Why does IVF with donor eggs fail sometimes? How many failed IVF attempts should be worrying? What is the solution for implantation problems and repeated miscarriage? You can watch the video recording from the webinar above to learn more about these questions.
If you have had at least one failed IVF with donor eggs or you are preparing for your first egg donation programme, this webinar is exactly for you. Find out what to expect, what factors affect the programme’s success or failure and what to look out for during preparations for your next egg donation cycle.
Patients deciding to use donor eggs typically do so after IVF with their own oocytes has repeatedly failed. It can, therefore, come as a saddening realisation to discover that IVF with donated oocytes is not always the magical hoped-for cure. Whilst the use of donor eggs is indeed associated with increased pregnancy rates, like any other fertility treatment it can unfortunately also fail.
In this webinar, Dr Maria Arque, a specialist in obstetrics, gynaecology and reproductive medicine at Fertty International Clinic, Barcelona, discusses the most common reasons for unsuccessful IVF when using donated oocytes.
There are three main recognised causes behind unsuccessful donor egg IVF treatments; the embryo, the endometrium and the blood flow and immunology.
Good quality gametes (egg and sperm) must be used in order to create a healthy, viable embryo and for those using a donor, the quality of oocytes will presumably be high. However, whilst clinics rigorously test all donors, around 30% of eggs retrieved still have the potential to result in aneuploid (abnormal number of chromosomes) embryos. This can be due to differing factors such as the regimen used for ovarian stimulation and also clinic specific lab processes. When looking at data and recently published papers around donor egg treatments, there is a suggestion that euploidy rates, in donor egg cycles, significantly differ between fertility clinics. On average, a 70% euploid (healthy chromosomally complete) embryo rate would be expected from donor egg IVF.
Male factor can also affect embryonic health and various testing, including karyotypes and DNA fragmentation, is always recommended.
Whilst a good calibre embryo is key for a positive outcome following any IVF treatment, it is important to understand that it is not the only determinant. In order to implant, a healthy embryo also needs a favourable environment. Anatomical uterine factors such as fibroids, polyps, adhesions or other malformations can affect embryo implantation. Clinics should fully screen the recipient’s uterine cavity, to look for any endometrial issues, in advance of any donor egg IVF treatments.
If an egg is fertilised and implants during a natural cycle, the newly pregnant body enters the luteal phase. During this stage of pregnancy, the corpus luteum naturally produces the correct amount of progesterone required to support pregnancy development. All of which needs to be closely replicated when undergoing assisted conception; transferring the embryo during the correct window of endometrial receptivity is imperative. Clinics should ensure the recipient’s endometrium and hormonal levels are ready to accept the embryo. Progesterone is usually prescribed, and recipients are monitored in advance of the transfer.
Another cause, which can affect implantation is the thickness of the endometrium wall.
Conditions such as endometriosis can lead to a thinning of the lining, or refractory endometrium, as can radiotherapy treatment for cancer. Clinics generally believe an endometrial lining measuring circa 7mm is optimal for an embryo transfer, although some studies have found similar results when transferring with uterine lining of 5mm; every patient and every embryo is different.
Blood flow and immunology might currently be considered as controversial subjects but are believed to have a negative impact on implantation. Conditions such as thrombophilia (an abnormal tendency to develop blood clots) and / or Natural Killer Cells may affect the recipient.
Dr Arque explains that although it is known a healthy immune system and good blood flow to the endometrium are essential for implantation, the current medical understanding surrounding these issues remains incomplete. She advises that immune testing and empirical treatments must be approached with caution until further data is gathered, and more definitive conclusions can be made.
Finally, Dr Arque stresses the importance of a healthy lifestyle; even though the eggs are being collected from a donor, the overall health and lifestyle habits of the recipient are just as crucial. Even before the embryo is transferred recipients should fully prepare themselves, abstaining from smoking and excessive exercise, drinking only in moderation and ensuring they are neither over or underweight, all factors known to have a negative effect on embryo implantation and pregnancy.
Whilst the use of donor eggs can truly help many women achieve their dream of experiencing pregnancy and carrying a child to term, they are not infallible.
