Watch the OnlinePatientMeeting with Dr Pavel Otevřel, Fertility Specialist at Reprofit, the Czech Republic, who answered patients’ questions about IVF treatment using donor eggs with PGS testing vs. success rates, cost and time frame.
The decline in fertility corresponds with the loss of eggs as a woman ages. Dr Pavel Otevřel explained that older women in the age group (+40) with age-related fertility decline are the main group of patients where egg donation will be recommended. In this group of patients, egg donation provides the highest chance of pregnancy. Another group of patients is younger women who suffer from an early ovarian failure (POF) or ovarian insufficiency, where their number of eggs and ovarian function are greatly diminished. There are also patients after chemotherapy, previous surgeries where ovaries were removed, a subgroup of patients born without ovaries. The most common syndrome is Turner’s syndrome, and many times, women born without ovaries are afraid that they have no source of estrogen, therefore their chances will be lower. Dr Otevřel ensures that their chances are extremely high, preparing the womb to accept an embryo is quite routinely done. Even if own estrogen is not produced, the outcome in patients with Turner’s syndrome is very promising. Another group of patients that will benefit from egg donation are patients with endometriosis. It is a disease that negatively affects the egg and consecutively embryo quality. Also, patients with repeated IVF failures often are recommended to go through the egg donation route.
Dr Otevřel emphasized that the age of the oocyte is the most important. Spermatozoa are created every 3 months, but a woman is born with a certain number of oocytes, and this is all she has for her entire life. Dr Otevřel compared the egg to a battery. Its energetic supply inside must be strong enough because all energy in the embryo is originated from the egg. The spermatozoa are totally exhausted after penetrating the egg. All energy in the embryo that is needed for implantation originates from the egg. If the egg is strong enough, it is a good start for implantation. The idea of egg donation is simple, we can substitute old batteries with young batteries. The recipient’s age doesn’t matter because we will use a young egg. Also, because the egg is under the negative influence of pollution and negative impacts from our environment. There is a higher risk of a genetic disorder in older eggs than in younger ones. For instance, the risk of Down syndrome being carried in a 25 years old donor is approximately 1:3000. While, in a 35-year-old woman, it’s 1:300.
Dr Otevřel later explained that at his clinic (Reprofit), fresh embryo transfers are performed. Therefore, the cycles of the donor and the recipient have to be synchronized. For this reason, birth control pills or hormone pills to trigger menstruation of both ladies are used on the same day, so it is a crucial moment that allows us to use fresh oocytes for further treatment. Before the synchronization, it is necessary to have time to find a suitable donor. There is no waiting time when it comes to egg donation. However, finding a suitable donor, preparing the synchronization, and endometrium can approximately take up to 3 months, from the decision until the pregnancy test.
I tried to describe to you that the genetic profile of egg or oocyte is the most important issue. If the egg is young, the probability that it carries some genetic disorder inside is low. A good illustration here is Down Syndrome, as you know everything about it. 95% of Down Syndromes are created from the egg and only 5% one chromosome more there is an additional chromosome, only 5% of those are created by spermatosis. PGT is the genetic testing of the embryo to exclude any genetic disorder. In practice, we wait five or six days of embryo development because we need to have a very good quality embryo. It is common in the egg donation program is good. We take a few cells from the embryo on day five. It’s divided into two parts, one part is a future placenta, called trophectoderm, and the second part is a future baby. Experienced embryologist takes a few cells from the trophic to bear. The embryo is frozen and will remain frozen separately. Each embryo carries its own code number, and its DNA is sent to the lab where it is screened. They evaluate it, and approximately three weeks later we receive the answer whether the embryo healthy or not. And what we are focused on PGT A it means pre-implantation genetic testing for the cause of aneuploidy and A PGT means we are looking for a good number and structure of chromosomes. You know each healthy human has 46 chromosomes. If there are 47 chromosomes, for instance, it could mean Down Syndrome. The patient will receive the list of embryos and with numbers where it is written that embryo number one carries 46 normal chromosomes, for example. We recommend it to be transferred. If number two is a triple tree, it’s 47, it’s Down Syndrome or Turner Syndrome.
