Dr Diana Obidniak, Head of International Cooperation Department at AVA-Peter, an affiliated professor at St. Petersburg State University, also a practising fertility specialist talked about the pros and cons of egg donation IVF programs. Dr Obidniak specializes in so-called difficult patients diagnosed with recurrent implantation failure, repeated pregnancy loss, diminished ovarian reserve, where there is no way to do IVF cycles with their own eggs.
Egg donation – when is it recommended?
When we talk about the egg donation program
, there are certain circumstances when we are pushing patients for this program. The aim is to minimize their time to pregnancy. Patients of advanced reproductive age are usually the ones where egg donation will be recommended.
However, the age limit is going up, about 10 years ago, all the guidelines said that women over 39-40 years old were recommended to try egg donation programs. Nowadays, it’s always the second line of therapy
. We have experience with embryo banking, there are different types of ovarian stimulation, so in many cases, we can manage to get good embryos with own eggs.
Unfortunately, when the woman’s resources are already exhausted, we have to implement a donation program and make it very delicately. Egg donation programs are
also recommended for women with ovarian failure due to menopause, premature ovarian failure or ovarian surgery
, for example, in patients with severe forms of endometriosis
. We can expect that after surgery, the volume of ovarian tissue may diminish, that’s why, unfortunately, in some cases, we have to recommend an egg donation program.
There is also a need for egg donation in patients with recurrent pregnancy loss or the inability to obtain euploid embryos.
Egg donor – selection process
Concerning the donor selection, you will find rather similar descriptions. In any clinic, this program aim is to be effective but also very pleasant for the patient. The main thing is to get a healthy baby.
At Ava-Peter clinic, only young and attractive women under 30 years old with their own healthy babies are considered. Ava-Peter clinic has the largest database of donors and vitrified oocytes in Russia. There are European and Asian phenotypes available. All donors undergo genetic testing on common heritage diseases
. We try to provide as much information as we can about the donor, such as the donor’s appearance, medical background, education, hobbies
. The questionnaire consists of more than 70 questions.
A special department of managers is always in touch with the donors to be sure that everything goes well. There is no waiting list, there are both so-called vitrified eggs in the database, and there is also a list of donors who are ready to initiate the treatment at your earliest convenience.
Regarding the selection process of the donor, at first, there is a general interview. Donors are asked why they want to be involved in such a program.
After that, genetic testing, such as Karyotype, is performed
. Screening of
so-called monogenic diseases is also performed.
Those are rare diseases, and it results only when both parents are a career of these monogenic diseases. They are considered rare diseases, but unfortunately, if the clinic doesn’t provide such screening, it can lead to dramatic results even in the egg donation program. When we are sure that the candidate is suitable and healthy, in terms of genetic competence to be involved in the egg donation program, we initiate a gynaecological examination and a general physical examination. We always assess hormonal levels, screen for infections and perform an ultrasound.
We do it several times because if the donor is involved several times, we repeat all those examinations, each time, before initiating the program.
When we talk about young women who already have their own babies, it’s not a guarantee that the quality of eggs will be good. That’s why we have implemented so-called trial ovarian stimulation following trial fertilization with a sperm donor. That way, we can get information on how the donor reacts to the simulation, what quality of eggs we can expect, what number of eggs we can expect, etc. It is a strict selection process, not more than 20 or 25% of applicants are approved.
Egg donation – clear benefits
The benefits of egg donation programs are for sure high success rates.
Success rates differ in different clinics, different countries, for example, at Ava-Peter clinic, it is from 65% to 70% depending on the quality of sperm and presence of concomitant diseases in a couple.
When we talk about success rates, we mean clinical pregnancy rate, we are not talking about fertilization rate or the number of embryos we obtain. The main aim is to make you pregnant.
Nowadays, such programs are highly effective, but we also need to assess the time to achieve a pregnancy. That’s sometimes the basis for a recommendation because when we talk about patients of advanced reproductive age or with minimal ovarian reserve, we always discuss alternatives. We can offer embryo banking programs, but that will take, for example, 6 or 7 months till we can start the embryo transfer. There is also a risk that some or all embryos will be abnormal, so after those 6 months, we may have to go with the egg donation program anyway. If we start with an egg donation program, we can minimize the time for pregnancy. This will also minimize financial expenses. All the physicians, all over the world, are recommended to take into account not only effectiveness and medical issues but also the cost and expenses the patient will take.
Egg donation – hidden risks
Egg donation is considered to be an effective tool in creating competent embryos. Is it applicable for all cases? Even when we’re talking about young women, and we obtain a good quality of embryos, we should expect that a great per cent among these good-looking embryos will be abnormal.
We have so-called 4 types of embryo quality according to morphological qualification. We assess it by their external appearance and then what type of quality we see.
