How to boost the success rates of IVF with donor eggs?

Pilar Alamá, MD, PhD
Director of the Ovodonation Programme at IVI Clinic Valencia, IVI Clinic Valencia

Category:
Advanced Maternal Age, Donor Eggs, Embryo Implantation, Embryo Transfer, Failed IVF Cycles, Success Rates

From this video you will find out:

How to boost the success rates of IVF with donor eggs?

Success rates of IVF with donor eggs

Are you planning to have IVF with donor eggs? Are you wondering if there is anything that can be done to improve the success rates of your IVF with donor egg treatment? Is it possible to boost success rates using techniques like blastocyst culture, embryoscope, assisted hatching (AH), PGS, etc.? Which additional procedures are recommended in which cases? Find out the answers to these questions from our webinar. MyIVFAnswers.com invited a reproductive health expert to present the webinar topic and to conduct a live Q&A session with webinar participants. Our expert in this event is Dr Pilar Alamá, MD, PhD, Director of the Ovodonation Programme and a specialist in reproductive medicine. Dr Pilar is a gynaecologist with many years of experience and she has been working at IVI Clinic Valencia, Spain since 2006.

Egg donation IVF outcome

IVF with donated oocytes is often billed as a miracle cure. However, as much as it has proven increased pregnancy rates, it unfortunately can and does fail.

In this webinar, Dr Pilar Alama, a specialist in reproductive medicine and coordinator of the oocyte donation program at IVI Clinic in Valencia, advises what patients and clinics can do to boost IVF with donor eggs. For any egg donation treatment, there are three main people involved: the recipient (female), the partner (male) and the donor. The donor is stimmed, the eggs are retrieved and fertilised, blastocysts are cultivated and finally transferred into the recipient. Whilst this is a standard assisted reproductive technique there are many different regimens and protocols favoured by clinics, so what exactly should patients be looking for and how can success rates be elevated? It is now widely accepted that egg donation IVF often provides the best option for couples where female infertility is a factor. This type of treatment may be suggested due to an advanced maternal age resulting in diminished ovarian reserve, repeated failed IVF cycles when using own oocytes or following medical procedures, such as radiation for cancer treatment. Research, into egg donation IVF, shows that regardless of the varying conditions which may affect female fertility, higher rates of pregnancy are still accessible when donated oocytes are used. Egg donation IVF cannot be undertaken in all countries. When it comes to fertility treatments there is no worldwide governing, regulatory body, therefore each country has its own specific laws surrounding assisted reproduction. IVI clinic is in Spain which does allow IVF, with donated oocytes, and was the first country in Europe to create definitive laws surrounding the treatment. To proceed with egg donation IVF in Spain, the following conditions need to be adhered to; donations must be anonymous, and donors should not seek financial gain. All donors need to be between the ages of 18-35, healthy and are required to undergo intensive physical and psychological testing. Finally, the donor must be chosen by the medical team who must guarantee the greatest possible phenotypical (appearance) and immunological (blood type) similarities with the recipient.

Many factors play a part in creating a positive treatment outcome for patients, following egg donation IVF, and Dr Alama outlines the most important determinants she believes will help to achieve a pregnancy, and live birth, when using donated oocytes.

A successful recruitment process followed by a suitable matching of the donor and recipient is crucial. Both women should be fully screened, and disclosure of all medical history is absolutely necessary.

At IVI clinic approximately 60% of women, who apply to become donors, are refused as only those who meet the strict criteria are approved.

How the donor is cared for is also incredibly important for a positive result, donors should be treated responsibly and with the utmost respect; they should never be overstimulated. Dr Pilar describes the ideal donor stimulation method as safe, short and efficient. Overstimulation can lower the quality of oocytes and clinics need to do everything they can to ensure their donors do not develop OHSS (Ovarian hyperstimulation syndrome). In addition, clinics hope that proven, successful donors are encouraged to return and donate again, and for this a positive experience is essential.

Preparation of the recipient’s endometrium is also key. Mock embryo transfers should be carried out in advance of the real transfer, and scans and blood tests need to be completed regularly to ensure correct hormonal levels and endometrial thickness.

