Pregnancy after 40

Explained by: Vladimiro Silva, PharmD, Ferticentro
Category:
Pregnancy after 40 #OnlinePatientMeeting
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From this video you will find out:
  • What’s the best option after 40:  own eggs or egg donation?
  • Can PGT-A really make a difference?
  • Are there a lot of women getting pregnant after the age of 40?
  • What are the solutions for single women and female same-sex couples?
 

Pregnancy in women over 40 years of age

Watch the recording of the Online Patient Meeting with Vladimiro Silva, PharmD, embryologist, CEO, founder and IVF Lab Director at Ferticentro, Portugal. He answered patients’ questions about IVF pregnancy after 40.

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Questions and Answers from the event

Are there a lot of women getting pregnant after the age of 40?

The answer is, yes. It is very interesting because, before this webinar, I did some research on those numbers, in the 60s, we already had a lot of patients getting pregnant after the age of 40. Now, the number of people getting pregnant after the age of 40 is more or less the same, it seems like a contradiction, but it is not. The difference is that in the 60s, people were getting pregnant at the age of 40. They were having their 3rd,5th or 6th child, nowadays, the difference is that patients are getting their 1st child after the age of 40. This is a consequence of our lifestyle these days. For the professional reason, personal reasons, everybody is delaying pregnancy, and sometimes it is not rare, that we see a 48-year-old patient getting to the clinic and saying I finally met someone with whom I’m prepared to have a child. So it’s a reality of our lifestyle, of our times.

What’s the best option after 40: own eggs or egg donation?

First of all, we have to assess every case individually, and if you ask me what’s a less risky option, it is clear that egg donation is less risky because the genetic risk depends on the age of the egg. If we are having treatment with your own eggs at the age of 42, the risks at 42 are significantly higher. We have two types of risks, we’re talking about the genetic risk, meaning the risk of having an egg with a chromosomal abnormality, and then we have the obstetric risks which are always there, regardless of whether we’re trying with own eggs or egg donation. So between our own eggs and egg donation, egg donation is certainly less risky, however, trying with own eggs can also be safe, especially if we use f.e. pre-implantation genetic testing. This way, we can assess whether an embryo has a normal chromosomal constitution or not. Nowadays we are using next-generation sequencing which is a technique used on the blastocyst stage which is a technique that gives us a great level of accuracy, and so at the end of the day, we can respond to the patients with a very small margin of errors whether their embryos are viable or not. If they are viable chances of having a chromosomal abnormality are still possible because in medicine we don’t talk about zero chances, but they are very low. Transferring a normal, what we call a euploid embryo to obtain from a woman after the age of 40 has more or less the same pregnancy rate as transferring donated eggs. So if the ovaries of the patients are still working, if the patient wants to try and do the pre-implantation genetic testing, it’s certainly a way of making sure that the treatment is safe and that the risk of having a baby with a chromosomal abnormality will be lower.

Can PGT-A make a difference?

It’s a hard question. Actually, this afternoon I was talking to a patient from France, and she asked me the same question, my answer was, no. Because the embryo would still be the same, so PGT-A a is about getting information, so if the embryo is a good embryo, it will always be a good embryo. If the embryo is a bad embryo, meaning if it carries some genetic abnormalities and chromosomal abnormality, we can do PGT-A, but the embryo will be the same, we cannot transform a bad embryo into a good one. So, PGT-A will give us information, and in that sense, it does make a difference because it is very important in terms of making a decision, it is very important to make sure whether we’re transferring viable embryos. However, PGT-A doesn’t change the genetic status of the embryo, and that’s very important because sometimes patients come to us and say, let’s do a PGT-A, so we can be sure we will have a viable embryo to transfer into the womb. It’s not like that, sometimes all of the embryos are genetically abnormal or have chromosomal abnormalities, so PGT-A is very useful to inform us about embryo quality, and it is also very important to help patients deciding whether they should try, or go to egg donations or whether it’s worth to keep trying with their own eggs. Also, PGT-A plays a very important role in another kind of situations, for example, this was another case from yesterday, I was talking to some other patients, they were telling me that they have tried five times in different countries, always with their own eggs, and they have transferred the total of 10 embryos, lots of blastocysts, Ii think it was seven blastocysts, and all were with negative results. In that case, PGT-A certainly would be very important because we don’t know whether there is a problem with the window of implantation in that woman, or if it is just a question of the embryos which are not genetically normal. So, if the embryos have a normal chromosomal constitution, in that case, we should focus our investigations in the genetics of the endometrium, the window of implantation, immunology factors, microbiota etc. There are lots of things to be evaluated than the genetic quality of the embryos. So in that sense, PGT-A can also help us to direct the investigation towards the identification of the reason for previous failures. So this is about decision-making, not about changing the status of the embryo, unfortunately, we cannot make the eggs and sperm in the lab, we just have to work with what we have.

