Preimplantation genetic diagnosis for treatment of RIF in IVF

Explained by: Evangelos Papanikolaou, MD, PhD, Assisting Nature - Human Reproduction & Genetics
Category:
From this video you will find out:
  • How often implantation failure happens?
  • What medical intervention can be taken to diagnose the cause?
  • When and why aneuploidy embryos happen?
  • What are the reasons for frequent aneuploidy?
  • How to assess the quality of the embryos?
  • What are the results of the genetic analysis of the embryo?
  • What is PGT-A? Is it invasive?
  • What are the real patient cases at Assisting Nature?

Is PGD a solution if I have had recurrent implantation failures?

In this session, Dr. Evangelos Papanikolaou, MD, PhD, Founder of Assisting Nature, Thessaloniki, Greece has been discussing RIF patients cases and talked about preimplantation genetic diagnosis and when it is indicated.

Is PGD a solution if I have had recurrent implantation failures? - Questions and Answers

What are the causes of more than 46 chromosomes in embryos? Or, causes of less than 46? Could high stimulation drugs be a cause?

The causes, as we’ve discussed earlier, are mainly the incapability of the egg to divide those 46 chromosomes into 2 pairs of 23. There is eternal incapability of the egg to divide strictly into those 2 parts to become a polar body. In the past, there were a lot of discussions about whether high stimulation might be the cause. And there were some papers back in 200-2004 regarding this issue. The truth is that the higher the stimulation the doctor retrieves more not mature eggs that at the end may divide into a blastocyst, but this blastocyst will be abnormal. The problem is not per se the drugs, the high stimulation, but that we retrieve all the eggs, all the follicles that we have in the ovaries and in the end we up with higher aneuploidy rate in that particular patient, but you should always to remember that if you’re a good responder If I’m a good responder and I produce a lot of eggs at the end, I  increase my chances of having normal eggs and in the end having normal embryos. High stimulation is not the real causative agent, but only it can change this result statistically. That’s why we need rational stimulation, so produce as many eggs as we can without any harm to your health, and we know that the perfect number of eggs is around fifteen. If we have more than this, there’s no benefit, less than this will cause lower pregnancy chances. So the maximum of eggs is around 15, and we should aim for this number if it’s possible.

In your experience what was the oldest woman, you have treated with euploid embryos and healthy live birth?

The oldest woman where we had 1 euploid embryo and live birth was 45. The chances of having a euploid embryo at the age of 45, as you know, it’s less than 1%. If you have 100 ladies at 45, in the end, one of them will become pregnant.

What are the costs for PGD testing?

With NGS, which is the technique that we perform our biopsy, the cost is 1,000 EUR for the biopsy itself, in Greece, plus 250 EUR per embryo. If you have one blastocyst, then you will pay 1,250 Euros. If you have 4 blastocysts, you will pay 2000 EUR.

In the beginning, we had 18 oocytes that fertilized, however, on day 6, only 3 are suitable for PGS. Why would only 3 be suitable, for PGS? Have they got to be very good embryos for PGS testing?

We do not biopsy everything, of course. The blastocyst should be above B or A to be tested. The problem here is that those blastocysts were already on day-6, which means that they were already very late in development. If you have a day-6 blastocyst, and it is perfect, the chances of this blastocyst to be euploid is around 10%, so it does not mean that if you have an excellent blastocyst on day-6, that this blastocyst is normal.  In this particular couple, the problem might arise either from the high number of eggs, maybe you have PCOS, or from the poor quality of the sperm or the poor quality of the stimulation. If they retrieved the eggs earlier, then you might end up with this late development as the blastocyst stage.

What are the criteria you use to select a mosaic embryo for transfer?

Mosaic means that if the blastocyst has 100 cells, 20 of them might be abnormal and 18 normal, or the opposite 18 might be abnormal and 20 normal.
Mosaicism, in some way, is a normal procedure in the development of the blastocyst. It looks strange, but actually, it is a normal procedure. So the embryo tries to avoid the abnormal cells because mistakes do happen in the best families. They try to abort those abnormal cells to the trophectoderm, unfortunately, we do the biopsy, so actually, the trophectoderm sometimes might be the protection shield for the embryo itself where abnormal cells are deposited. This is the explanation of mosaicism.

On the other hand, of course, mosaicism does indicate the embryo incompatibility to divide itself correctly. This might be the problem that in the end, half are abnormal, and half are normal, so these embryos cannot give life to a human.

The criteria that we use to select a mosaic embryo is that if we have less than 10% of mosaicism and specific chromosomes, our geneticist advises for them to be transferred. You can find this information in our leaflets on the Internet.

Do women over 42 often have enough embryos to perform PGS? Did you talk about 5 embryos?

I talked about 5 or 6 embryos, in total, from different IVF to define that someone has recurrent implantation failure.
So actually, we only need 1, as you know, the more we have if we are over 42, of course, the better chances for finding euploid embryos. On the other hand, if you’re 42 and your AMH is low, and if you take medications, but you won’t produce more than 2 eggs, we can do several natural cycles. We can deposit 2 or 3 blastocysts after 9 natural cycles, for example, and to do genetic testing on the 3 blastocysts after 1 year of trying that should be the maximum, so a doctor needs to put the threshold for how long you should try and out of this 2-3 blastocysts if you’re lucky, you can have a normal blastocyst. At the age of 42, this probability is around 15%.

I’m choosing between doing NGS and another method of PGS where the transfer is the same month. How much higher is the risk of Down Syndrome if I do regular PGS instead of the new NGS? And the miscarriage and implantation failure rates?

