In this webinar, Dr Elias Tsakos, FRCOG, Medical Director at EmbryoClinic, Thessaloniki, Greece, discusses the egg donation process, and how egg donors are selected and matched with recipients. He’s also talked about egg donation pros, cons, and dilemmas.
Over the years, there has been a massive change from IVF with own eggs to egg donation IVF in the western world. There are a lot of challenges regarding egg donation, there are a lot of dilemmas and advantages and disadvantages.
Dr Tsakos started by listing the indications for egg donation, and the first one is advanced reproductive age. However, he emphasised that advanced maternal age used to define a female age as over 35, nowadays, with the advancement of technology that has increased the success rates of own egg IVF in the late 30s female group, advanced reproductive age is usually women over 40. There are cases of ovarian failure like premature menopause, which can occur as early as 25, 30, the late 30s, or 35, it would include an ovarian failure secondary to surgical or medical chemotherapy or radiotherapy treatment of the ovaries. Even benign cases like endometriosis severe endometriosis and surgery could damage the ovarian reserve and may lead to some forms of failure.
Also, other conditions like infections or idiopathic unexplained premature ovarian failure are one of the causes of resorting to egg donation. Poor oocyte quality is another indication of egg donation, which is either expressed by a few eggs or low-quality eggs regardless of age. Recurrent IVF failure so any couple who’s failed multiple times to conceive through IVF would indicate an egg donation, and also miscarriages and pregnancy loss could be an indication for egg donation, especially when it’s associated with either poor oocyte quality through IVF or some kind of ovarian failure or advanced reproductive age. Genetic disorders, either karyotype or gene disorders, could form an indication also for egg donation. Last but not least are endocrine disorders like hypogonadotropic hypogonadism. These are the main reasons, but there could be some other categories that would indicate egg donation for certain couples.
There are several advantages of egg donation conception for couples or single women if they decide to opt for egg donation in the IVF process. The first one is a higher success rate, those rates can vary between 50 and 70% per embryo transfer, vastly depending on whether we transfer 1 or 2 embryos. In most European countries, including Greece, never more than 2 embryos are transferred in the egg donation cycle. In that case, the success rate per cycle could be as high as 70%, there’s a lower miscarriage rate and this is always compared to the own eggs’ treatment. One of the main reasons for that is that the egg donation cycles involve younger than 35 years old donors, although in many cases, donors are younger than 30. Therefore, the chance of miscarriage when genetic material is used from somebody in their 20s is much lower compared to using their own eggs IVF genetic material of someone in the late 30s, or 40s.
Another advantage is the fact that the donors are thoroughly screened, and vastly that screening is more in-depth compared to the own egg IVF. There’s also a lower physical complication rate for the recipient who is resorting to egg donation treatment because there’s no risk associated with ovarian stimulation, there are no risks associated with egg collection and hyperstimulation or infection. Egg donation also offers the pregnancy experience itself, the childbirth experience, the time to get prepared for this experience, the lactation experience, and the bond with the child from day 1 of the embryo transfer. Another advantage of egg donation is that it’s socially manageable, which means that it’s up to you, or the couple how to handle that piece of detail whether she or they talk about it or not, it is socially acceptable in western societies, more than it used to be 10 or 15 years ago.
The matching flexibility and availability are another advantage. Lastly, another big advantage is that egg donation is illegal, not in all countries, but overall in Europe and the U.S., egg donation is available, legal, regulated and cost-effective.
Dr Tsakos then focused on disadvantages, and in his opinion, it is a foreign genetic material issue. This is very hard for patients to accept, especially if there are some cultural, psychological, and ethical religious issues. All clinicians in IVF clinics have to accept that and also seek help, luckily there are a lot of resources to assist the patients to understand, and alleviate those issues and those complexities in the likes of donor conception. In regard to genetics, one important piece of information is the epigenetics issue, which means that not all the material is foreign. There is some good evidence that a small proportion of the DNA of the mother can pass on to the baby, and equally, the baby’s DNA passes onto the maternal circulation during pregnancy. There’s a lot of stress associated with the whole procedure, but also with the donor’s performance like if there will be enough eggs, will they fertilize properly and so on.
