First IVF Magazine
15 articles about IVF and Donor Conception by top IVF experts worldwide!

Should you do PGT-A for your donor eggs IVF?

Christos Roukoudis, MD
Gynaecologist & Fertility Specialist at IVF-Life Alicante, IVF Life Group

Category:
Donor Eggs, Genetics PGS / PGT-A

pgt-a-and-egg-donation-cycle
From this video you will find out:
  • What age-related factors may be involved with infertility in females and males?
  • How is PGT-A testing performed?
  • Does PGT-A increase the success rate of IVF?
  • Does PGT-A shorten the time to pregnancy in an egg donation program?
  • Why is PGT-A so controversial?

Is PGT-A recommended in egg donation cycles?

In this live event, Dr Christos Roukoudis, Gynaecologist & Fertility Specialist at IVF-Life Alicante, Spain, has talked about PGT-A and answered a question whether there are any benefits of doing PGT-A for embryos from donor eggs and explained how PGT-A works and when it is recommended.

Dr Christos Roukoudis, first explained that PGT-A (Pre-implantation Genetic Testing for aneuploidies) is a test for chromosome copy numbers that can be used during IVF to help determine the chromosomal status of an embryo from a biopsy of one or more cells. The results can help select an embryo with a normal number of chromosomes, the so-called euploid. But also, it can help us to avoid the ones that have an abnormal number of chromosomes, called aneuploid embryos. They may result in a higher tendency of an IVF failure or a miscarriage.

The number of oocytes starts to decrease after the woman is birth, as shown on the graph. Starting with puberty certain cohort of the oocytes are always recruited, and only one wins the race and becomes dominant. With increasing age, not only does the amount of eggs decreases but also egg quality is decreasing. Those oocytes accompany women during their reproductive life and also are vulnerable to damage in the DNA that they possess. This is one of the reasons why it’s so difficult to have success with own eggs in advanced reproductive age.

Meiosis

Every cell we have has 22 chromosome pairs and depending on the gender, we have an additional XX copy, or if it’s a male, it’s an XY. For a healthy child to be born with a normal number of chromosomes, the eggs available for fertilization must undergo a process of producing or having only one copy of each chromosome. This process is called meiosis, a similar process that occurs in the sperm of the male. The result is that the new life that is created possess 50% of the chromosome of each partner.

With advanced reproductive age, this meiosis process is disturbed and oocytes created have additional copies or don’t have any. This lack of integrity in the oocytes can result in unhealthy embryos that will not implant or lead to an early miscarriage, normally before the 12th week. It can also result in a child with a genetic disease, which happens less often. As shown on the graph, the risk is significantly increased with advancing maternal age, we see that Down syndrome, Edward’s syndrome is more likely to happen compared to a younger age.

PGT-A testing

PGT-A was suggested as a tool to identify those unhealthy embryos. Trisomy 21, Down syndrome and PGT-A testing have become routine methods for IVF to determine whether human embryos are to be clinically utilized or disposed of. The idea is that before an embryo transfer, we want to rule out the aneuploid embryos and only work with the healthy ones to increase the success rates.

Between the late 90s and now, some important events occurred, such as a single polar biopsy, biopsy of the first and the second polar body, the biopsy done on day-3, the cleavage stage, and then at the blastocyst stage when we perform PGT-A.

IVF with PGT-A

First, we have to perform the stimulation to obtain as many oocytes as possible. When the follicles reach a certain size, we do the egg retrieval, once we have the oocytes in the laboratory, the fertilization follows, the embryos will start to develop and on day-5, we’re going to perform PGT-A analysis, and we’re going to freeze them right away because we need to wait for the results almost 3 weeks.

How is the PGT-A test performed? Our biologists take around 6-7 cells from the cells, which are going to form the future placenta called trophectoderm, and we analyse it in our lab. When we finally have the analysis performed by Next Generation Sequencing (NGS), we can see if and in which chromosome pair we have an extra chromosome or possibly a missing chromosome, for example, it’s chromosome 13. As seen on the slide, there is PGT-A analysis done on several embryos, after an IVF cycle, a good amount of embryos was obtained, you can see that many embryos are abnormal, so they’re not suited for a transfer and out of those 5 embryos only 1 is normal.

In the proposed threshold, there are a few classifications like normal, mosaic abnormal, this gives us information about the amount of unhealthy DNA. Normal is if aneuploid DNA in a single biopsy is less than 20%, mosaic is if the aneuploid DNA in this single biopsy is between 20-30% and aneuploid if the aneuploid DNA is more than 80%.