While using egg donation, is it preferable having an open egg donor or anonymous one? 

Well, I’m relatively suspect to talk about this because I come from Portugal, and in Portugal, we have open donations. I will share you a story because it is how things happened in our country and I’ve changed my mind about this. Initially in Portugal until April 2019, it’s actually two years ago today, the egg donations were strictly anonymous in Portugal, and then from a date to the other, out of the blue, no one was expecting that the Constitutional Court will decide that donors should no longer be anonymous, even treatments that were scheduled for the next day had to be interrupted because donors would have to agree to be non-anonymous. So, it was a very sudden and unexpected move, we were completely against it, we and when I say that, I mean the whole scientific community, there were debates on national newspapers, TV show, social networks, I mean public events about that and most of the IVF doctors and embryologists were against that change in the law. Then, there was nothing we could do because it was the highest court in the country and so it was a final decision, there was no possibility of appeal. So, we had to work with this new reality, and so we started talking with our donors, and it was amazing to see that 97% of all of our egg donors accepted to be non-anonymous., 70% of our sperm donors also accepted that. On the other hand, and it was a very surprising effect on the number of donors, we’ve never had this many donors. It is a paradox, we were not expecting that. We have an egg bank in our two clinics, in Porto and Coimbra, and we have about 3,000 eggs in our egg bank, we have thousands of sperm stored as well, all from non-anonymous donors, all obtained in the last few years. Then we started talking to patients, and we came to realize that, it’s about giving options to the families, so if some family wants the donor to be anonymous, they can use an anonymous donor, but it’s like we’re closing the door forever. This door will never be open again. When we are using an opened donor, the door is still closed, but at the age of 18, the child born from the donation will have the right to request information and the ID of the donor from the National IVF authorities. This gives a lot of options to the families, to the children born, this is a guarantee from the Portuguese state. This means, that even we if a clinic closes, that information will always be available, and it will be available for 75 years. It will also be very important if, for some health reason, it is necessary to contact the donor. If the child at the age of 18 doesn’t want to know the donor, he or she could change their mind later on, at the age of 40, she or he can get access to that information, so I think it is more about having options. I’m definitely in favour of open donors because it’s up to the families and especially to the children born from the donations to decide what they want for their future. What they want to do with their lives, it’s their decision, it’s not up to us, up to the doctor, up to the intendant parents to put conditions on that. It’s the families, who have the power to decide. If someone says, I don’t even want to tell my kid that he was born from the sperm donation, that’s acceptable, it’s a private decision, and then the donor will be anonymous forever, but one can have that opinion initially, but we can change our minds in a year, or two years, or twenty years. It’s about making the difference between having and a reversible decision or something that we can change our mind about and especially leave the options open for the children that are yet to be born, and that particular information can have an impact on their life. In that case, it gets more serious because it is about having information that can be very important if, for some unfortunate reason, it is necessary to contact the donor.

I’ve always wanted a large family. Is there still time?

It depends on your age. Normally, I would say, yes. I mean here in Portugal, we can treat patients up to the age of 50, which means 49 years and364 days, so on the day of their 50th birthday, it’s no longer possible. Even when a patient reaches the age of 50, we have the right to transfer the embryos created in the 12 months before that barrier, so if that’s the case, we can still transfer frozen embryos after that age. We get that question a lot because some patients who are f.e. 42, they want a large family, and the egg donation is certainly the best option. Typically, in an egg donation cycle we get a lot of embryos like 5 or 6, I mean our average number of embryos is in an egg donation cycle is around 4 or 5 embryos, so that will give a large chance of having a big family, also there’s the possibility of banking the eggs from the same donor. So if the donor agrees to donate again, if we have more eggs from her, we can save those eggs for further attempts, and in that case, we have patients here at Ferticentro that had 4 children, all of them after the age of 45 through egg donation. It was a 1 twin pregnancy and 2 single pregnancies. If we are trying with the patient’s own eggs, after the age of 40, it’s very unlikely, that we will get a lot of eggs or a lot of good quality embryos that will allow the patients to have a large family, but I mean we can try as much as we can. In some cases, patients have their 1st child with their own eggs and then they are trying with egg donation, and so in most of the cases, there’s still time.

What are the solutions for single women and female same-sex couples?