At present, numerous discussions are taking place to find out whether there is an optimal uterine wall measurement, which will increase the probability of embryo implantation. Dr Faubel advises that a lining of circa 7mm is usually considered suitable, but that there is currently no specific ideal thickness agreed upon. The recipient’s progesterone levels are also a consideration, especially if an HRT (Hormone Replacement Therapy) cycle has been carried out. Recent studies have shown that the medication used in HRT cycles can lower progesterone levels. Again, there are various debates as to whether a specific level of progesterone can achieve greater pregnancy results, and many studies are being undertaken. At this point in time research is still inconclusive. Dr Faubel advises that medicated HRT and natural cycles are equal and are purely dependent on clinic protocols and individual cases.

Yet another controversial topic, when it comes to egg donation IVF, is whether fresh or frozen oocytes produce better results.

Dr Pilar explains that new vitrification processes have changed the future of IVF and would advise patients that the outcome, from using frozen eggs, can be just as good when compared to fresh. She points out that whilst the quality is comparable, it is not uncommon to lose one or two oocytes during the thawing process, which can mean that the use of frozen oocytes may result in fewer eggs available for the treatment. Vitrification has also changed the way egg donation IVF is synchronised. The use of frozen oocytes allows for a non-synchronised approach between recipients and donors. ‘On the go’ matching can take place, meaning there is no waiting list as pools of are donors are constantly being stimulated; the eggs have been retrieved and are ready to use.

Patients using vitrified oocytes are also afforded more flexibility for their treatment which is often better for overseas patients.

Whilst the use of fresh oocytes might not offer as much flexibility, a synchronised cycle does, however, ensure that recipients are pre-matched with their donors; this can sometimes lead to a more accurate pairing. Dr Faubel advises that both protocols are equal and that it is very much a personal choice for the patient and medical teams to determine what is best, in each individual situation. The decision could depend on the recipient’s health, needs and preferences, the clinic location and the patient schedule.

Donor egg IVF treatment outcomes

Advances in medical technology have also provided clinics with the opportunity to boost donor egg IVF treatment outcomes. Time lapse incubators ensure continuous embryonic monitoring, better culture conditions and greater embryonic observations and assessments. The use of time lapse equipment, therefore, creates the best opportunity for selecting the highest quality embryos which, in turn, increases the possibility of implantation and pregnancy. Dr Pilar also stresses that the use of time lapse incubators should enable clinics to only perform single blastocyst transfers. She explains that transferring just one five-day-old embryo creates an optimum situation for implantation. As the embryo selection is more improved, transferring just one, well monitored, good quality embryo typically reduces the amount of aneuploid (abnormal number of chromosomes in the embryo) transfers, which leads to a greater pregnancy rate per embryo.

Dr Pilar cautions against transferring multiple embryos, especially in older women, as there are many health complications associated with a high-risk multiple pregnancy.

Single embryo transfers also create the opportunity for any additional high-quality blastocysts to be vitrified and used for future family planning or following a failed cycle of egg donation IVF. Finally, Dr Pilar advises that clinics can help establish a successful treatment outcome by practising multi-disciplinary work. When all departments and teams across one clinic work together the best option for each patient can be found. Not all patients are the same and neither are all treatments and protocols, clinics must, therefore, recognize that every donor, recipient, and partner are unique. By creating an individualized treatment plan, which caters to every patient’s specific needs, the probability of a positive result and pregnancy to live birth is more likely to be achieved.

Success rates of IVF with donor eggs - Questions and Answers

Is the previous diagnosis of ovarian cancer in the recipient a barrier? It was 10 years ago. I still have one ovary and my uterus.

If the oncologist allowed you to get pregnant, then there’s no problem. It doesn’t matter if you had ovarian cancer in the past. If the oncologists told you that you can get pregnant, then there’s no problem for us. You are under 50 years old. And if the oncologist told you that you can get pregnant, then there’s no problem for us.

Did I understand correctly that you can transfer an embryo in a natural cycle without hormone therapy?

We can do that in some cases. For example, if a patient had a bad experience with hormone therapy, and they decide to do a natural cycle, then we can do that. For example, if someone has a problem with patches or other things, in that case, and in most cases we use foresight because we are not sure. When the recipient is on the middle line, then it’s okay, we have donors for them. We can use the natural cycle for egg donation. If the patient wants an embryo transfer in a natural cycle, then why not? It’s an option. We can do that.

