Dr. Anna Galindo Trias, from Gravida Barcelona clinic, is answering patients’ questions in regards to the reception of oocytes. This event can be informative for anyone who is interested to have egg donation treatment, be the recipient of donor eggs and learn more about egg donors and door eggs.
In theory, the pregnancy rates don’t depend on the phenotypes, so we could use any phenotype to create embryos and transfer it in a well-prepared uterus, and the result would be a pregnancy. The phenotype characteristics are more dependent on the regulations in every country, in Spain, the law says that the clinic has to choose, it’s mandatory – trying to find the most possible phenotype match from the donor to the family that this donor is going to. A family meaning the members of the family but mainly to the recipient. Sometimes if we don’t have the exact characteristics of the recipient, we look at the partner. If the recipient has brown eyes and the partner has green eyes, but I have a donor who is really similar in features, in the colour of skin, in other characteristics and the only characteristic that is different is green eyes, but the partner of this patient has green eyes, we do accept these little differences of phenotype. But mostly in Spain, it has to be a phenotype that is the closest to the recipient, we can’t choose really the phenotype of the donor.
This is another typical topic, but it’s slightly different in different centres. In Spain, the law regulation says it has to be anonymous, but what does it mean anonymous. It means that we can’t give any characteristics of the donor, it means that we can provide everything except the name and the address, this is a big frame of options from everything except the name and the address or nothing at all. Every centre defines what the limits are that are going to be put or the way they want to work. In our centre (Gravida, Barcelona) we decided with our ethical committees, to give to the recipients, the phenotype characteristics this means the colour of skin, colour of hair, colour of eyes, general features, height and weight, complexion, blood group and the age of the donor. This is the characteristics that recipients can know about the donor. Other centres are more restrictive. And some other centres are more open to giving more information.
It’s slightly different in different centres. We try to minimize the genetic risk in the offspring, this is a global idea, but we have to make specific points about it. How do we work with all these huge amounts of options that we have? We work with carrier maps or maps of genes. There are two types of genetical sicknesses, the dominant ones that mean that we have two copies of the genotype, one coming from our mother, one coming from our father, so these two copies are the same, but complementary. If there’s a sickness or mutation in a gene which is dominant, it means that either maternal copy or paternal copy has the copy that is alternated. It’s the wrong copy, the other copy is not going to be able to compensate for this problem, so the individual will be sick. These sicknesses are not a worry to us because we see it.
If the donor is a carrier of a dominant genetical problem, we see it, it’s going to be in her medical history, so it doesn’t worry us so much because most of them, they show up. The problem is when we have these the recessive sicknesses, which means we have two copies if there’s one copy which is wrong and one copy that it’s right, the right copy compensates the wrong copy, so the sickness doesn’t appear, it’s a healthy person carrying a sickness.
The problem comes if the exact mutation comes from the mother and from the father, so we have wrong and wrong, no rights to compensate, these are the recessive sicknesses. What worries us is what’s going to happen if we have a donor carrying sickness and the partner of the recipient is a carrier of the same sickness, that would be a problem because a quarter of the offspring, 25% would be a sick kid, so this is what we want to avoid.
We are carriers of many little mutations that the other copy compensates, so all of us are carriers of these mutations, the problem with the mutations, that are very low in the population has a very low frequency in the population, it’s not a problem because it’s very rare that the same sickness of these rare sicknesses is going to be the same in the donor and in the partner or in the other donor of sperm. The problem comes from sicknesses that are pretty common in the population, such as cystic fibrosis, the mucoviscidosis which in our area is 4% in the population. It comes out with thalassemia, which in our population could be more or less around from 5 to 25% depending on the areas. These are the problematic sicknesses because we except high enough chance to be worried that maybe the donor and the partner of this recipient could be carriers of these sicknesses that are prevalent in the population.
