- how the donor selection process looks like
- what physical characteristics from recipients are taken into consideration
- what Fenomatch® technology is about
- what impact epigenetics has on egg donation treatment
Epigenetics and phenotype matching in egg donation treatment
Will my baby look like me? Phenotype matching & epigenetics
If you’re planning IVF treatment with donor eggs and/or donor sperm, you might be wondering if your baby will look like you. With genetics research rapidly advancing, nowadays we realise that heredity is a much more complex issue than we previously expected. In this IVFWEBINAR with dr. Laura García, Medical Director of Clínica Tambre in Madrid (Spain), you’ll find the answer to one of the most exciting questions: which traits are inherited from the egg donor – and which (if any) from you and your partner.
Donor selection criteria
Choosing an egg donor is undoubtedly a complex and demanding process. Dr. Laura García starts her presentation with describing egg donors’ first selection criteria. In the light of the Spanish law, egg donors have to be less than 35 years old, they have to have a minimum height of 1.55 metres and a maximum BMI of 30 (with the ideal being around 20-25). At Clínica Tambre, potential egg donors are first invited to the meeting with the Nursing Team, during which they are checked in terms of medical conditions and hereditary diseases. They also have the whole egg donation process explained to them in details. If the donor is accepted, she then undergoes an interview with the clinic psychologist- in order to exclude any psychological disorders or mental health problems. If all this process turns out all right, then comes the time of medical tests. These include general health research (e.g. complete blood count, blood group +Rh and serology), gynaecological tests (ultrasound, count of antra follicles, smear test, etc.) and genetic assessment (karyotype, cystic fibrosis, x-fragile and basic recessive mutations as well as the carrier status test of more than 300 genes).
Sperm donors, just like egg donors, have to be less than 35 years old and have the maximum BMI of 30. Their minimum height should be around 1.70 metres. Their first consultation at Clínica Tambre is with the Andrology Team that confirms there are no medical conditions or hereditary diseases within donors’ families as well as explains the sperm donation process to them. Dr. Laura García says that the sperm donor selection process also includes an interview with a psychologist, psychological tests and medical assessment, such as general health research (e.g. complete blood count, blood group +Rh and serology) and andrological tests (sperm count, sperm and urine culture and PCR for chlamydia). If all of the latter is alright, the medical team will follow up with the genetic screening of a sperm donor (including karyotype, basic recessive mutations and the carrier status test of more than 300 conditions).
According to dr. García, the selection of donors is always done by the fertility centre (in order to respect anonymity) and is based on physical characteristics of the recipient, the recipient’s blood type, the doctor-patient communication, genetic matching and immunological matching (when needed). The latter is conducted when a patient has a story of implantation failures or repetitive miscarriages. In such a case, the KIR test is performed. It is a genetic test that allows assessing the risks of the embryo being rejected by the maternal immune system. If the results show that a patient is a negative prognosis KIR (KIR AA), a specific HLAC1C1 donor has to be selected to improve the chances of the ongoing pregnancy.
Important physical characteristics
Dr. Laura García admits that Clínica Tambre offers a wide donor pool – they have around 2500 samples stored in their bank, all respecting very strict security rules. Because of that, they may provide a wide range of phenotypes and – what’s important – no waiting lists for egg or sperm donation treatment. This results in a greater chance of finding the perfect donor in terms of physical characteristics and fertility results.
In order to provide as much information on preferred physical characteristics as possible, patients need to hand in the questionnaire (included in the consent form of the treatment) as well as their photograph (sent or taken at the clinic). The questionnaire is composed of two columns (one devoted to the patient and the other to her partner), and each of them includes such important data as basic body parameters (height, weight), hair type and colour, eyes colour and ethnic group. All of this is to make the donor selection process more effective.
At Clínica Tambre, there is also one important tool used in the donor selection process – namely, Fenomatch® technology. It is Facial Matching with a scientific tool that uses biometric technology to identify facial point distances. It allows for a very accurate selection of the donor regarding concrete facial features.
Dr. Laura García explains that in order to select the donor with Fenomatch®, they use a simple photograph of a patient’s face. The Fenomatch® algorithm scans more than 12,000 data points in order to find the donor with the greatest biometric similarity. Fenomatch® is a great way to assure that all aspects of a patient’s appearance are taken into account and thanks to it, donor-conceived children are more likely to look like their parents. Patients receive a report certifying the use of Fenomatch® during the donor selection process.
Epigenetics in donation treatments
In biology, epigenetics is the study of heritable phenotype changes that do not involve alterations in the DNA sequence. As gene expression can be changed depending on the environment, dr. García says that the phenotype can also be determined by our surroundings – and not only gene inheritance.