Do you have Skype consultation? I have tried to contact your clinic several times, but the coordinator says that I have to come in person to Spain. I appreciate that but could you have a Skype meeting before the personal meeting?

Yes, we have this option. I’m sorry about that. My last two patients were from overseas and we had a consultation over Skype. They were from America or South America. We have Skype service for our patients. In those cases, you only come to our clinic for embryo transfer and to meet us and make sure that everything is fine. We do have a Skype service for national or international patients so please try again.

I have read that the success rate of live birth with a donation is 50% if the egg donor is less than 35 years old. Is this true for recipients over 45 years old?

I talked about that a minute ago. It’s true that women over 45 years old have a lower pregnancy rate than women who are younger than this age but for that patient, it’s the only option to get pregnant so it doesn’t really matter. However, it is true that women over 45 years old have a lower pregnancy rate.

What is the success rate of egg donation in your clinic? Do you guarantee a specific number of blastocysts?

I showed you in the last slide that we are working with a number of blastocysts now. We guarantee around two blastocysts. This means that we have only one embryo transfer or two transfers. 80% of our patients have more than three embryos so we have to do two or three transfers. So we guarantee almost two blastocysts. But it’s true that more than 80% of our patients have more than three embryos. But we are still working on this for you so that you can be confident that you need two blastocysts to get pregnant.

The endometrium is more than 7 mm. How many days do you have to go ahead with the egg donation? Is there a time limit?

According to studies we did in the past women could be more than 50 days on estradiol but in our clinic patients are usually on estradiol for about 25 days and no more than that because we have a lot of donors. But in our clinic, the patients stay here for 20 or 25 days but no longer than that. It’s true that we have studies that say that it doesn’t matter even if it’s up to 50 days. In our clinic, though they only stay around twenty-five days. In most cases, it depends on the patient. Maybe they’ve planned to come to Valencia next week but the endometrium is fine. However, because they planned to come the next week, then we wait for the next week. For that reason, in some cases, it’s more than 20 or 25 days. In our clinic, we don’t have a problem with donors so a patient would usually spend 15 to 20 days under therapy.

Can the endometrium be too thick for successful implantation?

There are a lot of publications showing that there are pregnancies with an endometrium lining of around 4-5 mm and pregnancies do occur. It’s important to understand the reasons because there might be a problem with the endometrium if it’s too thick or maybe the uterus is small. Before the transfer, it’s important to analyze everything (polyps, etc.) to make sure that the patient can get pregnant. There are some therapies and medication that would help the endometrium to grow. We do have pregnancies with thick endometrium but, first of all, we need to analyze the reason why the patient has such an endometrium. We then make some follow-up treatment before the embryo transfer for the patient to get pregnant.

The references are from 2005. Isn’t there any newer research? Are those references still valid?

Yes, we do have newer research but it hasn’t been published yet. We have our own research that has been checked by an external company to validate it. We have improved our research a great deal over the last 10 years but I just wanted to show official results that have already been published.

Do you offer donor pictures? Or pictures of the donor as a child?

In Spain donors are anonymous. We take photos of all our patients, donors and recipients, and the people who do the matching have access to the photos but we don’t give these photos to anyone because in Spain egg donation is anonymous.

For endometrial preparation, you state no more than fifteen days of Progynova? Why is this, please? I took it for 24 days for a frozen transfer.

I talked about this before. The endometrial lining usually takes ten days to grow and sometimes we need to wait for the endometrium, but it depends on the doctor and it depends on the patient. It usually takes ten to twelve days. Then we can do the embryo transfer without any problem. We don’t have valid results in that case. At most, it takes seven to ten days. After that, the results are the same.

Would you recommend an ER Map after two failed egg donor transfers for the next cycle?