There are two types of confronting this, either by performing carrier map test in all the donors and all the partners that are in treatments. The carrier map is a list of 300 sicknesses from the most frequent to the lowest frequency that is not in the donor and in the partner of the recipient of the sperm donor, and we match the results, meaning we are not looking for a perfect genotype that doesn’t have the mutation, we are looking for risk of coincidence of the same sickness between the donor and the partner.
This is one approach where we decrease the risk a lot of the sickness because we are matching this risk but we don’t filter for carriers, so maybe the offspring is going to be a carrier of cystic fibrosis that is also common in the population and maybe we’ll have to advise that this child has to go for cystic fibrosis counselling when they want to have children, but usually, this information is not given, so what we decided is to go 50/50. We perform this carrier map excluding the donors for the most common sickness in the population such as cystic fibrosis but also other 16 sicknesses that are located in chromosome X, we do these tests on the donors, and if they are positive, we give them counselling, and we don’t accept these donors in our centre.
We have this common sickness excluded, and then the carrier map is optional for patients, for the recipients. The problem with carrier maps is that they are expensive, so if the recipients want to double-check other sicknesses that are low prevalence in the population, they have the option to do it. If not, we have the basic panel available, so we have the most common sicknesses in the population excluded, so we are good with this 50/50, we don’t create carriers of mucoviscidosis f. e. but we can also increase the number of tests if the patient wants to.
The good thing about the COVID- 19 is that it’s a very selective respiratory virus, so it likes a lot the lungs, it doesn’t like the reproductive tract. It’s been found in sperm, some specific molecules related to COVID, but we don’t know if it’s manipulation, if it’s real that COVID can go through sperm, we never found it in the follicular fluid so in the egg surrounding fluid we haven’t found it yet, or it has not been reported as far as I know. The bad thing about it is that it’s very common, we don’t want donors to be donating when they are positive with COVID. We test them when they’re starting the treatment, we test them for symptoms all the time when they come to the clinic, we check if they have any fever, cough or headache etc. Every time they come to the clinic, we test them for symptoms, and we test the virus in the throat, and in the nose, the PCR when they start treatment and when they are about to go for the pickup, we make sure that they didn’t go through treatment with a positive test for COVID. If they were positive, we wouldn’t use these eggs, we would finish the treatment.
There are several new rules for patients and the staff, not to be combined in the same waiting room, we disinfect all of the space, we perform tests ourselves, we take every measure to make sure everyone is safe.
In terms of quality of the embryos that are created from fresh or from frozen oocytes, the quality of the embryos and the capacity of these embryos to implant and to give birth are the same or equal.
The only thing with frozen eggs and as far as we have observed is they have a really good survival rate when we defrost them, but sometimes there are little steps in the middle that could lose some eggs, so when we compare groups of fresh and frozen, the implantation rate and the pregnancy rate are exactly the same, the only thing is that maybe you need one more or two more eggs to be equivalent in a number of embryos obtained of this group of eggs. It’s because of these middle steps that the frozen ones go through and the fresh don’t, so there’s a slight difference but not that much.
We work with frozen and with fresh depending on the timings, the phenotype of the recipient, f. e. with usual phenotypes like mine, that have Mediterranean skin, it’s the most common phenotype in our area, so we have this protocol to use fresh oocytes and take this more complicated treatment to give the most credibility to treatment, not on pregnancy rates but in a number of embryos, possibly one embryo more. In rare phenotype such as f. e. very light skin, red hair and green eyes, these phenotypes are less common in our population, so sometimes they don’t come at the same time the donor wants to donate and the recipient wants to receive, so in these cases, we work with frozen oocytes. We are happy working with fresh and with frozen, the only thing is slight differences.
The answer is absolutely yes, so egg donation doesn’t depend on having ovaries or having menstruation which is the functional part of the uterus. As far as the woman has a uterus and it is a normal uterus, even though this uterus hasn’t been working for a long time, we can medically wake the uterus up and create menstruation if the endometrium is not damaged because of surgeries or something that happened. We can create menstruation and create this receptivity that we need to be able to give the opportunity of getting pregnant. So women that have a uterus and you don’t have menstruation for a long time if they have the other characteristics favourable, we can really do the treatment with good pregnancy rate.