Donor egg IVF treatment can fail, even with a top-grade embryo. For a pregnancy to become established implantation must also happen, and for that a healthy endometrium and immune system is necessary.
It is important to remember that every person is unique, it is, therefore, the duty of clinics to provide a tailormade service for each individual. The window of endometrial receptivity is not necessarily the same for all patients and preparing the hormones and uterine cavity won’t always be achieved by using standardised protocols. A thoroughly personalised embryo transfer, completely in sync with the recipient’s body, is what clinics should strive for and is what will ultimately help achieve the only outcome wanted from donor egg IVF.
Read more about IVF with donor eggs failed cycles:
I understand from the information that you provided that you had two different cycles of egg donation with two donors and unfortunately you just got one blastocyst and it was of very poor quality. There might be a lot of different causes for this. One of the things that can be looked at is the egg donor, but I presume that this has already been done. Another thing is to study the male factor, apart from the semen analysis. Sperm DNA fragmentation and FISH are some of the tests that can be done.
I don’t necessarily think that this is what should be done from the very beginning. As I was saying before, in general, we aim to have 70% of the eggs that come from a donor euploid. As I was saying before, depending on the clinic and all the other processes that are done in the lab, I think I would probably recommend going for one donor, once and then if the treatment is not successful, I would look into changing the donor.
You should be able to ask for that from the clinic and they should be able to give that data to you.
Yes. Our clinic guarantees one good quality blastocyst per cycle.
There are some very small studies that are still controversial, related to melatonin, a hormone related to sleep. Melatonin has a very important antioxidant effect so I think that there is no harm in taking melatonin. At least, you’re going to sleep better and melatonin might also have a positive impact on the quality of your eggs, even though, as I said, the studies are small and the evidence is not that clear.
In general, when we talk about IVF and egg donation success rates, we are talking per cycle, not per transfer.
Ideally, a BMI considered completely normal should be between 20 and 25. The data regarding fertility is strong and very clear: whenever we have a BMI higher than 30, the likelihood of having a successful outcome is lowered. Whenever we talk about being overweight, that would be a BMI between 25 and 30, the data is not that clear. In studies linking BMI and egg donation, the outcomes do not differ that much between the groups that had a BMI of between 20 and 25 and a BMI between 25 and 30. As for overall health, to have the best fertility outcome, I recommend having a BMI between 20 and 25.
I think that, in the case of egg freezing, the AMH is important, but the age is probably the most important factor. The likelihood of having a successful cycle for egg freezing and then having those eggs euploid and then giving that patient a baby depends more on the quality of the eggs. This is mainly related to age so I would say that this would be a factor that it’s more important than the AMH in that sense. Obviously, with a patient who has an extremely low AMH, it has to be discussed with her that probably, even though the stimulation cycle, we might be collecting a very small number of eggs and therefore we might be to repeat the cycle several times to have a good number of eggs to freeze to have realistic options of having a baby.
I think that the most important thing that has to be taken into account here is that, the fact that there are fibroids present in the uterus doesn’t necessarily mean that they are interfering with implantation. When the fibroids are located in what we call the outer part of the uterus, they usually do not interfere with the likelihood of success. As you are already 49, we have to think that, if the fibroids are inside the cavity, this would probably imply surgery. After the surgery, you will have to wait some time until you can have the transfer. I think that one of the things that may have to discuss with your doctor is whether it’s necessary to do a hysteroscopy to rule out the possibility of fibroids inside the cavity before doing the transfer.
Unfortunately, I don’t have a list of all the countries that perform this. What I can tell you is that these processes are not available in Spain. As far as I know, the US allows for sex baby selection and genetic selection process but I’m not certain about what other countries do. Only in a few countries in Europe is this actually possible, but Spain is not one of those countries.
I have patients who are 36 and have a very low AMH and even though I explained to them that their chances of having a response to stimulation and coming up with a number of eggs was extremely low, they wanted to do the cycle, so we tried and we collected maybe one or two eggs. But they were young patients who had a successful outcome. I think that, again, age is extremely important in terms of deciding if it’s the moment to move to egg donation. Obviously, a patient who is young and has already tried several other cycles with her own eggs that didn’t succeed and aside from that has low AMH, I think that it’s time to speak about egg donation. I think the most important thing is to make sure that the patient is informed about all the options, that she is completely aware of what can be expected from each treatment and the success rates and problems that might arise along the cycle.
