If you’re over 45 and wish to become a mum, watch this Online Patient Meeting. Dr. Fernando Sánchez, Clinic Director at Ginemed, Spain, answered patients’ questions about fertility treatment for women after the age of 45.
The main risk if you are over 45 is hypertension. Hypertension during pregnancy often leads to what we call the preeclampsia. This problem is hypertension-induced. This is a risk because it is not so easy to solve it with the treatment and sometimes the only way to solve this kind of pregnancy is to terminate it when there is a risk for the mother. If it changes to preeclampsia, if there are convulsions, there can be renal failure, it can lead to the death of the mother. This is the main risk for the pregnancy, and the only way is sometimes to stop the pregnancy just to avoid this problem. The other risks are mainly diabetes in the pregnancy, but this is not so important because it’s very easy to solve only with treatment with insulin and subcutaneous insulin. The third risk is the risk of cesarean section. Practically, 90% of the deliveries at the age of more than 45 years is solved by cesarean section. It is better to have a vaginal delivery, but the decision is always on the gynaecologist. The rest is absolutely normal, exactly in women of 20 years or 30 years for years old. There is no difference, it’s only problems are hypertension, diabetes and cesarean section.
No, this is more a social than a medical question. Usually, life expectancy is more than 80 years. If you are a mother at 39, your baby will be more than 40 years before you die. So there is not a problem connected with the age, and there is no risk for the baby. If the mother is more than 45 years old, there is no risk for the baby. The age of the parents is important, of course, both mother and father. It is a little bit later for men than for women, but when we have men older than 50, the chance of having a baby is becoming low. When the man is more than 60, this chance is very low, and we need to increase the chances of a pregnancy with reproductive techniques. We have to use the selection of this sperm, just to be sure that this sperm is not fragmented, because, with age, the DNA fragmentation of the sperm is very high. For spontaneous pregnancies, it is very difficult, independent of the age of the woman.
I told you in advance, it is around 50% of having a delivery with one baby. Obviously, when transferring only one embryo, it ends pregnancies in around, 50%, and we avoid double embryo implantation to reduce the risk of twin pregnancies.
It is the only option, but well if you still want to try with your own eggs, you can try. But you have to know that the chance of becoming pregnant is really less than 2% or 3 %. The chance of having a healthy baby at 45 is less than 1% and is going lower with more advanced age. I’m giving you only the numbers at 45 years – 3% of becoming pregnant, and 1% of having a healthy baby. My recommendation is, not to try because this is a lottery. I think it is not the right way to do things. The most important factor when it comes to achieving pregnancy if you are more than 45 years, is to select a good donor. The uterus is not a problem, it is the same as if you are 20, or 30, or 40 years old, so it’s not a problem. The most important factor is if the donor is healthy and if it’s a good donor obviously. The age of the donor must be less than 30 because the chance of pregnancy with a young donor is higher than with an older one, so you should be looking for a good donor.
It depends on the country. F. e. in the UK, it is mandatory to be a known donor, in Spain, it is mandatory to be an anonymous donor. In Portugal, it is mandatory to be known. We have places in Spain and in Portugal, and so depending on the way you want, you can select anonymous donor, which is my recommendation always, or you can select a known donor if you want, in a clinic in Portugal.
Yes, the body mass index affects the success rate always independently of whether you use own eggs or donor eggs because when you have very high body mass index or very low body mass index, the chances of pregnancy are lowered. The difference is that if you are working with your own eggs and your pregnancy rate is 20%, with a body mass index over 30, your chances are only 10%. It is a very low number. If you use the egg donor cycle, the chances are normally 50%, they drop to 25%. This is still better than using your own eggs if you are 38-39 years old.
No, there is not. We don’t have a maximum body mass index limit, but, we recommend to reduce about 10% of the body weight if it is over 30, because of the chances of having complications during pregnancy increase a lot when the body mass index is high. It is not so important for becoming pregnant, it is not so problematic. I think you can get pregnant with 35, 38 body mass index. But once this woman becomes pregnant, this pregnancy could have more complications. The recommendation is always the same. If it’s possible, the BMI should be less than 30 and if you are over 30 at least lose around 10% of your body weight. Whether you are with the body mass index of 34 or 37, lose 10%.