The blood group is something that is usually required by our recipients. They want the same blood group because they want to be able to donate blood to the kids when they are older, and something happens, and this is a topic that it’s not exactly mathematics. As far as we are ready to get pregnant with embryos naturally that are a combination of us and our partner, we are capable of accepting pregnancies from all blood groups.
The blood group has two parts, the main blood group, which is AB and 0 or combinations and RH. The only problem that we could have is in a woman with Rh-negative that had before pregnancy with fetus Rh-positive and didn’t have the vaccines to naturalize the reaction. The Rh-negative mother when she’s pregnant with her Rh-positive kid could create these antibodies, the body learns that something is Rh-positive that the mother doesn’t have creates a reaction that can be stopped with little vaccines that are performed during the pregnancy.
If these vaccines are not given to the mother during pregnancy and when she delivers, the next pregnancy could be an issue if she carried a blood group Rh-positive. This is the only case when medically we give a negative donor if the partner’s negative because if the partner is positive we have the risk of positive in the partner, so it’s kind of tricky but if the partner is negative and the recipient is negative, and she had a previous pregnancy with problems with RH, it is the only case we have to give medically an Rh-negative.
In other cases, we could combine. Another thing is the social issue, some patients are not planning to tell the kids that it’s from an egg donation and they are worried about a blood group and when the kid is older, this could be a social problem or family problem. In partners or patients that are planning on telling the kids and not having the problem of hiding something, this shouldn’t be a problem.
That’s what it’s called epigenetics. In the last decade, we have learned a lot about pregnancies and expression of the genes, and one part is we’ve seen these kids coming from egg donation. I remember when I was younger but a long time ago when I started with these cycles and the mothers and the families from egg donation came to our clinic with already grown-up kids, I used to think, well we did a really good job this kid looks exactly like the mother and the father, specifically like the mother, and it was an egg donation, and I remember these thoughts because lately, we’ve learned that the individual has genetics and epigenetics.
Genetics is the book that has all information written in our genes, the basic information, it’s written with letters, and these letters are in words, and these words are the genes. But the way that these words are written by the recipient which is the mother, the recipient and the environment of these genes could activate some genes and not activate the author genes, so this means all the environmental conditions, the expression of these genes. This means that the mother also builds up the baby, gives these bricks, these proteins that create the baby and they are built-in the maternal way reading an external genotype but the way of the mother.
It’s a mixture of genetics and epigenetics, this epigenetic condition is very strong, emotional issues, risk factors for the future even for having cholesterol, even some phenotypical expressions that could go to the mother that is pregnant, so we have a lot to learn about epigenetics, but it’s there, and it’s not that the mother that carries the pregnancy doesn’t do anything, they do a lot, there is still more to learn about the epigenetics.
That’s a tricky question. I think that technology in the main of the labs in Spain, the UK and the US are mostly the same. The difference is the law in different places, and also the interpretation of the way to use this technology. In Spain we have this anonymous donation, we have a lot of donors, but there are anonymous. In the UK and the US, you can know the ID either later or at the moment of choosing a donor, that’s depending on the area.
In the US, you can choose your donor, you can choose the level of education, social issues and also if ethically you have this conviction that the right of the kid is to know the origins and even to have the opportunity to meet the donor possibly the UK and the US would be better scenarios compared with Spain. Also, there’s the way that we use technology for example in Spain, we use PGT which is the diagnosis of the chromosomes of the embryos to be able to choose exactly the one that has the most potential to give the baby so per transfer has the most capacity to implant and give a healthy child, which is the PGT, we have this technology in Spain but usually in egg donation due to the big span that represents to add more and more techniques, it’s not usually performer. While in the USin even in egg donation cycle, they perform this selection of the embryos because they want the most capacity of implantation per transfer, but also it’s more expensive.
