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IVF failure using donor eggs: embryo quality, implantation problems and miscarriage #IVFWEBINARS

Why IVF with donor eggs fails sometimes? How many failed IVF attempts should be worrying? What is the solution for implantation problems and repeated miscarriage? You can wath video recording from the webinar above.

If you have had at least one failed IVF with donor eggs cycle or you are preparing for your first egg donation program, this webinar is exactly for you. Find out what to expect, what factors affect the program’s success or failure and what to look out for during preparations for your next egg donation cycle.

IVF failures – embryo quality, implantation problems and miscarriage – Questions & Answers

Question:

We received 11 oocytes (from two donors), 9 got fertilized with my man’s semen, which is of good quality. On day 5, we had 6 embryos but none of them reached the blastocyst stage. On day 6, there was only one blastocyst left and of poor quality (CC). What can be the cause of such a poor result? (Additional information: the oocytes were sent by plane: the clinic doesn’t have an embryoscope)

Answer:
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.

Question:

To improve the chances of having good embryos, do you recommend ordering oocytes from two donors instead of one?

Answer:
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.

Question:

Do reliable clinics assess and publish the euploid rate of their oocytes donation program?

Answer:
You should be able to ask for that from the clinic and they should be able to give that data to you.

Question:

Does your clinic offer donor egg or embryo guarantees?

Answer:
Yes. Our clinic guarantees one good quality blastocyst per cycle.

Question:

I am very stressed out when it comes to treatment. It is very difficult for me sometimes to sleep. Do you recommend taking sleeping pills to improve egg quality?

Answer:
There are some very small studies that are still controversial, related to melatonin, a hormone related to sleeping. 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.

Question:

When we talk about IVF egg donation program success rates, is this in terms of embryo transfer or IVF cycle, which can include more than one transfer?

Answer:
In general, when we talk about IVF and egg donation success rates, we are talking per cycle, not per transfer.

Question:

Can you please confirm the best BMI to reach?

Answer:
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.

Question:

What is the AMH result that qualifies a single female for egg freezing?

Answer:
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.

Question:

I had a twin miscarriage at 49 last year. I was unsure why but was told it could be due to fibroids. I have not had the fibroids removed. Can I use the remaining embryo for another IVF?

Answer:
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.

Question:

Which countries approve sex selection and genetic selection process for to a single woman?

Answer:
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 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.

Question:

What is the AMH limit to decide that a patient should move to egg donation?

Answer:
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 the 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 the success rates and problems that might arise along the cycle.

Question:

What are the two most critical aspects a 48-year-old woman should investigate prior to selecting a clinic for egg donation with her husband’s semen?

Answer:
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.

Question:

At 51, do I stand a chance of success with egg donation? My period is not regular.

Answer:
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.

Question:

Which is better and has a higher level of IVF success: to transfer the embryos by airplane or to freeze oocytes for a longer time at the same clinic?

Answer:
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.

Question:

My wife has nine plus IVF failures with donor eggs and with adoption embryos. We only had one positive HCG and rest had implantation failures. The last attempt we did was based on ERA test and still with no success. What should we do now to resolve implantation failures, as my wife is only 43 years old?

Answer:
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.

Question:

Does endometrial scratching increase your chance of IVF donor success?

Answer:
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.

Question:

What is the age limit to have IVF at your clinic? Where are you based?

Answer:
We are based in Barcelona and the age limit is 50.

Question:

What do insurance companies offer, in cases of IVF failure after egg freezing?

Answer:
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.

Question:

Are there clinics that sell oocytes that are not mature?

Answer:
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.

Question:

Can you accept the transfer of embryos to your clinic?

Answer:
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.

Question:

Have there been any legal cases where IVF fails because the eggs, for example, have been misused or mis-frozen?

Answer:
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.

Question:

What healthy diet food program increases fertility and can help with a successful cycle?

Answer:
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 things, 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.

Question:

AMH of 3.5 and age of 34 single female what is your advice?

Answer:
I am not certain what units were used for that test (pg or pmol) which is an 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.

Question:

What can I do to have a balance of progesterone and oestrogen?

Answer:
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.

Question:

In the last attempt, my wife was asked to use Crinore 8% with Prolutex 25mg Clexane 0.4 and Estrofem with progesterone starting 144 hours before embryo transfer as indicated by ERA test. What should we do now in our next attempt as progesterone may still have to start 144 hours before embryo transfer?

Answer:
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.

Question:

What kind of food or medication must be avoided to guarantee a higher success of IVF and egg freezing?

Answer:
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.

Question:

Does acupuncture improve donor IVF success?

Answer:
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.

Question:

If we submit a letter from my wife’s doctor explaining what treatments she has undergone and still have had nine plus failures, can you help and provide advice? What would you do in your clinic as a step forward as we are looking to change clinic?