Egg donation

For women with exhausted oocytes reserve, the probability of fulfilling the desire to have a child with their own oocytes is very difficult, so egg donation is the option that can help achieve this goal in the end. It’s a treatment with a very high success rate, the pregnancy rates are around 75% with the first attempt at our clinic (IVF-Life). The reason for that is that egg donors are very young and they have the best oocyte quality. We do some tests before the treatment and before selecting a donor, a mapping of their own chromosomes that allow us to see if they have a higher tendency of producing unhealthy embryos. This factor allows us to have very high success rates, there is the success rate of the time spawn between 20- 25 years old

One of the publications from 2007 from the UK shows how the live birth rate decreases with the advanced maternal age of the eggs and therefore conclude how important healthy eggs are for success. We can see how extremely difficult it is to have success with your own eggs between the age of 44-46.

Regarding PGT-A testing in another publication from 2016 performed in the US, we can see that in certain groups PGT-A testing is beneficial. Patients of advanced reproductive age and a certain collective may benefit from PGT-A.
We can see that at a young age, the age of the donors is between 20-25, we have no significant advantage when we perform PGT-A testing, it’s rather the same when PGT-A testing is performed, you see that the live birth rate is high, so women have the success rate of the donors.

PGT-A – why is it controversial?

PGT-A testing is rather a matter of debate. For example, mosaicism is where a certain amount of DNA in the cell is not okay, it’s frequently found in pre-implantation stage embryos, and it seems that it represents a normal physiological finding at those stages. Chromosomally abnormal embryos may self-correct downstream, this explains the persistence of chromosomally abnormal cells in the placentas of healthy babies.

Another reason why it is criticized is that the average 5-7 cells of the trophectoderm biopsy that we perform cannot define the state of an embryo for 100%. Something that we are also not 100% sure about is the impact of damage that is caused by a biopsy, human embryos are sensitive to manipulation and biopsy.

Several case reports are showing that embryos tested as mosaic but in some cases also as aneuploid resulted in healthy babies. We have a high number of false-positive rates, which means that this test can show us that the embryo is unhealthy or not suited for a transfer, but in reality, it’s suited for a transfer. Consequently, one must conclude that many false-positive embryos are either not used in a treatment maintaining clear preservation or even get discarded, therefore, it’s also an ethical problem.

There is also a STAR trial, which stands for a Single Embryo Transfer of aneuploid embryo, it was a multicentric study including 4 countries and many centres. It was one of the largest studies undertaken, and it included 650 subjects. They were randomized, the primary outcome of the study was the ongoing pregnancy rate after the 20th week of pregnancy. It was found that the ongoing survival rate was not a lot higher regardless if PGT-A testing was performed or not. However, as shown on the slide, a certain patient group would benefit out of it, it was the group of 35 to 40 because the ongoing live birth rate was much higher. When PGT-A testing was performed at a younger age, so we’re talking about the egg donor, it didn’t make such a big difference at all.

Conclusions

It’s very important to see the big picture. PGT-A testing offers benefits when it is used properly, however, we mustn’t forget that not all couples will benefit from it. The patient should have an increased reproductive age and produce multiple embryos.

We must take into account that every time it must be an individual decision. All the factors of the couple matter, for example, if the couple faced multiple implantation failures, miscarriages, in such cases, patients could benefit from PGT-A testing. Patients who undergo egg donation need to look at the live birth rate of the donor, so they have the live birth rate of a 20-25-year-old, PGT-A testing doesn’t make a big difference, and it could be most likely counterproductive in the end. It’s because of false-positive results, and the ethical dilemma is also a matter of debate. One exception could be where the Karyotype of the husband or some findings could lead to a higher tendency of producing unhealthy embryos.

Is PGT-A recommended in egg donation cycles? - Questions and Answers

What are your thoughts on donor egg using PGT-A versus MitoScore and or male factor?

As I said before, egg donation gives us a very high success rate on its own, so there is no significant benefit out of PGT-A testing with egg donors. 

If we have a male factor, it’s not always possible to recognize a microdeletion in the karyotype. Some minor abnormalities that seem to be minor can lead to a higher tendency of producing unhealthy sperm/ eggs. In such situations, yes, PGT-A testing could help us a bit. 

What about increased male age as an indication for PGT-A?

