During this event, Dr Beatriz Fernández de Valderrama, Gynaecologist & Fertility Specialist at Vida Fertility, Spain, provided insights into the key aspects of egg donation. The discussion covered the concept of “genetic grief” and how each patient processes it differently. Dr Fernández de Valderrama also discussed the legal aspects of egg donation in Spain, the preparation process, donor availability and how donors are selected.
The event was hosted by Barbara Scott, Chair of the Association of Reproductive Reflexologists, Founder of Seren Natural Fertility, and author of Reflexology for Fertility. Barbara is an internationally recognized expert in reproductive reflexology who advocates an integrative, patient-centred approach to fertility care.
We all need to realize that treatment with the eggs of another woman is usually not an easy decision. The ‘genetic grief’ takes more or less time, depending on the patient or couple. That can create lots of doubts and questions, including legislation, donor selection, and IVF journey compared to previous IVF cycles with own eggs.
Something which helps a lot of patients when they are doubting whether to use the eggs from another woman — and which has been studied in the last years more and more — is the epigenetics.
Epigenetics is how environmental factors affect our genetics. It has been shown that in the fluid of the uterus, there are some molecules produced which allow a fetus-to-mother interaction — at a genetic level in the uterus. Through these molecules, the mum — the carrier — can inactivate or activate some genes in the fetus.
Which women would benefit from egg donation? Most of them are women of an advanced age with a low ovarian reserve or premature ovarian failure. Women with a lot of unsuccessful IVF with their own eggs or repeated miscarriages. In women, who have some genetic alterations.
How does the egg donation work in Spain? It is anonymous, which means the intended parent will not know who the donor is, and the donor will also not know who their eggs were given to. The only things you are allowed to know about your donor are her age and her blood group. The donor who is assigned to you must look as similar as possible physically to you.
Egg donation in Spain is a treatment which has already been practised for over 30 years. The success rates of implantation and pregnancy are between 50% and 70%.
How does it work at the VIDA clinic? First, you will have an initial medical consultation. You will tell your story, provide your medical history, what your wishes are, and the doctor will individualize the treatment as much as possible. The doctor will ask for any additional exams that might need to be performed. As soon as all these tests are ready, then you can start with the treatment, and the team will select a donor which is appropriate to you.
Then, your partner or a sperm donor would need to come to the clinic and leave a sperm sample, which will be used the day of the egg retrieval of the donor to fertilize the eggs.
What we have to do is: on the first day of the period of the donor, we will make an ultrasound to see that she is at a resting state to start the stimulation. If everything is fine, we start a simulation. What does it mean? Stimulation is giving some injections, yeah? Follicular stimulating hormone, which induces the growth of the eggs (the oocytes) within the follicles.
It requires approximately 12 days of injections of FSH or LH. You have to put in one injection—it is a tiny needle around 2 mm, more or less—which the donor has to inject in her tummy once daily. The doctor will do several ultrasounds from the moment she starts putting in her injections, which means every five days approximately. This allows checking whether the follicles are growing properly. After approximately 12 days, egg retrieval will be performed.
On the day the eggs are retrieved, they will be fertilized with semen. The next day, it will be shown how many of them fertilized. Those embryos—on day 1, it’s called zygote—will be put into an incubator where the embryonal development happens. They stay in the incubator until day 5, the moment where we want to transfer—in the blastocyst stage, on day 5. One can be transferred directly in a fresh embryo transfer, the rest can be frozen.
While they are frozen, your endometrium can be prepared, as the lining of the uterus needs to be of a certain thickness to implant.
How is the endometrial preparation done? To make the endometrium thick, you will be given some estrogen pills for 10 to 12 days to make it reach a certain thickness. If the endometrium is thick enough, progesterone will be added to these estrogen pills for 5 days. After that, the transfer will take place. One or a maximum of 2 embryos are transferred.
We always recommend to transfer one embryo. If it would not be safe, I would not let you transfer two. But anyway, medically, we will always recommend you to transfer one.
