By fertility experts from Spain.
Are you planning to start IVF treatment using donor eggs? Do you have lots of questions about egg donation, donors and the qualification process? You are in the right place. Watch the webinar by EggDonationFriends and Assisting Nature Greece: “Donor eggs – it’s all about quality, no. of eggs & qualification process“. We have again invited Dr. Robert Najdecki, MD, Ph.D., Co-Founder and Scientific Director of Assisting Nature, fertility clinic located in sunny Thessaloniki, Greece.
Deciding whether to use donor eggs or become a donor, is a huge decision to undertake. The process should be sensitively managed, with trust and respect operating between all parties involved, especially the clinic. So how can medical professionals ensure this happens, and how are the right donors and recipients matched, in order to create a positive treatment experience, for all?
In this webinar, dr Robert Nadjecki, co-founder and Scientific Director of Assisting Nature college of reproduction, in Greece, discusses the issues surrounding the use of donor oocytes (eggs), and outlines the procedures, and protocols, his clinic uses.
In today’s society, egg donation has become a widely accepted and pragmatic solution for many couples who have struggled to conceive, due to female factor infertility. Dr Nadjecki advises that, from research, no adverse effect on the relationship between mother, father and child, has been shown, despite the lack of a genetic link between the mother and her offspring. He describes egg donation as “the gift of parenthood”.
There are many factors as to why donor eggs may be considered, for couples trying to create their family. Low oocyte quality and quantity is widely accepted as the main reason, and this can come from varying determinants, such as early menopause, chromosomal and/or genetic anomalies, and in women who have undergone cancer treatment, and whose ovaries may now not respond to hormonal treatments.
As with any cycle of IVF, whether using donor or own oocytes, the primary, the objective is to transfer a healthy embryo for implantation, with the aim of a successful pregnancy and live birth. When using a donor, the medical process of fertilization is no different when a woman uses her own eggs; the donor undergoes the process of stimulation and the oocytes are retrieved, these are fertilized with the recipient partner’s sperm, and the embryo is transferred into the recipient, to carry.
For couples, who have undergone prior IVF treatment themselves, the majority of questions and concerns raised, tend to revolve around how donors are selected and screened, and how the actual process will be coordinated and carried out.
As Assisting Nature clinic is based in Greece, dr Nadjecki explains that he can only advise on Greek law; differing legislations could apply, depending on where treatment is sought.
In Greece all donors of oocytes, sperm and embryos must, legally, remain anonymous, and the act of donation is altruistic; it is voluntary and unpaid; however, compensation is permitted for travel and time off work. At Assisting Nature, all potential donors are initially screened and, if they are found to be suitable, further, intensive, testing is then carried out, including medical, genetic and psychological analysis. In order to donate, with this clinic, donors are required to be mentally and physically healthy, fertile and between the ages of 19 and 32. Alongside the donor, the recipient couple will also undergo tests, including blood analysis, endometrium screening and, for the male, a sperm analysis, checking for DNA fragmentation, or other potential issues, which could affect the outcome of the treatment cycle.
Despite the similarities, IVF with donor oocytes is a more complicated process, than IVF between just one man and one woman. In a donor cycle two women are being treated simultaneously, therefore schedules must be aligned and compassion, is required. Dr Nadjecki stresses how it’s the responsibility, of each clinic, to ensure that both women involved are shown due respect and care.
Once recipients have decided to go ahead with donor egg IVF, the matching can begin. At Assisting Nature this is completed by searching their database, using criteria such as phenotypes; height, weight, hair, and eye colour, skin tone and ethnicity. Blood and rhesus groups are also matched, along with education and personality types e.g. the introvert or extrovert natures, of the recipient and subsequent donor. After confirming a match, the final steps for the treatment are confirmed.
Assisting Nature will transfer embryos at blastocyst (five-day) stage, wherever possible, although dr Nadjecki warns that the route from oocyte to blastocyst is not always easy, or even guaranteed. It’s important to remember that, even from the same individual, not all eggs are identical and, as with embryos, they may vary in condition. This can be due, in part, to the stimulation protocol followed; donors should not be overstimulated. For embryos, the calibre of sperm used also plays a major role.