The most critical aspect is to look for a clinic where you can see the results that they have and that you can trust. I would also look at the facilities they give you in terms of organizing the cycle in the easiest way possible for you and your partner.
The fact that the period is not regular is not a major concern because with an egg donation treatment, we can even do it with someone who has early menopause or in a patient with low ovarian reserve, so that would not be a major problem. We would be using a protocol with hormone replacement therapy and that would be addressed so this is something that we take into consideration. In general, most clinics agree to treat up to 50 years of age; some clinics might be a little bit more flexible and go up to 51, but what I would suggest is that if you’re thinking about egg donation treatment this is the moment to try to get things started because otherwise, it might be too late.
If the shipment of the embryos and the freezing of the oocytes are done properly following all the legislation and the processes are the ones that should be applied, I think that in terms of success rates they should be similar. We have been vitrifying embryos for a long time so success rates with embryos and oocytes are high so this shouldn’t be a factor in deciding one way or the other.
In this case, I assume that the tests that I explained earlier were all normal, but I would say that it would be good to do a hysteroscopy, thrombophilia tests, and consider immunology tests. It is also very important to address lifestyle, to have a normal BMI, to avoid smoking and drinking alcohol, have a healthy balanced diet and exercise. Another thing to take into consideration is from the male’s side. I’m not certain what has been studied apart from the semen analysis and if there are any genetic tests that should be done as well. Maybe consider that there might be a place for considering or at least discussing the cycle with PGS to try to diminish as much as possible the chance of having another failure.
Endometrial scratching is a procedure that is done usually on the recommendation of the doctor in patients who have had a number of failures so far. It’s a procedure we will be indicated in patients who have had several embryo transfers, with good quality embryos, with no implantation. In any case, there is no harm in doing endometrial scratching.
We are based in Barcelona and the age limit is 50.
I am not sure what insurance companies offer, but I can tell you that, if something like this happens in our clinic, we would look for and stimulate another donor without charging you for that previous cycle, if we see that it’s because of the freezing procedure of the eggs. But this has never happened. If you are talking about failure after the freezing of your own eggs and they fail to thaw, this is a completely different situation that might be linked to the quality of your eggs, there might be some companies that offer such insurance. I’m sorry I don’t have a clearer answer to that but this is a matter for the insurance companies.
I am not certain about that but I would say that any clinic that follows the legislation should not be selling eggs that are not mature. The eggs used in the cycle should be mature eggs.
Generally, I would say yes but to be more certain of my answer what I would have to say is that there are some processes that have to be looked at. In general, what we do is that if the clinic where you have the embryos frozen follows the legislation, there should be no problem. Usually, the protocol that we follow is that our lab and the other lab are in contact and there is communication between them and accordingly it can be done.
I’m not certain about this. I’m sure that probably somewhere in the world that might have happened but I don’t have that information. What I would suggest is that if you are thinking about doing treatment and you would like to freeze your eggs or oocytes to preserve your fertility, you should look for a clinic that has experience, that is trustworthy and that you can rely on; that you can have some information about them and that you can get information about their results, but it is the best clinic that you can have and then you will have the certainty that they are following all the legal regulations.
In terms of the food program, there is no one healthy diet. Some of the studies, as I was saying before, we’re done with the Mediterranean diet and to have a diet that is rich in fruit, vegetable and pulses, to decrease your intake of animal products, fizzy drinks, dairy products and fatty processed food. This may lead to having a better fertility outcome. The most important thing, as I was saying before, is to check your intake of nutrients and to take some supplements, multivitamins and some supplements for preconception just to make sure that you have no issues with any vitamin deficiency, which needs to be addressed.
I am not certain what units were used for that test (pg or pmol) which is important information to evaluate the result. To estimate properly the ovarian reserve, it would be useful to also have the antral follicular count. For a single female who is already 34 yo and is considering motherhood as a future option, my advice would be to do a fertility preservation treatment.
