Choosing perfect egg donor for the IVF cycle
The egg donation process, for its many advantages and opportunities, still remains a touchy subject for many patients. The anonymity enforced by many European countries often makes patients uneasy – how sure can I be that the donor actually looks like me? What if my child ends up looking different from me? These are some of the most common concerns expressed by patients.
To dispel some of the myths and shed some light on the donor matching process, we invited Prof Evangelos Papanikolaou and Petroula Tatsi from the Assisting Nature clinic in Thessaloniki, Greece. Their clinic is considered one of the best in Europe, if not the world – and they’re kind enough to share their knowledge and experience with all of us.
As all of you know, egg donation treatments are offered mostly to patients of advanced maternal age (between 43 to 50 years of age), those affected by premature ovarian failure, women who have experienced multiple implantation failure, as well as former cancer patients and those suffering from chromosomal anomalies or genetic disorders. Fortunately, the negative effects of all of these medical histories can be bypassed simply by substituting the mother’s own oocytes with those of a healthy donor. Since the donors undergo very detailed testing before they’re allowed to donate, patients can be sure that the eggs they receive are of a sufficiently high quality.
The question, however, remains: why would anyone decide to be a donor? Many potential egg donation patients express that concern. As monetary compensation for donations are minimal (as dictated by the current legislation), why would anyone undergo such a time-consuming and sometimes physically uncomfortable process?
On the other hand, what about the patients? While their hopes often lie with the donation program succeeding, the prospect of undergoing such a treatment still is a stressful one. Many patients report feelings of doubt and guilt associated with egg donation, as well as a fear that they will not have a biological bond with their child.
From the clinics’ point of view, egg donation programs are some of the most sensitive undertakings to handle; the responsibility for the entire process is in the clinic’s hands. As such, doctors and other specialists involved with the process focus not only on the medical aspects of the program – examinations, tests – but also on managing patient expectations and their state of mind, by establishing accurate success rates, providing counselling and explaining the minute details of the process to dispel any doubts or concerns.
The initial visit to the clinic involves the specialists explaining the entire process as well as scheduling the donation program. Following all the required examinations, success rates are estimated for the patient. The sperm from the patient’s partner can also be cryopreserved at this point; as we all know, thanks to advances in cryopreservation, using frozen sperm does not differ at all from using fresh samples.
Following that, the initial donor matching process begins. As we mentioned previously, minimal monetary compensation ensures women who decide to become donors do so out of purely altruistic motives. They then undergo extensive testing to ensure they’re healthy both physically and mentally, and that they are fertile enough for donation. Additionally, they also undergo extensive psychological screening to ensure they understand the full implications of the egg donation process.
Different countries have different criteria and requirements for their donors. In Greece, for example, donors are aged between 20 and 32, have an AMH of over 2 and are proven to be fertile – that is, they already had a child or they had an induced abortion. Additionally, they need to undergo extensive testing – their hormones are measured, a thorough family and genetic history is established alongside existing treatment history, and full bloodwork is commissioned to rule out issues such as vitamin D or vitamin B12 deficiencies. On the psychological front, the MMPI test is used to filter out potential donors with behavioural or psychopathological issues.
Other parameters are also taken into consideration while evaluating potential donors: they cannot have any history of drug abuse or STDs; they must be in a good physical condition – only non-smokers need apply, while their BMI must be under 28. Additional factors, such as blood group and educational status are also recorded for the purpose of matching with recipients.
Donors must also undergo testing for infectious diseases – HIV, syphilis, hepatitis B and C, and more. Additionally, a genetic screening and karyotype analysis is ordered to rule out thalassemia, cystic fibrosis, fragile X syndrome and other genetic anomalies that could endanger the life of the child. Additional testing can be ordered by the patient couple, if required.
Assisting Nature also offers additional genetic testing on demand, if the patient is worried about autosomal recessive diseases or diseases linked to the X chromosome. Genetic Compatibility Testing and Next Generation Sequencing services are also available. Finally, embryos themselves can undergo genetic screening in order to rule out any genetic anomalies.