I think when you decide to go to one country and go for treatment, you have to think about what’s wrong and right for you, what’s your advantage or disadvantage. If you’re convinced that you need to know more donor information, you need to know more things about donor don’t come to Spain because it’s not the right place. In terms of quality of the labs, we are equivalent so if you have a lower budget but want a good quality, Spain.
When it comes to fibroids, it all depends on where they are located. The fibrous is the most difficult evaluation that we have. There are opinions in all the ways about fibroids. What we know is that a fibroid that is located in the uterus decreases the implantation rate. So as far as we can, we strongly recommend removing if possible and if they have size, that doesn’t compromise the structure or that the intervention is going to have a risk of losing most of the uterus. If they are of a size that the surgeon says okay I can remove this fibroid with no big damage to the uterus, we recommend removing this type of the fibroids.
The other type of fibroids talking about the ones that are inside of the wall of the uterus, these are called intramural fibroids, these are big discards because they are little balls that are in this wall that has to be really smooth and clean, and they interfere in the contractility of the uterus, they give a little lower implantation rates, but most of the times they are not as important as to be a contraindication for pregnancy. With fibroids that are these little balls outside the uterus, the problem is lower. Except if they are huge and they have a big occupation of the abdominal area, this means that when the user is going to be growing, there’s going to be a compromise of space and maybe these ones are the ones that don’t represent that high risk of losing the uterus in the surgery, so these big ones are considered to be removable. On the other hand, the options are big, and the recommendations are very variable between specialists sometimes with limited size which is 5 centimetres of a fibroid, some specialist says no way, you have to remove these, and some specialists say well okay leave it, so it’s kind of tricky.
If we are talking about the uterus that has many fibroids, removed several times with a lot of scars in the uterus and they still keep growing, sometimes such uterus is not capable of keeping a pregnancy. Because they have so many scars, so many fibroids and that causes a high risk for this pregnancy.
Endometriosis is another tricky indication because endometriosis is a tissue that is similar to the endometrium, the tissue that is inside of the uterus but being outside of the uterus, in the ovaries, inside of the abdomen, these creates lots of scars around, creates a little mess depending on the stadium of the endometriosis.
We know that when there’s severe endometriosis this scar tissue, this inflammation status of the belly creates a lower capacity of the uterus to implant but not null.
The key point nowadays is the adenomyosis which is vascular. It looks like there are lakes inside and at the limit of the endometrium and the myometrium, this gave us a lot of trouble because it’s kind of a sickness that is similar to endometriosis but right inside of the uterus. It’s very difficult to remove, and so dealing with adenomyosis now is very complicated but we are dealing with it, and we are getting women pregnant even with adenomyosis when it’s not really severe.
Usually, we don’t give this information. Since last year there is an obligation to report these babies to the government, so the government keeps track on these donations and makes sure that there are no more than 6 babies because of the not -known consanguinity when we talk about international egg donation is less a problem, but it could be a problem that two persons coming from the same egg or same donor could get together and try to have children, in this case of consanguinity the risk of recessive signals in the same family, it’s the same pattern of sicknesses.
This means that if we talk about the risk of two cousins or two relatives get together to have children, the pattern of signals it’s going to be similar, so the risk of the coincidence is going to be higher, so in these cases, we should perform this carrier maps to make sure that there’s no risk, so to avoid this possibility or minimize this possibility there was a calculation for all the population in Spain, and they concluded that 6 is the number of offspring that we can accept to minimize this point. At the moment we don’t really tell the recipient how many offspring turned out of these eggs, but we control this with these regulations.
