By fertility experts from Spain.
Watch the webinar in which Prof. Luciano Nardo from Reproductive Health Group is explaining the egg freezing process and presents a few patient case studies from his clinic.
My mom actually struggled to have children herself and so when my older sister found out that she had a low egg count as well and that she might also want to get pregnant, it was her doctor that thought it might be likely that the problem was genetic so that led me to get in contact with Dr. Nardo. I had an AMH test there where I found out that my egg reserve was also low and so I’m only 23 so I’m quite young really to be going through this. It was quite a shock and also quite difficult to process it all as it happened quite quickly for me. After discussing it with Dr. Nardo, we decided that my best option would be to freeze my eggs now so that I’d have more options in the future when I will be ready to start thinking about starting a family. Then, because obviously at 23 I’m not really ready to do that yet.
It all happened quite quickly for me so I didn’t have a lot of time to really think about the process or what it would really involve. Because I think it was about a week after having my AMH test and getting my results that I started the injections for my first round of egg freezing. Obviously, there are lots of things to consider. It’s a big thing to do with the injections, with surgeries and everything like that but I think the cost of the treatment was a huge factor to consider as well. As I said I’m quite young so this was something I never really planned or took into account financially that I’d have to do at this age. But, luckily, my family were able to help and support me with that which enabled me to go ahead with that. Like Luciano said before I had to consider freezing within 10 years so obviously at 23 that would potentially mean that I’d only be able to freeze my eggs until I was 33 which is still so young. But with such a low AMH level that that was something I had to do at this age regardless of the ten years.
I didn’t have time to have any counselling beforehand. However, I did have a few sessions during and then also after my first round of egg freezing. I found it really helpful and just nice to talk to someone that was completely external to the situation who didn’t know me and that I could just be open with. I’ve got a really lovely group of friends that are really supportive or as supportive as they can be but, obviously, you are the only person that really knows what you’re going through and they try to be there but they don’t know what it’s like. Like I said my family really supports it. They’re able to finance it for me. But, I think in some ways that made me feel kind of guilty if I would complain about it. Obviously, it’s quite a tough thing to go through. You feel tired, you can feel sick, you can feel just fed up in general and so having a counselor to talk to and just tell them how I felt and be able to talk through things was I found really useful.
I mentioned earlier that my sister was going through it just before I did. So it was actually her. She lives in London so it was actually her IVF doctor that recommended Luciano and his clinic so that’s how we first got in touch. I remember being really nervous for my first appointment. I didn’t know anything about IVF or egg freezing. I had no idea what to expect but they just took the time to explain everything to me from going through all the consent forms, how to do the injections, all of my options, and how I might feel and the support that was available. I just remember after that first consultation appointment feeling so relaxed and at ease that I could just ask any questions whenever I needed to and I felt completely reassured that the clinic would just be there to support me throughout the whole process really.
Obviously, it’s extremely nerve-wracking, especially, at the start, going into it not knowing what was involved. I think it can feel a little bit like information overload at the start which was quite difficult for me because I was still trying to process and accept that I was even having to do this. I think that’s the same for any woman. You take for granted that you can just have children and so to be told that you might not be able to or that it’s not going to be as straightforward as you thought can be quite difficult to accept, especially, at such a young age when it wasn’t even something that was really on my mind yet. However, once it all started it all just became a little bit easier. The appointments and the injections became normal and part of my daily routine in a way and as I said before my sister was going through it at a similar time which was helpful. She was able to tell me what to expect at different points. However, she’s married and they were freezing embryos which is obviously different and it also meant that she wasn’t really going through it alone. She had her husband there so whilst I had a lot of support from family & friends and also from the clinic like Luciano said with counselling, I was going through it alone in that sense. So the counselor definitely helped with that point as well I think. But I think overall I remember just feeling quite tired and sometimes fed up but I remember also being worried about the success of it and how many eggs would we get, doing the injections right and stuff like that. But I think you do get used to it all quite quickly. I also knew that I had the nurses and Luciano there at the end of the phone whenever I needed to ask a question, I could text them or call them so that really helped to reassure me that I wasn’t doing it alone either.
Obviously, embryo banking is different than egg freezing and we know that embryos are much stronger cells than eggs. Within our clinic the survival rate of blastocysts is 98%, the survival rate of eggs is about 80% so embryos are much stronger cells. They survive better than eggs but, realistically and based on the literature, the chances of success of having a healthy pregnancy using frozen eggs and fresh eggs is very much comparable. One of the best published studies coming from a Spanish group shows that the clinical pregnancy rate per embryo transfer using frozen eggs is around 55% and the clinical pregnancy rate per embryo transfer using fresh eggs is again 55% so that is very encouraging. Also, it’s very important given that we’ve been told the age of the attendee (41 years old). The clinical pregnancy rate obviously changes with chronological age. What we know that women that are chronologically older will have a significantly lower chance of success than younger women. For older women, the chance of success using frozen eggs probably will be 10% or lower.