If there is a strange number of chromosomes, we do not recommend to transfer this number. To do the PGT A on embryos from the outside donation program generally doesn’t make sense because the eggs are young, donors are young, and the ratio of embryos with a bad DNA is very low. The use of PGT A doesn’t improve your chances in comparison with fresh embryo transfer with the non-diagnosed embryo. Here are some statistics from our clinic. We performed almost 1,000 fresh embryo transfers in an egg donation programme, and implantation rate was 65 per cent, pregnancy rate 69 and a clinical pregnancy rate is 65 per cent. Only 37 patient in 2019 decided to wait and to do the PGT A on embryos and to transfer genetically tested embryos. I have to stress that it is not a big number because only 37 patient made such a decision. The success rates are sixty-nine per cent, clinical pregnancy 65 per cent. There is no comparison because there is no way to improve the egg quality, there should be some improvement estimated, but in practice, there is no difference. Doing the PGT A is not recommended to everyone. A different question is GTS. If the male partner carries any disorder we have to exclude this disorder in embryos. We test the embryos because there is a reason on the male side. If we know that the patient carries, let’s say, some microdeletion, and we would like to know if the embryo inherited such a disorder from the male partner. Doing it to improve your general chances to become pregnant doesn’t make sense.
I can imagine no medical indication or reason on my side. I can imagine the life situation that the couple would like not to face. For instance, being forced to decide in week 12 of termination of pregnancy if something wrong is detected via ultrasound on the fetus. They would like to do the maximum to prevent such a terrible life situation and that they would like to know that embryo is very likely genetically healthy before embryo transfer. it’s absolutely understandable. We can do it technically. The reason to do it is not to improve the pregnancy rate but to prevent any terrible situation in the first trimester of pregnancy. Normally, we do not recommend PGT-A, but we accept the request of patients, and we perform it. Regarding the costs in our clinic the first embryo test is 450 euro, and each every other embryo is 350 euro.
The donors must fulfil a lot of legal requirements, they are tested for STD, drug abuse, of course. They go through genetic, gynecologic examination and genetic counselling. We have a list of donors. They are open to donating and the couple, our patients, will have to fill in a questionnaire in which they can stress what is important for them. It is mostly how tall the donor is, the eye colour, hair colour, education, sometimes hobbies and blood type. One note regarding blood type- it is not important for the success rate. There is only one social aspect because we prefer the situation that all members of the family have the same or similar similar blood types. It is only the prevention of a situation in puberty when the child is older and could realize that his/her blood group is completely different from the mother’s or father’s group and they could start to think about it, and it could cause some relationship problems in the family. So there are some interesting statistics published that at the beginning of the treatment approximately per cent 80% of patients would prefer to inform child later about the treatment or sperm donation, but, in fact, only 15 per cent of the families finally do it. So back to question, the couple fills in a questionnaire, and each couple has their own coordinator who will instruct our donor program coordinator to find a donor from the list of potential donors. If the couple prefers to know something about the donor, we can provide information about the donor approximately six weeks before the collection. There is plenty of time to change the donor, to find a new one, in case the couple doesn’t accept this matched donor. We can provide information about education and general history, how many children she has from her, children born from her previous stimulation, how tall she is, the colour of eyes. On a special request, we can ask the donor for answers, but it is not common. There is a group of patients who don’t want to know anything about the donor because it’s a very sensitive issue. We can start the stimulation only after approval of the couple. We are not able to provide photos or personal information.
We prefer fresh eggs and I will try to explain why. The art of egg freezing is the highest technology in IVF. It is a very sensitive issue, and we invested a lot of money in the last two years to find the methodology and to find the best technique for freezing. I can tell you since 2019 or 2018 are happy with frozen eggs, and the success rate from frozen eggs are equal to fresh eggs, but there is a lot of effort behind this and for us, it’s still a backup strategy to use the frozen eggs. The first-line strategy is using fresh eggs, because it is still not 100 sure technology, and although we are happy with this, we are still not ready to convince the patients to come to us for frozen eggs as we are not convinced ourselves. It’s about the technology. Using fresh eggs is standard, using frozen eggs is almost standard.
