Do I Still Need Prenatal Tests After PGT-A Testing?

If you conceived through IVF and transferred a euploid embryo, does that mean you do not have to worry about the prenatal screening tests showing possible risks of Down syndrome or other conditions?

—Stephanie

The short answer is that prenatal genetic screening or testing should still be discussed and offered even if the embryo is euploid (chromosomally balanced).

The longer answer is that one of the benefits of IVF is it allows for the use of preimplantation genetic testing (PGT). There are different types of PGT, but because you asked specifically about Down syndrome (where there is an extra copy of chromosome 21), I’m going to focus on PGT-A or testing for aneuploidy, having fewer or more than 46 chromosomes. However, much of this applies to other types of PGT as well.

PGT-A has the potential to allow you to pick the embryo(s) that has the highest chance for a successful pregnancy and one that has 46 chromosomes (23 pairs), which are called euploid, for implantation. With most cases of PGT-A, once the embryo has reached the blastocyst stage (usually days 5-7 of development when they have roughly 50-200 cells), only a few cells (typically 5-10) of what will eventually become the placenta (trophectoderm) are biopsied and analyzed.

There are a couple of assumptions here. One is that these cells reflect the actual embryo (which at this point in development is called the inner cell mass), and another is that whatever abnormal cells may exist are evenly distributed throughout. So, the idea is that the small group of cells that are biopsied is not just an isolated group but, again, reflective of the overall future placenta and embryo.

We know that, on some level, these assumptions are not always correct. Human embryos are complex, and through PGT-A, we have good data that some embryos have both normal and abnormal cells, a phenomenon called mosaicism. We don’t have good enough data to give an exact percentage of how many embryos are mosaic. Mosaic embryos historically were not transferred with IVF because the assumption was that these would not lead to euploid fetuses, but this is changing now that some mosaic embryos have been found to lead to healthy pregnancies. Importantly, PGT-A was not developed as a test for mosaicism, so it is possible that some mosaicism is not diagnosed with PGT-A.

There is also potential bias and error introduced in the way these tests are currently performed. The current technology relies on making multiple copies of DNA in the biopsied cells in order to study it. So, rather than only analyzing the sample, we are actually analyzing copies of copies, which introduces potential error (amplification bias).

Finally, there are also other limitations in current PGT technologies and the way these tests are regulated. Current PGT-A cannot detect all potential genetic abnormalities in a pregnancy. IVF clinics and laboratories use different technologies and algorithms to perform PGT-A, and there is no governing body that has confirmed the accuracy of these tests in the U.S., nor any evidence of the superiority of one test or company over another.

Because of all of this, PGT is considered a screening test, and the American College of Obstetricians and Gynecologists recommends that further screening or diagnostic tests be discussed after its use.