Legislation is another stress factor, there is variability throughout Europe, one significant variability is that in the UK, the donors are non-anonymous, which has an impact on the availability of donors, in some European countries, egg donation is not legal, and in some others, it is legal, but it’s not available and so forth. There are some issues associated with this choice, so it may mean that although medically it could be fully indicated, there could be some logistical issues for the couples to face before deciding where and how to proceed with egg donation. That affects availability, which can be limited in various countries, and it could be an issue in deciding.
The next disadvantage of the egg donation program is that the cost is higher compared to IVF with own eggs. In general, it’s about double or even three times higher, depending on the country and situation. Although the cost-effectiveness of the treatment is better, this could adversely impact a couple that may be on a very tight budget. If someone has gone through 1 or 3 cycles of own eggs IVF, they can hardly afford one cycle of IVF, and egg donation IVF.
Some medical issues could also be important, for example, there is some uncertainty in regard to the genetic heritage of the donors although, throughout Europe, there is very strict legislation which controls and ensures that all the medical checks have been done and all the genetic tests have been performed.
Finally, what’s going to happen in the future with the offspring is also significant. Whether the child should be informed about the egg donation, if so, when is the right time, how to tell them, what support the parents get and so on. Nowadays, there are societies all over Europe and counsellors, nurses, midwives, and associations that can provide advice on those issues.
What are the dilemmas? There are four main dilemmas according to Dr Tsakos. The first one is anonymous versus not-anonymous egg donation.
In my opinion, there’s no right or wrong, ideally, we should have all the options, sadly we are restricted by the legislation of the countries, we work in so for example if I’m consulting in the UK, I only discuss non-anonymous donation because this is what’s allowed in the UK. If I’m consulting in Greece, I’m only discussing the anonymous egg donation because this is the only one allowed in Greece and most European countries.’
Another big dilemma is whether to proceed with egg donation at home or abroad. Before you decide, make sure you have examined all the options. Another big issue is frozen versus fresh transfer, there are also some medical considerations, which clinic to pick, and there are also some logistical considerations, among others. The more educated you are, the more basic knowledge you have about standard IVF facts based on your particular situation, and the more likely you are to make the right decision. It’s not an easy journey, whether it’s your clinic next door or it’s a clinic abroad.
Greece has become one of the top destinations in general for IVF, not just for egg donation but also for own eggs IVF, surrogacy, and all sorts of facility treatment, these are the main reasons why the clinics are of very high standards in general. there’s regulation and quality assurance, the clinics are obliged to have two ISO standards of quality control which is not the standard in most European clinics, in order, to apply for licensing and renew the licence.
The legal framework in Greece is considered quite liberal, it is not bad, according to Dr Tsakos, it’s out of date and requires urgent updates. Safety and success have been established. Egg donation in Greece is in general legally permitted and protected, it is allowed for singles and unmarried couples as long as the female is under 50, there’s no upper age limit for the male, and it’s anonymous. There’s legal compensation to the donors, the age of the egg donors is 18 to 35 years old. At Embryoclinic, the donors are in their 20s only and there’s a maximum of 10 families created per egg donor, there’s a national registry of donors to ensure that everything is done properly. That was established in 2020, there is a vast ability to find a perfect donor, this is vast because there is a vast availability of donors, young students coming forward to donate for various reasons and mainly altruistically.- Questions and Answers
It depends on your age, it’s a different definition if someone is 35 or 40. As you are 39, we would be very happy if we created one or two top quality blastocysts, so this is my definition for your age. It is very important to create blastocysts. I think most of us now, most clinicians and scientists, agree that embryo culture should go as far as the blastocyst stage because this is the time when we have a lot of information about our embryo. At 39, we would like to see one or two top quality blastocysts. If we don’t, we’re probably talking about poor quality. We may see no blastocyst at 39 or one, two blastocysts, which are not of good quality, either lagging in development or showing signs of fragmentation and so forth. For a 35-year-old, I would expect, hopefully, to have maybe at least two or three good quality blastocysts with one stimulation cycle, so the definition varies mainly depending on the age.