It is said that epigenetics controls genes. It means that the environment we live in may either activate or silence the determined genes – and this affects each person’s appearance. According to this understanding, epigenetics is hereditary and makes us unique. This is good news for patients undergoing egg or sperm donation treatment. It turns out that even if genes come from the donor, the baby may still look like the recipient. All of this is because of the influence of the environment!
Dr. Laura García points our attention to one very simple fact – our minds always try to search for similarities between family members. However, there are families where the kids look like only one of the parents – or none of them. On the other hand, many egg donation patients, after giving birth, say that other people tell them how their baby looks like them.
It is important to remember that donor selection is a very tedious process, including medical, psychological and physical requirements. The detailed selection regarding physical features significantly increases the likelihood that the donor-conceived children will look like their parents. What all egg donation patients should remember first of all is that the baby develops in their environment from the beginning – and this will have a huge influence on the phenotype thanks to epigenetics.
Questions and Answers from the event
When you say physical characterisation, what characteristics do you mean?
This is height, weight, the colour of eyes, hair and skin and complexity of the body.
What does KIR mean? What is HLA-C1C1 donor?
It is not a routine test – it’s only performed in women having negative prognosis, such as implantation failure cases or repetitive miscarriages. Then, in this recipient, we will test the KIR receptors, or receptors of the cells and of the lymphocytes. And then, if she’s having a negative KIR result (KIR AA), we really need to select a donor having a blood test called HLA with the result C1 C1.
Do you have Asian/Thai egg and sperm donors?
Yes, we have Asian donors and we have a very big sperm bank in our clinic so we have all of these characteristics.
Will I see a picture of the donor that you choose for me?
Unfortunately, it is not permitted regarding our law. So after the treatment, you will only know the age and the blood type of your donor. That’s the reason why you need to choose a clinic that you really trust a lot. As you cannot see the pictures, you need to have a lot of trust in your doctor, the clinic and their donor selection criteria.
If I have a baby using an egg donor and the child has a DNA test, will the child be related to me at all?
I suppose you mean the DNA test of the child and the DNA test of the mother (the recipient). Unfortunately, it will not be similar. So if the child does this kind of test, they could eventually know that you’re their mother genetically.
How much does the KIR test cost?
I’m very bad with financial issues but I think it’s something around 150 Euros. But please contact my colleagues at the clinic and the patient care coordinator and they will give you the right answer.
Can we do all the tests in our own country and come to Spain only once for the transfer? How many times do we need to come to the clinic on average?
Usually, if it is a recipient with a partner being the sperm donor, we do recommend coming for a first consultation visit to confirm that the sperm is absolutely fine. Then we will freeze the sperm, with the maximum guarantees, and then we will move to the egg donation treatment in the laboratory. So then you need to come the first time for sperm freezing and the second time for the embryo transfer. But of course, it’s also possible to come only once, for a period of around one week, for the sperm fertilisation of the eggs and the embryo transfer. So it’s one or the other.
I have got B-blood sensitisation. What does this mean for me when going for a female donor?
It probably means that you need to have a specific selection in terms of the donor’s blood type. We will need a specific doctor’s report confirming what sensitisation it is and what kind of a donor selection we really need to take into consideration. We do have very complex and specific cases in our clinic where we need to have the doctor’s advice for important donor-related questions. But that’s absolutely fine, there’s no problem at all.
Regarding B-blood sensitisation, what do you exactly mean? Do you mean that the female donor must have the same blood group like mine or my husband’s? I am B negative and my husband is B positive.
Usually, the sensitisation has to do with the negative Rh. It means that this person needs a donor which is negative as well. But in that specific case, we need to check what the sensitisation is, what other results there are and see if it’s only the Rh-negative that we need to select in the donor or if there are other specific antigens or any other tests that we need also to carry out in the donor.
What is the minimum education level of the donor?
For us, donor’s intelligence is more important than the education level. We need to have the personal abnormalities excluded and that’s the reason why the psychologist needs to confirm donors are absolutely fine. The majority of our donors are of the university level but we also have mothers who are working at home or taking care of kids. As they have their fertility proven, they can offer their eggs and help other people to conceive. So we don’t have a minimum educational level test – it has more to do with intelligence.
Can I opt for a specific donor’s nationality and exclude others?
Our law and our system inform us that donation needs to be conducted regarding physical characteristics – that’s why we will only take these into consideration and we will not exclude any nationalities.
