Key components for improving IVF success rates over the last years

Vanessa Vergara Bravo
Medical Coordinator at IVI Clinic Madrid, IVI Clinic Madrid

Category:
Success Rates

Key components for improving success rates over the last years
From this video you will find out:
  • the definition of successful IVF treatment
  • how the IVF outcome is measured
  • different strategies to improve outcomes
  • key changes in IVF laboratory work in 2006-2020
  • implantation rate in standard IVF cycles with PGT
 

What are the new components to improve the IVF pregnancy rates?

Watch the webinar with Vanessa Vergara Bravo, Medical Coordinator at IVI Clinic Madrid, who discusses the components that are crucial in improving IVF pregnancy success rates and those that have been developed over the last years.

What are the new components to improve the IVF pregnancy rates? - Questions and Answers

Do you use time-lapse incubators, and do you believe that they make a difference?

We use time-lapse incubators, it is a very interesting tool that we introduced a few years ago. It is a tool that helps to select better embryos. There are a lot of studies that find good results, some studies don’t. Scientific evidence is kind of contradictory. It is an incubator that permits us to see what’s going on with the embryo without opening the incubator every time and also, we use it but I cannot tell you how big is the impact of these incubators in the long term. Many studies established that we have some benefits.

What is the difference between PGT-A and PGS?

It is the same. PGs is just the previous terminology that was used. I don’t remember if it was one or two years ago that it changed and the PGT was proposed. PGT means pre-implantation testing, it gives us the ability to see some abnormalities of the embryo, so PGT-A or it could be a PGT-M which is the diagnosis of monogenic diseases in the embryo, or could be PGT-SR which is the structural identification of chromosome abnormalities in the embryo. But PGT-A and PGS it’s the same.

I am on an anti-seizure drug called lamotrigine because of a car accident (frontal lobe) does my medication make IVF more difficult, less successful?

It doesn’t have to be. The problem with the drugs is that we don’t exactly know how it is going to affect you. In these cases, we have a multidisciplinary group of specialists and a special person who has a speciality in maternal-fetal medicine, and we have this clinical special cases committee where we analyze all the recommendations of the neurologists of the embryologist, obstetrician etc. I don’t believe that we have evidence of teratogenic effects with this anti-seizure drug. In the transfer and the results of the pregnancy rate, it won’t have any impact in that. My only concern would be the teratogenic effect, but as far as I know, this doesn’t affect it. When we have these type of drugs, we have to compare, and we talk to the neurologist about the benefits of using the medication or stopping it. These medications have a very important indication, so usually, we keep them because there are no clear teratogenic effects. If we see a clear teratogenic effect of this anti-seizure drug we have to stop it, we have plan it with the neurologist and change it.

I am interested in your 100% blastocyst transfer. I have read that some women can not produce blastocysts, how do you manage those patients?

The thing with blastocyst is that we have to provide the best environment for the embryo. If the patient cannot get to a blastocyst stage, we can discuss options of transferring on a day-3, but we don’t find any benefit in transferring the embryos before. If they don’t survive in the laboratory, they will probably not survive in the maternal users, and so this will result in a negative pregnancy. If we don’t reach that stage, there are a few things we can do. What we do now, we try to have more available oocytes and give them the best environment in the IVF lab.

So you would recommend transferring only one embryo when receiving egg donation?

Absolutely, yes. We always recommend transferring only one embryo because as I said, we have a very high implantation rate which is going to give us the pregnancy rate. When you transfer just one embryo, the possibilities of a twin pregnancy are nearly zero, and we are going to avoid all the complications that I mentioned, so I am absolutely sure that we recommend doing a single embryo transfer.

I am in the UK. I feel very conflicted about PGT-A testing given that the HFEA advises very much against it arguing that there is no strong evidence for its use. What is your opinion?

What we have to look at here is what a patient wants and how the PGT-A is going to improve. Imagine that you have 6 oocytes and you will have 4 embryos if we do PGT-A, we have the opportunity of getting that pregnancy in the first try, a very high chance, and if you don’t do PGT-A, you are going to have the embryo transfer number 1, number 2 and then number 3 or 4. After transferring 4 embryos, in the end, you’re going to have the same possibilities of live birth, but per cycle, it shortens the time that you need to get pregnant, and it lowers miscarriage rates. There is no doubt of that, so I understand why and because in terms of public medicine and those things are kind of hard to say that it is going to improve the live birth rate. It is going to improve the live birth rate per transfer dramatically, and it is going to shorten the time that you need to get pregnant, and it is going to lower the miscarriage rate. If you are over 40 years old, you have a miscarriage rate of 30% without PGT-A, so you’re going to go through all these for a 30% possibility of miscarriage. It is very different in younger patients where the miscarriage rate is 11% of, and that’s what we reach when we find aneuploid embryo.

