Guaranteed blastocyst programs for complicated cases

We are using a blastocyst program or pregnancy guarantee program. Obviously, we need the sperm – this is the main thing. We don’t work these programs when we have to use sperm from testicle biopsy, so we need ejaculated sperm with minimum characteristics of normality so usually is more than half a million spermatozoa and more than 1% of normal forms and more than 10% of progressive motility of the sperm. So this is a minimum quality to be sure that we are going to have this blastocyst in a normal way.

The guarantee the number of good quality blastocysts in an egg donation program is because we work with semen donor. If there is low sperm count or abnormal morphology, we are going to work with this semen and we are going to try to have the number of blastocysts that there are in the program. Depending on the number of the blastocysts and the history of the donor,  because for this kind of problem we are always using proven donors that we have more information about the blastocyst rate of these donors, depending on these numbers, we do microinjection on a certain number of eggs just to be sure that we are going to have this blastocyst. Sometimes we have this blastocyst, sometimes we have more, sometimes we have less. The problem is when we have less, for example, in a two blastocyst program and we only have one blastocyst. So there is not a problem because we have one blastocyst, we do the transfer with this one. We have in the same program, for the same price is our commitment to getting you pregnant with the same donor, to have more embryos from the same donor. If you don’t have a pregnancy with this donor, we usually change the donor. We do another microinjection, another ICSI to have more embryos from another donor until we have the number of blastocysts you selected. For example, we have two blastocysts selected, we have only one,  we have two from another donor or we have four blastocysts, we have to continue working until we have at least the minimum number of blastocysts you selected.

When we are talking about the male factor, it is not only number, motility or morphology. These characteristics of the sperm are very important when we are trying to decide if we are going to work with IUI, sexual intercourse or we are going to use an IVF cycle or microinjection if we have low numbers. But when we are doing the ICSI cycle or IVF cycle or we are working in an egg donor program, for me the most important thing is not the number, is not the motility, is not the morphology, is the quality of the sperm. We have to know the quality of the sperm to know the quality of the genetic information that is inside of the sperm. You have to think that the sperm is only there to send the genetic information from the testicle to the egg and there’s a reason for sperm being so small, a reason for the tail to have the possibility of movement and to achieve this the sperm has to change a lot of things inside of this cell to reduce the volume and to change, for example, the proteins that are protecting the sperm, the histones. In the sperm, they change the proteins that are very small and they allow to concentrate this DNA, to pack this DNA of this sperm into a very small area. This sperm has a high risk of having problems with this DNA information. The DNA information is critical because everything is inside of DNA. If we have DNA  fragmentation, something is broken in the DNA chain, most of the time the egg can correct it with all the mechanisms that it has inside. The egg is very important, it’s very big and it has a mechanism to correct this DNA fragmentation. But sometimes it corrects well, sometimes not, especially when the DNA  fragmentation is so high. If we can take a look at the DNA fragmentation, we know if the quality of the sperm is good enough to have a baby is crucial to decide how we are going to do this microinjection on the egg. This is correlated with the miscarriage rate, it’s correlated also with the pregnancy rate so it is very important.

We have an algorithm to decide how many eggs we are going to fertilize depending on the sperm quality, depending on the number of eggs, the number of embryos that are selected in the guarantee programs, depending on the age of the recipient because, for example, for a recipient older than 35, we are only allowed to transfer one blastocyst. Also, depending on the results that we have had previously with this donor. The guarantee programs always have proven donors and we have information about the previous cycles about the blastocyst rate of this donor. Depending on this algorithm we decide how many eggs we are going to fertilize to have one blastocyst.

I think I answered this question previously: our commitment is to have this number of blastocysts. If you select one program and we are going to have the things you have selected in the program, we have four blastocysts guaranteed in the program, so we have to have four blastocysts. This is not possible to have three. Depending on whether we have a pregnancy or not, we are going to select the same donor or we are going to change the donor. If we have a pregnancy, obviously, we are going to select the same donor to have more blastocysts from the same donor just to have brothers and sisters from the same genetic field than the pregnancy we have. If we don’t have a pregnancy after the first embryo transfer, we can look for another donor and select another donor to have the remaining embryos that are in the guarantee program.