Next Generation Sequencing allows for more in-depth analysis of patient-donor compatibility than ever before. By analysing over 200 genes, the risks of genetic diseases can be accurately estimated. The list of examined genes and disorders associated with them can still be expanded in the future, although by now over 300 diseases can be detected before the oocytes are even fertilized. Although the “perfect donor” may never exist, current medical science allows us to get reasonably close.
Once a donor successfully passes all of these tests, only then can they be matched to potential recipients. Donors are matched based on physical appearance – their phenotype – with recipients, taking into consideration factors such as height, weight, skin tone, eye and hair colours and more. Greece, unlike other European countries, allows potential recipients to also learn about the donor’s education, personality traits, religious background, and interests and hobbies in order to ensure a better match.
Greek law is very explicit as to the rights of both the donor and the intended parents. Anonymity is guaranteed – neither party learns the other’s identity, while the child is legally considered the offspring of its intended parents; the donor has no rights to the child and can never learn its identity. Legal consent from both parties is needed to undergo the egg donation process, which can be withdrawn up to the point of embryo transfer. Up to two embryos can be transferred per cycle, while surplus good quality embryos can be cryopreserved for future use.
The legislation states in no uncertain terms that the act of egg donation is an altruistic, voluntary and unpaid act. The only compensation the donors are entitled to includes days off work, and travel and medicinal expenses. It’s a completely anonymous process, with the donor’s identity kept strictly secret by the clinic.
Donated eggs come in two varieties – fresh and frozen. Fresh eggs are fertilized on the day of retrieval and usually require less eggs to achieve the same goal as with frozen ones. The cycles of the recipient and the donor don’t require synchronisation in this scenario, although it can be done if time is a concern. However, sometimes the patient needs to wait a certain amount of time for matching eggs to become available. Conversely, frozen eggs are retrieved and frozen in advance. Cycle synchronisation is not needed – the eggs are simply thawed, fertilised and ready to be transferred within the patient’s natural cycle. The treatment is simpler and faster, as broader choices are available immediately.
However, frozen egg donations are not without their drawbacks. For instance, not all eggs retain their good quality after being thawed, which leads doctors and fertility specialists to require more eggs to achieve the same result as with fresh eggs. Some oocytes also don’t survive the vitrification process – although that’s a rare case, as the survival rate for cryopreservation is up to 96.8% in some cases. Overall, however, the choice between frozen and fresh eggs does not carry a significant difference in success rates.
The delivery rates at Assisting Nature for different kinds of donation are as follows: fresh oocytes, 68%. Frozen oocytes, 60%. Frozen embryos generated from frozen oocytes, 55%. These success rates reflect the results achieved elsewhere around the world.
Patients considering undergoing egg donation at Assisting Nature can be assured that the clinic takes every step possible to make sure the process delivers the best results. Only high quality eggs are considered, while just as strict selection criteria are applied to the sperm. Generated embryos are placed in a time lapse incubator, which allows embryologists to monitor their development process in real time. Only blastocyst stage embryos are transferred, and even those undergo screening to ensure only the best quality ones make the cut. Steps are also taken to ensure a successful implantation within a properly prepared endometrium.
The clinic also prides itself on attempting to create the perfect personalized donation program for each of its patients. This personalisation includes embryo transfer tests, ultrasound scans and hormonal tests, a prerequisite hysteroscopy to evaluate the status of the endometrial cavity and a personalised hormonal preparation plan to ensure the best possible conditions within the endometrium. Their high success rate speaks for itself.
Prof Papanikolaou sums up his presentation by recommending patients give themselves time to come to grips with the egg donation process. A therapist may be helpful in processing feelings and stress which is commonly associated with IVF treatments. As for stress though, he recommends leaving everything in the hands of the clinic – that’s what they’re for, after all.