I cannot send it now but if you want to contact me by e-mail, I will certainly be happy to do so. You can contact my clinic by e-mail at [email protected] I will make sure that you get the link to the publication.
There are no specific side effects from the injections. The injections to induce control, different stimulation for egg freezing. There are actual injections that have the same hormones that women produce monthly regularly. The difference is that the hormones that are produced physiologically fluctuate, hence why women have unifollicular ovulation which means only one follicle releases the egg. When women embark on egg freezing what we see is that they will be producing and they will be developing a much larger cohort of eggs. The reason why they produce a large cohort of eggs is because with the injections we normally give, they allow to support the cohort of follicles that were in the ovaries from the very beginning of the cycle. One of the possible side effects of the injections is Ovarian Hyper Stimulation Syndrome (OHSS) which is something I mentioned at the very beginning of this webinar. OHSS is when the ovaries produce a very large number of follicles and women can start having some fluid in the abdomen. They can, in some cases, have a swelling of the legs, they can have fluid in their lungs. Admittedly, the risk of ovarian hyperstimulation syndrome is very slim this day and age with close monitoring and tailored stimulation protocols. It, probably, affects 2-3% of women embarking on ovarian stimulation but that is, in our experience, the major side effect of the injections. There are no side effects such as changes in mood, changes in well-being because the hormones are essentially the same that women produce on a monthly basis.
A very long time. I think, in the UK, eggs have been frozen for probably two decades. I think the reason why egg freezing has not been advocated as much as it’s been now it’s because the technology to freeze eggs wasn’t as good as today. Vitrification which is the fast freezing helped the preservation of eggs and more importantly the preservation of eggs which means keeping eggs intact after thawing. Just to answer more directly this question – the first human birth from a cryopreserved oocyte was reported in 1986 so that is a very long time ago. If you think that the child that was born in 1986, now is 34 and was actually created in a laboratory using frozen eggs so it is not a research procedure – it’s not a research treatment – it’s well-established. Over the last 25 years, scientists have optimized the methods to cryopreserve oocytes and I think today scientists and clinicians would agree that vitrification is the technique to freeze the eggs and to allow these eggs to be preserved and well for a long time.
Yes, you do need to have a natural menstrual cycle before embarking on a frozen embryo transfer cycle. Now, of course, I think what we are talking now is the use of cryopreserved embryos, I suspect, blastocyst rather than the use of frozen eggs, but in a nutshell, yes, before you embark on a first frozen embryo transfer cycle irrespective of the reason why the embryos have been frozen, the recommendation is to have a natural period. If you don’t have a natural period, then in our clinic, we would recommend inducing a period before you start frozen embryo transfer cycle.
All follicles have got eggs. The issue is some follicles may not have mature eggs and hence why sometimes eggs are not collected at the time of a collection. Because eggs within the follicles may not be mature and fully detached from the cells. In our experience and in my all 20 years’ experience in the field I see that probably 80-90% of mature follicles will have an egg. Within our clinic, we probably collect between 80-90% of eggs at the time of each collection but we like the follicles generally to become mature before we trigger the final stage of the treatment.
Is age a factor? Yes, of course. Age is the main contributing factor as we discussed until now. Age is a main contributing factor to the number of eggs we collect to the quality of the eggs and to the chances of those eggs to be fertilized successfully in vitro when they’re defrosted.
Again, we’re talking about using embryos and the answer is no. We did a publication a number of years ago and we continuously review the practice at the Reproductive Health Group and we don’t see a difference between fresh and frozen. I think what has to be said that one approach may work better for some women than another one. It all comes down to the time for the transfer. I believe that the time when we do the embryo transfer is very important. Not all women have an endometrium that is receptive after a set number of days of progesterone. The reason why sometimes the natural cycle may work better than a hormonally controlled cycle is simply because they have the opportunity to reach that phase of the endometrial cycle when the endometrium is probably most adequate for successful embryo implantation. But in this day and age, most clinics like ours will have the ability to investigate the endometrium and the endometrial phase and detect when it’s the best time to do an embryo transfer. So if you have experienced tree failed embryo transfer cycles either with hormone treatment or natural, I think the next step would be to have an endometrial biopsy where the endometrium can be studied and that we can identify when is the best time to do the embryo transfer because ultimately the endometrium has to be receptive for the embryo to implant.
I think when we refer to chronological age is the chronological age at the time the eggs were collected and frozen, not at the time their eggs were defrosted and fertilized. If you have made the decision to freeze your eggs at the age of 32 and you use your legs when you are 39, your chances of achieving a successful pregnancy outcome are not based on your current age (39) but 32. I know in this case I think you say that you may have been 37 when you did freeze your eggs. 37 is older than what I would recommend being a good age for freezing eggs but still you may have a good number of eggs, good quality of eggs and use them when you’re 39 or 40. So your chance of success will be based on the age when you did freeze your eggs, not on the age when you’re going to use the eggs.
