By fertility experts from Spain.
Watch the Online Patient Meeting with RNDr. Tomáš Rieger PhD, Head of Embryology Lab, GYNEM, who answers questions about the pros and cons of egg/sperm social freezing.
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Regarding social freezing, the most important thing is the age of the woman. You are born with a certain number of oocytes which you will need in your life, and as a woman is getting older and older, the oocytes are getting older as well, and statistically, it was shown that after 32 years-old of a woman, the chances of more aneuploid oocytes is rising. So it is something that lowers a chance of successful pregnancy or future child. The best age is whenever the patient wants to start, and it ends when the patient is around 32-35, but it is also individual like everything in biology or medical stuff. Statistics show that around 32 years of age, the aneuploidy in the oocytes is getting higher, and the chances for success is getting harder.
It is a good question because sometimes we can see in our daily routine that some patients have expectations which don’t fit the right meaning. If patients come to our clinic or any other clinic at the age around 30 because they read something on the Internet or were talking to a friend and they were thinking about preserving their fertility for future, possibly they didn’t find the right partner or husband, it’s good to get to the fertility clinic and freeze their oocytes for the future use. When a patient comes to the clinic at the age of 40 because they think that maybe it’s time to preserve their fertility or keep oocytes for future, at such age the percentage for success is not really good. It’s important to know before somebody is thinking about social freezing to get the information right and think about if this possibility is right for a 40-year-old.
There are not any age boundaries in the Czech Republic. The age limit for IVF treatment in the Czech Republic is 49 years old. If somebody will come in who is 40 years old and wants to freeze their oocytes, and wants to use them next year, we can thaw them and use them for IVF cycle, and it can be successful because when I say the statistics are getting lower, it doesn’t mean that they are zero. There is still some chance, but it’s just lower, so there are no age boundaries for social freezing, it is only good to know that in more advanced age, the chances are going down and it is important to know about it. Some statistics show that when you are plus, in order to get blastocyst, you need around 30 oocytes because not every oocyte is mature, is not fertilized, or the embryo will not Reach a blastocyst, and even it does, you need to keep in mind that not every blastocyst is good enough to become a healthy child. When you take all these things in place, and you count how many oocytes you need to have a good chance is 30 oocytes, at the age of 40.
There are many studies which are done on frozen gametes and fresh gametes and comparing them. Again, it depends on the age when we have fresh or frozen gametes of the Young patient, the statistics show that there are just slight differences in the higher age. These differences are getting bigger, but still, there are chances with the frozen gametes in the higher age still for the success. On the other hand, fresh is always better than frozen, and this is pretty much the same with every biological Staff. I have to admit that the fresh is always better than a frozen because the freezing process is something which is not natural, the scientists work hard on it and on the procedures to reach the highest level of surviving of the oocytes, gametes and embryos but when you compare the fresh and frozen ones, still the fresh is better. There are some cases when the fresh samples cannot be taken, or the patient has some frozen oocytes, let’s say from 10 years ago, and they are ready to become a mother now, and in this case, frozen oocytes when they are ten years younger are better than the fresh ones that are now older. It depends on the individual patient, their needs, their situation and what can be done in their individual case.
The main factor is once again, age. When somebody is young and freezes the oocytes at the age of 25, the chances with frozen oocytes are pretty much the same as with the fresh ones. It’s around 45% in IVF procedure which also depends on the quality of sperm of the partner, but these oocytes are good. The freezing procedure with these young oocytes has a 95% survival rate. The fertilization rate in frozen oocytes is quite similar as with the fresh ones at this age. When we’re talking about oncofertility preservation, it again depends on the age. If a patient is 39, and we know that sometimes this is the only way for her to have a baby in the future, again depending on the quality of the oocytes and of course, age is always against us, the chances are becoming lower. If we have a 45% survival rate in younger patients, it is going down to around 15% in patients who are 40, and with older age, the percentage will again lower. But, as I said before everything is individual in biology, I had patients who froze oocytes at the age of 45, and one and a half year later they had a successful outcome, and she got pregnant and gave birth to a healthy child. When the chances are going lower, it doesn’t mean that it’s going to be zero, only the expectations should be a little bit more realistic.