It would be useful to have information about your menstrual cycles and a hormonal blood test done between CD2-CD5 to check FSH, LH and estradiol and another one on CD21to check progesterone. If there are any alterations, you should discuss with your Doctor how to address them.
The medication seems to be very clear and the progesterone was prescribed as a result of the ERA test so I would still prescribe the progesterone start according to the ERA result test.
In general, it’s something that it’s probably just common sense. What I would say is to try to avoid smoking or alcohol and to control the intake of caffeine. I wouldn’t necessarily say that there is any specific food that we should completely avoid but the less you eat unhealthy food the better. My advice is to diminish the intake of animal products, food that has a high percentage of saturated fats and refined sugars. Try to follow a diet as close as possible to a Mediterranean diet, with lots of fruits, vegetables and drink mainly water.
That’s a question that I get from a lot of patients. As far as I know, there are some studies saying that acupuncture can have a positive outcome in fertility treatment in general and in treatment with donor IVF. I would suggest to patients is that if you have the time and can afford it I have no problem with acupuncture at all because it is something that might have a positive effect. But there is no clear definitive evidence around this even if there are some studies saying that it might have a positive effect.
That would be no problem at all. We can definitely do that. What I would suggest is using the same email address that you have provided before and we can discuss your case having a proper medical consultation.
I assume that you still have frozen embryos after the last cycle so I think that if the embryos were of good quality and the transfer did not work it does not mean that the embryos that you have from the previous donor are necessarily not good because as I was saying before there is no guarantee that 100% of the embryos are going to be euploid. This might of have been bad luck, so if you have good quality embryos from the previous donor you can use them with no problem. If you don’t have frozen embryos from the previous donor what I would suggest if the treatment has not worked before, that you try to change the donor.
I think that I would consider doing another IVF cycle with pre-implantation genetic screening. Another thing that is important is that we don’t have information about your partner and it is important to assess that there is no hidden male factor that might not have been diagnosed.
This is something that should be very individualized with specific cases. Maybe for patients who are 51, we might assess the case in a medical meeting, but that’s something that I cannot give a definitive response to without having assessed the case before. This is how we would do this usually.
I would recommend doing a dummy cycle in patients who have had a premature ovarian failure or have had a long period of amenhorrea and have not received hormonal replacement therapy or oral contraceptive pills. In general, we use dummy cycles to see the response of the endometrium and that way we can ensure that we are giving the right dose of medication. I don’t think that it’s necessary to do several dummy cycles before the actual transfer. If you have had a couple of cycles that failed and the thickness and the quality of the endometrium are ok, I don’t think that it is necessary to do any dummy cycles.
This depends on the stage of the embryo we are transferring. If we are transferring a frozen embryo on day 3 the progesterone should start 4 days before, in the morning. If we are transferring on day 4, progesterone should start 5 days before, in the morning as well. If we are transferring a blastocyst on day 5, progesterone should start 6 days before, again in the morning.
These are natural medicines, and as I have said before with other natural medicines, we don’t have any definite evidence that this is going to help. With primrose oil, there is no problem at all in taking it. With MACA, so far, there have been some disputed studies so it is something to discuss with your consultant.
There are a lot of studies into this but not many of them have included a lot of patients. Some of the data says that in patients who take more than 600 mg of caffeine a day, more than 3 cups) might have a negative impact on fertility. In general, our recommendation is to not take more than two coffees a day. But we need to have more evidence about this, but there is no need to completely give up coffee if you really like it.
I would need all your information to assess the situation, so if you can email me that would be the best thing to do.
In terms of when to start the progesterone, I would follow the doctor’s advice because this is based on the result of the ERA test and is exactly the window of implantation. After having had several failures with egg donation I think that PGS is something that might be considered, at least to see the percentage of the embryos that are euploid and to see if this is higher than expected and if that are any factors that might increase the likelihood of having aneuploid embryos. At least after several failures, PGS will decrease the risk of having a transfer of an aneuploid embryo. And just to clarify, NGS (next generation sequencing) is one of the techniques that can be used for PGS. It is the technique that is used in most labs nowadays.