Questions and Answers from the event
What is the chance the baby will look like me? Is the recipient-donor phenotype match enough to be 100% sure?
A 100% certainty can’t ever be achieved – who’s to say the child won’t resemble its father more than its mother? This is true for natural births as well. The aim of the phenotype match is to ensure the donor’s contribution to the process is as close to your own as possible.
What happens when the child wants to know their origin once they’re grown up?
encourage parents to strongly consider this issue during the first five or ten years of the child’s development. According to our research, children conceived through egg donation have a less than 1% chance of accepting the circumstances of their birth. Parents usually talk about the topic with their children once they are mature enough to understand that the source of the egg doesn’t actually matter; that the egg recipient is the actual mother, as she is the one who gave birth to them and who raised them their entire lives.
Do you recommend performing day three transfers at all, or are blastocyst stage embryos the only ones that give the highest probability of implantation?
We only recommend day 5 transfers. The blastocyst stage is the final period of the embryo’s development at which it can be kept in the laboratory. Those two days matter – they allow us to observe embryos longer in order to more accurately estimate their chances of implantation, as well as perform diagnostics such as PGD.
Would you recommend PGS testing in general, or only in specific cases?
I don’t think PGS testing should be used universally at this point; it’s still an invasive procedure which only examines the karyotype and not actual genetic markers that matter in implantation. It’s a screening tool, but it’s not a genetic testing tool. However, great effort is being put into making it less invasive; in several years, I believe nobody will perform IVF without PGS.
Do you have your own donor database as a clinic, or do you share a database with other clinics? How large would such a database be?
We have our own database, which is also made available to an international authority for auditing purposes. Currently, we have around 250 phenotypes within the database.
Is there a difference in success rates (in egg donation) between fresh and frozen embryo transfers?
We addressed that during the presentation. Freezing of embryos does not harm their implantation potential. The rates are the same, although freezing eggs allows us more time to perform additional testing or to prepare the recipient’s endometrium.
Is it okay for an embryo to be frozen twice? Let’s say an embryo is already frozen and we want to perform PGT-A testing for aneuploidies – we would have to thaw the embryo and freeze it again. Will that process harm the embryo?
In the majority of cases it is not necessary to freeze the embryo – for instance, PGT-A testing is done before freezing the blastocyst. However, if the embryo is already frozen, what we can do is thaw it and perform a microarray PGT test, which gives us a result in 24 hours. Afterwards, we can perform a day 6 transfer – as you know, many clinics perform day 6 transfers with excellent results.
I have recurrent miscarriages. We transferred PGS tested embryos, which still resulted in a miscarriage. What further testing would you recommend?
In our clinic, we only had one case of miscarriage after transferring a PGS tested embryo. The probability of something like that happening is extremely slim – below 5%. You should undergo testing for thrombophilia, immunological testing, maybe even a hysteroscopy to rule out any congenital abnormalities with the uterus. If the tests come back negative, try another cycle using PGS. If it fails again, the next step would be to look for genetic anomalies that can’t be discovered using a simple karyotype mapping.
Sometimes, however, the reason for recurrent miscarriage may be something simple – for instance, the mother being immune to her male partner’s rhesus group.
What characteristics are most commonly inherited if the donor is matched with the recipient, from a genetics standpoint?
The appearance of the child – its phenotype – is not only decided by the donor’s DNA, but also the DNA in the sperm. As such, what the child inherits is dictated by both the egg and the sperm, and which genes are dominant or recessive. Some traits can also skip a generation – children may sometimes inherit traits such as eye colour from their grandparents.
However, because donor matching is performed primarily on the basis of the phenotype, characteristics such as eye colour, hair colour, skin colour, height, weight, blood type and others are always shared between you and the donor.
Is there any legal requirement to store personal information of the donors? The child may want to know where exactly they came from in case some gene therapy or cell healing treatments become available in the future.
