PGT-A & Egg Donation: all you need to know

Dr Serafeim Pousias, My Fertility, Greece: First of all, endometriosis is a cause of infertility. The main cause. Endometriosis is toxic for the eggs themselves—poor quality eggs, poor quality embryos, and, of course, recurrent pregnancy losses.

That’s why, when we see that and we extract the endometriosis—of course, stage four is a severe case of endometriosis—I can guess that there is no more ovarian reserve there. So, of course, if she already had the procedure done to extract the endometriosis, then the success rate with donor eggs is very high and similar to others.

Of course, we have to be careful to choose the correct protocol for embryo transfer. Sometimes you use a different protocol with women after surgery with endometriosis. It’s not the same protocol that all the other women use. But overall, the success rate will be mostly the same if the endometriosis has already been extracted.

Dr Sofia-Paraskevi Trachana, My Fertility, Greece: I totally agree with Dr Serafeim. Endometriosis is a very severe condition for fertility. However, this lady had egg donation, so it’s not a matter of the poor quality of the eggs now, but how her body reacts to endometriosis. She has severe endometriosis.

The first thing she should have done so far is to check inside the uterus—to have a hysteroscopy to check the baby’s room, if everything is okay, in order to transfer the embryo. I think that if she insists a little bit, maybe two or three cycles, she will have her baby.

Dr Serafeim Pousias, My Fertility, Greece: First of all, it depends on which GnRH injection was used. There are different types—some cover ovulation for one month, others suppress the cycle for three or six months.

If she has done only one GnRH 0.1 injection, then she should check her hormone status in order to see, and also check other endocrine factors such as steroid or prolactin, to see where she’s at and why she’s having anovulatory cycles.

But if the injection was only 0.1 for one month, it is not responsible for missing an LH surge after 6 or 7 months. Usually, after 2 or 3 weeks, the body itself resumes the cycle. So first of all, she has to do an examination to see her overall hormone status.

Dr Sofia-Paraskevi Trachana, My Fertility, Greece: I totally agree with Dr Serafeim. I just want to ask how she is detecting her ovulation—just with the ovulation test, or is she doing blood tests? Because sometimes we don’t do the ovulation test in the correct way, and sometimes we may miss our ovulation. So, if she wants to be very sure, she needs to perform an ultrasound and some blood tests, just to be sure.

Dr Serafeim is absolutely right that it cannot be a result of the injection after seven months. But I have to ask—usually, when we are doing a fresh embryo transfer, we don’t use ovulation suppression with GnRH.

This is something else. When we use induction of ovulation with GnRH, it is a frozen cycle. We don’t perform an embryo transfer in that case because you would have a luteal phase defect.

That’s why I think maybe she misunderstood and took the GnRH injection one day after the embryo transfer—I don’t know.

Dr Serafeim Pousias, My Fertility, Greece: I have worked in Germany, Austria, and Greece. All of them required a licence. I don’t think there is a country that legally offers PGD without a licence. Unfortunately, we need the licence.

In Greece, they are considering not requiring a licence only for PGT-A, but this has not been formalised yet. Legally, there is no country that allows PGD or PGT-A without a licence because there are medical considerations. The embryo is considered a potential child, and since it involves genetic material that belongs to the parents, a licence is required to do testing.

Dr Sofia-Paraskevi Trachana, My Fertility, Greece: In Greece, it’s relatively easy to get a licence. My experience with the UK and other European countries is that it is very difficult to get a licence for genetic testing.

Dr Serafeim Pousias, My Fertility, Greece: The Greek legislation says that for women above 40, they can do PGT-A. The indications are: two or more failed cycles, being above 40, or miscarriages. Not all conditions have to be fulfilled, only one.

Dr Sofia-Paraskevi Trachana, My Fertility, Greece: Yes. Just apply with your identity, and you will receive the licence within two weeks.

Dr Serafeim Pousias, My Fertility, Greece: Do you mean the embryo is aneuploid? If so, you do not transfer it. You move on to other embryos, either from the same donor (other oocytes, other embryos) or from another donor.

From international banks, there is usually a guarantee for embryos. If it fails due to aneuploidy, and if the karyotype of the donor was normal, then the issue might come from the sperm. That’s why, when we do PGT-A with donor eggs and it fails, we have to check the sperm as well.

Dr Sofia-Paraskevi Trachana, My Fertility, Greece: Donors are usually young, between 21 and 31 years old, but even they can produce aneuploid embryos. There is no guarantee. The probability is very low, but it exists.

Dr Serafeim Pousias, My Fertility, Greece:  Yes. If we see that the donor has produced aneuploid embryos, she may be removed from the system. However, even young women can have one or more eggs that are not genetically correct.

