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What happens to an embryo biopsy sample – from lab to the final result?

Carolina Andrés
Embryologist, Andrology Laboratory at Clinica Tambre, Clinica Tambre

Category:
Genetics PGS / PGT-A, IVF laboratory

embryo-biopsy-in-the-ivf-lab
From this video you will find out:
Carolina started her presentation by explaining that her IVF lab team at Clinica Tambre is divided into two parts, the andrology laboratory where all the procedures related to the semen analysis are carried out including Spermiograms, Comet fertility, Chromosperm, Sperm freezing, etc., and the IVF laboratory where the oocytes are picked up, fertilized, and embryos are taken care of including genetic testing and vitrification.

Preimplantation Genetic Testing (PGT)

Thanks to PGT testing, it’s possible to detect if the embryo has a correct genetic context or if it has any genetic alterations in the structure of chromosomes. In some cases, it’s possible to detect if it’s a carrier of a certain disease that can be transmitted from the parents. How does it work? On day 5 of embryo culture and the following days, instead of transferring an embryo, an embryo biopsy is carried out and embryos are frozen until the PGT result arrives. How do the embryos get to day 5 of development? After the egg collection, oocytes are inseminated by conventional IVF or ICSI (Intracytoplasmic Sperm Injection) where one sperm is introduced to each egg. At this point, the embryo culture will begin. Embryo division will be supervised each day until the last day of embryo culture, which will be around day 5 or day 6. It is important to note that on day 3 of the culture, an embryologist will perform a hole in the outer layer of the embryo, which is called the zona pellucida. This allows better access to the cells that will be biopsied, this method is called Assisted Hatching. The Gardner grading system is then used, which allows for evaluating day 5 blastocysts quality. Embryos with very good quality, so letters A and B will be considered for biopsy, the aim is to obtain 3 to 5 cells from the trophectoderm, which is the outer layer of cells present in the embryo. Those cells will be sent for genetic analysis. The cells are taken with a biopsy pipette, these cells will be separated from the embryo itself using a laser, which does not harm the embryo. Once these cells are separated they are going to be introduced into a tube, the embryo is frozen, and it will remain frozen until it can be transferred, and the result is revealed. After the biopsy is performed and the embryo is frozen, the cells will remain stocked until they are sent to the genetic laboratory. This normally does not take more than 2 days. Once the cells are sent to the laboratory, it takes approximately 15 days to get the results, in the case of PGT-A, in the case of PGT-M, it can take a bit longer, and this will be individual for each case, but it can take up to a month. After the results are ready, you will have a consultation with the doctor to discuss the results and the following steps to take.

Genetic lab

What happens in the genetic laboratory? As soon as the cells are received, the DNA is extracted, and it is sequenced by Next Generation Sequencing (NGS), which is the latest technology in genetic sequencing, The machine reads each chromosome and can detect the different abnormalities previously described. The profile that is reported by this machine is analysed by the most experienced genetic professionals who prepare the reports and send them to the clinic. As a result, there could be 3 different scenarios, euploid embryos, which are healthy transferable embryos that are always the first ones that would be transferred, aneuploid embryos, which do not have correct genetic content and therefore must be discarded because they cannot be considerate for a transfer, and mosaic embryos, which means embryos with correct and incorrect genetic content. These embryos may be only considered for transfer if no euploid embryo is available and after genetic counselling, where all the risks of transferring these embryos are well explained.

What happens to an embryo biopsy sample – from lab to the final result?

During this event, Carolina Andrés, Embryologist at Clinica Tambre, explained the embryo biopsy process.

Do you offer Non-invasive embryo testing at Clinica Tambre?

At the moment we do not offer this kind of testing, we only do Preimplantation Genetic Testing with biopsy. It’s something we are looking into, it’s a technique that’s being developed, so we are looking into it, but we’re still cautious.

One of our embryos has been diagnosed as a high-risk mosaic. What is the risk of transferring this? What is the percentage of success?

This is something that must be individualized. Mosaic embryos, especially high-risk mosaic embryos, can be transferred after genetic counselling. The genetic counsellor will be the one to explain in more detail the possible risks and the chances of success.

My 5th IVF/ICSI transfer is underway including PGT-A because of a history of live birth with a rare genetic disease, age is 36 and there is a lack of many successful embryo transfers. From this current IVF round: 24 eggs, 10 embryos and then 3 euploids. All 3 are classified as high A or high B. With this history including age, would you recommend 1 or 2 FETs? Which to transfer first?

