In this webinar session, Dr Halyna Strelko, Chief physician, and Reproductive specialist at IVMED, Kiev, Ukraine, discussed egg donor conception, how the donors are selected, and who can become a donor. Dr Strelko has also discussed egg donor pros, cons, and indications.
In Ukraine, there is a document called Order of the Ministry of Health of Ukraine where it is described who can become a donor. It says there that a woman should be less than 36 years old and have no bad habits, such as smoking, alcoholism, or drug addiction. She needs to be in a good health with no hereditary diseases, and no contraindications, such as cysts and endometriosis.
All egg donors need to do various blood tests, and drug tests and go through screening for infectious or inherited diseases. It is necessary to perform a psychological screening as well.
Only 20% of all candidates who contact the clinic via the Internet pass to the primary interview. After the primary interview, around 30% are scheduled for the first visit, and after that, only approximately 1/5 continue the examination. Around 3-5% of all candidates became donors at the IVMED clinic. The selection is quite strict, but it is necessary.
In 2020, there were 268 egg collections, and the total number of eggs obtained was, 8714 at the IVMED clinic. The average egg number for retrieval was 31,4. The women selected usually have high AMH levels. From this amount, the team tried to see the quality of eggs according to age.
We can see that number of follicles is slightly higher if we have a very young woman who is less than 25 years old, oocytes number is also slightly higher, but if we look at the number of mature eggs, there is no much of a difference. It’s around 24 mature eggs at 25, and around 19 in a donor who is more than 30. If you look at the percentage of Q1, which means the best quality eggs, you can see that the percentage is the highest (73.2%) in the group between 26 and 30 years old.
It’s necessary to understand that even if we have lots of eggs, we need to remember that not eggs will be fertilized and reach the blastocyst stage. Not all blastocysts will be of good quality and without genetic abnormalities. The average number of usable oocytes per cycle is around 17%, and average fertilization is 15%, blastocyst stage is 11%, with the genetic testing on these blastocysts, around 65% of them are normal.
On average, the aneuploidy rate is around 65% in most of the clinics, but in some clinics, it may be less or more. It may depend on laboratory conditions, some culture mediums, cultivations but also gamete and embryo manipulation methods as well as lab air and purity. Therefore, it is important to know if laboratory conditions correspond to standards because they can influence the results.
Father’s age can also influence the aneuploidy rate because the older partner’s reproductive age, the more DNA fragmentation he will have. It will result in fewer blastocysts and more aneuploid embryos. After 50 years old, even a healthy partner may have more DNA fragmentation, on average, it is double more compared to a male less than 39 years old.
How many eggs do we need to reach a positive outcome?
Some causes are related to egg quality, however, in egg donation, it is avoided because the eggs come from a young donor. Some other causes are not related to egg quality, and these are:
The aneuploidy is mostly caused by age, in the young reproductive group, we will have a rather lower level of genetic abnormality in eggs. Is it necessary to do genetic tests on embryos produced with donors’ eggs? On one hand, the percentage of genetic abnormality in young donors’ eggs is not very high, on the other hand, some percent of the blastocysts may have a genetic abnormality. Another aspect is mosaicism when there are normal and abnormal chromosomes in the embryo. Genetic selection with the use of PGT-A (Pre-implantation Genetic Testing for aneuploidies) may improve the probability of pregnancy. When we are selecting only normal embryos, the probability of pregnancy is high, but if we add another method of selection, for example, Time Lapse (the embryo is monitored when it is developing, and a photo is taken every 5 minutes), it will increase the chances even more. The best embryos will be selected with the help of AI. From this point of view, PGT-A may be helpful because it shortens the time of pregnancy.
It’s important to mention that not all cells in the trophectoderm have equal genetics. For example, if an embryologist will take 5 cells from 1 place, 2 are abnormal, there is 40% of this embryo is mosaic. If by chance, the embryologists will take the other 5 cells from a different place of trophectoderm, it may be possible that all cells will be normal. There is also a chance to get a false result, when an embryologist takes 5 cells from another place, all 5 cells might be abnormal. If you don’t have a lot of blastocysts, it is necessary to discuss PGT-A testing and whether it is necessary. In such cases, it may decrease the number of embryos available for transfer. All these embryos have a chance to implant and give a healthy baby. The results of genetic diagnostic are not always 100% accurate. When there is an abnormal genetic result, it does not mean that it’s impossible to do the embryo transfer, it means that there is a lower chance and could result in some problems after, so it is necessary to do more diagnostics if the pregnancy will be achieved.
