In a group like this, dedicated to research on euploidy, it might seem odd to be talking about whether or not to test embryos for euploidy at all.
But here’s the crux of what you need to know:
So what you choose to do, ideally needs to be based on an understanding of your particular situation, your own clinic’s policies, the lab’s reporting structure, and your cycle planning in terms of euploidy add ons.
Let’s start by diving into a quick overview of what PGT-A testing is. It stands for Pre-Implantation Genetic Testing for Aneuploidy. While previously PGT-A testing was done on day 3—once culturing embryos to day 5 blasts became the norm, day 3 embryos tended to be frozen, but not tested (after multiple studies showed that biopsying at day 3 impacted transfer and live birth outcomes).
So in most cases these days, embryologists biopsy the trophectoderm (the part of the mebryo that becomes the placenta) on day 5, 6 or 7, right before they freeze the embryo. Ideally they want 100. They’ll try and take between 5-7 cells (the number of cells taken differs
PGT-A for women who can produce lots of blasts (or do so across multiple cycles), and may otherwise waste months and months transferring whole chromosome aneuploid embryos with close to a 0% chance of live birth is
I want to be clear, PGT-A is pretty damn reliable AS LONG AS, you know these things about YOUR SPECIFIC EMBRYO and YOUR SPECIFIC CLINIC AND LAB. These are the exceptions, though. In our age bracket (40+), people who have aneuploid embryos are much more likely to have simple, whole chromsome aneuploid embryos. Nevertheless, knowing and understanding the exceptions are critical.
NUMBER OF CELLS BIOPSIED The embryologist isn’t fully able to control exactly how many cells they take from the embryo. But the less cells taken, the less likely that the result is correct. If your clinic reports the number of cells biopsied, then you can take a look to determine any embryos that may not have had enough cells biopsied to have given you the most accurate result. While this may not necessarily change the result, it increases the likelihood that you may have gotten a different result (especially in cases of mosaicism). Note I found an excellent study on this which was released in March/Apr 2024 but I cannot refind it. I’ll post it here when I do. But the accuracy of 3 cells biopsied was very low, and of 4 cells (in the vicinity of 70% likely to be inaccurate).
LAB CUT OFFS FOR ANEUPLOIDY Most to all human embryo trophectoderms are mosaic. Just like vitamin B12 levels considered high in Australia are considered normal in Europe, like most things in biology, mosaicism is a spectrum, and its definition is determined by lab cut off rates. At one end, we have euploidy, and the other, we have aneuploidy. But in fact, only 0% aneuploid cells is fully euploid and 100% aneuploid cells is aneuploid. Everything else is mosaic. So you need to know what your particular lab’s cut off rates are. And it’s important to realise that lab cut offs can change AND that it can also depend on the methodology chosen by the lab on your specific embryos
Igenomix Type 1: 70% mosaic = Aneuploid/abnormal Type 2: Euploid (50% or less mosaic), Aneuploid (more than 50% mosaic). Igenomix added Type 2 just in the last year after research showed that for embryos with 50% mosaicism and below, 99% of the time, when the ICM was checked, all ICM cells were euploid. You can read more on their exact process here in their user manual
Progenesis
40% mosaic = Aneuploid/abnormal 20-40% mosaic = Low level mosaic <20% mosaic = euploid/normal
Cooper Genomics (Reprogenetics)
80% mosaic = aneuploid 40-80% mosaic = high level mosaic aneuploid
20-40% mosaic = low level mosaic aneuploid
<20% mosaic = euploid
This meta analysis looked at many of these studies: https://obgyn.onlinelibrary.wiley.com/doi/pdf/10.1002/pd.5828 The ones we should really care about are the TE/ICM studies (although this analysis included both). When not including segmental aneuploidy or mosaicism, the concordance between Trophectoderm and ICM for whole chromosome aneuploidy or mosaicism was around 95%. That’s still not nothing, that’s a 5% chance that placental cells are aneuploid while the ICM (what becomes the baby) may be euploid or mosaic.
ANEUPLOIDIES WITH A HIGHER THAN AVERAGE CHANCE OF LIVE BIRTH
Segmental Aneuploidy: with a reported live birth rate of around 20%-25%, segmental aneuploidy is probably the best chance at a live birth that you may have (if you have a segmental aneuploid in your already produced embryos). This is unsurprising given that the meta analysis noted at point three, when including segmental aneuploidy, found very low concordance rates between segmental aneuploidy found in the trophectoderm and the same aneuploidy found in the ICM. https://link.springer.com/article/10.1007/s10815-024-03282-8
POLYPLOIDY EMBRYOS: This is where an embryo has a whole extra set of chromosomes (e.g. instead of two sets = 46 chromosomes, it may have a 3 or 4 or even 5 sets of chromosomes). There hasn’t been any specific studies on this, but having collected and tracked data within the PGTA Abnormal group on Facebook, we have data to suggest that PGTA has reduced predictive value when it comes to polyploid embryos. Especially XX polyploids (some data suggests XY polyploids are more likely to end in molar pregnancies). If you want access to the data on polyploids please tag me in on that group so I know you are a member and I’m happy to share the link to the data. I cannot share it with non members as it contains member name data.
SURVIVABLE SEX CHROMOSOME ANEUPLOIDY EMBRYOS (low level life impact - XXX and XXY): Again there haven’t been specific studies on this, but we now have 2-3 examples of full anueploid XXX embryos transferred which ended in the live birth of an XX karyotype confirmed female baby. This likely means again, a reduced predictive value of PGTA as it relates to sex chromosome aneuploidies. Further, some may argue that full aneuploidy of XXX and XXY are not life threatening and in most cases, those affected are never aware they have a different karotype unless they do testing later in life. They live normal lives and studies have have suggested lower IQ or reduced fertility were based on extremely small numbers (25 people).
CHAOTIC EMBRYOS The definition of this changes depending on the lab - for instance, Igenomix defines Chaotic has having 6 or more chromosomes affected as does the study that looked at this, so you would need to apply that note when assessing your own embryos against this data). This small research study found that when rebiopsied (even just from the trophectoderm), that embryos with 6+ chromosomes effected, 38% were found to be euploid. This suggests that PGTA has reduced predictive capability when it comes to chaotic embryos. And these embryos are worth transferring. This study didn’t share the age of people whose embryos were biopsied to important to note that rate of euploidy could be age-representative. https://www.fertstert.org/article/S0015-0282(22)01577-1/fulltext#:~:text=An embryo is labeled as,as chaotic are typically discarded.
ARTIFICIAL INTELLIGENCE SCORES THAT INDICATE A HIGHER THAN AVERAGE CHANCE OF IMPLANTATION If you do have a standard whole chromosome aneuploid embryo (or complex aneuploid where multiple chromosomes are affected), and you also have IDA (an artificial intelligence score that is assigned to help determine the likelihood of implantation and live birth), then this may assist in at least predicting aneuploids that are more likely to implant and lead to a live birth. As an example, if you are over 42 and have an embryo with a score of 9.3-9.9, then the chance of live birth is around 15%. Now this is untested (so a portion of these would be euploid), but prioritising aneuploids for transfer is time efficient if you are considering transferring them at all). https://www.vitrolife.com/our-products/idascore-intelligent-data-analysis-for-embryo-evaluation/