If both of the embryos implant, it will be a twin pregnancy. It works perfectly—now there are a lot of twin pregnancies—but this already means that it is a risky pregnancy; it needs closer monitoring. This may mean more risk of premature delivery. Since 2 babies take up more space, there’s a higher risk of gestational diabetes, cervical insufficiency, or hypertension during pregnancy.
Usually, 2 trips to Spain are required for the sperm sample or any missing tests, etc, and embryo transfer.
What if I want to do a fresh embryo transfer? If you decide that you want to do a fresh embryo transfer—meaning that exactly when the embryo reaches day 5 in the incubator, we transfer it—we need to synchronize your cycle with the cycle of the donor so that you are both at the same point.
For that, we would give you both the pill to put you both in a resting state, and we would stop the pill at the same time. Five days after, we would start stimulating the donor and, in parallel, start preparing your endometrium.
These are the tests you will usually need to do before starting the treatment:
It depends on the clinic. At VIDA Fertility, there are the donors who come to the clinic, and the team is responsible for the selection process.
We are the ones who stimulate the donors, make the ultrasound controls, and do the egg retrieval, so the process is from the beginning to the end.
70% of these patients are usually students, and 70% of them are Spanish. The other 30% are mostly from Latin America. They are all in a range of age from 24 to 25. However, the allowed age to donate is from 18 to 35 years old.
What criteria do the donors need to meet to be selected as donors? The age range is one criterion. Then, they need to have a good ovarian reserve. They go through several examinations to see that they are physically healthy. They must also go through a psychological test and be approved by a psychologist.
Then, they will be tested for 300 genetic diseases. 300 recessive genes will be studied. If they have a mutation in any of seven specific genes, they will be directly discarded. If they have mutations in other genes, it’s okay—we all have mutations. Having the mutation does not mean that the disease is going to express. They just have the mutation.
Why is it interesting for the partner to also do the genetic test? Because we are testing recessive genes. This means that, in order to give the disease to the descendants, both the man and the woman need to have the same gene mutation. If that is the case, there is a 25% chance of transmitting it to the descendants. If only one of the partners has it, the disease is not going to be transmitted.
The chances that both partners have the same genetic mutation are rare—extremely rare—but possible. So I highly recommend that this test also be done by your partner or your sperm donor.
Then, the donor can be selected. Out of this pool of selected donors, a donor that is most suitable for each patient will be assigned.
The endometrial preparation can be done either by synchronizing your cycles—if we’re going to do a fresh embryo transfer—or we can prepare just with the cycle you’d like to. We always start with the first day of your period for the endometrial preparation. If you’re doing a frozen embryo transfer, you choose the cycle you want to start with, and with that period, we begin.
After 12 days, when the endometrium is thick enough, we add the progesterone. Five days after that, we will do the embryo transfer. With a single embryo transfer, the chances are around 50% to 70%. With a dual embryo transfer, the chances increase a bit more—up to 80%.
In the first place, they need to do several tests, which are blood works, okay? And then the Pap smear, the serologist to say they don’t have any sexually transmitted disease, and so on. These are basic tests to start. But once we start the treatment for the endometrial preparation, they need an ultrasound after 10 to 12 days, because after these 12 days, usually, the endometrium should be already thick enough and prepared for the transfer.
If it is already thick enough this day, we could add the progesterone and 5 days later would be able the transfer. This one ultrasound can be done in their country with no problem. They can go to their gynaecologist, do this ultrasound, and then forward the results to me. And then, the moment I see it, I will answer and tell: okay, so it’s thick enough, or we need some more time. We add progesterone, and the transfer will be on this day, or I will just keep the indications according to the ultrasound that they make with their gynaecologist.
We don’t have Japanese egg donors, sadly. This would be very nice, but they do not come and donate in Spain. So what we do have is Asian-like egg donors, okay? So with the characteristics—physical characteristics—similar, but not Japanese donors.
After 3 failed embryo transfers, we would like to start investigating new things. It does not only depend on the embryo factor. This is like up to 70%, but there are other factors which take place in a pregnancy. That we have good endometrial development, that it thickens properly for it to implant. However, there are a lot of cases where there may be an underlying chronic endometritis. This is an inflammation of the endometrium—the mucosa of the uterus.