I’m very happy to talk about this subject as well because here in Portugal, we have patient-friendly legislation. Single women and lesbian couples are allowed to do IVF treatments, and so in the case of single women, we can even use donor sperm or double-donation if they require that, until the age of 49. With lesbian couples, things are more interesting because the Portuguese legislation has some unique features. First of all, lesbian couples don’t have to be married to access IVF treatments. Our legislation gives both partners exactly the same rights over the embryos. Let’s say a lesbian coupe is doing IVF with donor sperm, and then they have five embryos, they transfer the embryo to one of them, she gets pregnant the other embryos belong to both partners. If they divorce, the destination of those embryos has to be defined by both elements of the coupe, regardless of who gets pregnant or who donates the eggs, so regardless, of who’s DNA it is, they both have the exact same rights over the embryos. So this is truly a shared project for lesbian couples, and we can have the reciprocal IVF, or shared motherhood or ROPA method technique that allows one of the ladies to be pregnant with her partner’s eggs. So when we have the embryos from this coupe, they can either be transferred to one or another person in the coupe, and our legislation previews that, and we have specific consent forms for that, and if the child is registered in Portugal, they both have the exact same parental rights over the child, and they have the exact same rights over the embryos. In some countries, the embryo belongs to the woman who gave the eggs, while here it always belongs to both elements of the couple. On top of this, especially a lot of single women and a lot of lesbian couples, they ask us for identifiable donors, it’s not like they are looking to find a father to their kid, it’s just because it is pretty obvious for the child that he or she were born from donations, and so they want to give them the possibility of having access to the ID of the donors. That’s very important for most of them, it’s actually very rare that one of these single women or lesbian couples requests us to use anonymous donors. So I think there are plenty of solutions and nowadays, with our modern legislation, I would say, everyone, is very protected, in terms of their legal rights over the embryos, and also on parental rights.

Are there a lot of women getting pregnant after 50?

Unfortunately, not. The legislation in Portugal has changed regarding female age, at the beginning of 2018. Back then, we were accepting patients until the age of 52, from a biological point of view, the odds of having a pregnancy stays the same, regardless the ag, as long as the uterus is okay. It would be biologically possible, the obstetric risks will increase, that’s for sure, however, if a patient is taking good care of herself, following the directions of the gynaecologist very strictly, I think that will be possible and safe. Right now, due to our legislation, the only cases where women can be getting pregnant after the age of 50, will be in those cases where the embryos are created before and they are within the 12 months that we have to transfer those embryos. So it is possible in some countries, but not in Portugal.

To prevent poor quality of eggs, do you suggest freezing earlier than the age of 30 years old?

It will depend, but the general response will b, yes. Nowadays, it is very important to stress that since the beginning of 2013, the American Society for Reproductive Medicine issued that practice committee report stated that egg freezing should no longer be considered as an experimental procedure but could be routinely offered to patients since it was safe, and the pregnancy rates and live births that we were getting from eggs from younger women were very similar to those obtained with fresh eggs. As long as we’ve mastered the vitrification techniques, so now worldwide several vitrification techniques that we have worked very well, we’re getting survival rates above 90% for frozen eggs, so it’s definitely a solution. I am a strong advocate for social freezing because I think that it is certainly a way to preserve fertility in women. We have to bear in mind that in the best-case scenario, those eggs will not be used. Everyone should try to get pregnant as early as possible with her own eggs and naturally. Those frozen eggs are there just as a backup should infertility come later in her life. I mean those eggs are for women to use as if they were their own egg donors. If they collect their eggs at the age of 25, and then at 45 they are trying to have a baby, those eggs will have the same properties that they had 20 years before, so it’s like she’ll be her own egg donor. There are lots of things that can happen in life these days, and they cannot move on with the pregnancy. I do think that egg freezing is a very good solution, especially, nowadays with such good odds of survival. When we’re talking about the 90% survival chance, we’re also talking about 10% non-survival chance, so a lot of these eggs would not be viable, and this is why we should use them as the last resource.

For egg donation in your country, do you have eggs from tall, blond women? I am 6 foot blonde with green eyes, and my husband is asking this question because he wants our child to have some of these features from me.