In my opinion, no. In Greece, it’s not legal to do PGT-A or Preimplantation genetic screening. In my opinion, it’s not necessary because we’re talking about young, healthy potentially, fertile or donors with non-fertility, so there’s no indication to look for aneuploids.
I’m afraid, yes, is the answer. Absolutely, yes. Generally, the miscarriage rate is lower with egg donation or embryo donation compared to IVF with own eggs. However, miscarriages happen, and no one and nothing in the world can ensure that they’re not going to happen. This is a human issue, of course, egg donation usually is used for women with some sort of adverse reproductive history or advanced age, so the chance of having issues other than embryo quality is there.
The miscarriage rate is a combination of the quality of the embryo, which with embryo donation is as near perfect as possible and the quality of the environment that we implanted in. As well as the quality of the recipient, so yes, it is likely. I mean, we’ve always thought that a big proportion of miscarriages is due to the embryo quality. We’ve always known that the implantation environment, which involves not only the uterus but also all the pelvic environment, the hormonal, the biochemical, the blood environment of the female is also important.
Don’t wait until you become the late 40s before you resort to egg donation. The risk of miscarriages and the ability to carry a healthy pregnancy is one of these reasons. If there is an indication for egg donation and if you exhausted your chances with IVF with your own eggs, do not delay your egg donation too much. Then, there may be additional factors that will adversely affect implantation and pregnancy performance.
The straight answer is yes. Although the question is: how low is low, and how do we measure it? In general, progesterone is an important hormone for both achieving and sustaining a healthy pregnancy. However, our ability to measure the levels and our ability to agree on the perfect level is not near perfect.
Yes, it can cause miscarriage, but no, we can’t be sure how low is low and so forth. I do have anxieties about whether it’s properly absorbed and what’s the best route of administration. We’re having conferences every year regarding what’s the best route of administration and if we should combine it and use the oral, vaginal route, etc. What’s best? Is it injectable? Is it just progesterone, or should we add estrogen, for example, or even other hormones, especially in IVF with own eggs and so forth.
It’s an endless discussion, in my opinion, progesterone is important, and we need to ensure that we’re giving it at the correct dose, maybe a little higher than the standard recommendation, just to ensure that absorption is 100%.
I can’t see a huge difference between the two options, so as I said in my practice, I use fresh eggs and frozen blastocysts. We have audited that in our hands, it produced better results and a better experience. I can’t see any difference in what you’re saying now. Embryo adoption doesn’t much differ from fresh egg donation with sperm donation. Whatever you choose, ensure that the clinic can guarantee that you have top quality blastocysts, whether they’re produced from fresh or frozen egg donation, perhaps is not that important or whether there’s already embryos available of top quality.
I do not have a straight opinion on this with my limited counselling knowledge. I would suggest that you find a good counsellor. Each couple, each individual are different, and there’s no right or wrong, there’s what’s right or wrong for you. For some couples depending on the social circumstances, backgrounds, religion and so forth, it may be best to tell the child at a proper age. What is a proper child’s age depends on the child. Please, do not try to sort everything out before you even get pregnant because it’s virtually impossible.
You’re not going to be the same when you’re pregnant, you’re not going to be the same when you have a newborn, a toddler, a teenager, and you don’t know what kind of child you’re going to have. Although we like to have things organized beforehand, I think it’s too much stress, and I have seen amazing situations. Do not try to fit everything into a pattern because those patterns may change. Overall it’s a very variable decision, it’s a complex decision that has to be addressed and readdressed and depends on the couples or the single mother’s dynamics but also depends on the child’s or children’s dynamics.