I have to say that there is no scientific evidence and big studies were searching for this influence of freezing on the future child, and no evidence was found that the freezing itself can somehow affect the health of the children. It can affect the chance to get pregnant, but when the patient is pregnant from the frozen embryo transfer or embryos derived from frozen oocytes or frozen sperm when the patient pregnant, there is no difference in the health of a baby or any genetic disorders or illness. The freezing is completely safe for the cells, it only affects the pregnancy rates a little bit.
It depends on the law system in each country. In the Czech Republic, we have an age limit for IVF treatment set on 49 years old, so when somebody freezes sperm or oocytes at the age of 20, they can be frozen for 30 years. ESHRE recommendation is that the embryos should be used up to 22 years after the freezing but this is mostly because there are not so many cases where there is a bigger gap between the age of freezing and the age of the transfer. Looking at it from a biological way, the freezing itself or staying in the cryo tank, in a nitrogen liquid it slows the time. When we lower the temperature to the liquid nitrogen which is – 197 degrees of Celsius it will slow the time for the oocytes, so one hour in the liquid nitrogen for the embryo is like let’s say a few seconds or maybe less so if you keep them there for about 20, it’s like maybe one hour for the embryo. As you can see, the freezing is quite safe and can last very long, it can be stored up to the limit of each country when there is a set limit for the treatment itself.
This is quite an interesting question. I believe it should not really affect the egg quality, the eggs are like there the whole time, your whole life, and the whole procedure takes one year, so when you have like one year of procedure of waking up oocytes from the ovaries, and they are growing up to the stage of oocytes pick up so when you’ve been on that diet a month, which is only one month from 12 months, it should not affect the quality of oocytes. The genetic information is the most important thing, and it is there in the oocytes already, it shouldn’t be somehow affected by diet, so I believe you should not be worried about this.
The short answer to this question is, yes. When the embryo is derived from the frozen eggs, it has to be normally developed to the blastocyst stage, this development has to take 5-6 days. What is normally done on the fresh oocytes and then when the blastocyst is reached, and the quality of the blastocyst is good, the PGD technique can be done on this embryo without any a bigger risk. When the oocytes are frozen and then it’s thawed and it’s fertilized with sperm and becomes an embryo, in this period of 5 days everything in that cell is replaced, every molecule in the embryo is renewed in this process of 5-day cultivation. The embryo derived from the fresh or frozen oocytes has the same chances of surviving the biopsy.
When we are testing the embryos, there is some risk of damaging it. The biopsy is not a natural process, we have to cut a few cells 4 to 10 cells from the embryo, in the blastocyst stage the embryo already has around 100-150 cells, so these 4-10 cells shouldn’t be missing in the embryo, but there is a chance that the embryo will be vulnerable to be damaged. Sometimes, we can see that when we do the biopsy, the embryo may not behave very well and the embryo will not survive the process The biopsy has some small risk, and it always depends on the quality of embryo that’s what we explain to our patients. When the embryo is of top-quality, it will survive the PGD testing without any harm, in like 99%, but when the embryo has lower quality, it’s not optimal, the risk of damaging the embryo and the biopsy process is raising, as I said before it’s not natural and because it’s quite a hard technique it can do some damage.
The slow freezing method wasn’t really optimal, so I would not have any big expectations. 10 years ago, I started to work in this field and then there was only slow freezing method available, and we did some freezing of oocytes using a slow method, but I experienced that the chances for pregnancy, the chances for surviving the oocytes for fertilization was much lower than in the fresh ones. Let’s say we can take the chance of having a half maybe if they were frozen at age 37, this is again a little bit older age, not as optimal, as I’ve said, the optimal age is between 32-35, as with age the risk of abnormalities is higher with age, so if you have 16 of them with the slow freezing I would expect that 12 oocytes would survive. If everything will be optimal, 10 of them can be fertilized, you will get 2 to 3 blastocyst possibly more or less. When we will do perform genetic testing on these embryos, 2 from those 3 can be somehow damaged, the chances are not optima, but as I said it’s all individual, so it can happen.