Yes, of course. This is a biological field so it is impossible to be sure that we are going to have the exact number of embryos that are in the guaranteed program. We can have fewer embryos and I explained before what happens when we have fewer embryos. Sometimes we have more embryos. The most frequent answer is the number of embryos we selected but we can have fewer or we can have more. If we have more embryos, obviously, these embryos are from the women or the couple and they can be used whenever they want. There is obviously no charge for these embryos and the couple can use them whenever they want. No cost at all, obviously.

Yes, PGS is not recommended in a general way and, obviously, is not recommended because of the age of the mother. The PGD is completely different because we are looking for illnesses that we know. We have to avoid this illness but the PGS is invasive – we are taking a couple of cells of this blastocyst just to do the analysis. We have to vitrify this blastocyst and we have to thaw this blastocyst later to do the transfer. This is an aggressive technique and it takes away a little bit of the chance of implanting this embryo. The indication to do this is repeated miscarriage because one of the reasons for repeated miscarriage would be the chromosomal genetic abnormality of the embryos. Other indications can be some problems with the FISH test of the male partner, for example, if we have some translocation or inversions in the karyotype of the father. Also, in my opinion, it could be a good idea if we have a lot of embryos and we don’t want to do too many transfers. Where there is an older mother and we have a lot of embryos, we have, for example, ten embryos and we want to select 2-3 for a transfer for this woman instead of doing ten transfers on these embryos. This is a good test. It has some indications, not too many indications and, for me, the most important thing is to be sure that there is no indication like the age of the mother. But, for example, a miscarriage could be a good idea but not to avoid a miscarriage only in cases when we have repeated miscarriages, several cases.

Yes, two repeated miscarriages according to the classification of the European Society of Reproductive Medicine. The male’s age, 60, is very high. We have to be sure that this sperm is normal not only in morphology or motility. We have to be sure that this sperm is normal in the DNA fragmentation testing. We have to be sure that is normal from a chromosomal point of view with the FISH technique at least with 5 chromosomes just to analyze. If this semen is normal, from this situation we can go with all 8 mature oocytes. I think there is no need to do PGS because we are working with egg donor less than 30 years old. So the risk of having a problem with one of these donor eggs reaching the blastocyst stage is very low. And you can be safe in this situation. Obviously, with this history of 5 blastocyst transfers is not logical not to have a pregnancy. Think that with one blastocyst from a donor IVF cycle the pregnancy rate (ultrasound/heart beat) is around 68-70%. After 5 blastocysts there must be a problem, for sure, in the semen or in the endometrium. But, probably, there is no problem in the DNA of the donor.

Depending on what kind of problem he has. Sometimes there is a translocation, depending on what kind of translocation, what number of chromosomes is involved, depending on inversion, for example, chromosome 9 has very low importance, we have more than one-third of this inversion is more important but depending on what kind of problem. Obviously, it is the same if we have donation or surrogacy that there is no change at all. If we have a chromosomal problem in the male, the problem will be with the embryo that will be transferred to the mother or surrogate.

We usually recommend immunologic testing only when we have previous problems like repeated implantation failure or repeated miscarriage cases. Usually, for normal cases, it is not recommended because it is very unusual to have problems from an immunologic point of view, apart from the normal things like controlling vitamin D or something like this. To do immunologic testing I’m talking about especially endometrial biopsy, looking for natural killer cells or looking for key receptor HLA-C or HLA-G immunologic testing. So this kind of test I only recommend when we have previous problems, especially repeated implantation failure.

The recommendation is four blastocyst guarantee because I told you the chance of becoming pregnant with one blastocyst transfer in an egg donor program is around 68%. So if we have two blastocysts, we feel we are lucky, we are going to have two babies. But if we are not lucky, we can probably have only one. This is the most statistical point of view, the most frequent is to have only one baby. With four blastocysts we are almost sure that we are going to have two babies and probably we have even one remaining embryo in case of having bad luck. Probably the best recommendation is to select the four blastocyst guarantee program.