It does not matter if you have severe endometriosis or you have multiple failures if you are changing to donor egg cycle. When you use donor eggs, the chance of pregnancy is very high. Apart from this, the problem could be if you have tried several times with a donor. In this case, probably the problem must be inside of the uterus, and you have to do a different study looking for genetic questions from your husband or itself. You have to look for genetic problems in your partner, or you have to look for problems with the thrombophilia on your side, or you have problems with immunological reaction during the transfer. Looking for the KIR receptor or for HLA-C in you and your partner. Looking for the window of implantation is also important, but this is a problem of reception because when you are using donor eggs you can have bad luck with one transfer and not become pregnant, but with two transfers, the chance of not achieving a pregnancy is very low, about 5%. If you have had more than two transfers, my recommendation is to do a genetic study on your partner, FISH analysis from the semen, karyotype and DNA fragmentation of sperm and doing an immunologic test on you, looking for natural killers in the endometrium, looking for KIR receptors, looking for HLA-C receptor on natural killers also and also looking for chronic endometritis, looking for 138 plasma cells in the endometrium.
The same same same supplements we recommend for every woman. There is no difference between the ages. The recommendation is always to take folic acid and if it’s possible to have a diet with low inflammatory products and also you can take some antioxidants. It can help to increase the chance of pregnancy, f. e. melatonin or coenzyme Q10 or selenium. Another recommendation is regarding the microbiota, the bacteria we have always in the vagina. If it’s possible to take a supplement of lactobacillus. The chance of pregnancies is higher, but it is the same if you are younger or you are older. The recommendations are the same.
CD138 is a type of cells we are looking for in endometrium. We do an endometrial biopsy, and we look for different things. Normally, when you are doing a study for repeated implantation failure, one of the things you do is hysteroscopy where you see the internal cavity of the uterus, and when you are doing that, you take the material to biopsy. In the material you look for the natural killer, an immunologic cell that receives the embryo when you transfer the embryo inside the uterus and you look for plasma cells. Plasma cells are the marker of endometritis, chronic disease or infection of the uterus. These plasma cells have a marker which is called CD138. This is the immunohistochemical marker of chronic endometritis. So sometimes we talk about CD138, and we are talking about these plasma cells as a marker of chronic infection.
You have to study the liver. This is the same problem whether you are going to have a baby with donor eggs or your own eggs. It is a medical problem, and you have to control it. Especially, with analytics and you have to be under the control of your internist just to give us the authorization to do treatment with egg donation cycle or with your own eggs cycle. Usually, if there is only a fatty liver, there are not many problems, because there is only a question of diet just to avoid some kind of food. The problem is when the liver is increased, and there is fibrosis of the liver. In this case, sometimes we have some problems, and we need the help of internist, but with fatty liver normally it is a big problem.
If you are now 51 or 52 the best prognostic factor to become pregnant is to have a baby before, so you have more chances now to have a normal pregnancy and a normal baby than when you had the first child. My recommendation, if you are healthy and your doctor gives you permission, there is not a problem. Don’t delay too much, because it is best if babies are as close as possible in age.The recommendation is to go on with it, and the chance will be very high.
There is no indication at all to have the same blood type as the donor, and there is no difference if you use the same blood type or a different blood type. Usefully, in the fertility clinic, we used to select a donor who is compatible with the couple. The idea is not because it could be a problem for the pregnancy or the baby. But when we have a baby, and this baby goes to school and does a blood test in the classroom and accidentally discovers his/her blood type is different than parents’, it could be very hard. I could tell you that 100% of the clinics, select a donor with a blood type compatible with your blood type and the blood type of your husband or your partner now. Just to avoid an awkward situation when the child is unaware of the programme.