Answer:
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.

Question:

I am years 51 old now. I removed a fibroid last November 2017 and am ready for another IVF treatment. What is the success rate for frozen embryo? I can confirm previous were of good quality and were frozen should I decide to use the same ones again?

Answer:
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.

Question:

I’m 39. AMH is 8, AFC-12 and I had had two IVF with my own eggs that failed. I had two blastocysts in the first IVF cycle and one good quality in the second one. Should I try with my own eggs or should I consider egg donation?

Answer:
I think that I would consider to do 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.

Question:

Can your clinic be flexible to accommodate a 51 or 52-year-old patient for IVF?

Answer:
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.

Question:

Do you recommend a number of dummy cycles before the actual cycle for embryo transfer having had a couple of failed cycles?

Answer:
I would recommend doing a dummy cycle in patients who have had 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.

Question:

When should progesterone start before ET?

Answer:
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.

Question:

I understand MACA and Evening Primrose oil is good for hormonal balance. Is this correct?

Answer:
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.

Question:

Is coffee harmful to fertility?

Answer:
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.

Question:

Can your help in determining why I have had recurrent miscarriages?

Answer:
I would need all your information to assess the situation, so if you can email me that would be the best thing to do.

Question:

My wife had IVF failure with egg donation and embryo adoption. We had only one +HCG. In the last attempt, the progesterone started 145 hours before embryo transfer based on ERA tests. The doctor says we need to start progesterone at the same time like in the previous attempt, that is to 145 hours before the embryo transfer. What would you do if you were our doctor? Would you keep the progesterone window more or less than 145 hours or so do you recommend PGs or NGS this time. We have chosen proven fertile female below the age of 25 and would choose the same in the future.

Answer:
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.

Question:

How long does implantation take and what should a woman do in this period of time?

Answer:
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.

Question:

Do you recommend fresh or frozen embryo cycle for patients?

Answer:
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 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.

Question:

Does fresh or frozen cycle have a higher success rate?

Answer:
It’s very similar.

Question:

Does overstimulation affect implantation negatively?

Answer:
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.

Question:

At what age or at what aspect can we say that egg freezing or IVF is impossible or of high negative risk?

Answer:
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 are going to be aneuploid, we want to make sure that we don’t give false expectations about the real chance of success.

Question:

Why do some clinics only tell the age of after having a positive? Isn’t this unfair.

Answer:
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.

Question:

What test should you do before starting egg donation? What tests do clinics need before starting?

Answer:
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 the confirmation from their doctor (specialist or GP) to make sure that the patient doesn’t have any formal contraindications for fertility treatment and pregnancy.

Question:

What kind of donor programs do you offer at your clinic?

Answer:
The programs that we offer are:
Just for Transfer: it is an egg donation program where the patients do all the tests and follow-up in their own countries and then fly into our clinic in Barcelona just for the embryo transfer.
Egg Donation from a Distance (This program is not available for all countries, it depends on the legislation) where the patients would not have to fly to Barcelona at all. If you are doing the treatment with your husband, you provide the sperm sample and do all the basic tests in your local clinic. The sperm would be frozen and shipped to our clinic and then we can look for a donor that matches your physical characteristics. The embryos are created in our clinic and when the embryos are at the stage of blastocyst, they are frozen and shipped back to your local clinic. You will do the preparation for the frozen embryo transfer in your local clinic and you will do the transfer there. If there are any surplus embryos those would be shipped there as well so you will have all the embryos from the batch at your local clinic, without the need of having to travel to Barcelona for the frozen embryo transfer.

Question:

Are there any supplements men can take to improve their sperm to help with egg donation fertilization?

Answer:
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.

Question:

Do you use frozen or fresh eggs? What are the chances in both cases?

Answer:
We use both frozen and fresh eggs. We try to prioritise 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.

Question:

What about supplements for women, besides prenatal?

Answer:
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.

About an author:

The webinar’s presenter was dr Maria Arquè who is a specialist in obstetrics and gynecology and reproductive medicine. She has worked in a few renowned IVF clinics in Europe. Dr Arquè’s professional interests include preserving fertility for men and women, IVF and reproductive health research, fertility education for patients and the impact of lifestyle/diet on IVF with ICSI success rates. She has studied and worked in Ireland, did some of her training in reproductive medicine in the USA and is now an International Medical Director at Fertty International in Barcelona, Spain. Dr Maria is proficient in a few European languages: English, Italian, Spanish and Catalan. She knows basic French.

dr Maria Arque

dr Maria Arque, Fertty International, Barcelona, Spain

All patients inspire me. Each of the patients I meet every day has a different background and a different approach towards their infertility diagnosis. I learn from all of them every day and I’m grateful for it. The biggest lesson I have learned from my patients is that resilience and perseverance are key if you want to succeed.

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