There’s a lot of things we can do before we proceed with the egg donation. It is important to know a lot about the uterus. There are some cases when a patient has a very small uterus. A ureteroscopy can help with that. You can help endometrium to grow better than before the ureteroscopy. It is important to focus on the uterus. You can do an ERA, and you can do, for example, a ureteroscopy, sometimes you need to change the donor because it could be because of the genes. You get pregnant, and we analyze the other things that need to be analyzed, e.g. thrombophilia, we need to be sure that there are no problems in the patient. We can look for this kind of clue, but we need to focus on the uterus to be sure there are not any problems that prevent you from getting pregnant. We use this tool (ERA) in cases that the patient does not get pregnant after some trials with the egg donation treatment. But we can use the ERA test and we use hysteroscopy in some cases because there might be some abnormalities you can see in the vagina, in the vaginal ultrasound, and maybe with ureteroscopy you can find some things that if you prepare, and we do surgery, that will improve the chance to get pregnant. Question:

What are the different kinds of cycles for the recipient woman in egg donation with fresh or vitrified blastocysts? Natural cycle with own ovulation or hormonal injection of diphereline in a cycle before the transfer? What are the differences?

The first question. We are going to do a normal cycle of egg donation. I suppose that you’ve undergone therapy and you have a donor and that you use the donor’s oocytes. In that case, we can do the normal therapy and you can do the embryo transfer in about 20-25 days. In that case, if the patient has the blastocysts, and they have their frozen embryos that are classified as fit for an embryo transfer, they can prepare for the transfer. I don’t know how many embryos they have and which one is the embryo they are going to transfer, which one would be in the results. When you go to the transfer, you don’t know how many embryos you have. You are allowed to use a frozen embryo transfer. In those cases, we have the frozen ones to use as spare. When we place those aside and we do the embryo transfer, there are fewer cases of embryo therapy because after ten days you can do the plan on the programme of the patient. In that case, we are going to do normal egg donation treatment with fresh or vitrified oocytes, or we can use both. We can use a mixed protocol. The patient will start with estrogen and other hormones for five days, or we can use the classic protocol and they do a vaginal scan and make sure that all is fine. They administer an injection in the luteal phase and start with the estrogen with the menstruation. We can use both treatments three times. It also depends on the patient. If the patient has vitrified oocytes, planning is easier. Whether the patient is going to travel to the clinic the next week or they would like to travel in two months — it all depends on the patient. We can use all combinations as I showed you before. It depends on the program you choose. The difference is only in the logistics. We can do whichever. It all depends on the logistics, on the patient’s plans. If the patient comes from Canada, for example, if we have a donor for them, we can vitrify their embryos. And when they come here, they come for a frozen embryo transfer. And, if the patient lives closer or in Spain, we can do a different program; it depends on the patient.

Is PGD testing recommended if the patient has had several natural miscarriages and is 45 years old? Do you see more successes with PGD testing?

It depends on miscarriages. If the miscarriage was in the past, and there were no oocytes, then I think there are no indications to do a PGS. If the only reason for the miscarriage was with the egg donation treatment, and they have failed a lot of times, and the sperm is not very good, it could be a reason to do a PGS. The women were around 45, and we’re talking about egg donation. Our donors are younger than 35, so, in that case, if the patient has lots of abortions with egg donation treatment, it could be a reason to talk about PGD. However, we would need to talk this through, because it is not easy to decide whether to do a PGD with the egg donation treatment.

How important is it to match the blood type of the donor? In my case, zero Rh minus.

Thank you very much for that question, because that question has been frequently asked by patients. It is true that the combination of the blood type is more a social reason and a theoretical issue than a medical one in all things except the Rh zero negative. In your case, we would always give you a zero negative donor. It’s important because one thing is the social reason. If you are A and your husband is zero, or if you are B, there are no medical reasons to try to avoid this combination. It’s important for other issues. If you are negative, then, in that case, we would give you a negative donor, because it would be an easier examination, contrary to the Rhesus type. For us, that’s important, so, in this case, we would use a zero negative donor for you. The blood type of your husband or your family does not matter, but, in that case, we can use zero negative.

Is it wise to lose some weight before getting pregnant?

We have a study that says for women with a BMI more than 30, they are more likely to have abortions. For this reason, it is the usual recommendation to lose weight before doing the embryo transfer. It is a healthier option because women with BMI over 30 have more abortions, but also because they have more problems with their pregnancies. They may have diabetes, more premature delivery, more obstetrics, more illnesses, in many cases. For this reason, we try to avoid treatment in women with BMI more than 30. But, in that case, we don’t have any options but to try and explain to them that they have more risk of having problems than if they are slimmer.

What would you recommend after three failed cycles of frozen egg donation (including miscarriages at 8 weeks)?