You need to do a test because repeated failure implantation is not a logical situation. The age is a problem when you are working with your own eggs, once you change to donor eggs, that is not a problem at all. If you have had three babies, there is not a problem with your husband, there is not a problem with the sperm, there’s not a problem with all the immunologic part. If you have done the transfer with donor eggs, the chance of becoming pregnant is more than 99%. You have to do a test, and there could be a problem with chronic inflammation in the uterus, a chronic infection. Another thing is looking for the window of implantation. It is very rare to have this problem, the only problem must be in a change in the uterus after your pregnancy, so check if you have new fibroids. If you have new polyps or infection. You can test it if you are doing the transfer out of the window of implantation because there is no other way to have a problem with the results. I assume you are doing the transfer with blastocyst and you are transferring with young donor material, less than 30 years old.
The early menopause is not a problem to become pregnant. The early menopause is a problem to become pregnant with own eggs. When you are using egg donation cycle, it is the same as if you didn’t have it. It does not matter if you are six years or ten years without a menstrual period. It’s only a question to have the period for 2-3 months, and after that, you can begin the preparation for the transfer. Regarding fibroids, depending on what kind of fibroids they are, whether they are in the outer part of the uterus, we call it sub zero’s fibroids, there is not a problem at all. You can try to achieve pregnancy with big fibroid, five or six centimetres, and there is not a problem. Sometimes with these fibroids that are inside of the uterus which we call it submucosal, they are in the inner part of the uterus, very close to the endometrium, even with a small fibroid of 0.5 centimetres or 1 centimetre, you have to do a surgery to remove it before trying to get pregnant. You have to have surgery in advance of becoming pregnant, and sometimes after the surgery, you have to wait for around 6 months to 1 year before trying to get pregnant.
Sometimes, it is better to have blocked tubes than to have open, especially when you have a problem like hydrogenises, some amount of inflammatory liquid inside the tube because this inflammatory liquid can go inside the uterine cavity and compromise the pregnancy. In these cases, we block the tubes before doing an IVF or before doing an egg donation cycle, so the blocked tube is not a problem.
The transfer must be done on a day, so it’s better to do it on blastocysts, they are better than four embryos on day-3 because the transfer must be done on day five and this saves money. I prefer eight mature oocytes because probably you work with late mature oocytes, and when doing a cycle you will have around three 3.3 or 3.4 mm blastocysts. So it’s a question of number probably. You will have more success if you work with mature oocytes than if you work with a number of embryos guaranteed, but probably the answer to this question is more economic than clinical. If you have more than one embryo you can select this better one, because you always select the best embryo in a cohort of two or three. If you have three blastocysts it is better if you work with eight mature oocytes than a guaranteed number of embryos.
Before the next transfer, talking about the same donor for these three embryos, and you have transferred two of these three embryos of the same donor probably, you have to think if this is the right donor. If you have done two transfers and there is no special problem with the transfer, you don’t have any special problem, and you have no fibroids, or polyps or something like this, and there’s no a pregnancy, the problem must be with the donor. I think it is better not to do this transfer and go for another donor. This is one of the things you can think about. The second thing is the same as I said before. You have to look for different problems because you have to do a transfer with a good donor. You have to look for strange things in the genetic factors on your partner, you have immunological factors or if you have thrombotic factors or an infection or change of the window of implantation. Because there is no logical explanation for not becoming pregnant after two transfers. It’s necessary to do a test. Another thing you can think of is changing the donor and not to transfer this embryo.
There are not many things to do differently. It is the same I said before. The recommendation is to have all the tests on repeated implantation failure, because after two cycles is not logical not to be pregnant. So we have to think again on all the tests from the anatomic point of view: ultrasound, hysteroscopy and from the genetic point of view, thrombotic point of view. You should also test for the right window of implantation. When you are talking about the pregnancy rate of over than 70 %, you can have bad luck, but if it is repeated, it is very difficult to have bad luck in two different transfers. So if this happens, you have to look for not frequent things, and I wouldn’t do another cycle without having all the information. I can have regarding you and your partner. Send me this information, and I can check on your chart and see if there is something special to do.
There is not. It is not difficult to do, the only problem is, it is not allowed in any country in the world. They are working with this on animal studies, and it is incredible how it changes because if you put the cytoplasm of the donor in the recipient egg, the chance of pregnancy is completely different, but there’s no way to do it. This is illegal in humans, so no.