Another important point is the correct protocol. There are several types of protocols, which can be used during the preparation of the endometrium for embryo transfer. They may influence the result. Generally, there are 4 types of protocols:
Hormonal replacement therapy may be with antagonists (GnRH-a), which means that we switch off the ovary and then give medication which imitates a natural cycle or without antagonists in case of menopause. Another option is a natural cycle with luteal phase support or without it. A modified natural cycle can also be used and mild stimulation.
When we compare the natural cycle and artificial cycle, we can see that all parameters are better in a natural cycle. The difference is not very high, it’s between 5-10% but it is important to know that protocol of endometrium preparation may influence the success rate. It was also shown that the artificial cycle may result in spontaneous abortion more often, again, the difference is not very high. Another thing shown was that in an artificial cycle, there is a higher probability of some obstetric complications. The egg donation per se and the artificial cycle may increase the probability of preeclampsia because in an artificial cycle there is no corpus luteum and it produces not only progesterone but some other active substances. Statistics show that in the egg donation cycle, the risk of preeclampsia is between 13-18%. When we have a twin pregnancy, it is even more, it is almost 28%. Therefore, if you are going to have replacement hormonal therapy, it’s better to transfer just a single embryo to avoid twin pregnancy.
Multiple studies reported an increased risk of preeclampsia in women conceiving by IVF, it is only around 5-6%. However, in egg donation cycles, the percentage is much higher. The reasons for it can be because of some immune issues, there may be some complications related to late reproductive age like diabetes, and heart disease, which is more common after 40 and especially after 45 years old. The arterial hypertension risk before 50 years old is around 26%, but after 55, it is around 60% and more. That is why in most countries, there is some age limit for IVF treatment and egg donation programs. The risk of gestational diabetes is around 20% in egg donation programs, the risk of placenta previa is 2 times higher, and there is also an increased risk of thrombosis, heart attack, stroke and so on.
The current political situation is not so easy, we are doing a lot of egg donation programs for Ukrainian patients. In Kyiv, it is quite safe, but the problem is travelling from abroad, there are no direct flights, only by train, we hope it will end by the end of the year. Ukrainian official documents say that egg donation is anonymous, so here at the clinic, we cannot show the photos of the donors. However, if you contact an agency that is helping with finding egg donors, they can show the photos. That is how it is resolved, we use egg donors’ photos when they were children.
In Ukraine, gender selection is not prohibited, so we can do that. As I’ve mentioned it is difficult to travel, but we have patients who come for 1 day, they are prepared in their countries, and we monitor that as we are in touch with them, they come for 1 day, and they can go back the next or 2 days later.
Yes, 99% of the donors are Ukrainians. We also have some Chinese patients, and we had donors from Kazakhstan, but not a lot, and now we don’t have any new donors from other countries, only from Ukraine. We give information about age, and if you say that you want a younger donor, we can do that.
It may be because, for example, especially for Ukrainian patients it is quite expensive, so we propose to share donors, which is less expensive. We have different packages, with 6-8 oocytes or 12 oocytes, 18 oocytes, it depends on your preference, but in most cases, 8-10 eggs is enough. If there is a low sperm count or very high DNA fragmentation or previous attempts with very low blastocyst formation, it is better to take a donor with a proven high blastulation rate and more oocytes. Oocytes can sometimes repair this DNA damage.
We try to help to select phenotypically more or less similar, it is difficult to find a very similar person, but we always try to select as many things as possible, for example, if a couple has brown hair, blue eyes and so on, both donors should have the same characteristics. We always try to help and select the best donor. There are some artificial programs like Fenomatch that helps, unfortunately, due to the current situation, we are not able to use them, but when it will be possible, we will implement them.
We have experience working with sperm that was frozen 40 years ago, and we had a good embryo quality, and we’ve got a successful result. The main problem is that after 20,30, and 40 years, cultural medium and methods of thawing and technology change. Therefore, it is difficult to find the same medium that will be available for this particular method of freezing. When it comes to sperm, in most cases, it doesn’t matter because sperm cells are not that easily damaged and can stand such a procedure much better. If the eggs were frozen by modern method 5 years ago by vitrification with modern solutions, it is also not an issue. However, if the eggs were frozen with slow freezing 10 or 15 years ago, it may be an issue, not because of 10 years, but because of different technology that was used then.