Implantation takes about 4 days, not less. When we transfer the embryo at a blastocyst stage this would be in the next few hours but I would also say to all patients is not to do anything that they might regret. There is no need to stay at home resting in bed, not doing anything at all. I usually recommend having a normal life, not to avoid sexual intercourse or physical exertion.
This is a very extensive topic and we would need another webinar to answer this. To sum up, there is growing evidence that we have very good results when we do a frozen embryo transfer because hormone levels are more similar to a natural cycle and therefore it looks like the receptivity of the endometrium might be a little bit better. This is something that not all clinics do and we don’t do that for all cycles. I would say that our current practice is, with patients who have a good ovarian reserve and a good response to the IVF cycle with high levels of estrogen and have a risk of hyperstimulation ovarian syndrome, we don’t do the fresh embryo transfer to avoid the risk of OHSS. For us, safety comes first. We know that a frozen cycle gives at least as good results as a fresh cycle. In any case, every situation and the patient should be individualized. If we have a patient with a limited number of eggs with just one embryo we would probably do a fresh transfer.
It’s very similar.
Basically, overstimulation or hyperstimulation ovarian syndrome can have a detrimental effect on implantation. It is triggered by the HGC pregnancy hormone so if you get pregnant it’s going to get worse and to control it is going to be a bit more difficult. Nowadays, we have all the tools to try to diminish as much as possible risk of hyperstimulation ovarian syndrome in our patients and also have the technology in the labs to have very good results with frozen embryos. So, from my perspective, there is no need to put any patient at risk and whenever we have a risk of hyperstimulation ovarian syndrome we recommend freezing the embryos and differ the transfer without any kind of doubt.
I would say that, in general, the likelihood of having a successful outcome of doing an oocyte preservation cycle at 40 or above is rather low. I would discourage a patient from doing that if she is 42 or 43. If the patient is 40 or 41, I would discuss, depending on the level of AMH level and the antral follicle count and being aware that a very high percentage of the eggs that might be collected is going to be aneuploid, we want to make sure that we don’t give false expectations about the real chance of success.
Every clinic has different protocols and different ways of working but in our clinic, we always inform the patient about the basic characteristics of the donor before having the transfer. You know that in Spain egg donation is anonymous so we cannot provide a lot of details about the donor and the only information that we can provide is the age, ethnicity, hair colour, eye colour, skin, height and weight. We always give that information before the transfer.
In general, the basic test. We usually ask for a general hormone blood test, full blood count, renal and liver function tests. We check thyroid function, as this is very important for having a successful outcome. We also ask for the results of a PAP smear test and an ultrasound to assess the uterus and the ovaries. In some cases, we might ask for more tests depending on the medical conditions the patient might have. If the patient suffers any medical condition, we require a confirmation from their doctor (specialist or GP) to make sure that the patient doesn’t have any formal contraindications for fertility treatment and pregnancy.
The programs that we offer are:
There are a lot of supplements on the market for preconception and I wouldn’t be recommending any specific one as most of them have very similar content. What I would suggest that it is very important to have a healthy lifestyle, to not smoke, to drink very little or no alcohol and to have an active life, to do sports and to have a healthy diet. What I’m trying to say here is that even if you are taking supplements if you are not addressing your lifestyle benefits of the supplements are going to be limited.
We use both frozen and fresh eggs. We try to prioritize the matching of the recipient so we have the same results with both frozen and fresh. We have a success rate of about 60% per transfer (80 % cumulative pregnancy rate) when we do a transfer with an egg donor taking into consideration that, from the male side everything is completely normal.
I think the main supplements that you need you are already taking, so there is no real need to take anything else if you already have a healthy diet. There is an economic interest in terms of supplements and the effect that they might have. The evidence is still very unclear and there are a lot of very small studies making the case for some supplements. I would suggest focusing on a generally healthy lifestyle and the prenatal or preconception supplements should be enough. It is important to make sure that the prenatal supplement that you are taking has at least 400 mcg of folic acid. Avoiding spending extra money on something that might have no effect.