That depends on a couple of things, and one of these things is the money If you have money the recommendation is to try at least one time with your own eggs before going to do egg donor cycle. If the money is a problem for you, the recommendation is to go directly to an egg donor cycle, because the chance of having a baby is completely different. If you are 43, your chances of becoming pregnant would be around 15%, but you’re going to have around 60% of miscarriage rate, and you may lose the pregnancy. The chance of having a healthy baby at home at 43 years old is around 4% or 5%, no more than this. For me, 4% or 5% is more than enough to try a pregnancy, but we are talking about expensive treatments around 4000 or 5000 euros for each treatment. If the economic factor is important, go directly for pregnancy with egg donation, because you are going to have 60% of pregnancy and delivery rate at 43 years and will be completely different, but there is not a medical question. It is this social question again.
If you are 42, the recommendation is to do it. If you want to do an IVF, do a normal IVF, there is no reason to do a mini IVF. There are not more pregnancies with the lower stimulation, there are no chances if you do a mini IVF. You are going to have fewer oocytes, and you are going to have lower chances of becoming pregnant. My recommendation is at least try one time but if you are going to go for an IVF cycle, do a normal one with high doses unless you have done a cycle before with high doses and no results. Then you can go for egg donation, but there is no indication for a mini IVF cycle.
We transfer two embryos if you are less than 45. You assume the risk of twin pregnancy. For example, when you are 40 or 42 or 43 you can decide if you want to transfer two embryos. If you assume the risk of a twin pregnancy, you have to think that when transferring two embryos the chance of having twins is more than 50%. Twin pregnancy is another risk factor for pregnancy about premature termination. The reason not to transfer more than one embryo in a woman over 45 years is the decision of the ethics committee of the clinic. To avoid this kind of risk in a woman over 45, because the risk of preeclampsia, the risk of hypertension during pregnancy increase with age and also increase with the number of foetuses, so in twin pregnancy, you face a higher risk of having preeclampsia. If you are 48 years old you have a high risk of having a pregnancy, but if you are 48 and have a twin pregnancy this risk is increased by 3 and the risk for twins is increased by 6, so it is 18 times higher.
There is no medical indication for doing a mini IVF. It was recommended around four or five years ago. There is some publication showing the mini IVF is a very bad idea because there is less acceleration on the eggs, but after that, there have been no studies that we have done with mini IVF. There is no recommendation you can have mini IVF for example if you have classical IVF with 300 units you have only one or two oocytes. We can then repeat using 75 to 150 units because the result will be the same with 300 units as 75 units because probably we are going to have only one oocyte which is the same if you decide to go in a natural cycle. You are going to have only one egg. Mini IVF is only acceptable if you don’t want to spend too much money on medication and you have tried previously.
There is no difference. There are a lot of studies talking about the embryos, and mainly it is a differentiation because today the embryologists have to classify the embryo. They have to put this embryo in a number. When you are talking about embryos or blastocyst, this blastocyst changes from hour to hour, so you can put this embryo classification, for example, AA and you see this embryo one hour later or two hours later, you put BB and, you see this embryo one hour later, and you change the classification again. There is no difference. There are some studies done, then they take videos of the blastocyst. These videos from different embryologists even may have different classification, changing from one to the other. I have one AA or BB embryo, it is a fantastic embryo, and the qualities are very very good, then don’t worry about it. It will be good.
The difference between using fresh or frozen eggs is that when you have to use frozen eggs your chances are a little bit lower, around five points lower than with fresh eggs nowadays. It is great when you use fresh eggs. The problem with using frozen eggs is that you have to warm them, and the survival rate of frozen eggs is around 96% to 97%, depending on the quality of the egg. It could be a little bit lower but, with donor eggs, it is around this. You lose a couple of eggs when you use frozen eggs. Depending on the quality of the lab, there could be a deleterious effect with vitrification. My recommendation is to always when it’s possible, to use fresh eggs and the same if you can use fresh sperm. It is better than frozen. However, sometimes it’s more convenient to use frozen donor eggs, if you are looking for a very special phenotype it’s much easier to find when you have frozen eggs, than if you have to call a donor for doing the cycle at the same time as the recipient. If you are sharing the eggs between different recipients, it depends on the number of eggs you have. If you have eight mature eggs, it is the same if you share with two recipients or you have one donor for you. It is not a problem of the if there is one recipient for you, the problem is the number of eggs you have. You can have a donor with many eggs you can share, and there is no problem, but you have a donor with a low number of eggs, and you share, basically, you’re leaving fewer embryos for each recipient.