I suppose that if you have done all the extra tests and you have done hysteroscopy, you have done the ERA test, you have done thrombophilia, all these kinds of things, then maybe change the sperm. There are some people who say this has no effect. There are many cases of couples who do egg donation treatment with the sperm of the husband in the first cycle, second cycle, third cycle. They have had the same sperm with different donors. Perhaps before deciding to have the next IVF treatment, try to change the sperm; if it’s normal sperm, try it in combination with another donor. Perhaps a sperm bank is an option for you to consider.

Prior to embryo transfer, do you perform any blood tests? How many days progesterone does the recipient have before transfer?

We are doing a study in Valencia at the moment. We are performing blood tests to establish the prediction levels to know the best option for patients to get pregnant. Now, we use our experience. It is important to look at the blood test before the embryo transfer. In our cases, where patients take ten doses of progesterone; this starts on the day of the donation. The dosage is one, two, three on the first day, and four, five, six and ten on the second. This means that the day we are going to do the embryo transfer, the patient has taken ten doses of progesterone, and we have changed the way the patient is taking progesterone. We have improved our pregnancy implantation through doing this with ten doses of progesterone. Progynova is not needed. There are different options. First, you do the frozen embryos with egg donation, and when you have the frozen embryos, you do the transfer, and you can avoid taking medication. There are alternatives.

How long after the endometrium of the recipient reaches 6mm can you keep the recipient waiting for a fresh donation? After the endometrium is 8mm, can the recipient wait another two weeks for the transfer taking Progynova?

That depends on whether the patient has been taking Progynova for fifty days. But it’s true, that if you have an endometrium at 8mm, and you do not have a donor in the next two weeks, we would repeat the latest scan in one week to be sure, and the endometrium is 3mm and all is fine. In our clinic, in most cases, the patient is more than 20-25, because they plan that day, and they need a measurement of 8, but we have data so that we know you can have estrogen therapy for fifty days, and there is no impact on your result. But, according to our protocol, you have a newer scan in one week/ten days to make sure the endometrium continues to fall to become perfect, and there is no impact on your chance of becoming pregnant.

I was told that the ERA test was only accurate for the month that it was taken in. The clinic does not recommend it. What is your professional opinion? Can it help implantation?

We studied that in the first study with ERA, I think, maybe, five or six years ago, and I was one of the authors of the paper of that publication. Thank you for that question. We have studied that, and in Valencia we did the first study with ERA. I think this was five or six years ago. We studied some patients during the study and two years later to be sure the result would be the same (and it was). The patients came in 2006 and 2008, and the results were consistent in more than one cycle, about two years later. The results would be the same even over four or five cycles. In our cases, we do the ERA in one cycle and the transfer three, four or two cycles later, believing the results to be the same. We do the ERA in one test and the transfer later. The ERA test could help implantation. Sometimes we don’t really know how many patients have had an abnormal ERA test, where the implantation has changed or diverged from the norm. We didn’t know the results of the ERA test in the cases of about 20% of the patients. However, we can always do the same; we can change the sperm; we can do a PGD. Rather than removing one dose of progesterone, we can help people get pregnant when we have a window for doing so in the normal manner We can help these 20% to get pregnant.

Are there any other treatments and specific diets that should be used before egg donation with a donor?

There are a lot of people who talk about the pros and cons of diets which can help you avoid cancer. It’s important to be a healthy woman who doesn’t smoke and has a good BMI. It’s also important not to get stressed and to do sport regularly. All this will improve your body and improve your chances of getting pregnant. If you have a medically approved diet and if you eat properly with rice or paella, there is also a greater chance of your falling pregnant. It’s true to say that we have many patients who are very worried about what they eat. In a nutshell: by improving your life you are also improving the chances of pregnancy.

Can we do fresh or frozen embryo transfer on a fresh cycle without blocking ovulation? Which is better? To block the ovulation or not? If the recipient ovulates and has the transfer after, does this mean her body produces its own hormones and fewer estradiol pills are required after the transfer?