The thing is, most of the time, this chronic endometritis is asymptomatic. If it is an infection, the mucosa is inflamed, and it is more difficult for it to stick. What I recommend in these cases is to make an endometrial biopsy. This is easy, it’s done also with a canal, and you don’t need anaesthesia—it’s like a Pap smear. We will take some cells from the uterus and analyze them. If it comes that you have chronic endometritis, we can give an antibiotic therapy for 2 weeks and then repeat it.
What else can we check?
Also in the uterus, with this same sample, we can do another test which is to check the microbiota. So I suggest—it depends on also, it’s also an economical question—but when I tell my patient to check for CD138, which is the parameter to see chronic endometritis, I suggest already to do the microbiota.
The other thing we can do with the same test is the ERA—the endometrial receptivity assay. This measures the window of implantation. The window of implantation is the moment when the chances for the embryo to implant are the highest. By most women, it’s the same—by 80% of the women—after 120 hours of progesterone. But in some women, this window may be displaced.
She may need fewer or more hours of progesterone before the transfer to have a higher chance. This can be done with the same biopsy to measure all three of these parameters. If I had to choose one to start, it would be to rule out chronic endometritis.
What other factors may affect it? When it is not the embryonal factor and it’s not the uterus, it is the coagulation. The coagulation factors may make the blood thicker. If you have any kind of abnormality in your coagulation and the blood is thicker— The blood carries oxygen, and the endometrium will be supplied with blood and with oxygen for the embryo to implant.
If the blood is thicker, the transport of oxygen is more difficult and the chances of implantation are also less. I would do a thrombophilia analysis. To start stepwise, I would do these two things. I always analyze this, and if I don’t see any defect, then is when I go further to the immunology. This will be the last factor which may affect it. There are several things which can be checked. The natural killer cells, may be in a certain range.
Now there are medications, if they are increased, which we could give. We could also check the compatibility, the acceptance of the fetus by the mother—like with donor organs—by measuring a thing which is called KIR-HLA. By then, we can check if you need a certain specific donor to be assigned to you so that you accept the embryo better. I don’t know if some of these tests would be done, but if not, I recommend you do them.
Exactly. It can also be a male quality issue, of course. For example, if these things happen—now that after 3 transfers with a donor, it didn’t work, or if with the eggs of this donor, we try then to change the sperm to see if the results are different with it.
Usually, if we are talking about a spermogram which is the analysis of the sperm in a man where we see the concentration, the motility, and the morphology. If all of that is okay, and it is a man under 45, who does not smoke, who does not consume a lot of coffee—it should actually be okay.
But there is something which the spermiogram does not check. And a lot of times, it’s done after when things don’t work, and which I find very helpful— It is to check the sperm quality, which is not done in the spermogram— To check the genetics of the sperm, and to check the fragmentation. Every man has fragmentation. These are like breaks in the DNA chain which codes our genes. This is not normal fragmentation, but we all have a certain amount. Now, in this case, males have fragmentation, but if this is increased above a certain level, this may also affect the rates of fertilization, as well as conversion to blastocysts, That there may be less amount of blastocysts, or that there are fewer chances of implantation or a higher risk of abortion.
With her eggs, it’s not going to work, because the thing is: if she’s menopausal, first of all, she will probably have no more reserve. She will have no follicles.
First of all, we would do an ultrasound to check that. She may, most probably, not have follicles—no place where we can make eggs grow. And if she may have one residual or something like this, the most probable is that, if we stimulate her, if we give injections to make it grow, she’s not going to respond, and it’s not going to grow. Or if it grows, the follicle may be certainly empty.
And if we get an egg, it may be very, very, very hard to get a blastocyst. So it is impossible, so to say.
Something different would be if she’s premenopausal already—the chances are way lower because the genetics are very altered in the eggs and still low chances, but we are talking about something else. The second part—the way to prepare them—yes, a postmenopausal woman can conceive with donor eggs.
Because, as I say, we take the term “age” out, and we are concerned about the uterus.