At the moment, vastly in Europe, we can’t choose if we are going to have the vaccine or not, so all we do is wait for the national guidelines to tell us if we are candidates or not. I don’t know which country you live in, but nowhere in Europe, as far as I know, we can choose, so in general, fertility patients who are low-risk patients for COVID-19 disease, younger patients in their 30s or 40s, they’re not eligible for the vaccine.
Now, if you are eligible either because you are a health worker or a carer or when your time comes with the vaccine, my general advice, although you have to follow the local guidelines, is to go ahead and have it. I think this is the overall standard of advice. Some scientific societies and this is the standard advice in the UK, in the U.S. related to fertility or even natural conception, advise going ahead with the vaccination. There were some concerns about whether women should have the vaccine or not before conception, but I think it’s very clear now from the American and the UK societies that if your term comes to go ahead and have the vaccine.
Frankly no, not at the moment. It’s been a surprising situation in which many donors, especially in our practice, came forward because of VOVID-19 wishing to donate to help couples. There’s no shortage of donors at the moment. However, there is a concern that most of the clinics, including ours, have. There’s a lot of patients now wishing to come. Our international patients stopped coming out for almost a year now, and so there is this concern not from the donor’s point of view, but from the clinic’s ability point of view to properly treat patients if there’s a huge number coming in, so my straight answer is no.
Thankfully, the donors are coming forward, and we’ve had no shortage, maybe because they’re staying at home, and they’re not going to university, and there’s a lot of altruistic energy in Greece at the moment. People wish to donate eggs, blood and so forth, so thankfully, there’s no shortage of donors, but there is a small concern whether the clinics would be able to deal with a sudden influx of patients that we’re expecting from the middle of May onwards.
Not in Greece, in Greece, it’s anonymous, and as far as I know, the same applies to Spain, The Czech Republic. Most European Union countries like Greece have the legislation of anonymous donations, so there’s no obligation, there’s no connection between the child and the donor. In the UK, it is possible due to the non-anonymous egg donation legislation. So it is possible to be connected between the donor and the child when the child turns 18.
Most of the clinics either do one method or the other, so it’s very difficult to quote. I don’t know, I haven’t got an answer to that. We did a small audit in our clinic, and we found that fresh egg donation with the use of frozen blastocyst gave us the best fertility outcome in terms of success rate but maybe in other clinics hands, it would work differently. I don’t know, you would have to individualize.
With frozen eggs, there are thawing issues. Please remember that an egg, whether fresh or frozen, is a potential embryo, and the overall loss from eggs to blastocysts could be as high as 60-70%. For example, if you have 10 vitrified eggs from an egg donor, yes, you may have 7 or 8 fertilized and, equally, when you have fresh eggs, you have a loss in fertilization, and then you may have another 50% loss in culture. Unfortunately, I am aware of clinics, for example, using frozen eggs, and they’re using a much smaller number than 10, for example, they’re using batches of 3, so maybe 6 eggs. With 6 eggs, yes, you may have only 4 fertilized and then out of those, you may have 1 or 2 blastocysts, so it’s not so much the fresh versus frozen issue as it is the fertilization effect and the culture effect.
We must be prepared for losses, whether it’s fresh eggs or frozen eggs, and in my opinion, this is causing a lot of stress, not only to our couples, not only to the donors because the donors are also stressed, they’re the human beings, they’re making decisions, they want to help, they get very disappointed when they find out that they have, for example, small fertilization or small rate of blastocyst formation.
Also, there’s a lot of stress within the clinic. For us, it’s a very, very bad day when we have maybe one blastocyst out of an egg donation cycle, and if that blast is not perfect. In my practise, we don’t want to face that when the recipient has made all the effort to prepare themselves, to have the scans, to take medication, to have a good endometrium, and then to fly out and come here and to say I’m sorry – we only have 1 more morula, not even a blastocyst. In general, we like to discuss it with recipients and discuss preparations for an embryo transfer once we have blastocysts in hand and when we have secured at least 3 top quality blastocysts in a cycle.
