PGT-A | Pre-Implantation Genetic Testing for Aneuploidies performance: how and why?
PGT-A which means Pre-Implantation Genetic Testing for Aneuploidies is the new name for the PGS (Pre-Implantation Genetic Screening). Knowing how the techniques is performed we also know what are the reasons to use it.
Explanation of the details and description of all steps along the process is given by our 3 experts in #IVFANSWERS:
- Dr Victoria Walker – Fertility specialist – Institut Marquès
- Dr Maria Arque – International Medical Director in Fertty International
- Ester Padilla – Senior Embryologist – ProcreaTec
Answer from Dr Walker - Fertility specialist
PGS is Pre-Implantation Genetic Screening. Nowadays it’s more commonly known as PGT-A – Pre-implantation Genetic Testing for Aneuploidies. This means each embryo is tested to ensure that the chromosomes for the embryo in question are correct both in number and appearance. Currently, embryologists use two moments in an embryo’s development during which the chromosomal load can be assessed – day 3 and/or day 5 of the embryo’s life.
On day 3, the embryo consists of eight cells. What embryologists do is use a laser to create an opening within the embryo’s shell in order to extract one of those cells. This biopsy doesn’t hurt the embryo and doesn’t impair its further development. The chromosomes are removed from the cell and analyzed, with results being available within 48 hours. If we find that the embryo is genetically normal and is continuing to develop within the lab, it can be transferred.
The day 5 biopsy takes place when the embryo is at the blastocyst stage. In this case, embryologists only weaken the embryo’s shell – as it grows, it will push through that weakness, allowing some of the outer cells to come out through the opening. That part of the embryo is called the trophectoderm. On day 5, embryologists can take four or five cells without actually touching the inner mass of the embryo, which later becomes the fetus. Following the biopsy, the embryo is frozen, chromosomes are extracted and analyzed; the process takes up to two weeks. If the embryo is chromosomally normal, we can perform a frozen embryo transfer at a later date.
What are the pros and cons of both approaches? The day three biopsy gives us very quick results, allowing for a fresh embryo transfer, which – in egg donation scenarios – still gives us a slightly higher chance of success. However, there is some evidence that some embryos found to be abnormal on day three may self-correct before day 5 and become chromosomally normal; which means we could potentially be discarding a small portion of viable embryos.
The day five biopsy gives us a more reliable result, as four or five cells have been analyzed. There is still, however, a question of whether the cells that we have analyzed are representative of the rest of the embryo. We also aren’t certain whether an abnormality detected in the trophectoderm is a bad thing, because we know of the existence of mosaic embryos – both normal and abnormal chromosomally – that can result in healthy live births.
So, essentially, the process is the same – a biopsy is performed and the chromosomes analyzed. However, it’s difficult to say which of the two ways is currently better.
Answer from Dr Arqué - International Medical Director
The process of PGS testing begins with creating embryos and letting them develop in a laboratory. Once they reach the blastocyst stage, we perform a biopsy of the trophectoderm, which is the part of the embryo that becomes the placenta. We take a couple cells from the trophectoderm and send the sample to a genetics laboratory. The cells have their karyotype tested, which tells us whether or not the embryo itself is chromosomally normal or not.
Once we have the results, we will schedule another consultation with your doctor to discuss the results and further options. These options will obviously depend on the results of the testing – whether your embryos are normal, abnormal, or mosaic. Mosaic embryos contain both genetically normal and abnormal cell lines – a geneticist will be able to tell us if the degree of mosaicism allows for a safe transfer of such an embryo.
In some cases, the results may not be conclusive – if that happens, we simply perform the test again.
Answer from Ester Padilla - Senior Embryologist
PGS (or, as it is currently known, PGT-A), is usually performed on day five or six of embryo development, in the so-called blastocyst stage. Previously, it used to be done on day three; this approach, however, is now considered to be inferior. The reason for that has to do with what the embryo consists of in each stage: on day three, embryos usually are made up of around eight cells, while a blastocyst stage embryo has hundreds, clearly divided into two types, the inner cell mass (which will eventually become the child), and the trophectoderm (which will develop into the placenta). As the blastocyst has a greater number of cells, performing the test is safer.
The test consists of a biopsy – embryologists take a couple of cells from the trophectoderm and sent them off to a genetics laboratory for analysis. Note that we don’t touch the part of the embryo that becomes the actual child. The laboratory analyses the cell sample and determines whether or not the embryo has the correct number of chromosomes or if any abnormalities are present.
Once the sample has been taken, we freeze the embryos using a technique called vitrification, which allows us to safely store specimens in nitrogen tanks.
Once the results from the genetic laboratory come back, we schedule the transfer of one healthy embryo. If we have more than one candidate for implantation, we can base our choice on the embryo’s morphological quality before the freezing process – we do this by reviewing the parameters recorded during embryo development. The rest of the healthy embryos will remain in storage until the patient decides to have them transferred.
Although it may sound like a complicated process, it’s an established technique performed often.