Why would the progesterone (P4) level be low on the day of ET? Is it something to do with different people absorbing progesterone differently?

It is not well known. I wish we had that answer because progesterone has been a part of many types of research and many investigations, but it depends on the way we are administering that progesterone. There are many types of administration of progesterone, we have the intramuscular one, we have the vaginal one, that is the one that is preferred in Spain. There are some groups in the United States would prefer the intramuscular one, and now we have the subcutaneous injection of progesterone.

What dose of vaginal pessary progesterone do you prescribe? 600mg, or 800 mg?

We use 800 mg of progesterone in egg donation or cycles where the patient doesn’t produce any progesterone. If you have an IVF with own eggs and you go for the embryo transfer, the luteal corpus in the ovaries produces progesterone, we do have to give some support, but it is not as high as 800mg.

For Duo-stim, how many days after first egg retrieval do you start the second stim? Three, five, seven or nine days?

It is from 3 to 5 days after the egg retrieval.

I am planning to do a budget egg donation programme. Its 12 frozen oocytes from 2 different donors (6 from each for example). I also use a sperm donor. I’m 38. I had 5 failed IVF with my own eggs. The doctor said I don’t need PGD/PGS in case of egg donation. What is your opinion on this? Isn’t it better to not fail again and not to transfer the wrong embryo again? Also, I really want to transfer 2 embryos, is this too risky?

This is a very easy question to answer for me. First of all, I don’t understand why you’re going to have 2 different donors. We have the egg donation of a good number of oocytes from one donor and we have very good fertilization rates with a sperm donor. Even with 6 oocytes, we have a good fertilization rate, and we’re getting the blastocysts. About what your doctor said in regards to PGD/PGS that you don’t need because of the egg and sperm donation, it’s true depending on the countries law. It’s not that you don’t need it, because of course if you did PGT-A you would have more possibilities of euploid embryos but this is not absolutely clear when the age of the donor is less than 35 years old, so in countries like Spain it is not allowed by the regulation on the law, we don’t have an indication of a PGT-A when we have an egg donation when we don’t have a male factor.

What is your opinion on ERA Test? How valuable is this information and can the receptivity change in time? How long is the result of ERA test valid (lifetime or a certain time)?

ERA test helps us to evaluate the endometrium. When we have patients that have failed in previous treatments. Imagine that we have very good embryos that were transferred and they were euploid embryos or embryos from an egg donation, and we don’t know what’s going, we do the ERA test to see the window of implantation of receptivity of that embryo, and it helps us to give more time of progesterone or less time of progesterone to fit our patient in that specific time where the endometrium is more receptive. I don’t know if it’s going to change in time, but we think that it won’t because the ERA test is based on how your body reacts with some medication to the expression of genes that may favour. I don’t have anything that can make me think that it’s not going to be valid. If you receive the same medication in one month or six months and I understand that your endometrium is going to respond in the same way.

I’m thinking of using egg donation at IVI Barcelona. Do all IVI clinics have the same equipment, incubators and protocols?

We do have the same protocols in all the clinics and the same equipment. In IVI Barcelona they have excellent results, and we are benchmarking of all of our outcomes every month, so this is something that you can be sure.

What do you recommend to support/enhance the implantation process? Any extra medicines (beside progesterone), supplements, acupuncture, anything else?

I know that some things may help, but there is no strong evidence with any type of extreme medicine after the embryo transfer. We don’t recommend supplements accepting except the folic acid f. e. It is true that some years ago some studies said that acupuncture helps the implantation, but we don’t recommend it.

I’m considering twins? Do you think that would cause complication as I am 44?

It is not recommended to look for a twin pregnancy at any age, and if you’re 40 or over 40, the risk of complications like preeclampsia, diabetes, premature delivery is even higher, so I won’t recommend that. You should go for one single embryo transfer, and after that, you can go for the next treatment a couple years after that.

Are differences in progesterone quality, absorption depending on the kind of administration (intramuscular vs oral vs vaginal)? Any of them is better than others?

There is no specific answer to that. All the ways of the administration seem to be good, we prefer the vaginal way of a route of administration because it doesn’t hurt, the intramuscular option hurts as it has to be injected daily. In some countries and some clinics like in the United States, there are a lot of doctors that prefer using the intramuscular option. The studies right now don’t show any big difference between the different routes and vaginal option works really well.