It is not a problem if the cycle becomes shorter or longer and there is no change in terms of fertility window with own eggs. The fertility window is not related to age and or the menstrual cycle. You can be menopausal, or you can be 20, 30 or 40 years old. There is no change in the fertility window. Usually, it is one to three days, and it does not depend on the menopause.
We know implantation is a physiological time when the embryo could implant in the uterus. From a physiological point of view, if you put an embryo in the uterus, there is only a couple of days, no more than two or two and a half days when the uterus is able to accept this embryo to implant and to follow like normal things. Most of the time during the cycle, the uterus is not receptive to this embryos, and you could put the best embryo you have inside of the uterus, and it wouldn’t implant. This is a relationship between the hormonal status of the uterus. You need the progesterone, but not too many days of progesterone and not too few. And you need certain levels of estrogens and these changes. The hormonal changes induce changes also in the immunological status of the endometrium. You need to combine the immunological status of the endometrium with the hormonal status of the endometrium to have the possibility for this embryo to implant. This is the time during the cycle we call window of implantation. It is the only time when you put the embryo inside of the uterus, and this embryo can implant and this when we are talking about the day of the transfer usually. It is correlated to day five when we do the transfer on a blastocyst stage. This embryo has to induce some changes in the uterus to implant. This implantation is around day seven after the alleged ovulation time, so this is the time we the call window of implantation. You can do some genetic tests, immunological tests or anatomical tests on that and look for different characteristics of the endometrium and decide if you are on the right time or whether your endometrium is in advance or in the delay of the time we are supposed to transfer the embryos.
At this moment, it is illegal in any country in the world. There are only very few places in the world where you can have a baby with three DNA. One of them is the UK. When you are using some mitochondrial transplant to avoid some kinds of mitochondrial diseases. But for increasing the chances of pregnancy, it is illegal. In India, it is also illegal.
If we are talking about the pregnancy rate with beta HCG positive is 77% with ultrasound positive is 68%, and the delivery rate is 55%. The delivery rate is a little bit lower than expected because we don’t have the results of some women. In the end, we count these results as negative. If you look only at all recipients, we have the results the delivery rate is around 62%. In any case, it is very good. As to the ethnic origin of the donors depending on the ethnicity of the recipients, you have black, Caucasian, Chinese, Mediterranean. We are able to help with all kind of ethnicities. With Asian or Japanese donors, we often work with frozen eggs as it is easier to freeze them and keep them for a long time, and those donors are rare.
It is not necessary for all the patients and probably will be only necessary for around 40% of the patients, and 60% can work pretty good with classical IV. The problem is there are very expensive cycles. You have to do a lot of things to have egg donor cycle in terms of work, in terms of time, in terms of travelling, in terms of money, so the risk of having low fecundation rate if you do a classical IVF is not acceptable from our point of view. I prefer to do ICSI just to be sure that the fecundation rate of the eggs is highest that I can have. So it is not needed, but we do ICSI for all our patients.
Well, the embryoGLUE is important if you have had repeated implantation failures, or you have repeated miscarriage. If you don’t have this kind of situation, the embryo GLUE is not an advantage in comparison with normal IVF supplementation. We always do as much as we can to improve our chances. Sometimes we need to do endometrial scratch in the previous cycle before the transfer which increases the chances of pregnancy. Sometimes we need to put HCG inside of the uterus. Sometimes we need to use colonies rating factor to increase the chances of pregnancy. Sometimes we need to use platelet growth factor =, but it depends on the women, and it depends on the case. From a general point of view, there is nothing special to do in an egg donor cycle to increase the pregnancy rate. Sometimes with women with three failed cycles, you need to do special things, depending on the tests. For example, imagine you have your KIR AA, your husband is HLA C2, so in these cases, you need to use the colony-stimulating factor to increase the chance of pregnancy. But is not for all, it is for special cases, for a special woman.