It is described in one picture from my slides. A recipient needs birth control pills or hormonal replacement therapy, norethisterone one package is enough to synchronise the menstruation. The second thing is so-called down-regulation injection, which is a single shot used before the menstruation and the goal of this injection is to exclude own hormonal activity or estrogen activity For the endometrium preparation we need no interference between hormone replacement therapy and our own hormonal effort on hormonal hormone produce map. That downregulation shot is used mostly in the cycles, and after restoration, we recommend estradiol which is estrogen pills. Pills are the first-line treatment, but it could be substituted by my gel, or by plasters and in combination with progesterone which is mostly recommended intravaginally. Administration of progesterone six days before the embryo transfer. In a simple cycle, it is a birth control pill, down-regulation shot of estrogen preparation and progesterone preparation immediately before the implantation. I’m not talking about a patient with a specific history of immunity problems, hematologic problems. Such patients have specially tailored cycles according to her previous testing or treatments. Each patient has their own coordinator, and the coordinator can provide prescriptions. In some countries, our prescriptions are acceptable. We can provide contact to an online pharmacy who are able to prepare the parcel. Some pharmacies in the UK can accept prescriptions sent via email, so coordinator is able to help and some GPs or gynaecologists locally in the country of recipients’ residence are able to cooperate and they are happy to help and to prescribe the medications. I think the most common approach is to send electronic prescription, and the patient is able to pick it up locally in their country.
As doctors have to recommend one embryo because of the safety of pregnancy. The success rate is a little bit higher in favour of two embryos transfer, but the difference is not big. The difference between single and double embryo transfer is only six per cent. We can improve the success rate slightly by transferring two, but the improvement is very small. On the other hand, the success rate with one embryo is very good, and it’s risky to transfer two, because of all complications. If we transfer one embryo there is a risk that the embryo could split in two but having twins after single implantation is very rare. If we transfer two embryos, the probability that the transfer will result in twins is 40 to 45 per cent, and the complications connected with multiple pregnancies are at least fourfold higher in comparison with a single pregnancy. Typically you can expect preterm delivery, hypertension, diabetes, placental abruption, bleeding from placenta. These common complications are four times more common in twins than in single pregnancies. A lot of couples indeed decided in favour of two embryos, and the treatment resulted in absolutely beautiful twins. They are perfect beautiful In photos, but despite this, we have to recommend one of the safety. There is only one exception if the patient has a repeated implantation failure with donated egg treatment. In this case, we are more open to transferring more than one embryos because the probability that the first attempt after three previous failures will work is not so high. In every case, it’s about the consultation we have to inform the couple, and we accept the decision couples. Summarizing this question, one is a recommendation because of the safety of pregnancy.
The minimum is that the partner, the male partner must be here on the day of egg collection or if there is any reason he could come before and have the sample frozen. So the minimum is one visit for the male partner and one for the female partner on the day of embryo transfer. It is the minimum. We can do a lot of long-distance. We need to lady to undergo an ultrasound, the measurement of endometrium approximately 10 days before the embryo transfer is scheduled. We appreciate knowing the ultrasound scan, thyroid gland hormone levels before the transfer cycle is initiated. It means one month before the embryo transfer is scheduled. It could be done the long-distance in cooperation with local doctors, and the lady could come over here only on day of embryo transfer. In practice it works like endometrium measurement is performed in the country where the couple lives 10 days before the embryo transfer, then the couple arrives one day before the egg collection when they have an appointment with the doctor and coordinator. On the day of egg collection, it is time for finalizing- to ask all questions, to get a recommendation and repeat the measurement of the endometrium, to make a snapshot of the womb by wire ultrasound, to sign all the papers that are needed to be signed. After the male partner provides the sperm the couple stay here for five or six days until the embryo transfer. They could come both of them on day of embryo transfer, and it is recommended, mainly for psychological reasons to stay overnight and to fly or drive back the day after embryo transfer. It means seven days of stay here. Staying overnight after the embryo transfer is only recommended because of the well being of the patients as it’s absolutely understandable that they are afraid of travelling. We haven’t found any difference between patients flying home immediately or staying overnight in terms of outcomes. There is also research on this topic, and a lot of researchers haven’t found any advantage of laying in bed or staying overnight.