How then, can clinics ensure that only good quality embryos will be transferred, into the recipient, and therefore increase the chances of a successful outcome?
PGS (preimplantation genetic screening) and NGS (next generation sequencing) can now be used to detect any abnormal, or aneuploid, embryos. The screening is usually carried out by embryonic biopsy and analysis, with the results enabling embryologists to select the euploid (“normal”) embryos, for transfer, which should then offer over a 60% possibility of implantation.
IVF, with the use of donated oocytes, can be a very successful way for couples to conceive and research, from Assisted Nature, shows a 59% ongoing pregnancy rate from their treatment when using donor oocytes. For an egg donation program to be a positive experience, for all involved, dr Nadjecki advises that recipients, and donors, should look for clinics with a high ethical core, offering sensitive and well-orchestrated coordination, between all participants, in addition to a well-trained medical staff, demonstrating professionalism whilst understanding that each fertility journey is always unique. His belief is that all donors and recipients are individual and need to be treated that way; donation programs should be tailor-made, and personalized, for every person involved in the journey.
It depends. In a case where we have very good sperm and a confirmed donor, the chance of having a good blastocyst with a good EGS is very high. In this case, it may be 100%. Where sperm is abnormal or of lower quality, the chance of aneuploidic blastocysts is much higher. PGS is the answer to our patients and a transparent way to answer whether they have a normal blastocyst. In this case, we would have over 60% possibility to have good test results and a normal implementation.
The DNA fragmentation test is a way to tell the percentage of damaged sperm in the sample. Through DFI we are able to determine the percentage of damaged sperm and, if this is under 30% we are okay to proceed. If the DFI index is over 60% we have a problem and we must inform the couple that there is a high chance of having an abnormal blastocyst. We then help them decide what to do; whether they want to perform IVF with the husband’s sperm, knowing the risks, or to proceed with the donor sperm.
Of course, it’s possible but actually, we don’t use it every day. The quality of IVF treatment and positive outcomes depends, in general, on blastocyst quality. We perform a hysteroscopic evaluation with some scratching and, if we have checked the recipient’s uterus for any complications, such as fibroids, the chances of having a negative result due to antibody reaction is very low. In these cases, we would use, at the time of embryo transfer, an intralipid infusion.
Under Greek law, we are obliged to match the blood type and rhesus type of the donor and recipient. I think that from the point of view the couple, this of value as you know you will never have problems related to this.
At every stage, we have an assessment of eggs and, afterward, of the embryos themselves. After collecting the eggs, there is an assessment to be sure that they are mature and are ready for vitrification. There is a very simple biological test for this and an egg that is not mature or is abnormal does not proceed to the process of vitrification: only good eggs are made ready for further procedures.
We keep patients for one hour in our unit to rest after which, they are ready to go home. In Greece, there is no obligation to stay for a long period of time and there is no connection between pregnancy rates and resting periods after embryo transfer. This is a very short procedure and, if there are no complications, the blastocyst, which is placed in the endometrium is ready to start implantation, exactly as in the normal process of fertilization. We prefer to not keep the patient in for a long time and, as I said, there is absolutely no connection with positive or negative outcomes.
This is something we discuss with the patient to decide what they want to do. If we have good blastocysts, it may be that a single blastocyst transfer is best, to avoid the risk of twins. If the blastocysts are of lower quality, or if we need to perform a second embryo transfer, maybe, in this case, we will transfer two blastocysts. However, in every case, this is a matter of discussion between the patient and doctor.
It’s about 8% in our clinic.
No. As I explained in my first webinar, we have many options. Which eggs we use depends on an agreement with the patient and whether the patient is able to be here to be involved in the process of sperm sampling or for the donor pick up. We prefer to have a frozen sperm sample and to use fresh eggs, but whether we use vitrified eggs or not isn’t really the point. The point is to have very good sperm and with very good synchronization and conditions.