When we take into account the number of embryos to transfer, that’s the decision that is always taken by a medical team. At our clinic, we mostly recommend transferring 1 embryo, especially if it’s a euploid blastocyst, that would be our first recommendation, but obviously, each situation is different. We also have to take into consideration the background history of the women and the risk of having a twin pregnancy, so that’s why the decision must be made by the medical team. Which embryo is transferred first, that’s something that the laboratory normally will decide, taking into account the quality of the embryo, but also its development. One that has the best embryo culture development and the best morphological aspect would be considered to transfer first.

I’d also love to hear about the new non-invasive Chromosome Screening (NICS) method. What does the research say about that? How does it compare to PGT testing? Is it better since it doesn’t damage the embryos?

It has its pros and cons, non-invasive PGT does not damage the embryo, but it is also seen that the percentage of accuracy is not the same as one of the invasive methods. We cannot compare the techniques because one of them will provide more precise information, and the other less precise.

What does it mean if an embryo has PGT-A result of ‘no DNA’?

There could be different scenarios. When we receive a result where there’s no identification result, it could be that the quality of the embryo is not good enough, even though, the embryo has a good morphological aspect, the quality of the cells themselves may not be as good. Normally in those cases, we receive information from the PGT laboratory and depending on what they have seen, they would recommend rebiopsying those embryos.

Do you transfer mosaics, and have you had successful live births with mosaic embryos? Any more information you can provide on this would be helpful.

Yes, we have transferred mosaics, and they have led to healthy pregnancies, but you have to take into account the risks, and even though there are healthy pregnancies from such embryos, the patient must be informed about the risks of having an unhealthy pregnancy. The transfer of mosaic embryos is a very particular case, and as I said, the genetic counsellors are the best professionals who will have more information about the chromosomes that are implied and how this could affect the pregnancy or the probability to have a certain disease in the embryo.

Can you test previously frozen embryos?

Yes, of course, there’s a risk when we thaw an embryo to re-biopsy, and that’s something that we have to take into account, but normally the embryos that are being biopsied are embryos of good quality and so the risk of that embryo not surviving is normally low. Therefore, we do recommend thawing the embryo and re-biopsy them, so we can test embryos that have been previously frozen without any problem.

What is your opinion on day 7 euploid embryos? Can they work, and have you ever transferred them?

We would not normally do that because it is true that the aneuploidies can increase on day 7, but as we are undergoing PGT, it’s a good situation where the embryos are developing slowly, so we could have a good opportunity to give them a bit more time. They are considered for biopsy, and if they are euploid at the end, we could consider transferring them. We would prioritize embryos from day 5 or day 6 and then we could go to day 7 without any problem as long as the genetic content is correct.

How do you prioritize euploid embryos for transfer? Do you prioritize the morphology of the trophectoderm or the Inner Cell Mass first? Also, would you prioritize the grading over the day of development?

Normally, when we prioritize embryos for transfer, we take many aspects of the development but also the morphological aspect into account. It is very important to take into account that the embryo is euploid, which means that they have the potential of implantation, but we would take the morphology of the embryo into account as well. If had an embryo of good quality, for example, a blastocyst AA on day 6 and day 5BB, we could prioritize the one on day 6 for sure. We normally prioritize the quality of the trophectoderm and then the Inner Cell Mass.

 Do you consider the time-lapse result?

That would be taken into the equation as well, not only the morphology but also how they have been developing throughout the days of culture.

What is the average chance of a euploid embryo with good morphology leading to an ongoing pregnancy of a Clinica Tambre?

These questions are very difficult to answer, this depends a lot on the age of the oocyte, and patient history, so it’s very, very difficult to say on average because we have many scenarios.
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Authors
Carolina Andrés

Carolina Andrés

Carolina Andrés is an Embryologist at Clinica Tambre, Madrid, since 2017. Carolina graduated in Health Biology at the University of Alcalá de Henares in 2015. She obtained her Master's Degree in Human Reproduction from the Complutense University of Madrid and the Spanish Fertility Society in 2016. In 2017, she also obtained a Master's Degree in Cytogenetics and Reproduction Biology from the Autonomous University of Barcelona. She speaks Spanish, English and French.
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.
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