I don’t know about Greece, maybe in Athens because there is a bigger Asian community in Athens. In Thessaloniki, no is my answer. We do have a starting population of Asians, some wonderful people in most of the schools. We have some Asian students, my daughters have Asian classmates. In terms of donors, as far as I’m aware, in my clinic, at least, we don’t have any.
The answer is it depends on the size of the myoma you had removed, on the location of that myoma, on the type of surgery you had, whether it was open laparoscopic, robotic, and of course, depends on the healing process that happened afterwards. In my opinion, the best person to ask is the surgeon who did the surgery. If I can give you some examples, I take 10-centimetre fibroids out, but if they’ve been laparoscopically or robotically, if they’ve been subserosal, so, outside the uterus, it doesn’t matter, if they have a small stem, I can advise my patients to have an embryo transfer in 2 to 3 months. 6 centimetres in the uterus, I would still ask my surgeon. The standard advice is a minimum of 6 months, to be honest.
It’s not one month per centimetre, but a six centimetre is a fairly large fibroid and if it’s in the uterus that means that the incision of the uterus was at least 5-6 six centimetres, so in general, I would allow a good 6 months to heal.
Yes, on both. Yes, we do have donor embryos available for single ladies, and yes, donations are made from couples.
The cut-off age at the moment is 50. Technically, there is time to go ahead with egg donation, but that means that you will only have one chance at embryo transfer. You shouldn’t be over 50, or you may be a couple of months over. If the embryos are created before you turn 50, there is a leeway of a couple of months due to the epidemic for embryo transfer. Technically, you may even have 2 chances for embryo transfer before you turn 50 which is not bad provided you can travel, or you can get organized fairly quickly.
I can specify what tests they are having. I mean, egg donors in Greece are having extra Karyotype DNA testing, which the majority of own egg patients do not have, and yes, that could reveal some issues that would alter our approach. Egg donors have a full cystic fibrosis screening, the full gene of cystic fibrosis where the majority of all the patients who use their own eggs do not have, most of them haven’t even heard of it before and again. Sometimes, we identify some issues that may affect fertility, they have the fragile X genetic screening, which is some genetic screening affecting mental disorders which may not have an impact on fertility, but it definitely has an impact on the offspring.
They have a full endocrine profile, they have a full screening in terms of psychology, they have biochemical profiles, they have the pap smears sorted, they have all the infection screening and so forth. On top of that, in Greece, they have genetic thalassemia screening. My usual quote to my patients is that I know about my donors more than I know about myself, and this is vastly true, so yes, if own eggs patients had that screening, they may have a better chance.
Why are these extra screenings performed? The answer is I don’t know. Certainly, in the UK they’re not performed. They may be considered after multiple failures. In my practice, in Greece, to be honest, own egg patients have at least the Karyotype test and at least the standard cystic fibrosis gene test, the most common gene which is DF508 test, but yes, unfortunately, in most practices, these are not included in the baseline testing presumably due to cost issues.
With egg donation or embryo donation, the chance of disease of the offspring or chromosomal anomaly depends on the age of the donor of genetic material. If the donor is in her 20s, the chance is negligible, of course, then there is a chance associated with the sperm donor, whether it’s a partner or a sperm donor from a bank. However, pregnancy at 49 is a potentially complex pregnancy, potentially a high-risk pregnancy based on the female age, so it has to be managed, as such, by a very experienced obstetric team.
Provided that all the necessary tests have been performed beforehand and provided that essentially, there are no major medical issues, the vast majority of pregnancies conclude with a healthy pregnancy and a healthy delivery. The miscarriage rate, of course, may depend on some background issues of the carrier of the 49-year-old. Overall even a 49-year-old who is fairly healthy, fit, on no medication, with no serious past medical history, fairly slim, and well looked after by a good team, the vast majority have a good outcome.