In some countries children can find out some more information about the donor when they are 18 years old – is this the case in Spain?
In our country, regarding our law, the donation is absolutely anonymous. So it is not an option for a child to find out anything about the donor. The only information is what the clinic reveals to the recipient.
What are the most liberal/transparent countries in terms of donor information?
I think in the U.S. there are some states where patients can really select their egg donor. In Europe, there are different laws so you need to check how it works in every country.
Is this KIR test very new? I’ve never heard of it. Is it similar to the ERA test?
The KIR test has nothing to do with the ERA test. The ERA test is an endometrium receptivity test to confirm how many days of progesterone are necessary to do the embryo transfer. The KIR test is absolutely different. It is a receptor in our lymphocytes and women having KIR AA are more likely to have miscarriages or implantation failures. So then we need to select specific donors to try to reduce the impact of KIR AA.
I don’t understand exactly what you’re testing with the KIR test. What are you seeking to understand about the woman who has had implantation failure? What do you understand about the donor? What is it that has to be compatible?
If there is a woman having many implantation failures, we’re going to do a lot of tests but we will also select a specific donor to try to maximise the chances of an ongoing pregnancy. If there is a woman having lots of embryo transfers (with no implantation) or repetitive miscarriages, we know it’s sometimes due to coagulation disorders, chromosome disorders or partner’s sperm. However, sometimes it’s also because of the immunological condition. So this KIR test has something to do with immunology of the recipient. If there is a kind of a negative effect of a woman’s own immunological system, we need to select the best donor in terms of immunological system as well as to try to make it work best – giving her the maximum options of an ongoing pregnancy.
Do you recommend a couple who has never had a natural pregnancy (due to endometriosis) to have KIR and HLC tests done before the transfer?
If they have never had an implantation failure and everything has to do with endometriosis, it wouldn’t be necessary. I’ll just go ahead with the normal screening of the recipient and the donor.
What does KIR actually mean?
KIR means the receptors of the NK (natural killer) cells that allow for the implantation of the embryo. So if we’re having implantation failures or repetitive miscarriages, we’re going to test these KIR receptors in the lymphocytes in the NK cells. In this way, we will confirm if patients are having bad prognosis KIR (KIR AA) and if we need to select specific donors in terms of immunology.
Does KIR AA occur when your immune system is overactive and it attacks the embryo?
Yes, it could be expressed more or less like this. Of course, if you want more information on that, we can have a specific consultation via e.g. Skype to inform you what the exact meaning is. In other words, it’s a situation when a woman having KIR AA has fewer chances of implantation because her own immunological system could affect and attack the embryo.
If there is no common DNA at all, then what exactly is epigenetics?
Epigenetics says that the DNA of every embryo will be absolutely different depending on the uterus and the environment (meaning a diet, exercise, etc.). This is the environment that will modulate the expression of the DNA. Of course it has nothing to do with the transmission of the mother’s own DNA. It only means that the same embryo in different women can have different expression – in terms of physical characteristics, personality, the expression of genes that has to do with diseases, etc. And this is the meaning of epigenetics – the environment will modulate the expression of the embryo.
What if the baby doesn’t look like me? Is there any guarantee?
Unfortunately, there’s no guarantee in life. I’m a mother of two children, they’re my own children and there’s one that really looks like me and the other one that doesn’t. So it is not guaranteed. This is biology and not mathematics. What we can guarantee is that the donor will look like you – but we cannot guarantee anything that has to do with the baby. But of course, the child will be your baby, no matter how he or she will look like. That’s the one thing we know for sure – so don’t worry, everything will be perfect.
How does epigenetics affect the physical characterisation of the potential child?
Epigenetics cannot change the colour of eyes or type of hair – this has more to do with the general expression of the embryo. As I was telling before: it is the fact that the same embryo in one uterus will be completely different from the embryo in another uterus – depending on the kind of pregnancy, care that is taken, vitamins, sport, etc. So epigenetics it’s not about the physical characterisation of a potential child.
Do you do any IQ tests for egg donors?
No, we don’t. But that’s the reason why we have the psychologist in our clinic – and not all the clinics have a psychologist. She’s doing an interview directly to check if everything is all right in
terms of donors’ intelligence and she’s doing the tests to confirm there are no IQ problems and personality disorders.
Would you be able to transfer two embryos or is there a limitation of only one embryo at a time?