Not everybody agrees on the definition of repeated implantation failure. This is very simple – you have to have at least four embryo transfer before no pregnancy, at least in three different transfers, at least two of them have to be in the blastocyst stage. This is the definition. Also, the mother has to be less than 40  years old. We don’t talk about repeated implantation failure, for example, in a couple where the woman is 40-41 years old because we can do a lot of transfers for women over 40 and the problem here is not repeated implantation failure, the problem is genetics. We have to have at least two blastocyst transfers because sometimes we see patients who had transfers on day 2 or day 3 and the chance of becoming pregnant with this transfer is much lower. We need at least to have two blastocyst transfers and also we need a certain number of embryos transferred. The number we select for doing these four just to be sure that from a statistical point of view we passed the 93% when we are going to do the transfer and you transfer more than four good quality embryos usually you pass this number of 93%. So this is important and also it’s important that these embryos come from two different cycles because sometimes we have a cycle with a lot of embryos, with a lot of eggs. Such a cycle works very badly. It doesn’t give pregnancy and we repeat the cycle probably with fewer embryos, probably lower quality but we have a pregnancy. So it’s important that these embryos come from two different cycles. Such a situation we can consider a repeated implantation failure because we don’t have any reason for telling these women “okay, you have this bad chance.” Repeated implantation failure is not a question of luck is because we have something, we have to study it very hard to be sure that we found what happens at that time.

If you have two embryos transferred, there are two embryos transferred in terms of implantation failure so when we are looking at the first part – the embryos transferred, we need four embryos transferred with this. Here we have two embryos but if we are looking at the second part that is the number of transfers. We need three transfers. Here we only have one transfer so here we have two embryos transferred but only one transfer. We need at least two more embryos transferred and we need at least two more transfers on the same patient. If these embryos are, for example, day 2 – we need two more blastocyst transfers.

Repeated implantation failure for women over 40 doesn’t exist from a  theoretical point of view because when we are talking about repeated implantation failure we are talking about problems that don’t have any explanation. In women over 40 we have an explanation for this implantation failure and it is the egg quality in terms of the number of chromosomes. We have more aneuploidy in the embryos in women over 40 and this is the reason for implantation failure. So the solution to this is a change. Obviously, we don’t recommend to change to an egg donor program if we have a couple of 40 years old but if we have, for example, a 40-year-old couple, we have done four embryo transfers at the blastocyst stage and we don’t achieve the pregnancy, in this case, the indication is to change to egg donor program. This case we can classify as implantation failure. Obviously, this is not true for all patients and we have to look at the case in question very carefully. For example, it is not the same if you are 40 years old but you have done PGS and we are transferring euploid embryos or it is not the same if you are 40 years old now but you had the transfer when you were 37-38 years old and you didn’t have a pregnancy at that age. Every case has to be looked at very carefully. You have to take into account everything. Mainly, if you are over 40, the indication is to do the transfer but if you don’t have a pregnancy it is recommended to change to an egg donation program.

First of all, change the donor. OK, you have had three transfers with the same donor and only one miscarriage? It’s not a good result. Probably, there is a problem with this donor cycle. It may sometimes be a problem with the donor or a problem with the cycle. But it’s not logical to have only one miscarriage after three transfers in an egg donation program. The first thing is to change the donor and to go for another donor and to do the cycle with another donor.

We have no problem with Caucasian, South American, Arab, Nordic, African, Afro-American, South African, North African donors. The only problem we have is with Asian donors. The only waiting list we have is for Asian donors especially Japanese. This is complicated with Japanese and Chinese donors. We have some Vietnamese and some Southeast Asian donors but there are the only ones we have problems with. As for the rest, there is no problem. As for Asian donors, it is difficult because Asian people don’t like to be donors. This is completely different from the Europeans.