I don’t know if you have ever been to Portugal, but we have to acknowledge that the typical Portuguese person is not that tall and we’re not the country with tall, blonde women. However, we do have donors from all phenotypes f. e., in our clinic we have donors who are 6 feet tall, so that’s not a problem, if we’re talking about someone who is 5.3 or 5.5 feet tall, we will certainly have a lot more available donors, but we do have tall, blonde women. The most important information when patients ask us for a donor, we always give them the donor characteristics beforehand, so the patient has to accept that donor., It’s not like I’m giving you a donor number 12 or 2 and then you will see how the child looks like. The patients have to agree with the donor that we are offering them, and they have to be happy and completely committed to the process. We can’t disclose the donor’s ID, but we can share information on the donor’s phenotype, the height, hair colour, eye colour, blood group, age, nationality etc. We have a huge database of donors, we have more than 2000 donors registered in both of our clinics, and we’re getting new donors every month. In our population, our average height is a lot lower than in the Nordic countries and the Netherlands and so on, but we do have some occasional donors that are very tall. Here in Coimbra where Ferticentro is based and in Porto, we also have a huge University community where we get donors from all nationalities, from Germany, Spain, Italy, Ukraine, Russia, France, the UK, Brazil, a lot of them from Angola and so on. Usually, we try to find a suitable donor, but I am not going to lie, we don’t have as many 6 feet tall donors, as we have more normal Portuguese donors.

I’m 39 and had 3 failed embryo implementations. I now have 3 frozen embryos (own eggs) for transfer after COVID19 allows with controlled cycle. I wanted to know if we can do chromosome testing on frozen embryos (5day development)? And what can I do to improve the chances of implementation?

The short answer is, yes. Even if they are frozen at the blastocyst stage, we can warm those embryos, we can do the chromosomal testing, and then we have to refreeze the embryos and transfer them. We have done that several times, although it is not ideal, we prefer to do the embryo biopsy which is the step required for the chromosomal testing before freezing the embryos for the first time, but this is not something unusual, we have done that a lot with success. That’s definitely something that we can do. And what can be done to improve the chances of implantation, in this case, there are many options. The first step would be to check whether the embryos are genetically viable or not. If the embryos have a normal chromosomal constitution, that’s the first step, those would be great news, and then we would focus on the endometrium because if you already had 3 failed embryo transfers, we need to know where the problem is. If some of these 3 embryos are diable, this probably means that some of the previously transferred embryos were also diable, and so, in this case, we should focus our investigation on the endometrium. Normally, we say that while studying the implantation, we always check for several factors: gynaecological factors like fibroids, the uterine abnormalities and muscle malformations etc. We can do that with an ultrasound scan, and also with a hysteroscopy. Then we can check the window of implantation which is a very important factor, and I’m sure some other speakers have addressed this in some of the other Communications. The window of implantation has become more and more important these days, we know that after 5 days of progesterone, the endometrium is ready to receive a Day-5 embryo. However, in some patients after 5 days of progesterone, the endometrium is still not ready, or the other way around, the endometrium is no longer ready. By doing an endometrial biopsy after five days of progesterone, we can test the endometrial receptivity, there are several tests in the market, like the ERA test, the ERMAP, he Win-test in France and so on. We can then see when it is the best moment for the endometrium to receive and implant an embryo. Also, there are factors associated with the immune environment, people are talking about NK cells, KIR genes, and also thrombophilia which are methodological factors, and microbiota because all women have bacteria inside their wombs, we just have to make sure that those bacteria are the correct ones, we have to make sure that they have at least 80% of lactobacillus and no pathogenic bacterial development in there. There are ways to test for all of those things, all of those issues are associated with implantation failures and luckily, most of them, I would say almost all of them, are curable and so there are solutions that can be explored. I would say that if one of your embryos or all of them are genetically diable, you shouldn’t transfer it before checking for all these other factors given your past history of failed embryo transfers.

I’ve had 3 IVF cycles using donor embryos/sperm. I’ve had two miscarriages around 5,6 weeks. What kind of tests should I be asking for? I am 50

Those miscarriages with donor embryos and donor sperm, so we’re already talking about double-donation. The odds that the causes were genetic are little because, with a double-donation, most embryos are diable, and I would say it seems unlikely that the cause of this miscarriages is of genetic origin. I would focus on testing the endometrium, to test the window of implantation, the infectious causes, immune factors, all those I’ve mentioned before.

What can you suggest to help improve egg quality? My embryos do not make it to blastocyst, and I am a poor responder. I’ll be 40 in May, I am a single lady. 