At the moment, everything is stored in accordance with the GDPR. However, European guidelines also clearly state that in case of a genetic problem which can affect the health of the child or the donor, either the parents of the child or the donor are required to disclose that information to the national authority concerned with regulating IVF treatments. If it turns out that every child born through the donor’s donations need to be tested, the court may decide to break the anonymity clause.
What are your thoughts about the natural FET cycle, compared to a medicated FET cycle? I recently tracked my endometrium lining during my natural cycle (scans on days 2 and 14) and my lining was much better than it has been during a medicated cycle.
There are many studies that show no difference between the two types of cycle. However, some patients respond better to no hormonal treatment at all. The only disadvantage of a natural cycle is less flexibility when it comes to scheduling the transfer. Otherwise, there are no other drawbacks. If your embryos are frozen, we can perform the transfer during the natural cycle without any preparation.
Would you recommend FET on the day the embryo is thawed or on the day after the culture?
This is a very easy question – we thaw the embryo in the morning and transfer it in the evening. As the embryos are already in the blastocyst stage, there is no reason to wait another day.
Do you only have Greek egg donors? Are other phenotypes available?
You only need to live in Greece for just a month to realise we have access to almost every phenotype – we have Mediterranean donors, European donors, North African donors, Arab donors… the list goes on. Greece is a very diverse country due to our location and history.
I have immunological issues. What treatments are available to me?
In cases of repeated implantation failure we provide high doses of corticosteroids combined with intralipid infusions. However, like I said in my presentation, I’m not convinced that immunological issues are a major cause of RIF – I believe it’s only the cause of less than 1% of all cases.
Do you perform embryo donation or embryo adoption? We also suffer from male factor infertility.
Both, actually. These types of treatments are quite rare, as few couples donate their embryos. For male factor infertility, we would recommend a sperm donation.
I have multiple non-operable myomas. How can I prepare my uterus? Last year I was pregnant with a donor egg, but I lost the pregnancy shortly before the end of the first trimester. I also have autoimmune thyroiditis.
As long as none of the myomas are sub-mucous, they shouldn’t be a problem – I saw women with eight, even ten myomas deliver healthy pregnancies. However, without having ultrasound or MRI results, I cannot give you an accurate answer. If there are more than five myomas, you should consider a laboroscopic myomectomy. Within four months you can be healthy enough to attempt another cycle.
As for the thyroiditis, your endocrinologist can help you control your thyroid levels and, if there are no contraindications, we can increase your dosage of corticosteroids during the progesterone treatment phase.
Do you have another webinar coming soon?
There will be another webinar with Assisting Nature in May. All the information will be available on our website. We host a different webinar every Tuesday.
How does matching work with embryo adoption? Is it similar to a double donation process? Is there strict phenotype matching? Is the process available to single women?
We do phenotype matching, although it’s impossible to be strict in this procedure, as there are fewer patients when compared to regular egg donation. Whether you’re single or not, it makes no difference – the procedure is available to you.
I had one embryo transfer with hormone replacement therapy (estrogen and progesterone). During that treatment, I had my own ovulation, which meant the transfer didn’t succeed (the embryo was healthy after PGT). Does it happen often that a woman has her own ovulation during HRT?
The first question should be: why did your clinic perform a transfer if you had your own ovulation? It does happen – about 5-10% of the time recipients experience ovulation. It’s our obligation to identify if you’re ovulating. If that happens, we can cancel the transfer, freeze the blastocysts, change the patient’s medication and wait a month; because of the changes to medication, we have a 100% certainty this situation does not repeat itself.
How do you handle the stage of corticosteroids? Do you have to subsequently reduce them after three months of pregnancy?
Yes – we stop all of the medication after ten weeks of pregnancy, including the corticosteroids. We halve the dose over three days, quarter it over the next three days; after six days you take no corticosteroids.
How often are intralipids transferred?
In cases of repeated implantation failure they are always available. The patient can also request intralipids themselves.
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