The expectation is between 8 to 16 eggs. We mostly use mild stimulation, so we don’t use 300 or 200 units for stimulation. It is about 100 in donors a week because we put the safety first of and we estimated between 8 and 16, and we guarantee two top-quality embryos. It must be expanded or hatching blastocyst on day five. Basically it doesn’t matter we start if we started with four embryos or 40 embryos We are happy with a yield of 8 to 16 eggs and we guarantee at least two top-quality embryos.
There is no gene which can be detected for Hashimoto, so it doesn’t make sense to investigate the embryo to exclude Hashimoto. In this specific case of a patient with Hashimoto, we have to be focused, in cooperation with the patient’s endocrinologist, on the good treatment. We need good substitution of thyroid gland function at the time of embryo transfer. The statues of the patient, in this case, is more important than testing the embryos.
I can use our statistics because the average age of the donor is 26 or 27. Let’s say it’s a typical donor. We do the PGT A on the embryo of this lady, and we will transfer genetically tested embryo created from 27 years old donor and male partner of the recipient, and we transfer one embryo. We have a pregnancy rate, it means there is a positive test in 64.9 %. The patient will have a positive, test the clinical pregnancy rate, meaning there is heart beating, of no defects detected on the ultrasound, is 51%. It is because despite GTP A there is a risk of miscarriage. It’s absolutely the same answer as I would give for not genetically tested embryo 65 per cent of a positive pregnancy test, 50% and 51% of ongoing pregnancy.
The Czech Republic, it’s a specific country, because of them I don’t know exactly the reason, but in the Czech Republic, almost 98% of cycles are performed by using ICSI in the egg donation program. Maybe it is because of the donated eggs are something special. It’s kind of treasure, yes, so in egg donation treatment we are happy for each matured egg, and we would like to have a good factorization rate and fertilisation rate,i.e. how many embryos there are created from oocytes. Factorization rate of ICSI is higher than a factorization after conventional IVF. ICSI is standard here in the Czech Republic.
In egg donation treatment the Down Syndrome is not inherited from a donor. If the donor is healthy, male or female. The moment when the Down Syndrome develops is the maturation of egg or in the process of egg development. It is a so-called de novo mutation. It is not possible to check each egg for Down Syndrome, and it doesn’t make sense because it is information about the embryo.
It was likely to change, but I’m not sure what will happen now when COVID complication appeared. We were told by my lawyer that maybe in two years it could be changed but I’m not sure now. I think there will be a lot of priorities and I’m afraid that it will become a marginal topic. I’m not optimistic about it. It is very important but it’s true we might need to wait for such laws to change. Don’t wait and try to find a different country where it could be allowed.
It must be requested, and it is paid separately. I can mention, by the way, the possible a strategy that could be used because some couples have a wish to undergo the transfer of the first fresh embryo to be prepared normally and to undergo a standard transfer of the fresh embryo. That surplus embryos are frozen. If they are frozen, why not let them be tested. It could be a strategy to transfer the fresh embryo first and in the meantime, you can receive the information if the frozen embryos are genetically ok. It’s very important information from the future decision-making process because these are embryos with the realistic chances to become a baby it could be also the strategy to transfer one fresh and the rest to let freeze and be tested.
It’s partly the scientific question. For sure that ERA test makes sense only in patients with repeated implantation of failure, or after two failed embryo transfers of good potential. It can explain the implantation failure, and it is the time to start to think about it. The second thing is that we are waiting for big studies confirming the ERA test sensitivity. ERA tests are a really good idea if they could bring the change. The studies that have been published until now, are very optimistic but they were published by the investigators, which brings the questions if the ERA test is a miracle, or not. In this year 2020, we are expecting the studies confirming that ERA tests have any scientific basis truly. If you have repeated failures, I would do it in Spain.In corona time to utilize the time because my personal experience is that ERA test could make sense, but the evidence is slim.
It is a genetic test, so it is not changed by delivery, by birth or by age. It is said the results will be the same lifelong.
The ERA is a test done once. It’s valid forever.
Yes, I do the be PGT-A and its results it’s a huge and sensitive issue we have no space to discuss it in more detail. For many many reasons, I am open to transfer mosaic embryos because it could result in a healthy child. Every time it is done after detailed consultation with a genetic specialist explaining the pluses and minuses. Generally, yes, we do it.