It always depends on the number of patients who undergo or are participating in the study, and what I read was that it can be up to 40% of pregnancy rates which is almost the same as with the fresh oocytes. In our clinic, we have a smaller number of the cases, it was about 33%, but it was done only on 20 patients last year. Not every patient wants to use frozen embryos or embryos derived from the frozen oocytes, so we had a 33% success rate but done on a small number of patients. It depends on the age again. If the age of the patient was less than 32 when she froze the oocytes, the chances can be similar to fresh ones, maybe a little bit lower, but it’s going to be over 40% for sure.
If you are using donor oocytes when the donor is 23 years old, this is completely fine, there shouldn’t be any problems or risks. Slow freezing of the sperm is normal, there is new fast freezing, vitrification for the sperm options available, but it’s not often used. The slow freezing of the sperm is used, and we use it every day, and the results are quite good. It more depends not on how it was frozen but what was the quality of the sperm. So when if your husband had normospermia and you will have these young eggs, the chances are really high, in our clinics, chances in these cases are around over 60%, and if you will do a PGT-A screening on the embryos, it will increase the chances. Choosing the best sperm depends on quality. I don’t know how many sperm did your husband have at a time of freezing. If it was like 20 million or 4 million, it depends because when there will be more than 10 million sperm per millilitre, motile sperm per millilitre there can be used FertileChip or MACS system for choosing the best sperm. 40 million after thawing, that’s completely fine. In our clinic, we have 4 ways of pre-selecting the sperm before the fertilization, and they can be all combined. With a sperm sample of this quality with 40 million motile sperm after thawing, all of them can be used. My recommendation will be FertileChip which is the method focused on the motility of the sperm and only the sperm with the best motility can go through this chip, and the embryologist can take sperm with the perfect motility on the other side of the chip, and then that can be used for the fertilization. My favourite combination is when I am doing a FertileChip for the motility and from this best moving sperm I’m using IMSI procedure which will allow me to zoom the sperm much more, so I can see the quality of the cell whether there are some backflows, some cytoplasmic disorders or some morphology problems etc. Because of this better view of the sperm, I can choose even from this pre-chosen sperm the best one for fertilization, and if you undergo some of these techniques. I believe the chance will be much higher. What I would recommend with this sample will be FertileChip and IMSI procedure.
The risk of ovarian cancer with a higher number of injections is not so high. Everything is individual, so your doctors who are performing the stimulations, who see you during the stimulations can check your health and reaction of your body. They should tell you if there is some increased risk of some problems, but it’s not really often or normal. We have cases when our patient had 8-10 cycles, and I never saw that there was some like increased risk of some problems. I read some articles, in some studies, there was a little bit higher chance or some problems with a higher amount of stimulations, but it always depends on your doctor who has to tell if it is safe for you or not. I’m not a doctor, so this is not like the right question for me, but as I said, I never experienced some bigger problems with a higher number of stimulations. If the patient is reacting well under-stimulation. With 8 frozen eggs derived at the of 37, the chances of the aneuploidy are higher with age. If you have 8 oocytes, and if all 8 will be thawed successfully, the fertilization rates are around 85%, in most clinics, it is pretty much the same of 85-90%, so let’s say from 8 oocytes, 7 can be fertilized but not every fertilized oocyte will reach the blastocyst, so I would expect from 7 embryos, you will have like 2 or 3 blastocysts, and it can happen that if there will be 2 blastocysts, one of them will be fine and one can be aneuploid, but it is also possible that both will be aneuploid or both will be okay, it is really hard to say, the chances are 50/50.
We are quite commonly doing some transportation of gametes or embryos from abroad from European countries, even from the US or more distant countries, and it depends on the embryos quality or the quality of the eggs but also the quality of the laboratory, whether they know how to properly freeze the oocytes, whether they used a good technique like vitrification process and all these things can really affect everything. The transportation itself does no extra risk or harm so if the PGS testing is illegal in your country and you are convinced to do this genetic testing on your embryos the transporting to another country shouldn’t somehow affect the quality and the transporting is not a problem. The transportation companies have really strict rules on how to transport, they have good equipment. We are cooperating with a company which transports within the whole world for us we did more than 50 transports, and we never experienced any harm of the cells or the embryos. It is possible if the quality is not good enough or it was not properly frozen in a previous clinic and sometimes after thawing, they can be useless, or we transferred them, but the chance for success was really small and the pregnancy wasn’t achieved, but it was not because of the transportation, it was because of the quality of the embryos before the freezing.