In 100% of times, we do recommend to transfer only one embryo. We try to avoid transfers of two embryos because we want to maximise the ongoing pregnancy, meaning the healthy baby and the healthy mother. If we transfer two embryos, there is a possibility that one or both of them will split out and then it could be triplets or four babies in a pregnancy. So we do recommend to transfer one embryo at a time. But of course, if the patient is asking to transfer two embryos at the same time, we need to take her health problems, particular situation etc. into consideration and see if we can accept it or not.
What about lymphotherapy? Do you have any experience in using it and what about the use of G-CSF inside of uterus?
We do have the immunologist unit in our clinic and, depending on each patient and their results, we do recommend what type of immunological treatment is necessary. We know about G-CSF inside the uterus but normally, we are not doing it. We are more likely to go for corticoids, such as Prednisone, or immunoglobulin infusions or even Dolkin, etc., but not really that kind of approach.
Could you kindly explain how the KIR test is carried out and in what way you would match a patient with an appropriate donor?
The KIR test is a blood test that will only be carried out in recipients who have adverse bad events such as implantation failures or repetitive miscarriages. Then, if they are having a negative KIR result (which is the KIR AA), we need to have a blood specific test in the donor to confirm that the donor is HLA-C1C1. In case of the KIR AA, the best combination to maximise the ongoing pregnancy is HLA-C1C1.
My understanding is that NK cells are Natural Killers cells. Women who have high NK cells are prone to miscarriage because NK cells basically attack the embryo. This is what KIR checks for – am I correct?
KIR and NK cells are in the same field of immunological conditions but they are different. We
can have normal NK cells range and percentage but by contrast, we can have the receptors
of NK’s that are bad prognostic. So it’s kind of the same but these are different tests and different possible problems in terms of immunological disorders in a pregnancy.
Are bloodstream NK cells the same as NK uterine cells?
It’s kind of different if you check in the blood and in the uterine cavity. Not in all articles they are referred to as blood or uterine cells – so it really depends on the literature. In our clinic, we are traditionally taking into consideration the blood NK cells.
With a donor egg, the mother will be the biological mother and the legal mother but not the genetic mother – is that right?
Yes, it’s absolutely right. This is the correct approach and the correct phrase for egg donation.
How do you find out the age of the donor after the embryo transfer? Is it on the report with a picture of the embryo transferred?
Yes, after the embryo transfer, when the woman gets pregnant, we will reveal the age of the donor. It’s very important during the pregnancy to inform your gynaecologist about the age of the egg – simply to know the risk of Down syndrome.
I have one child that looks exactly like my husband. If I use an egg donor, what is the possibility that the baby looks like his father and brother? Is there a way to find out the dominant gene?
We have lots of patients reporting that, in egg donation, the baby looks 100% like their husband. So I think it has more to do with our tendencies and what we want to see. Of course, we need to take each couple and their preferences into consideration and confirm if we can select the physical characteristics of the husband.
Does the transfer of donor eggs occur in a fresh cycle? I would go for a fresh cycle rather than for a frozen one.
95% of our embryo transfers are always with fresh cycles. Only if we know that the recipient is not flexible in terms of dates and she needs to have a specific date of the embryo transfer, we’re going with vitrified eggs. But otherwise, we usually go with fresh donation.
Which tests are recommended for someone with several IVF failures with donor eggs?
We really need to study this case. If there were a lot of embryo transfer failures with donor eggs, then we need to do endometrium tests, such as ERA or endomeTRIO tests and hysteroscopy. We also need to check coagulation and immunological disorders, such as KIR, NK cells, thrombophilia and check if we need to use complementary treatments. We also need to study embryo. If there is a suspicion that the embryo was abnormal because of the sperm, we’re recommending the patient’s husband or partner to do specific tests in the sperm, too.
If we try an embryo adoption, what will be the best kind of test for me?
We would need to study your case individually. Perhaps it would be best to do the endometrium test to confirm if there are no abnormalities in the reception and also to check if we need to go for coagulation or immunological tests. If it’s only your first round, then it’s not necessary to add any specific tests.
How can you tell the age of the embryos?
We’re not going to tell the age of embryos because embryos have no age. We can only say if the embryo is day 3 or day 5. Of course, if you are talking about the age of embryos that are frozen in our clinic, we cannot transmit this information. However, it is important to know the age of the donor because it’s different if she is 20 or 28. You will need to transmit the donor age to your ob-gyn to do a specific follow-up during your pregnancy.
How long can frozen eggs and embryos be stored?
Embryos and eggs can be stored till the age of 50 of the recipient. Of course, we recommend transferring them earlier (before the age of 50) but this is still the possibility.
Is there a difference in price between a fresh and a frozen cycle?
No, it’s exactly the same price – there are no differences.
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