We sometimes use both. The problem is that there is no ovulation because if you ovulate, the window for implantation could move, and you can’t use embryo transfer. You don’t really know if the implantation is being done at the most opportune moment. It is possible to do hormone therapy treatment without analysis if you make some reviews of the embryo. The results may be the same, but you need to scan more frequently to make sure that the patient doesn’t ovulate because this could change the endometrium. If ovulation occurs, then you need to use less medication. This will cause disruption to the natural cycle. It’s not good to do hormone replacement therapy and wait for natural ovulation to avoid medication, because if the ovulation had started before then, then the endometrium has started to change. It is not good to avoid medication because there are some things you cannot control and you end up doing the transfer later than if it had been done the normal way.

After having the transfer of the egg are there any recommendations about what to do next? Should the patient stay in bed or stay in the hotel for one or two days?

We did a study in Valencia four or five days ago and divided the patients into two groups. One group stayed in bed in their room for thirty minutes, and the other half of the patients came back to their rooms on foot, dressed, and said goodbye. We have changed the protocols according to the results. In Valencia, the patients don’t stay in the clinic;, the patients do the transfer and the examination and we don’t give them any recommendations; the patients take a plane and return to their countries.

Do you have a device for high natural killers, apart from Intralipids?

I’m sorry I don’t have any information on this since it isn’t my speciality. I could try to find the answer later.

After a positive HCG test and taking 6mg Progynova and 1,200 mg utrogestan, is it important to test the estradiol and progesterone levels? How often? I have heard the progesterone tests should be done, but nothing about the estradiol levels during the first twelve weeks. Are estradiol tests unnecessary when taking 6 mg of Progynova daily?

I think it is necessary to test the progesterone levels when a patient wants to get pregnant. I believe that the pregnancy and the medication they take is sufficient to reach a good level. We study the hormone levels before the embryo transfer to see if there is any rise in progesterone levels before the transfer so that we could move the window for the implantation. We don’t use any blood tests to determine hormone levels. We don’t examine the patient’s estradiol and progesterone levels when the patient gets pregnant since we do not see this as being important for the development of the pregnancy. Estradiol and progesterone levels are important during the treatment before embryo transfer. If you do not have a perfect endometrial line and your estradiol levels are below 60, all this should be studied before the transfer.

Do you do uterus scratching?

We are doing a study about this because there is a lot of controversy about scratching. We don’t have the results, but we don’t believe that the scratching has any impact on implantation. Now, we are doing a study on egg donation treatment using randomized clinical trials to be sure of answering the question as to whether it is useful or not, since we don’t yet know.

Could you explain what the implementation period means? How is it determined, and can it be extended for longer periods with medication?

The uterus is not always receptive to an embryo being implanted. The embryo could be implanted at any moment in the cycle, but the moment of the endometrial is the best time, and this is known as ‘the window of implantation’: the moment of ovulation. The window of implantation is about 21 to 24 days into the cycle. However, with some patients, this may be later: 24 to 27 days. Medications will not change the window of implantation. Progesterone is the medicine that will attempt to open the window of implantation. There are patients who need this medication to move the moment of transfer. We try to harmonize the moment of transfer with the endometrial by using progesterone. At first, we saw that the window of implantation was always the same — 21 to 24 days — but now we know that’s not true for all: some patients have this window from 18 to 21 days and some later.

Is there any acupuncture treatment that would help before the transfer?

There are patients and clinics that do this, but we have neither the facilities nor the experience. We don’t have enough research to conclude that acupuncture would help all patients to get pregnant. There are, however, patients who perform this treatment on themselves and believe this may help.

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Authors

Pilar Alamá, MD, PhD

Dr. Pilar Alamá has a solid educational background in treating infertility: she graduated in Medicine and Surgery from the University of Valencia, Spain in 2001. She did her specialisation studies in Obstetrics and Gynaecology at the Dr. Peset Hospital also in Valencia. Dr. Pilar Alamá has received a Ph.D. in Medicine and Surgery with the highest qualification from the University of Valencia. Her thesis was on cryopreservation of ovarian cortex. Our expert has received various awards and merits: Diploma in Research Methodology and Design and Statistics in Health Sciences. Dr. Alamá is also a member of the Spanish Fertility Society (SEF) and the European Society of Human Reproduction and Endocrinology (ESHRE). Dr. Pilar is also very active in research: she collaborated in a several Human Reproduction research projects and has written ten international and four national medical publications. She is also an advisor/director of four dissertations in the area of Assisted Reproduction.

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