Well, the thyroid function is another tricky issue. I’m convinced that the function of the thyroid it’s very important in the capacity of getting pregnant and also in the early development of this embryo. So thyroid has to be ready to increase the production to give this hormone, the T4 to the baby and to the mother. TSH is the hormone that stimulates the thyroid, that gives the order to the thyroid to produce this T4. When TSH is less than 2 or 2.5, we consider that the thyroid it’s going to be ready to increase this production. When the TSH is over 2.5 even being normal because until it’s over 4 or 5, we don’t consider that this person could have a problem of production in normal life. We recommend supplementing a little bit, especially when there are antibodies antithyroid, which we always test when there’s TSH over 2.5.
We know that style of life and also diet and sports but also toxics, they all represent something on the reproductive tract. There’s a lot of products like flaxseed oil or other products that have been named in the list of risk of miscarriage, but in my opinion, we need more knowledge about them because when it comes to supplements, we don’t really know. A few years ago, vitamin D was almost forbidden in pregnancy, right now we know that vitamin D is important. So we need to know more, there are just a few papers about it and what I would say is as far as the patient or surrogate it’s good to take supplements but regular supplements, vitamins for pregnancy, and make sure that the style of life is healthy.
For donors we recommend a style of life, we give them a list of diet that they should go through, of course, they’re young they say yes, but they are pretty healthy all of them, we don’t let donors who are overweight to go through treatment because of the risk inside of the treatment for them and also the style of life and but we can’t be with them 24 hours a day, so that’s my opinion.
Levothyroxine is the copy of T4, which is the hormone that thyroid products, so it’s the molecule that we usually use to help the thyroid in these patients that we think that the thyroid is not going to sustain this increase of production that pregnancy or all treatments require. The dosage of levothyroxine depends on TSH, age, depends if it’s over 5 or if it’s less depends on the weight of the patient, also depends in the style of life, depends on the diet, so it’s very variable in different ways.
Personally, I don’t think so. The anti-thyroid antibodies in theory just have a target which is the thyroid, so in these patients with antibodies positive in a normal thyroid function what we do is a close follow-up of the function of the thyroid when we go through treatment. On the other hand, if a patient has autoantibodies also could tend to have anti ovarian antibodies which don’t always happen, so it’s not that the anti-thyroid antibodies go to the ovary and decrease the ovarian reserve. Some patients with anti-thyroid antibodies could have also another autoimmunity, would have this tendency to antibodies that could lead to precautious low ovarian reserve, but it’s not a direct effect, it’s just the way the person is and the antibodies that she develops.
You should know that we are capable of taking care of the embryos, but we are still weak in evaluating the embryos just looking at them. This means that we really take care of them, but the only way nowadays that we have to grade them is by their characteristics, we can take a look in some points of the development, we can look at them continuously with Embryoscope or other time-lapse and see the intermediate steps of these embryos, but sometimes embryos lie.
We grade the embryos, in our clinic we grade the embryos from A to D meaning A is excellent, B is good, pretty good, C is threshold, D is not adequate, so when there are embryos, day-3, they have one letter , which is A, B or C depending on the fragmentation, on the size of the cells, on how they divide, when they divided etc., so when they get to blastocyst stage which is day-5 or 6, they have two letters, one is the trophectoderm, which is going to lead to the placenta and the membranes and the inner cell mass which is going to lead to the embryo and we grade two areas separately, the fetus area in a cell, it’s going to be A,B,C or D and trophectoderm is also going to be A, B,C or D. In our clinic, we transfer combinations of A and B, we only transfer C in fresh cycles when there’s nothing else, when we don’t have anything else and as far as the embryos alive we transfer a C embryo or a combination with C.
In terms of freezing the embryo when we ask for these characteristics of the embryos, it give us the idea of how is the embryo, the vitality of the embryo but also the nice-looking embryos are the ones that have more probability to have a correct number of chromosomes, but not all the time, they lie sometimes for example Down syndrome embryos are beautiful or gorgeous embryos and they are trisomy 21. In terms of vitality or the metabolic capacity of this embryo, we freeze embryos of A or B combinations because we know that we are asking from these embryos some exextra effort, which is freezing them and hoping they will survive in good conditions after defrosting.