For example, a 21-year-old woman might produce one egg per cycle and have a 24% chance of pregnancy. After 6–8 months, her chance reaches 80%, but not 100%. Not all eggs are genetically correct. The reproductive system has limits. There is never a 100% success rate, whether you are 20, 30, or 40. Above 35, the ratio of abnormal embryos increases exponentially.

Dr Sofia-Paraskevi Trachana, My Fertility, Greece: We must be honest with patients: egg donation has a success rate of 60–65%, not 100%. Even with donor eggs, there can be unhealthy babies born. However, this probability is very low. That’s why, for women of advanced reproductive age, it is better to use donor eggs, because the chance of an aneuploid embryo is lower compared to using their own eggs.

Dr Serafeim Pousias, My Fertility, Greece:  Let’s say we have a donor, and a woman orders 10 eggs. She gets 10 embryos. Statistically, one of them may be aneuploid, but that does not mean the others are not healthy.

Dr Serafeim Pousias, My Fertility, Greece:  The accuracy of the PGT-A is independent of age. The euploid ratio depends on the age of the woman.
Around 44 and 45, the ratio to get a euploid embryo is around 5% or below 5%. So, let’s say we have one woman, 45 years old, 100 embryos, only five of them will be euploid. That’s why the success rate above 44 with IVF with your own eggs is around 2%.

Only to add something: this goes not only to the woman who is 44 or 45. If the man is also above 45, then the semen also has genetic failures. That is also a factor. For women above 35, the ratio for abnormalities is higher, but for men above 45, the ratio goes higher than this one.

Dr Sofia-Paraskevi Trachana, My Fertility, Greece: I totally agree with Dr Serafeim. The accuracy of PGT-A is something totally different. It has to do with the technique. This technique is well known in genetic laboratories. So yes, the PGT-A is 99.9% accurate. About the success rate, about the possibility of having a healthy embryo at age 44–45: yes, the possibility is low, below 5%. However, we’ve seen spontaneous pregnancies at age 46–47 leading to a healthy baby. So yes, everything can happen.

However, for the average woman at age 44–45, they have to try a lot. They have to do a lot of egg collections. They need a pool of embryos to determine if any of them will be euploid. Furthermore, they need to be strong.

Dr Serafeim Pousias, My Fertility, Greece: If the egg donor has Fragile X, this is not a donor. We exclude this.

Dr Sofia-Paraskevi Trachana, My Fertility, Greece:  It was in the list of the investigations I showed in my presentation. If a donor is a carrier of Fragile X, she can’t be a donor. Which technique we use depends on the genetic lab. They will decide. Usually, it’s PGT-M. However, it’s a matter for the genetic lab. Even for us, we give all the investigations to the genetic lab, and they decide what they will do. But usually, it’s PGT-M.

If she has an abnormal karyotype, or if she is a carrier of a bad disease, whatever it is. This also applies to other countries, because a donor from, let’s say, Sweden can donate her eggs to someone in Spain. So the demographic stats must be considered. Which conditions are overall for all the people.

Dr Serafeim Pousias, My Fertility, Greece: For the androgens and progesterone, of course.

Dr Sofia-Paraskevi Trachana, My Fertility, Greece:  Other hormones should be measured on very specific days if she wants to be sure. That’s why I mentioned that she needs an ultrasound to see if something is growing in her ovaries, a dominant follicle. Then, on a very specific day, she needs to do a blood test for progesterone, for LH, for estradiol. At the beginning of her period, she needs to do a prolactin. She needs to do TSH for the thyroid gland, for adrenal, for androgens.

Dr Serafeim Pousias, My Fertility, Greece:  But if you haven’t had a period for the last seven months, then just perform an ultrasound first to see the endometrium thickness. If the endometrium is thin, just do the exams.

Dr Serafeim Pousias, My Fertility, Greece: That is according to the technique. Sometimes the cells are dividing, but they cannot perform PCR to detect the DNA from the embryo. Sometimes, the membranes and DNA inside those cells are broken. It’s about the technique.

If that occurs, it means we cannot test the embryo. We cannot perform an embryo transfer. That also relates to a false parameter. It’s also why, after PGT-A, there is no 100% survival rate of the embryo; it’s 95%.

Dr Sofia-Paraskevi Trachana, My Fertility, Greece: It is a matter for the laboratory technician as well. In Greece, only some IVF clinics can perform PGT-A because they have trained embryologists and trained geneticists in the genetic laboratory. However, sometimes it happens because we don’t have enough cells from the embryo to get an accurate result.

In that case, we have two options:

• Not transfer the embryo.
• Rebiopsy the embryo—thaw the embryo, take some cells again, freeze the embryo, then wait for the results.

