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.
Egg donation – legal aspects & selection process
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.
Psychological screening
- oocyte donation is an emotional experience for both the donor and the recipient
- oocyte donation program should include a thorough psychological screening of all individuals involved
- donor mental health assessment is vital to ensure that the donor makes an informed decision before beginning a donation program
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.
Donor’s age
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.
- in young age groups, there is no statistical difference in the quality and quantity of eggs
- proven fertility does not exclude the possibility to receive eggs with poor quality
- quality of eggs is mostly a ‘personal’ characteristic of egg donor
- approximately 60-70% of all mature eggs, on average in all age groups have excellent quality
Egg donation – outcomes
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?
- the average number of embryos per ET in egg donation cycles is 1.4
- we need to calculate how many eggs we should take to receive as a minimum 3 euploid blastocysts to have a minimum of 1 or 2 transfers
- we should retrieve around 8-10 good quality eggs (depending on the sperm quality) to have 4-5 blastocysts, and 3 euploids
Causes of age-related decline
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:
- general health problems (diabetes, hypertension, heart disease)
- myoma, endometriosis, polyps, endometrial disorders
- infections inside the uterus (chronic endometritis, coagulation problem and immune disorders
- decrease of coitus frequency
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.
Mosaicism
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.
Embryo transfer protocols
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:
- replacement hormonal therapy
- natural cycle
- natural cycle with triggering of ovulation
- low dose stimulation with the triggering of ovulation
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.
Conclusions
- before the initiation of the egg donation program, it is important to find out the protocol of egg donor selection and screening
- the average blastulation and aneuploidy rate in IVF clinic (to understand how many eggs you will probably need for successful treatment), it would be good to have 3-4 euploid blastocyst
- a careful check of own health, including genetic screening of your partner
- in case of pre-existing diabetes, thrombosis, hypertension, and so on, it is very important to do a check-up and stabilize it
- in some cases, the obstetric risks can be very high, for example, if a woman has diabetes before the treatment
- the protocol of endometrium preparation may cause some complications