We have to consider the previous attempts. If we are talking about the very first embryo transfer with donated eggs we try to lead the patient to decide for one, but if the patient insists on two and she’s open, or the couple is open to the risk of pregnancy complications, why not.
Including the basic price is 5300 EUR, and the PGT A is an extra payment 450 per the first embryo, and 350 euro per any other embryo each.
We have no difference between the programs, so it’s the same price for all and the difference is cost only caused by the numbers of frozen embryos. If there are six frozen embryos it is a little bit more expensive than in case when only one embryo is frozen. I can provide information about cases when you take home a baby. It’s data from 2018, and in case of fresh embryo transfer it’s 47.6 and with the frozen embryo transfer take home baby rate is 27.7. It’s lower with frozen embryos, and I have to stress that.
Mosaic embryos happen rarely. Their rate is approximately 25% of aneuploidy and euploidy good result validity is 75%. And it makes sense. There is a possibility to avoid synchronisation and to wait for the frozen embryos. There is the question of false-positive results of PGT A. If I was a patient, knowing what I know now, I would prefer fresh embryo transfer without genetic testing because I would be afraid that a good embryo would be discarded because the PGT-A result would come out positively false. Talking only about the statistics, you can use frozen embryos to avoid synchronisation.
It’s a typical observation that the first three days of embryo development depend on eggs and day four, five and six depends on the sperm. The processes of embryo development are changing in day three. In day 4 it will be in the stage of morula creation, and if there is something wrong in day four, five or six ait is probably because of the sperm. If it happened only once, it is only bad luck. It’s not possible to make a final diagnosis after one observation. It must be repeated. We would like to distinguish if the problem is more likely in sperm we in such cases we recommend to split the yield of eggs and one half of egg is cultivated with donated sperm and the second half with the husband’s sperm. Then we can compare the development and if there is atypical, bad development only in the husband’s part, it could be a confirmation that the problem is really in the own sperm.
It is not about attempts, it’s about your attitude and age. We have a good experience that it makes sense to support ladies to struggle with their own eggs until 40 to 43 years of age. 1.07 is still promising, and we have a very good experience with the mild or soft protocols in such a group of patients. The breakdown is between 43 and 44. After 43 or let’s say in group category 44 plus only sometimes we can act to achieve the pregnancy. I can tell you from 108 patients who have undergone the treatment in 2019 in the age category 44 w only had two babies, two babies. It’s a very low success rate but in the age group 42- 43 it’s 25 – 22 % of the success rate of taking home a baby. It is mostly about the age and about the personal attitude and strength to try again.
Yes, because it is mentioned in the legislature and there must be a strong reason. Let’s say a patient with serious diseases, and only very early, we are not open to doing surrogacy only because of the repeated failures. It must be a confirmed case, but generally, I can answer yes it is.
We have a coordinator for Switzerland so haven’t had any really serious problems. I can answer generally yes. I think it depends on the country. Maybe this question will be answered by our french-speaking coordinator specialized for Switzerland. I’m sure we can solve it.
In this case, it’s absolutely necessary. Downregulation injections to exclude your hormonal levels to achieve a good outcome, and there is no difference. It is not a special group, but the patients with PCOS are not candidates for egg donation program. I can remember only a few ones because PCOS is recommended to be solved in a different way. Back to your question again, there is no negative effect of PCOS on egg donation treatment outcome.
I have no explanation, I don’t know. It is similar to the weight of newborns after frozen oocytes transfer, they are bigger than from fresh, and nobody knows why. It could be epigenetic, etc., it means that the body of the mother is able to partly affect the genetic profile of a baby despite it is different. The body of the mother, the recipient is not able to change the genetic profile. The body of the mother can trigger or to stop some genes to show which gene could be used and which couldn’t. When it comes to preeclampsia, the answer is Aspirin. If you tested positive for preeclampsia in the first trimester, low doses of Aspirin until the third trimester can prevent it.
In the Czech Republic, there are companies which have accreditation of the Ministry of Health, but now in the COVID times they are allowed to travel through Europe, but the courier must go back to quarantine after a return. We can provide contact with this courier but the waiting time for the transportation of embryos from Spain to the Czech Republic will be longer than usual because they have to schedule their trips. It is more complicated to arrange.