There is no reason for fresh transfer anymore. As we know, the endometrium is always better outside the simulation. On the other hand and NGS is an excellent technique at the moment for identifying abnormalities. The only reason to perform it the old way with micro ways of PGS is when I have frozen embryos, for example, from another trial or another center, and I do transfer them to another center, and I want to know if I have 4 blastocysts, for example. Let’s say I have 7 blastocysts in another center, and I transfer 4 of them and I have no pregnancy and I don’t want to continue, and I still have those 3 blastocysts. If I want to know if these 3 blastocysts are genetically normal, only then we can do this old way of PGS on day-5 and transfer them the next day on day-6.

Would clinics be willing to do regular PGS on some embryos (for immediate transfer) and NGS on the rest and freeze? (I have PCOS, so I might get many)

It’s up to you, and you should have a thorough discussion with your fertility specialist and your senior embryologist. Let’s say you have 10 blastocysts, then we would freeze, let’s say 4 of the blastocysts without doing PGS, and we do NGS on the rest of them, waiting for the result.  I don’t agree with doing a fresh embryo transfer, and in women, especially in a woman like you with PCOS, it is malpractice.

Can ubiquinol help to fortify the eggs?

I don’t think that all these additives, in the end, can improve the quality of the eggs.
I think that in the coming years, we will have a real pharmaceutical agent that makes these mitotic errors not to happen anymore in the egg, and a lot of women within the next 50 years will not need any IVF because they would produce euploid eggs and euploid embryos.

For which reasons sometimes embryos do not reach the blastocyst stage? Is it because of the quality of the egg? I did 4 IVFs, in the first one, I had 4 blastocysts (I was 30), and on the 3 other IVFs, I only got 4 embryos in total, and they always transferred them on day-2 or 3. All of them were negative. I never got them tested, but for the next IVF, I would ask to test them.

Sometimes it’s the sperm, and sometimes it’s the egg, so they don’t know if the eggs don’t look really well if they’re dark with a lot of micro vacuoles. They can say that this lady does not produce good eggs from the beginning and say they would not expect to have good blastocyst, whatever is the fertilization rate. On the other hand, if the sperm is bad, especially morphologically, they are looking at it for 1 or 2 hours to identify morphologically good sperm, then they inject it into the egg, which indicates a male factor. Until the day-3, the embryos develop with the machinery of the egg, and only after day-3 it comes from both the female and male genetics, so the combine and work together to divide into a blastocyst. We say many times that if after day-3, we don’t have a blastocyst, it indicates bad sperm. But we don’t say this if the embryologist sees that the eggs are bad morphologically from the beginning. You were young when you had those 4 IVFs and getting only 4 blastocysts is a very bad number. I cannot give more explanations having only this information, but definitely, you should do the genetic testing of your embryos in your next cycle or one after that, and only then you can decide if going for egg or sperm donation is an option.  Do not decide that after 1 abnormal genetic testing right away because it can only be a bad coincidence of a bad cycle.

Is there anything that can be done to improve sperm morphology? Would you have any recommendations?

Yes, with sperm it is much easier.  Firstly because if the embryologist is experienced, she or he can choose a good morphological sperm.  So the first one is the selection per se on the day of ICSI. Another thing that we can do is PICSI, we do sometimes select morphologically better sperm.  We can, of course,  give some antioxidants to help the sperm morphology, but I sometimes laugh because if someone is still smoking, and he’s taking all those antioxidants, it is useless to take all this medication, there is no improvement of the sperm.

Do you tend to get higher quality embryos with the short protocol than the long one?

I don’t believe that we have better quality embryos with any of these protocols and the best protocol is when we prepare it individually for the patient. From the studies that we’ve done on patients from the same category, let’s say women who are less than 39 with both protocols, the percentage of the euploid embryos is the same. I don’t think that there is any interference in the protocol with the genetic quality in the end.

What would be the maximum size of the follicle at trigger?

The optimal size for the follicle to be triggered is 17-20. But keep in mind that one doctor will measure it 17, and the other one 21. There is a lot of deviation from doctor to doctor. However, answering your question, I think that the follicle that is more than 22 or 24 does not have a chance to produce a good quality embryo.

What could be the reason for empty follicles or follicles that grow fast, but the eggs are not mature?

90% of empty follicles, it’s a mistake of the patient or the doctor or the ovulation triggering injection. Empty follicle syndrome (EFS) is what we call when we have empty follicles repeatedly, it happens very rarely.

 

Authors
Evangelos Papanikolaou, MD, PhD

Evangelos Papanikolaou, MD, PhD

Evangelos Papanikolaou, MD, PhD, is a Reproductive Medicine Specialist as well as a world-class recognized specialist in fertility treatment. Dr. Papanikolaou is the author of dozens of medical publications and has been at the forefront of several innovations and improvements in IVF treatment and is the main visionary and founder of Assisting Nature IVF Unit. He is ESHRE and EBCOG accredited as a Reproductive Specialist.
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 travelling, biking, learning new things or spending time outdoors.

Share With FRIENDS

Share on facebook
Share on twitter
Share on linkedin
Share on pinterest
Share on whatsapp
What are you looking for?
Type in a keyword e.g. implantation failure, embryo implantation, failed ivf...
Strategic Partners

Disclaimer:

Informations published on myIVFanswers.com are provided for informational purposes only; they are not intended to treat, diagnose or prevent any disease including infertility treatment. Services provided by myIVFanswers.com are not intended to replace a one-on-one relationship with a qualified health care professional and are not intended as medical advice. MyIVFanswers.com recommend discussing IVF treatment options with an infertility specialist.

Contact details: IVF Media Ltd., Block B, The Crescent Building, Northwood, Santry, D09C6X8, Dublin, Ireland.

5639 patients’ questions answered by 172 IVF experts during 287 events.