Not really because sperm come out of the fabric every three months, so if the karyotype is okay, it’s not a strict indication to do PGT-A testing because of higher male age. There is no data about it.

What are your thoughts on CRISPR, and before PGT-A?

For me, it would not make any sense to do it prior. I would like to have a Karyotype before, this is enough for me. It’s also significant to make an individual decision to see what the couple has been through, what they have done before, everything.

Is it better to get a donor egg having the same blood type as myself?

There are plenty of investigations in this field where they say the blood group doesn’t play a role. The only reason is if you want to keep it a secret because technically, your children could find out through the blood group if their blood group is the same as yours and your husband. For the success of the treatment, it doesn’t play a role at all.

So far, we have had 5 failed transfers with one egg and 1 miscarriage. We recently tried a donor egg with 1 excellent and good blastocyst, which failed. If we try egg donation again, would you use PGT-A testing to check for implantation failure, or the donor round was just bad luck. We have a 5-year-old child conceived naturally.

This is a case where I must look into details. I must look, for example, if there’s any other reason for the miscarriages, the genetic integrity of an embryo is a very important reason, but we also have other reasons, such as the womb, the uterus, immunological deficiencies, celiac disease. There are many things, so first, we need to do our homework and see what happened. I don’t think that PGT-A testing would be a big game-changer in your situation, from what I see. You have already proved that you can conceive, you can have a baby and have a normal pregnancy. The only thing is that with PGT-A, we could have success with the first attempt, the cumulative rate is the same regardless if I have 3 embryos or 2 embryos, the cumulative rate is the same, but with PGT-A testing, we could have success a bit sooner.

As I told you before, this is a matter of debate, in the end, so I would first have a look into your history, you can feel free to send your file to me, and I can have a look, and I can tell you if I would do anything different. Don’t compare your own trials with the egg donation because most likely your transfers were done in a more advanced reproductive age, but I would be happy to give you a second opinion.

Any relation between egg donation failure and celiac disease in terms of success?

Yes, there is a relation there because if somebody has celiac disease, it means that someone has antibodies against glutamine, there’s the Anti-transglutaminase antibody and the Anti-Gliadine antibody.

If somebody has celiac disease, they have those antibodies in their blood, and those antibodies could attack the ongoing pregnancy, regardless if you do egg donation or an IVF treatment with your own eggs, celiac disease could play a role. It’s very easy to test for these antibodies, and the solution is much easier, you need to take the gluten out from your diet.

robotic-surgery-benefits
choosing-a-sperm-donor-cryobank
prp-older-patients-is-it-beneficial
nipgta-is-it-valuable-enough
the-number-of-cycles-needed-for-a-successful-pregnancy
PGT-A-over-30-ivfwebinars
Authors
Christos Roukoudis, MD

Christos Roukoudis, MD

Dr Christos Roukoudis graduated in Medicine from the University of Patras (Greece) and specialized in Gynaecology and Obstetrics at Sana Klinikum Hameln (Germany) and Fürth Hospital (Germany). Furthermore, he is specialized in reproductive medicine, minimally invasive surgery, endocrinology and regenerative medicine. Dr Roukoudis joined the IVF-Life Alicante team in 2020, where he is highly regarded for his excellent professional and personal approach to patients.
Event Moderator
Caroline Kulczycka

Caroline Kulczycka

Caroline Kulczycka is managing MyIVFAnswers.com and has been hosting IVFWEBINARS dedicated to patients struggling with infertility since 2020. She's highly motivated and believes that educating patients so that they can make informed decisions is essential in their IVF journey. In the past, she has been working as an International Patient Coordinator, where she was helping and directing patients on their right path. She also worked in the tourism industry, and dealt with international customers on a daily basis, including working abroad. In her free time, you’ll find her travelling, biking, learning new things, or spending time outdoors.
Free Download
Fertility Road Magazine
The only magazine devoted to IVF and donor conception!
15 articles & 68 pages of "All About IVF"

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: The European Fertility Society C.I.C., 2 Lambseth Street, Eye, England, IP23 7AG
Copyright 2022 MyIVFanswers.com
Donate to the European Fertility Society today!
Your gift will ensure that the European Fertility Society will provide support and education for patients struggling with infertility.
One time donation:
Monthly donation:
How to prepare for IVF.
A beginner's guide.
+ DO'S AND DON'TS BEFORE IVF - REVEALED!
AS FEATURED IN FERTILITY ROAD MAGAZINE!