The answer is yes, but in the Czech Republic, it is not legal. So we can tell the patient’s about the sex of the embryo only in cases when they have some genetic problems connected with one of them. Some illnesses are going only on the male so when we have 2 embryos, and 1 of them is male, and one of them is female, and we know that the male will be affected with a genetic illness, we will not transfer a male embryo, and so the patients know that they will get the female embryo. In the Czech Republic, it is only possible to find out if there is a medical reason.
At your age, I would say that it will be approximately 50/50 chance that embryos will be genetically normal.
It can be done, because what we usually do when we are discarding the embryos, well we discard them, but if a patient wants and pays for it, as such techniques are requiring additional payments, so if the patient wants to pay, we can take part of the embryo, and it can be whole embryos that can be sent to a genetic lab, so it can be done.
We have a system to grade the embryos, it’s called Schoolcraft and Gardner system, and it’s used worldwide but when we have two embryos and one of them will be let’s say 5-AA and one of them will be 5-CC. If the results of genetic testing will be euploid, I will still recommend the patients to choose the one with the better quality. It depends on the time-lapse video or data from the development of the embryo, and if we can check how these two embryos are developed over time and we can see some morphokinetics parameters which can help us to choose the one embryo with a better implantation potential. Even when both are checked, the development can be different, and the final quality or the data from the development can show us which embryo has a better chance.
This is a tricky question, I’m not sure, I need to check the law on that. We are just unable to tell the patient’s the sex of the embryo. Somebody can tell, that they will transfer the embryo, but they only want a girl as they have 3 boys, and after the transfer, we would tell, them that the embryo was a male, the patient could take some pills, do something which could affect the pregnancy, this is something we don’t want, so in this case, I believe we shouldn’t inform about it, even after the transfer.
In the Czech Republic, we mostly have Czech donors of Caucasian ethnicity. There are a few donors that are more like Indian donors.
From my point of view, I don’t think it will increase your chances. I don’t see the reason for it because when you use egg donors, you know that the donor is young because f.e. in the Czech Republic and other countries, the donors have to be maximum 35 years old. If a donor will be 25, the oocytes should be fine, there should be the lowest chance of aneuploidy which can be around 20-30%, and these oocytes usually are not fertilized or the fertilization is not successful or the development shows problems during the development so the embryos are not reaching the blastocyst stage. There were five big studies done worldwide with thousands of patients in each study, and it shows that the chances of getting a healthy child were not better in the group with the PGT-A testing compared to the second one without the testing. In some studies, it was the same, in some groups without the testing it was more successful, in some studies, there was no difference. No study shows that better chances are with the testing than without it. The only different thing was the level of miscarriages level in all these five studies, in the group with the PGT-A it was lower. But the chance of becoming pregnant with a healthy child was the same in both groups and from my point of view because I can see how the embryos react on the biopsy, on the freezing, and so if there is not a particular reason for the PGT-A, I would say it is not necessary.
It was published by ESHRE in 2010 in London, there was a big study done in regards to PGD testing, it was comparing all of these 5 studies on PGD cycles and cycles without PGD and the results showed that the chances are pretty much the same.
I have information from our company which we are cooperating with that transportation is now again possible, even from the UK, but still, it is possible from the UK as well, so it can be transferred. This limit, as you’ve mentioned, we have the same, we have 12 years for oocytes and 22 years for sperm. If you will sign, that you agree with the procedure, we can do this, we can fertilize those oocytes with sperm which you will get to us, and we can freeze the oocytes or embryos, and we can transfer the embryos back to the UK. I believe that maybe it will be better to get the cells to our clinic, do the fertilization, and then come here for transfer, but possibly because of the pandemic situation, the transport will be an easier option for you, it can be done.