That is what we say, a million-dollar question. Unfortunately, there’s very little that we can do about this. In some cases there is room for improvement, there is room for optimization in the ovarian stimulation so we would have to see how is the ovarian stimulation. There are different ways of stimulating woman’s ovaries, in some cases with poor responders, mild stimulation IVF sometimes gives good results. That’s something we can try, we can also try different protocols, there is an ongoing discussion for years whether doing, sort of a priming treatment with DHEA could improve the quality, a lot of initial studies pointed in that direction, however, randomized control trials have failed to prove that those kind of treatments were really effective. In practical terms, I would say that the best strategy to pregnant with your own eggs would be to bank as many eggs as possible. Sometimes, we can do repeated stimulations, we always tell our patients that we should aim to get 10 eggs. It may be difficult, sometimes we get 1 or 2 eggs at once, but we can try to work with what we have, we culture the embryos, we do the PGT-A, that would be one of the options. There are lots of vitamins, patients have to be as healthy as they can, and they have to have a normal BMI, those are the issues that we can control, but sometimes all of that is already assured, and still, their ovaries don’t work. We can use those vitamin supplements that are in the market, unfortunately, their effect will not be radical. We can try to bank some eggs, we can try those strategies with DHEA, but at the end of the day, our hope is, that maybe there is room for improvement on the ovarian stimulation level, but sometimes, the other solution would be to move on to egg donation. We would have to assess your case individually to properly reply to you.

Do clinics vary in technology to help achieve pregnancy?

Yes, of course. There are many new technologies, the IVF world is always evolving. Nowadays, we have the EmbryoScope which was a very unusual thing 5 or 6 years ago, and now we can see the embryos dividing and developing without touching them, without manipulating them, always providing them with the best and stable environment. That’s one of the most recent technologies. We also have things in the lab like Culture Media, microscopes, air filtration systems etc. I mean the IVF lab is being increasingly optimized from a technological point of view. Some clinics have all the latest technologies, more recent which I believe will be our case, but some don’t have the same conditions for financial reasons because they are sometimes in countries or institutions that don’t have access to those kinds of technologies. I mean, there is obviously a limit which technology is important. If you ask every doctor or embryologists, he will certainly tell you what is best, and he would prefer to use. At the end of the day, we have to remember that the first IVF child was born in 1978, she will be 42 years old this year and conditions were terrible back then. So if the eggs and the sperm are good, life finds its way. Sometimes, technology is not that important, the psychological factors are also very important, the type of care, the stimulation strategy, this is all a part of a process that includes the medical staff, nurses, psychologists, the technology is only the tip of this process, we always want to provide our patients with the best possible condition, however, sometimes that’s not enough, and if technology alone was the solution, then it would be very easy.

Are donor embryos available at Ferticentro and is there a waiting list?

There are donors available, and no, there is not a waiting list. Here, in Portugal, the embryos can be frozen for 3 years and afterwards, they can be donated to other patients. Most of them, are anonymous because as I said at the beginning, it was in 2018 that our legislation changed, and so the most recent frozen embryos that we have, which are already available for donation, have been frozen on the 24th of April 2017. Back then, the law still required the anonymity of the donors, so there are embryos available for a donation, but they are from anonymous donors, and there is no waiting list at the moment. If you asked me that very same question a year ago, I would say that there was a waiting list, this changes a lot, there are there is a lot of demand on those donated embryos. We can we try to assign them to our patients as fast as possible, but as of today, we have available embryos from all phenotypes that have been donated by other patients.

Can you give us tips on how to choose a clinic for the first time? I am 42.

I always tell patients, nowadays most of the clinics are doing an excellent job. We have great clinics everywhere, there are lots of clinics working with the most recent technologies and brilliant doctor, so I would say that you should choose a clinic that has access to the most recent technologies. It’s important to have personalized treatment because patients are not numbers and we need to know their names, we need to know what happened in their lives, and we have to have a direct connection with them, that is a very important factor. The availability of technology is a good indicator of the kind of commitment that the clinic has to provide. A good service, so experienced doctor, people that are in the field for several years, clinics with good infrastructure, we don’t want to do the treatment in a factory of babies because that’s not something personalized, but it’s important to have a certain number of cycles done because some of the techniques that we use, like f. e. embryo vitrification and Warming, those require a lot of practice. At Ferticentro, we warm and freeze thousands of thousands of eggs and embryos every year, there is no single day that we don’t do that including weekends, so it’s very important to have a good number of cases, so we can have the experience and the skills to provide a good service. On top of that, I think it’s very important to have trust in the clinic, good communication with the clinic, experienced and skilled staff.

Could you provide an idea of how much egg donation costs at Ferticentro? How long does the process take in terms of choosing a donor through to embryo transfer?