Yes, we use these drugs and medicines in the process of preparing for embryo transfer. We start to use the corticosteroids, aspirin and sometimes heparin injections from the moment of fertilization; that is five or six days before the embryo transfer and continuing until we have a positive test. Afterwards, we review this on a case-by-case basis.
We start with estrogen from the first day of the patient’s period and progesterone on the day that we start fertilizing the eggs. If Day Zero is the patient’s normal day of ovulation, we would perform this 6 days before the transfer. We give normally give progesterone vaginally, with a vaginal cream, or with subcutaneous infusion or injection, depending on the patient. We continue with progesterone until there is a positive pregnancy test and we can detect a heartbeat. After that, we decrease the dose step by step.
Not every blastocyst has the implantation ability, even though they have tested euploid. Not all blastocysts are equal. The endometrial lining was described as perfect, but what about at synchronization? In every patient, we measure the progesterone and levels of estradiol. If the level of progesterone is high, we stop the transfer and start again from the beginning. This is very important for synchronization and we have had cases like this, which can lead to negative results. In conclusion, synchronization of the transfer involves a very detailed hormonal assessment regarding substitution protocols and needs to be checked at least two or three times to see what the progesterone level is. Of course, it is important to have very good endometrium and to be sure that the measurements are good, using the same doctor and the same ultrasound equipment. I have also seen cases where the endometrial scratching was not absolutely normal, so we prefer to do a hysteroscopy evaluation here, to see the endometrium and to be absolutely sure that we are able to evaluate the condition of the uterus.
We use corticosteroids, usually two tablets per day, and in our opinion, this is enough to have the very small suppression effect required. We start this medication five or six days before the embryo transfer. In very rare cases with immunological problems, there is the option to start this medication from the beginning of the cycle.
No. It’s not necessary. Most of our patients return to their countries the same day, or the day after the embryo transfer and then continue medication and wait for the results of the test done in their own country. It’s not necessary to stay here only for this reason. You can combine the treatment with a vacation in Greece, of course, and there are very many attractive places here with many well-known tourist resorts within 100 kilometres of our clinic.
If this is of importance to the patient, and for some, it is not, we will do all we can to find the best match: height, weight, eye colour, and hair colour. This is an absolutely normal procedure.
Yes, we do. In our opinion, PGS is a very good way to answer certain questions and to be more transparent with our patients. We can say with certainty that the blastocyst is euploid, and, if a blastocyst is euploid, we have a greater chance of a successful pregnancy. However, with a negative pregnancy result, where the PGS was normal and we transferred, say, two euploid blastocysts, we must look elsewhere for a diagnosis, perhaps some dysfunction in the endometrium and perhaps perform hysteroscopic scratching. PGS in IVF procedures is the future for us. At the moment, it is an expensive procedure and this is the problem. Probably, in the next five years, the price of PGS will be more acceptable to more patients and will become a routine procedure in all IVF centres. It has real value for doctors and for patients.
The first step is to collect all the recipient’s patient details and, of course, by law, we are required to match by blood type and rhesus. This is the first step. The second step is to look at the height and weight, eye and hair colour. For some of our patients, education is very important. In very rare cases, a recipient will request a donor from Africa, not always easy for us. With our recipient patients’ concerns in mind, we try to match the donor accordingly. However, the most important thing is matching the blood type and rhesus group because this is obligatory in Greece.
Every further test is very good information for us and has a value, and, of course, the endometrial receptivity test, from a genomics point of view, is a very precise test. There is a great discussion about this test; it’s not for all patients, not in very simple cases or if the patient is going to have their first embryo transfer. However, if we notice that there are some problems with synchronization, with rising progesterone levels, it is very important to determine the implantation window, something which is very different for every patient. In these cases, we would we recommend ERA, but only in certain special cases, not as a routine procedure.
Donors spent a long time here completing a history that we double check. They then complete another medical history and all of this data collected is checked and cross-referenced. We collect a deep family medical history based on the CRM American Society of Medicine guidelines. We test and the donors talk with the staff in our donation office in a very detailed, very involved process. The donor visits our clinic many times to be confirmed to the next step in the process. All this data is checked again and again. We have three levels of checking their medical history in setting the status of the donor.
