticipate a heavy reliance on my GP who is not taking appointments for the foreseeable?

Your fertility clinic should be able to manage your endometriosis. It’s not always necessary to be addressing the endometriosis before egg freezing because sometimes we use what we call a long protocol for the patients with endometriosis which gives us a much better outcome. It doesn’t necessarily mean that you have to have any surgical intervention to address the endometriosis before egg freezing but again it depends on the grade of endometriosis. There’s not that much information again, here to go by, but I can tell you that, no it’s not mandatory to have surgical intervention before egg freezing for your endometriosis and at the same time fertility clinics should be able to manage this for you, you don’t have to wait to get a GP appointment unless you’re planning to get the whole endometriosis thing addressed at within the NHS. I hope I’ve answered your question because there are certain stimulation regimes where you can still stimulate women with endometriosis and yet get a good outcome.

I am 50, and I have worked recently with a 27-year -old donor that has two kids. The donor donated a few times, and the usual outcome was 18-20 eggs. However, in my case, the results were the same in terms of eggs count, but I winded up with 4 blastocysts and only 1 good one after PGS testing. Given that I have had normal DNA fragmentation test results, what could be the reason for such results?

That is quite a poor outcome especially if your donor is 27 years old. If your donor is 27 years old, she’s got two kids, she’s donated a few times, a good number of eggs, only 4 blastocysts – that’s not good, and only 1 normal after PGS testing, so you’re also saying that your partner has had a normal DNA fragmentation test, it’s really challenging but the outcome should have been much better. I think the DNA fragmentation would have been the first thing I would think about because people always kind of focus on the egg and egg quality but they don’t necessarily sometimes realize that the other half that makes the embryo is a start. The importance has to also be given to the sperm quality, but you’re saying that the DNA fragmentation is normal.

I would recommend using a technique such as choosing sperm with more intact DNA and then there are some procedures now available, or equipment available in the market, one of them is called ZyMot which we use here at IVF London, and it’s microfluidic channels through which sperm swim but sperm only with good or no DNA fragmentation swim through it and then we pick the sperm which has swum through and use them for ICSI or IVF. I would also question stimulation here because if the donor is young with proven fertility, a good number of eggs why did you not get good blastocysts, so something is not adding up here it would be very difficult to troubleshoot based on that little information, but it could be anything from sperm to mismanagement of the cycle.

When is the best day to do the AMH test and AFC count? 

AMH test can be done at any time in the cycle, there is no set time, but the AFC is best done between day 2 and day 4 of your cycle.

I am 38 I have done egg freezing twice at 37, but only 8 eggs have been collected. How many live births are expected out of 8 frozen eggs? I’m thinking of doing freezing for the third time. How many times are safe to take IVF injection not be worried about increasing the risk of ovarian cancer? Is a 37-year-old frozen egg better in terms of quality or a 39-year-old fresh egg?

If you have two cycles of egg freezing and considering that I have said that an embryo is potentially better than an egg in terms of outcome what I would suggest is if you are considering another cycle, and it would be very wise to consider another cycle. I would consider embryo freezing now, just to kind of keep your options open in both directions but yes a 37-year-old egg is more potent than a 39-year-old, but if you’re going to be creating eggs at 39, then you potentially should start looking at furthering the process which is trying to create embryos out of it. However, that is if you have a partner right now, or if you don’t have a partner right now then one can potentially look at considering just freezing the eggs or using donor sperm, so I have a very good friend of mine who’s had two cycles of egg freezing which is again 38, and now she’s gonna be coming through for embryo freezing using donor sperm, she’s still single. It just tries to keep all the options, there is the pursuit of having a child, but I wouldn’t worry about the risk of ovarian cancer and stimulation, I wouldn’t worry about premature menopause. The most important thing to do is try and make sure you add more to that freezer because in another year or two the scenario would be very very different.

You may conceive naturally as well, there’s nothing to say that women in their 40s don’t conceive naturally, you may, but again this is an only insurance policy and looking out for something which is unprecedented because you never know this may be the routes that you may need to take in order to conceive.

What do you think about PRP – ovarian rejuvenation for women with low ovarian reserve? 

The evidence is very weak on PRP, it’s very much in its infancy. Most fertility clinics do not advise the use of PRP when it comes to getting better quality eggs. I think we’re quite fortunate in the UK, any kind of new technology needs a lot of validation whereas in some parts of the world these procedures are unregulated. All I can say is that in my opinion, PRP doesn’t have enough evidence to suggest that it improves ovarian reserve or egg quality.

How many embryos do we need to freeze for 100% success?

There is never a 100% success. If you are in your 30s, then you should look to freeze about 15 – 18 eggs if possible to give you a very good chance of getting pregnant, but we can never tell you what the magic number is to obtain 100% because there are so many variables. When it comes to the embryos, it depends on the genetic status of the embryos, so you and I both know that having embryos is one thing but having those embryos to be genetically normal is another. I can just tell you that if you reapply genetic screening to those embryos and if you have 3-4 normal embryos out of the genetic screening or after PGS, then you are most likely to get pregnant with live birth, the chances are extremely high.

I am 47 with lupus. I am stable. Is it possible for me to go for egg donation treatment? 

If you are stable and your condition is managed, then you can potentially go for egg donation. I would seek the opinion of your fertility specialist, you need to seek the opinion of your consultant who’s managing you for your lupus. You can then safely embark on treatment, so I wouldn’t like to give a very clear answer to that because I think it can be a complex one, you’re saying that your condition is managed, but the green light has to be given to you by your consultant.

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Authors
Alpesh Doshi

Alpesh Doshi

Alpesh Doshi is a consultant Clinical Embryologist and a co-founder of IVF London. He is also a co-founder and director of the Embryology and PGD Academy. Alpesh previously worked at the Centre for Reproductive and Genetic Health in the leading capacity as a Director of Embryology for 19 years and was pivotal in optimising the success rates. He was also an honorary consultant at the Reproductive Medicine Unit at UCLH NHS Trust. He holds a postgraduate degree in Human Reproductive Medicine and has qualified from the prestigious Imperial College School of Medicine. Alpesh is a Diplomate of the Royal College of Pathologists and also an ESHRE certified Senior Embryologist. He has been an executive committee member of several international embryology societies and holds a very active interest in promoting education platforms through these professional bodies. He was among the first scientists to bring the egg and embryo freezing technology of ‘vitrification’ to the UK in 2007. He is a world-renowned expert in the biopsy of human embryos for genetic testing. Alpesh has authored several papers in high impact journals and written several book chapters in addition to being an honorary lecturer at University College London where he teaches embryology on two of the Master’s courses. He has been an invited speaker in many international conferences and workshops as well as several Health chat shows on television including Zee TV and ITV’s This morning. Alpesh has a special interest in fertility preservation, preimplantation genetic diagnosis and genome editing of embryos.
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Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is managing MyIVFAnswers.com and has been hosting IVFWEBINARS dedicated to patients struggling with infertility since 2020. She's highly motivated and believes that educating patients so that they can make informed decisions is essential in their IVF journey. In the past, she has been working as an International Patient Coordinator, where she was helping and directing patients on their right path. She also worked in the tourism industry, and dealt with international customers on a daily basis, including working abroad. In her free time, you’ll find her travelling, biking, learning new things, or spending time outdoors.
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