I was receiving 1200mg of progesterone (3 x a day 2 capsules), is it not too much? (I was not feeling very well when taking it) with no successful implantation.

First of all, it would be interesting to know why you were receiving that high dose of progesterone because it’s not the normal dose that we use. Possibly, your doctor has seen a problem in your previous treatments or maybe a certain progesterone level that was not okay, and they didn’t have any other option. For us, it is not the usual way to start a treatment, we do that when a patient has a very low progesterone level during the luteal phase.

Is every IVF pregnancy a risky one? Are there higher risks to lose the pregnancy with donor eggs than with own eggs?

Not all the IVF pregnancies are risky ones, and the studies on the obstetrical outcomes are the same if you transfer one embryo between natural and IVF record system. There is no higher risk of losing a pregnancy with the donor, considering that the donor is younger than 35 years old, we have a lower risk of failure if everything is ok with the uterus, and you have no other complications, you don’t have more risk of losing the pregnancy.

We were lucky to have a baby (5-month-old) from last years through fresh embryo transfer even though I’m in menopause. We still have 3 embryos left for FET, we’re trying for another one when the situation with the COVID is better since it’s in Prague and we’re from the US. How will the doctors know which one is the best to transfer?

These frozen embryos that you have it will be very important to know if they are on day-3 or they are day -5, so if they are at the cleavage or blastocyst stage. We have physical characteristics of the embryo, morphological characteristics of the embryos, and they choose the best. If they don’t have any PGT done on them, it’s only based on morphological basics of the embryos.

How do you select your donor? Is it base on finance or voluntary? What is ethnicity, any blacks? If so, where are they from?

We have a very strong program for selecting donors. We select the donors because it is a voluntary act, they come here because you know that Spain is the number one country in the world for organ donation and for that same reason the donation of tissues and cells is very well seen by society, and they are all altruistic girls that come to give their eggs to other couples. In Spain, it is not allowed to pay for the donors, as it happens in other countries, so what we can do is have some compensation for all the inconvenience of going to the clinic and the travels and everything, but we cannot pay them. Everything is voluntary, and it is an altruistic act. Ethnicity depends only on the ethnicity of the receptor. If you’re Caucasian, you’re going to get a Caucasian donor. If you’re African, you’re going to get such donor. We do have black donors, they usually come from Africa, immigrants that come from Africa to Spain and they live here.

Do you have better results, and proven results that the pregnancy was achieved after adapting the ERA test result?

Yes, we have better results and some studies show that we have good results and some studies show that it doesn’t help. We recommend it if you had recurrent implantation failure after transferring good embryos and after studying everything else. We should have some information about the endometrial receptiveness. We have a lot of cases where we have used it, and after that, we think they have changed, so it’s a tool that we use, and we recommend it.

I have read stories of people transferring a PGT-A abnormal embryo but then having a healthy child. This does concern me, how could this happen?

This is a very hard question. It is not exactly a PGT-A abnormal, it is how you do the diagnosis with the PGT-A and how does the genetic lab does the interpretation of those results. What had happened in the last day years is that the technique the next generation sequencing (NGS) can see in mosaic embryos and these mosaic embryos have an implantation potential, and they do have the potential of giving a healthy child. We have changed that policy during the recent years, and after the deep genetical counselling, we are transferring mosaic embryos. In those embryos, all these cells in a blastocyst are not the same time, and it seems that the embryo can grow and give a healthy child, even though you can have more lines in chromosomes in the cells.

Authors
Vanessa Vergara Bravo

Vanessa Vergara Bravo

Dr. Vanessa Vergara Bravo is an obstetrician-gynecologist. She completed her degrees in Colombia, Panama and Spain. She has been a Medical Coordinator at IVI RMA since 2014. Dr. Bravo is a Global Associate of Fertility and Sterility Editorial Board and a member of many medical associations, among others ESHRE and SEF (Spanish Society of Fertility). Between 2016-2020 Dr. Vanessa Bravo was a Coordinator and Professor of Clinical Module of Master in Embryology of European University of Madrid and also a Lecturer in National and International congresses/ workshops of SEF, COGI, ESHRE.
Event Moderator
Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is an International Patient Coordinator who has been supporting IVF patients for over 2 years. Always eager to help and provide comprehensive information based on her thorough knowledge and experience whether you are just starting or are in the middle of your IVF journey. She’s a customer care specialist with +10 years of experience, worked also in the tourism industry, and dealt with international customers on a daily basis, including working abroad. When she’s not taking care of her customers and patients, you’ll find her traveling, biking, learning new things, or spending time outdoors.

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