There are different names for this procedure. It is endometrial biopsy or endometrial injury or endometrial scratch. It is something like D&C that we do in cycle previous to the transfer and this induces an immunological reaction in the endometrium which increases the chances of pregnancy in the next cycle. It is not for all the woman, but when you f. e. have a lower immunological profile in your endometrium, you need to increase this immunological profile, because you need more help from your natural killers’. In this case, is the endometrial injury or the biopsy of the endometrium increases the chances of pregnancy, and it must be done in the previous cycle before the transfer? Usually, it is performed in the second part of the cycle, on day 22 or 23 of the cycle. After this scratch, you have the menstrual period, and you prepare the transfer for the next cycle.
Adenomyosis is always a problem your chances of becoming pregnant are lower, and your chances of having a miscarriage are higher. You have to do the treatment in order to avoid the complication of adenomyosis, and this treatment is not always successful. Sometimes, even with the treatment, we couldn’t increase the chances of pregnancy and usually, this treatment is blocking the hormonal axis of the hypothalamus, hypophysis ovaries and you have to use generate analogue in the for 2 or 3 months to block all the axis, and you are in amenorrhea for 3-4 months. After that, you can do the transfer of the embryo and this transfer the recommendation is to do from the frozen cycle, not from an IVF stimulation cycle. In regards to the cysts, it depends on the cyst. If you are talking about ovarian cysts if this ovarian cyst we can have a problem. If you are talking about functional cysts not hormonal, there is not a problem. If you are talking about endometriosis, it could be a problem in the ovaries. If you are talking about one cyst, like a dermoid cyst, there is not a problem to become pregnant. If you are talking about a cyst in the endometrium, there are the sign criteria for the diagnosis of adenomyosis, and I told you that having adenomyosis lowers the chance of pregnancy.
There is not too much difference in the pregnancy rate or delivery rate when you are talking about egg donation or embryo donation. It is always better to have an egg donation because the donor is younger, but when you are talking about the embryo donation, you are talking about embryos that previously have given a pregnancy, usually a twin pregnancy, and that’s the reason for this couple to leave the remaining embryos for embryo donation. These are embryos of very good quality. In our experience, the difference is around 5 points between embryo donation and egg donation in favour of egg donation. The main difference is regarding the things we know about the donor. In egg donation, we have a lot of information about the donor in terms of genetics, history of the family, personal history. We know the donor is completely healthy, and there is no risk at all. When we are talking about embryo donation, the information we have is less detailed. There are things we don’t know. A donor has to have a mandatory psychological interview and we don’t have a psychological interview of a couple who is going to have an IVF cycle. The donor must have tests on 300 diseases that are recessive hereditary diseases, and we have more than 300 hereditary diseases. The couple who is going to have an IVF cycle doesn’t do these tests. For the donor, we have information about r Zika virus. The other difference is when you are looking for phenotypic characteristics. With donor eggs, you can select the right phenotypic characteristics with no problem. In embryo donation, there is no way to select the phenotypic characteristics the only thing you select, is the race. The results are pretty good in both cases.
Usually, it is mandatory to check the progesterone level if you are doing an IVF cycle. For an egg donation cycle, if the endometrium is has a good thickness, it is not mandatory. You can do it obviously. The doses we use is minimum 800, so we changed to eight hundred around two years ago really, and there is no problem with the progesterone level. The dosage that s recommended by different guidelines is around four hundred milligrams. Before we used six hundred milligrams. Now we are using eight hundred milligrams, we are using four hundred milligrams plus 25 milligrams in subcutaneous injections and with both of them, you have always good levels of progesterone. There is no need to control this level.
It is not possible here in Spain as you have to use an anonymous donor and in Portugal, we have a clinic where you can use known donors, but these donors are known to the baby, not for the recipient. We are talking about donors that when the baby is 18 years old, they can ask for the identification of the donor. Using the donor of a sister or a niece or something like is possible in the UK, but not here in Spain or Portugal.
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