All these kinds of programs are good because they are offering some peace of mind. We don’t talk about this but we have in our clinic a personalized program. In this personalized program, we sit with the couple or the women and we decide what we want to do. For example, the last couple I treated was a 43-year-old woman and the chances at this age are very low. But I told her if you want to try it, we can try it. For me, is very important to have the opportunity to do IVF with own eggs. Obviously, the problem is the cost. We decide we want to do three cycles with own eggs and after these three cycles, we are going to go to an egg donor program because, for me, the most important thing is that this couple has to go out of the clinic with the baby. Probably, if we only do the three IVF cycles it can be difficult but if we do an egg donation program, we have more chances. But if the couple wants to try with own eggs, we can organise the cycle, select the cost that is much more lower than cycle to cycle because we decided, at the beginning, all the treatment and see if she gets pregnant with her own eggs. The cost is much more lower. The guarantee programs are more expensive if you get pregnant at the first try but usually are much cheaper and there is a psychological peace of mind that is very important in terms of getting pregnancy.

The difference in rates is very low. Probably, embryo adoption can have around  65% pregnancy rate and a double donation can have around 73-75% pregnancy rate but there is a very small difference in terms of success. The main difference is that you can choose some things. When you are using embryo adoption, you mainly have the race guarantee only. So if you are Caucasian, the embryo will be Caucasian but we can’t guarantee even the blood group, hair colour, eye colour, etc. So it is very difficult because we are talking about the embryos that are already created with a previous couple. Also, the information we have on this couple is much more scarce than the information we have on a donor. We have the following information on the donors: psychological tests, genetic tests, infections, family history. So these are the main differences. In double donation, you can select whatever you want. When you use embryo donation, you cannot select anything because there is an embryo that we have but the results are always the same; a little bit better than in double donation but not too much.

There is an important difference. When you are using fresh eggs, the chance of pregnancy is around 7-10 points higher than when you are using frozen eggs. Also, what is important, when you are using frozen eggs, you have a certain number of eggs, for example in 6 eggs program. When you are thawing these eggs and 1-2 of them die, at the end you have 4-5 eggs, you have 1-2 less. If we are working with fresh eggs and you are in the 6 eggs program, you always have 6 eggs, always.  No problem with this. If this donor has 2-3 more and there is no way of vitrifying 1-2 donor oocytes, these eggs go to the same recipient. So in the end, you are going to have more eggs. In the end, you are going to have better results. Thawing is important and not always it is done in the best conditions that you can have. Technically, it is a little bit complicated and depending on the quality of the lab, you can have more problems or fewer problems. For example, we have an egg bank and we use eggs mainly from the Italian clinics and depending on the clinic and the lab, we have different results with eggs of the same donor. So we use a donor in two different clinics and the chance of getting pregnant with one clinic and the other clinic are completely different and depending only in the way they thaw these eggs to do the egg donation cycle. My recommendation, when possible, is to use fresh eggs. If it’s not possible or is very complicated to have fresh eggs, using frozen eggs is always a possibility but, in this case, you have to look very carefully for the clinic and the quality of the lab.

When we are talking about this kind of guarantee program, the main difference is from the economic point of view. My recommendation for all my patients is to go directly for 8 mature oocytes. This, obviously, has no guarantee in terms of blastocysts but usually we are going to have three blastocysts and sometimes even four. The most frequent number is three, sometimes we have two – it’s possible. But in terms of economic terms, usually, this is more recommended because it’s more economic. This is the only difference – the economic advantage. From a psychological point of view, it is better to have blastocysts but economically mature oocytes. When you do a guarantee program, you always have to pay something for the guarantee. My general recommendation always is to talk with the doctor. For me, it is not a problem to organize the cycle with you.  If you know what do you want and you tell your doctor, I can tell you that you can go for a personalized program. Maybe you would have to do two or three cycles if you want it but usually, it is much cheaper and you are going to be much more relaxed and, obviously, you are going to do whatever you want, you are going to select the treatment you want. Talk with your doctor and explain things very carefully what you want. I’m sure your doctor is going to give you different options.