Yes. We routinely control the level of Estradiol, LH, and progesterone during donor stimulation and of course during substitution protocols in our recipient. We also routinely check Estradiol, LH, and progesterone to have a balance between the levels of hormones. This is very important to us.
We select for the recipient and in most cases, we prepare files on between two and five donors for every recipient. We allow them to think it over and to choose the donor, with our advice.
Since we started our programme, we have gathered some statistics showing that three blastocysts is the average, and, of course, more if the sperm is good. Three blastocysts it’s a minimum for a woman to have at least two embryos to transfer and then have an over 65% cumulative pregnancy rate in our clinic.
We have a two-step confirmation of this data. During the first meeting, we collect some information and afterward we give them a very detailed medical history to take home and to bring to their next visit. We match what they wrote in the first meeting against what they answered at home. If the donor is confirmed to the third step, this process is repeated with another staff member and checked for the third time. It would be a very rare donor who could give incorrect or unrealistic data on three occasions, at three different times to three different staff members; we haven’t had any such case.
It depends on the age of the patient and the normal function of the endometrium. It’s not easy to count and say that this patient must have seven or eight or nine millimeters thickness. In some cases, for some patients, seven millimeters is enough and this is their thickest possible. For another patient, 10 millimeters maybe low. It is very important to check it and to have a monitoring cycle, sometimes without medicines, or in some difficult cases or special cases, with the use of some medicines to see the reaction of the endometrium to the medicine. This is not a routine procedure but it’s within our strategy of personalizing reproductive treatments. We must see every patient as an individual, to check everything from the beginning as no two patients are the same. It is absolutely critical to prepare procedures for every individual patient, but the short answer is that we prefer the endometrium to be over seven millimeters.
We routinely use Kitazato freezing solution for blastocysts and after thawing we do assisted hatching or collapse by a laser before freezing, but not both: one technique is enough. We have done some research and the results show that it’s very important to leave the blastocyst after thawing for over three to four hours to see the condition of the blastocyst after thawing. Then, if you wait longer you can have the normal hatching, natural hatching without intervention from us. I can say that in half the number of blastocysts, we have noticed this process of natural hatching. This is the answer to patients who are here and who are waiting for embryo transfer. In many cases, the lab waits to see natural hatching. This is the reason that we prefer to wait some hours, but in many cases, this is not easily synchronizable with the patient; some blastocysts may be ready in three or four hours, and others need five or six hours. Then we use all available procedures, natural hatching or laser hatching, depending on the decision of our lab director.
Yes, of course. It is a new trend and good practice to prepare genetic panels that have all the available mutations of the same nationality, for example for Europeans, North Europeans or East Europeans. We use these panels here with, as example antigens for breast cancer, very common now, and of course for many others. We have a test which we call the Colour Test where we are talking about 30-40 types of mutation which involve the breasts, ovaries, endometrium, stomach, colon and other organs. I think that it’s the future in the screening of not only donors but all IVF patients. Its use will grow because it is of real value to all of us.
Pre-implementation genetics screening will show us if the embryo is euploid, that it has a normal karyotype, that we will have no problems with some genetic diseases based on karyotype. Pregenetic testing and those panels we discussed earlier are about other mutations which are, for example, in one of the partners or in general in the population living in one place in the world. This may be a monogenetic disease and we must say here that, while we try to test for all of these, this is impossible at the moment. There are very many monogenetic mutations that are very difficult to test for and therefore exclude donors from the pool. The tests which we perform now every day are getting better and better, but still, we have many monogenetic diseases that we can’t test before the procedure. I think that in the next few years further research will improve the situation, but at the moment we must say, while we do all our best to examine the donor and recipient and, afterward, the blastocyst, it’s still not enough to have all genomic information. It’s getting better and it’s not the end of the story.
Low AMH tells me there’s an issue with your ovarian reserve. The dose of hormones you receive during your next cycle has to be adjusted to match your AMH. Some low AMH patients experience more success with a smaller dose of hormones. However, if your embryos cannot achieve the blastocyst stage, this means your egg quality has deteriorated to the point where the only viable option would be egg donation.