We have seen that endometrial development also turns difficult from 45 years old onward, but it works. It also works. What I tend to do with these women is to make a test cycle—a mock cycle—to see. Before I’m going to do any kind of transfer— It is cheap because you just need to buy estrogen pills, and the estrogen pills are cheap— And I see how it is growing and if you need, for example, a little bit higher dose of estrogen than another woman, to see for the real cycle how I need to prepare you.
I usually do this with premature menopausal women or irregular cycles. This usually works. It’s not a problem, in the end, to get an endometrium— Unless it is a woman, like I said, who had a lot of endometrial or uterus operations or a very atrophic endometrium. There we may have a little bit more difficulties. But without these characteristics, it is okay to prepare the uterus in a menopausal or postmenopausal woman. She would be prepared the same way as another woman, and she can conceive the same way.
I would say so. If she had so many failed IVFs, also by using PGT-A, I don’t know if she got any euploid embryos or not. However, the next step would be donation. I mean, we could discuss your case more, analyse it if she would like to tell me how it went with PGT-A and if I see chances of trying it another way. However, I think, after so many tries and at your age, for sure, the most recommended from my side would be egg donation.
Actually, yes, a single woman can have treatment—every woman can, whether single, married, or divorced, it doesn’t matter. Sadly, the law in Spain is that if you don’t have a partner, you cannot bring your own donor—it’s illegal. The donor has to be assigned here.
Not necessarily the same, but compatible. If it’s not compatible, there will be a rejection—it’s not going to be accepted. It’s like when you do a blood transfusion. For example, AB+ blood can be given to everyone but can only be received from AB+. You have to see, hematologically, how it will fit. You cannot just give a random blood group.
No. We don’t select by nationality. We select donors according to whether they pass all the required tests. Patients are not allowed to choose their nationality or other factors—it’s anonymous. The donor is assigned according to physical characteristics.
I’m sorry, but the thing is, if it were a totally natural cycle, then yes, no medication. But a modified natural embryo transfer always means we have to monitor follicular growth and give the Ovitrelle injection. There is no way around it.
We are talking about euploids. We check according to the chromosomes. So, how is the embryo chromosomally. If we need to check specific genes, it will be PGT-SR, not PGT-A. Then, if we need to check the embryo for a specific mutation, for example, because the mother or father has it, then we can go and do PGT-SR. But in general, the PGT-A we do is always to check the embryo chromosomally.
Yes, of course, you have a chance. Like I said, we take the eggs of a younger woman, so it’s perfectly okay with the uterus. It is interesting to know about this fibroid because fibroids may make implantation difficult if they are in the uterine cavity. Fibroids may sit at different points in the uterus.
If we have the uterus, and inside is the cavity, and the myoma (fibroid) is here, we need to remove it because it doesn’t leave a place for proper implantation and growth. But if it is on the walls or outside, it’s okay – you can conceive perfectly with it. Myoma only needs to be removed if it takes space in the uterine cavity or deforms the cavity from the outside. Myoma is a benign muscular tumour – just that the muscle of the uterine wall got thicker at some points, and it is hypertrophied muscle.
This is not dangerous, just in case you have symptoms, or it grows too fast or involves the uterine cavity, then it is suggested to remove it. Please, in the first case, check the story of this fibroid – where it is, it has grown a lot, and so on. Then we can move forward. But it is no problem – fibroids are something pretty common, around 40% of fertile women. This is a case which is often okay. We remove the fibroids, and afterwards, there is pregnancy with no problem.
We just need to make the uterine lining grow, and we do that with estrogen.
There are two ways to characterize them. One characteristic is morphological – we have A, B, C, and D. A will always be the best classification, D the worst. But I have also seen euploid embryos class D implanting and euploid class A not implanting. But we, of course, take it into account.
Yes – I would still do it. Because, in the end, it’s your uterus
If the father or the mother has a specific genetic mutation, and we know it from the beginning, we will not only do the chromosomal testing of the embryo but also check for this specific mutation. One thing is the chromosomes – and within the chromosomes, there are billions of genes. We would go check specifically for this one.