The costs will depend on the program. Our standard program costs around 6,000 EUR and some add-ons can be added to the cost like using the EmbryoScope, with all the possible add-ons it will not go above 6500 EUR. There are other possibilities, you can have a guarantee f.e. you can have a guarantee of 5 blastocysts, in that case, it will cost you more, I don’t know the costs by heart but that it’s certainly around 10000 EUR. We always do our best, we try to stimulate the egg donor in the best way possible, we try to get as many eggs as we can without putting the donor at risk, and we try to fertilize all our eggs with the male partners or the sperm donor sperm to get as many good quality embryos. However, since we are working in biology, sometimes that’s not enough, and we don’t get those 5 blastocysts that we agreed on. In that case, the patient is entitled to a new cycle with a new donor, without additional costs. These are financial guarantees because, from a biological point of view, we don’t have better or worse donors, all of our donors have been thoroughly evaluated and approved, and they are always considered to be at the same level with the same likelihood of pregnancy. So in our standard program, there is included, if there is no male factor or no significant male factor, we assure a minimum of 2 blastocysts and 6 eggs. Regarding how long the process takes, normally, we ask the patient’s information on their medical history, we evaluate them, we will probably have an online consultation with them, those are free of charge, just to discuss what we need, we can request additional testing if something is missing, we might need to communicate with the patient’s own doctor and then we are choosing the donor. It usually takes a day till we suggest a donor, and if the patient accepts. Then, it depends on clinical aspects of the patient, so usually, from the first day of the period until the day of the embryo transfer, it takes between 20 and 21 days, it’s the typical length of time for biological reasons to prepare an endometrium. We always prefer to have the embryos created before, so we ask the male partner to come over, leave the sperm sample, we can create the embryos beforehand, we can also do it in a synchronized cycle, the difference between what we call a deferred cycle or a freeze-all cycle and the synchronized cycle will be the uncertainty because if there’s some problem with the donor if she makes a mistake and she won’t produce enough quality eggs and, so on, we can always move to another donor with the patient’s approval. If we’re doing a synchronized cycle, we have to wait for the egg pickup to see how many eggs we’re going to get. Every day we will have new information, so it’s impossible to predict what would be the quality of the embryos 5 or 6 days later. Usually, starting a process from zero and to receiving the embryo transfer, it can take between a month to a month and a half, assuming that there are no other issues.

Can a donor seek information about the child born using their genetic material?

No, it’s forbidden. So the donors have absolutely no rights over the child. They cannot seek or request that kind of information. The donor signs the document where she states, that if she has some genetic disease that is found after the donation occurred, she will inform the clinic. So in those cases, the families will immediately be notified about something that’s been fund. Luckily, we’ve never had that, but that can happen and, this is why the IVF authorities are there, to make sure that everything goes well. So to clarify, the donor cannot seek for the information about the children, they don’t even know whether there are any children born from their donations.

Which is more viable and has more chances of a successful pregnancy, fresh or frozen transfer? 

Normally, nowadays, the embryo survival rates with the vitrification methods are always above 95%, very often we have results even above 98% of survival. If the embryo survives the vitrification process, the chances of implantation are the same as before the vitrification. According to our experience, it is the same and actually nowadays the tendency worldwide is to do more and more frozen transfers, instead of fresh transfers because while we are doing a frozen transfer, we have time to prepare the endometrium, to optimize uterine conditions, to receive the embryos and so on. Sometimes, we’re doing a frozen transfer just to optimize the endometrium. We’re doing it as an elective procedure, so we could do it fresh, but we prefer to do it frozen because that will allow us to to do a better endometria preparation. It has also been shown that children born from frozen embryo transfer tend to have better parameters while they are born in terms of time, of pregnancy weight at birth, and so on than children born from fresh embryo transfers. Recently, I was reading the statistics from the United States, nowadays, more than 70% of all egg donation cycles are done with frozen embryo transfers. The reason why everybody is doing this is that not only it takes a lot of uncertainty from the process but also because this allows us to optimize the endometrium. I would definitely prefer to do a frozen embryo transfer rather than a fresh one, but it is a personal opinion. Some other clinics will probably think otherwise. I don’t know, but the worldwide tendency is towards a frozen embryo transfer.

Can I use a member of my family as a donor? 

Unfortunately, not. Because even though the donors are non-anonymous, they are anonymous for the Barents. The only person that has the right to get access to the donor ID is the child born from the donation.

You said you have donors from France, does this include Martinique or Guadalupe the French Islands? 