Absolutely, yes! It is well-established and is our practice to perform pre-implantation genetic testing of embryos, especially in women that are chronologically older than 37 because of the increased risk of having embryos that can be aneuploid which means genetically abnormal. Just to give you some figures because I like to share numbers with my patient population. If you are under 35, the risk of having an embryo as a blastocyst that is genetically abnormal is probably 30%. If you are over the age of 39, the risk of having genetically abnormal embryos is about 80%. So creating embryos, genetically testing the embryos and selecting embryos that are genetically competent i.e. normal increases the chances of successful pregnancy outcome but also reduces the risk of miscarriage. It is not a coincidence that all the women have an increased risk of miscarriage because as I just said they are more likely to have genetically abnormal embryos. So pre-implantation genetic testing which means taking a biopsy of the blastocyst and sending the cells to a genetic lab for the tissue to be examined and then we get the results and say e.g. out of these embryos or blastocysts this one is good; if you transfer that embryo, you’ve got a better chance of success in terms of a healthy live pregnancy.
Yes, absolutely. I think endometrial thickness and trilaminal appearance are just ultrasound features. They’re not going to tell me if the endometrium is in the right phase of the cycle, is it receptive or not? For our patient population that have had repeated failed embryo transfer cycles, we like to test the endometrium by taking a biopsy after a certain number of days of progesterone to assess whether the endometrium is in the receptive phase or not. This can be done by assessing the expression of some genes in the endometrium and based on the gene expression, the lab is able to tell us whether the endometrium is pre-receptive, is receptive or is post-receptive. So it is very important to think that actually it’s not just the thickness of the endometrium, it’s not just the appearance of the uterus, it’s not just the appearance of the endometrium that will determine how successful an embryo transfer is going to be, how good the endometrium is, but, also whether per se the endometrium is receptive or not.
I assume that we’re talking about genetic testing of the embryos. If you have had repeated embryo transfer cycles, I think two things are to be done. One is obviously in subsequent cycles to test the embryos; two is to check that endometrium is well prepared for the implantation. So it’s not just the embryo it’s also the endometrium.
The one we use is called ERA – endometrial receptivity analysis or the endometrial receptivity assay. We do that within our clinic as part of a combined test called endometrial test so we’ll not just be looking at the expression of genes during the implantation window or receptivity window, we also are excluding the presence of an abnormal microbiome. We’ll be looking at the expression of lactobacillus and excluding the presence of abnormal bacteria.
From the time you’ve made a decision to when you can start the treatment that very much depends on what stage in your menstrual cycle you’ve made the decision. If you make a decision when you’re mid-cycle, probably we will be waiting two weeks in order to start the hormonal treatment. From when you start the treatment itself so from when you start the injections to when you have your eggs collected, it’s probably less than two weeks. We say probably between 12 and 15 days at the most. Most women that come to our clinic to have their eggs frozen don’t have to wait and to start the process. After the first appointment, we organize the blood test, we organize the medications that are delivered to the home address and then we organize the online appointment to sign the consent forms, and this is all done within a day or so. Then, they’re given the protocol and receive the medications teach session by one of our fertility nurses done online. They will be starting the injections on the first day of the period.
No, the endometrial receptivity test is done as part of a medicated cycle so we prepare the endometrium with some estrogen and then we add the progesterone. After 120 hours after or five days of progesterone we do a biopsy and we wait for the results of the biopsy to see if the endometrium is receptive or not.
Actually, it’s not it is relatively cheap. The cost of storage is GBP 300 per annum. Unlike other clinics, we don’t charge a fee for 10 years because we don’t believe that women know at the time they freeze their eggs whether they’re going to keep them for up to 10 years. We like to charge an annual fee and that is 300 pounds a year.
I think if you have concerns about what has happened before, you shouldn’t wait until you have a failed cycle. I think you should consider having your test done, first, your endometrial receptivity test done as soon as possible and then you make a decision whether it’s worthwhile. Also, having the implementation of genetic testing of the frozen embryos.
We have had embryos frozen for a few weeks because we couldn’t do a fresh embryo transfer so embryos and eggs can be frozen for one day, for one month and eggs, at the moment, for 10 years. Embryos can be frozen for 10 years, too. There’s no concern. For storage, there is no monthly payment. There is an annual payment and that is 300 pounds within our clinic. It would be difficult to charge per week or per month so hence why we just charge for a calendar year. The time they’re frozen, they pay the 300 pounds storage fee and they don’t pay anything until 12 months later.
It’s not a matter of surviving the PGD test. The test is done after the cells are taken. It’s done in the laboratory. I think perhaps the question is what are the chances that embryos blastocysts will not survive the biopsy? I always say to my patients that the risk of the embryos being damaged by the biopsy is significantly lower than the embryos per se being abnormal. I think in our lab the chances of blastocyst being damaged by the biopsy and the embryos not being able to be used in subsequent cycles is below 5%.