We usually divide them into excellent, good, average and poor. In your medical report, you probably have seen some figures and letters, for example, 4AA, 3 BB, and it is precisely the mode of assessment of the embryos by their external appearance. Unfortunately, this way of embryo assessment doesn’t provide objective information about their genetic competence. One of the trails shown on the slide has demonstrated that there is a bad correlation between the quality of embryos by their external appearance and their genetic competence. When we are talking about excellent embryos, the prevalence of abnormal embryos among this category of embryos will be close to 40%, it’s a very high rate. In poor embryos, we will find only 25% of normal embryos, so more than 75% would be abnormal. That’s why, some time ago, we have tried to implement pre-implementation genetic testing even in egg donation programs. Several years ago, it was a very common opinion among fertility specialists that the egg donation program is so effective that there is no need to add more technologies. However, according to our empiric experience, we have started to implement this practice, and we have represented our own results showing that:
For sure, the prevalence of abnormal embryos is lower than in the general population because the donors undergo a very strict selection, they are already approved by genetic mode of investigation. There is a recent investigation called ‘Major factors involving an implantation rate of PGT-A euploid embryos in egg donation program over 35 years where they divided all the patients into two groups. Group A consisted of 188 egg donation programs with PGT, and group B consisted of 58 egg donation programs without PGT. They wanted to compare their outcomes of clinical pregnancy rate and live birth rate. In group A, the implantation rate had much better results. In a group where an egg donation program was performed with pre-implantation genetic testing, the implantation rate was 46%, and in group B without pre-implantation genetic testing, the implantation rate was 20%, which is not a very high result.
In many clinics, you might observe a 46% of implantation rate in the program without pre-implantation genetic testing. It is important to look at that great difference because the technology used was the same, physicians were the same, their achievement to the patient was just the same, but the results are very different.
Dr Obidniak emphasized that when we are talking about egg donation programs, we usually use the biological material of the partner or husband, the quality of sperm also plays a crucial role in this process. One of the trials was called: Evaluation of the impact of quality of sperm morphology on the rate of aneuploidy rates in donor oocyte program. We already have data that proves that in all programs, a male factor will have an impact. If we have severe male factors, we should expect that the outcomes will be worse even in the egg donation program. There was a significant difference between the groups with different sperm quality, so these results suggested that diminished sperm quality is correlated with the aneuploidy rate in pre-implantation embryos.
The author has observed total aneuploidy, trisomy, monosomy, severe defects in the embryos.
Embryos – good clinical practice
By good clinical practice, we mean performing pre-implantation genetic testing and selective transfer of one embryo. Why is it so significant? We have started to do the selective transfer of one embryo several years ago, and physicians of the so-called ‘old school’ of reproductive medicine were worried because usually, they wanted to transfer 2 embryos. It’s associated with vitrification technology (freezing the embryos), and back then, we hadn’t had such a great and safe technology of freezing the embryos. The physicians were not sure that this freezing method would not have a bad impact on the quality of embryos. That’s why they didn’t want to use vitrified embryos. Nowadays, vitrification, also called ultra-quick freezing of the embryos is safe, you can be sure that it will have no risk of defreezing. There is never 100% of positive results, but it’s close to 99%, so you shouldn’t be afraid of freezing the embryos.
The importance of implantation
The main goal in this whole process is to make sure you’ll be able to take your healthy baby home. However, a good embryo is not a guarantee of pregnancy.
The very beginning of your pregnancy is the process of delicate interaction between the embryo and the endometrium, and it is called implantation. For many years, it was thought that in this process, there were just two main players – embryo and endometrium. Around 20 years ago, a team of investigators, among them Benkhalifa, demonstrated there are more players such as cumulus cells, sells, microenvironment and various growth factors which play an important role, contributing or hindering successful nidation.
When we talk about IVF success, we always should assess all other factors, even in patients who had ineffective IVF because of bad quality of eggs or advanced reproductive age and where an egg donation program could be the solution.
The main players are embryo, endometrium and also concomitant pathology
. We know that, for example, thyroid function has a great impact on the initiation of pregnancy and progression of pregnancy. We should assess all these features.
In every egg donation program, the endometrium is a very significant player because it is a natural biosensor of embryo quality. It has such a fragile balance between their capability to accept the embryo, we call it receptivity, and the capability to block the embryo implantation, so it’s called selectivity. This balance can be altered by functional and morphological alterations. When we are talking about morphological alterations is one of the most common defects which we observe. We take into account:
- inflammatory process (chronic endometriosis)
- hyperplastic processes (polyps or micro polyps)
- intrauterine synechiae (adhesions between the layers of uterine)
The endometrium is the internal layer of your uterus, it carries your uterus inside. The cavity of your uterus can be considered as an apartment for your future baby. If those conditions do not seem very optimal or proper for the embryo, the implantation will not occur. We may also observe so-called biochemical pregnancy when this interaction between embryo and endometrium has started but then were interrupted at the very early stage.