We don’t have donors from Martinique or rather, at this very moment we do have a lot of patients from Martinique or Guadeloupe. We do have donors that match those characteristics because here, in Portugal we have a population of people coming from Brazil, from Cape Verde’s. I always tell patients that we are probably the first country that started globalization 500 years ago, so this is why we have so many phenotypes in our egg bank and sperm bank. In Portugal, we have direct relationships with lots of countries, in South America, Brazil, in African countries such as Cape Verde, Angola, Mozambique and so on, and, from those countries, even India we have people with some characteristics that are more typical in Martinique or Guadeloupe. We do have a lot of patients from those Island.

Do you have also donated embryos of other phenotypes? Not only Caucasian?

Yes, we do. We even have Asian phenotype donors available, not that many, but we have, also, Black donor, mixed-race donors, there’s no problem.

My AFC is 8, AMH is over 8. Can we freeze on day 3 to be able to bank?

I am assuming that AMH over 8 is pmol/L otherwise it would be fantastic if it was ng/L, but AFC at 8, I can say we’re had pregnancies with a lot worse than that. Here in Portugal, we cannot bank embryos, we can freeze eggs and accumulate eggs, and then fertilize all the frozen and fresh eggs at the same time, but we cannot accumulate embryos before transferring them into the womb. What we would advise, is to freeze the eggs, and then move on with fertilization later. This would also be a lot cheaper because every time we create an embryo, it is a new procedure while freezing eggs and then doing one ICSI procedure will be significantly less expensive.

My periods are changing in the length and schedule. They are getting shorter, lighter and further apart. I am 45. Can I still go for the egg donation? I had a natural birth at 36.

I mean we would have to evaluate your ovarian reserve to see whether you are still producing eggs, whether the ovaries are still working or not. Those signs are not good, as your periods are changing in length and getting shorter, those are probably signs of ovarian insufficiency coming up. I would say, that you need to move on as quickly as possible, I would definitely recommend that you do an ovarian reserve assessment which includes the AMH hormone, FSH and AFC, so we can have an idea whether it is still possible to stimulate or not. I would say that if FSH is below, then it would be great if AMH is above 0.5 nanograms per millilitre, it will also be good and, in that case, we can still do an ovarian stimulation, but we definitely shouldn’t waste time. You should put things in motion as soon as possible unless you decide to go via the embryo donation path or the egg donation path, in that case, there’s no problem, you still have time.

Can you implant two embryos at once in your clinic? Transferring to blastocyst can increase the chances of pregnancy? Is it risky after 40?

The answer is yes. We can implant two embryos at once, it’s the maximum that our legislation Allows, however, it is a decision based also, on clinical criteria, so if a woman has a small uterus or some other risk factor, we would definitely recommend just one embryo, but we don’t close the door to double transfers. We would have to assess the embryo quality, the personal history of the patient. We do a lot of double-embryo transfers, but we always try to avoid twin pregnancies. Transferring 2 blastocysts can obviously increase the chance of twin pregnancy. We have to consider every blastocyst as an individual possibility of implantation, so every single blastocyst has more or less a 60% chance of being euploid according to recent studies, and so since the odds of implantation are individual after transferring one blastocyst at the time, two times or after transferring 2 blastocysts at the same time, the number of implanted blastocyst would theoretically be the same, however, two things should be considered while making this decision. First of all, the risk of twin pregnancy with 2 blastocysts, there is a significant risk of twin pregnancy. Second of all, if there is a problem, let’s say in the window of implantation, by transferring 2 blastocysts at the same time, we would risk wasting both blastocysts. If we transfer one and we have a negative result, there’s still time to correct whatever could be wrong, and then do the second embryo transfer. So it’s a hard call, but it can be considered, we have to take these decisions on an individual basis. So there is no definite answer to this question, we have to assess.

What can be done to increase the thickness of the endometrium? 

This is another million-dollar question because the endometrial thickness issues are the worst kind of problems that we have in our clinic. So we want for the endometrium to be at least eight millimetres trick. If it is seven, we are already relatively happy because with seven millimetres. The results are already acceptable. If it is less than seven, the chances tend to drop significantly. What we can do to increase the thickness of the endometrium, there are several protocols. We can try protocols with increasing dosages of estrogens. We will also have to balance that with the risk of side effects, there are a lot of other drugs that can be used as vitamin E, pentoxifylline, sildenafil, so there are different things that can be added to the protocol, that in some particular patients have given better results. We had a patient recently, where we never had good quality endometrium, we kept cancelling cycles, and then we decided to try with a natural cycle. Without this knowing why – the endometrium grew perfectly, and, we transferred her the embryo, and, she immediately got pregnant, the pregnancy is already at around 20 weeks or so. Unfortunately, there are still cases where the endometrium l never grows above 4 or 5 millimetres, some experiments are being done, and some trials with stem cells, especially in Japan, that makes the endometrium grow, but we didn’t have good results for that until now.