But this is very difficult for the embryo. It has already had a biopsy, it was frozen, then thawed, then rebiopsied, then frozen again, and then thawed again, if it is healthy and used for transfer. We have seen pregnancies after this procedure. However, it may be a problem for the implantation rate. It may affect the ability to implant in the uterus. If she has other embryos, maybe consider using the others. If this is the only embryo, maybe think about rebiopsy. But there is a risk to the embryo.

Dr Serafeim Pousias, My Fertility, Greece: It’s a matter of choice. It’s faster to use frozen donor eggs, of course. A fresh donor requires finding the donor first. In Greece, we need to find the appropriate donor, stimulate the donor, prepare the endometrium, do the oocyte pickup, and then see how many embryos we have at the end.

Dr Serafeim Pousias, My Fertility, Greece: The first thing to do is a hysteroscopy to see if the endometrium is okay, or if there are any adhesions. That is the first step. If she doesn’t want to use a surrogate, we should note that it’s not only about the lining thickness, but it’s also about the morphology of the endometrium.

We’ve had patients with Asherman’s syndrome. I had two patients with Asherman’s. There was no endometrial cavity due to adhesions. The lining thickness was 5 mm, but the morphology after hysteroscopy was perfect. Both became pregnant. So, if this is the only problem in considering a surrogate, I’m not sure why they are going directly to surrogacy. It’s not only about the thickness, it’s also about the morphology.

Dr Sofia-Paraskevi Trachana, My Fertility, Greece:  There are many things you can do to achieve a thicker endometrium. We’ve seen many pregnancies with endometrium below 7 mm, even below 7.5 mm.

I understand that maybe they have just one euploid embryo at the age of 44–45, so it’s very important for them. We are on the same page. However, I believe she needs to investigate a bit more—why she has such a thin lining—and use different protocols for endometrial preparation. Then move to surrogacy if there’s no improvement. If the morphology is also not good, then yes, surrogacy is an indication.

Dr Serafeim Pousias, My Fertility, Greece:  Yes, it is safe to transfer two embryos, and it does increase pregnancy chances. But it also increases the chance of twins. With twin pregnancy, there are more obstetric complications to keep in mind. At age 40, the percentage of preeclampsia is higher. With twin pregnancy, the risks double for gestational diabetes, preterm labour, and pregnancy loss.

If she has donor eggs and excellent quality embryos, like a 4AA or 5AA, and she wants one baby, she can transfer only one embryo. I had a patient at 49. We used donor eggs. We had three embryos, and I suggested transferring only one embryo to avoid a twin pregnancy. But if she wants two embryos from the beginning to have twins, yes, of course, it is safe—if there are no other conditions or uterine complications, such as recent surgeries.

Dr Sofia-Paraskevi Trachana, My Fertility, Greece: I totally agree with Serafeim. Yes, two embryos can be transferred. But my advice is: if this is her first embryo transfer with donor eggs, she should transfer just one. If the first transfer with one embryo fails, then she can move to transfer two embryos. However, she should know that there are some risks with twins, and the most important is premature labour.

If she has no contraindication for twin pregnancy, like thrombophilia, autoimmune disease, or a severe health problem, then it’s okay. But she needs very close monitoring during pregnancy if she achieves a pregnancy with twins.

Dr Serafeim Pousias, My Fertility, Greece: Just to express a different opinion, it’s not wrong to do a second transfer with one embryo again, especially if you have excellent quality embryos and want to avoid twin pregnancy. That’s also not wrong.

Dr Serafeim Pousias, My Fertility, Greece: We only get what you order for the eggs, and we don’t want to miss any fertilisation. We prefer to do ICSI when we are doing IVF.

The indication for ICSI is the sperm parameters, but also if we have a low number of eggs. When using donor eggs, we most likely have around seven eggs. That is not many. So, to ensure fertilisation, we perform ICSI. It also depends on sperm quality and DNA fragmentation of the semen.

Dr Sofia-Paraskevi Trachana, My Fertility, Greece: I totally agree. It’s better to do ICSI in order not to lose any fertilisation, because maybe the sperm will not fertilise. Let’s say the woman gets about eight eggs from the donor. The sperm, either from her partner or donor sperm, might fertilise only 6 out of 8 eggs.

When we have a donation, we want the maximum fertilisation rate. That’s why we prefer ICSI because we put the sperm into the egg, and we maximise the chances for the eggs to get fertilised.

Dr Serafeim Pousias, My Fertility, Greece: In general, if we have plenty of eggs, we perform IVF.

Dr Sofia-Paraskevi Trachana, My Fertility, Greece: If we have plenty of eggs, we can split some eggs with IVF, some eggs with ICSI. So we see how the sperm and the eggs go with one technique and the other technique. It is individualised.