Chronic endometritis is the condition involving the breakdown of the peaceful coexistence between microorganisms and the host, immune system in the endometrium, resulting in a special type of chronic inflammation in the endometrium, characterized by non-apparent clinical signs.
The clinical signs of chronic endometritis are very latent, in most cases, you will pay no attention to them, for example, the characteristics of your menstrual bleeding can be a little bit altered. During your menstrual bleeding, you may notice some brownish bleedings. However, most women do not pay attention to that, and nobody sees these signs except the woman. That is why it is crucial to listen to your organism, you should be open with your physician and tell them about anything you’re worried about.
The prevalence of chronic endometritis differs very much. In the general population, it is present in about 10%. Patients with several ineffective IVF attempts or recurrent implantation failure or especially in repeated pregnancy loss, this rate can go up to 66%, which is very high. When we see a patient with a dramatic history of several ineffective IVF attempts, we always check the endometrium, especially if there was a history of several ineffective egg donation programs, because we see such patients all over the world.
Another thing is functional alterations: compromised implantation window. It can play a great clinical impact, and generally, it’s the basic knowledge about our physiology. It’s not that implantation is just the delicate dialogue between embryo and endometrium, this dialogue should also be synchronized. The synchronization of the processes of embryo development and the maximal endometrial receptivity is necessary. In the egg donation program, we already have the embryo developed till the stage of the blastocyst. In 65% of women, this stage of the blastocyst, in natural life, will be synchronized on the 6th day of producing progesterone inside the body. In many protocols, especially in our traditional understanding of endometrium preparation, it is recommended to place the embryo into the uterus after 5 days of administration of progesterone. However, actual data demonstrates that it’s just about 65%, it’s not that much if we talk about woman’s happiness. Unfortunately, we have patients with ineffective egg donation programs in different clinics with good embryo quality.
ERA and BeReady tests
Nowadays, we have two tests called the ERA test and BeReady test, which will help us identify the right time to perform an embryo transfer.
It requires doing a biopsy of your endometrium and assessing their expressions of a panel of genes to be sure that we know their proper time to perform a personalized embryo transfer. On the slide shown, the investigators have compared several groups of patients, all the groups were standardized by age, BMI, the number of embryos per embryo transfer, they have compared frozen embryo transfer, fresh embryo transfer and personalized embryo transfer. Comparing the two groups, frozen and fresh embryo transfer, we see the result is high, it’s close to 60%. However, in a group of personalized embryo transfer, the rate of clinical pregnancy was 85.7%, which is very high.
On the slide shown, there are some samples of results of the BeReady test analysis report. The green area means the endometrium is receptive, and if we see a low score, it means the endometrium is pre-receptive. If we have a high score, it means that the endometrium is already post- receptive. Sometimes if there is a very high displacement for this window of implantation, we have to repeat these results. In most cases, one examination provides enough information to enhance your outcomes.
The woman was 44 years old
, she had 9 embryo transfers in her medical history
. She had 4 embryo transfers performed with her own oocytes and 5 with the egg donation program.
She started her treatment 10 years before her application to Ava-Peter clinic. She had a rather difficult medical history, she had severe endometriosis, chronic endometritis with severe activity and autoimmune components
. We suggested an egg donation program following pre-implantation genetic testing, her husband’s sperm quality was also bad because of the age, and there was some concomitant pathology
. We implemented pre-implantation genetic testing (PGT-A), and among 6 embryos, we observed that just 2 of these embryos were good.
When we were sure that we have enough embryos, we started to prepare the uterus for embryo transfer. We performed a hysteroscopy, her uterus was covered by micro polyps.
Unfortunately, it’s not that easy to detect these micro polyps by routine ultrasound, and that’s why she wasn’t aware that she has some problems with her endometrium. We removed all those micro-polyps, after that, we performed delayed frozen embryo transfer in a natural cycle because, despite the age, she had a rather regular menstrual cycle. If we can implement embryo transfer with no additional hormones, we usually try to minimize our intervention and make it a natural cycle. As she also had an autoimmune component, we recommended PRP therapy, it’s so-called Platelet Rich Plasma, this plasma has great antibacterial activity and also it contains many growth factors which make a very delicate recovery of natural resources of the endometrium. We have obtained clinical pregnancy
, we transferred just 1 embryo, the delivery was performed naturally, without a cesarean section.
I believe that implantation is a: Symphony Orchestra. It doesn’t matter if it’s an egg donation program, conventional IVF cycle or surrogacy program, that doesn’t change it. Also, an egg donation program is an effective solution only in the context of receiving a competent embryo. Sometimes, there are indications for pre-implantation genetic testing and its implementation in egg donation programs, and in my mind, good clinical practice in the reproductive field requires attentive assessment of all factors which can have an impact on the implantation process.