Can a patient choose a donated embryo or it’s always the clinic Staff that chooses according to the phenotype.?

Well, it’s a dialogue. We talk to the patients, we tell them a little bit of the story of that embryo, we will not tell them who their parents are. We will tell them something like this is a couple where the lady was 34, the man was 35. They had a baby, they don’t want to have more babies, and so they have donated this embryo, they were Caucasians, 1.85 tall, we will share the characteristics of the parents, and we will suggest that embryo based on the patient’s characteristics. We cannot provide patients with a list of available embryos so they can choose one, it’s not like that. But we try to match the recipient’s characteristics with the characteristics of the embryo. The embryo comes from two different persons, so we do have to balance that. It’s always a joint decision.

Are couples happy to donate their embryos to a single lady?

The patients don’t know to whom they are donating. They just say that they make the embryos available for donation, and then we donate them.

What’s the live birth success rate at Ferticentro? 

To clarify success rates depend on a lot of issues. If we’re talking about treatment with own eggs or egg donation. According to all statistics from our countries Europe, United States, Australia I mean everywhere Spain, Portugal, the Czech Republic and in all the countries where egg donation is more usual, we always get from 60 to 70% of success rate. Live birth rates differ from implantation rates because we have to count the miscarriage rates and the miscarriage rates are around 7 or 8%, and it also depends on the age of the patient. This is the limit of the biology we can isolate groups of patients where we have 80% of pregnancy rate and, also groups of patients where we have 5% or 10% of live birth rates. I would rather talk with patients individually. Recently within one Patients Association, there was a survey just to confirm the success rates between their members in our clinic, and out of 300 cycles, or so, we have 71%, but it was luck because we know that 71% is above the average. What we can expect is something between 60 and 70%, it changes according to patients conditions, treatment whether there’s a male factor or not, and so this is of little value. If we’re transferring 2 blastocysts to our patients, we will get a better pregnancy rate. I would say that when we are thinking about success rates, we have to start thinking about biology, and biology gives us 60 to 70%. I was actually reviewing statistics it will depend after the age of 42, certainly, it’s below 5% or something around that. Now, we’re also getting very unusual cases because with single women and lesbian couples. We have a lot of patients who are not infertile, meaning that they have never tried to have the baby, and they are trying for the first time at a later age. They have a generally better prognosis that increases the pregnancy rates, so we do need to know the ovarian reserve, I prefer to reply to that question based on ovarian reserve, age, uterine conditions and previous history. Success rates can come from many factors, and there are many confounding factors. If we have 10 embryos on day -1, and only 2 of them are diable, but we don’t know if we will have 20% of pregnancy rate if we culture those embryos until the day- 3 maybe we can identify that 4 or 5 of them are not good. Maybe on day-3, we have only, let’s say 6 embryos, and 2 of them are still diable, so chances have risen from 20 to 33%. If we further culture those embryos until the day- 5, maybe we will have 4 blastocysts, and so it’s 2 out of 4, and we have 50%, but they are always still the very same embryos. We are playing with statistics, it’s very easy to trick statistics. We also know, that we if we play with cumulated pregnancy rates, after 3 blastocysts transfers, each one giving 60% if this were just mathematics, we would get 90% of cumulated pregnancy rates. We have to be careful while looking at statistics, and we do need to think that we’re working with biology, and biology gives us 60 to 70%.

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Authors
Vladimiro Silva, PharmD

Vladimiro Silva, PharmD

Vladimiro Silva, PharmD, embryologist, CEO, founder and IVF Lab Director at Ferticentro and Procriar, two of the leading IVF centres in Portugal. Doctor of Pharmacy, Faculty of Pharmacy, University of Coimbra. MSc in Health Economics, Faculty of Economy, University of Coimbra. Post-graduated in Health Services Management, Faculty of Economy, University of Porto. Post-graduated in Clinical Analysis, Faculty of Pharmacy, University of Porto. Author of hundreds of lectures, oral communications, posters and scientific articles in Portugal and abroad. Vladimiro Silva speaks: English, French, Spanish, Italian and Portuguese.
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Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is an International Patient Coordinator who has been supporting IVF patients for over 2 years. Always eager to help and provide comprehensive information based on her thorough knowledge and experience whether you are just starting or are in the middle of your IVF journey. She’s a customer care specialist with +10 years of experience, worked also in the tourism industry and dealt with international customers on a daily basis, including working abroad. When she’s not taking care of her customers and patients, you’ll find her travelling, biking, learning new things or spending time outdoors.

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