PGS (pre-implantation genetic screening) is a process in which doctors test cells from an embryo with the hopes of better identifying the best embryos to transfer, and preventing the transfer of embryos that would have resulted in failed implantations, miscarriages, or offspring with chromosomal abnormalities. PGS (which is also known as comprehensive chromosomal screening or CCS) is a tool to prioritize embryos with the best chances of healthy live births.
Chromosomes are crucial components of our bodies – they contain all the information that informs our cells how to function. Imagine our chromosomes are encyclopedia volumes – we get one set of 23 volumes from our mother’s egg, and one set of 23 volumes from our father’s sperm. The different entries in those volumes are our genes, which tell our cells what to do.
Having extra or missing chromosomes can be catastrophic. Usually, for a pregnancy to proceed at all, an embryo must have the correct number of chromosomes. Otherwise it will fail to implant or lead to a miscarriage. There are exceptions for a few specific chromosomes, where a pregnancy can proceed to term with the incorrect number of chromosomes – the resulting children will have a health issue like Down Syndrome, Turner Syndrome, and a few more.
The primary goal of PGS is to predict which embryos are “euploid,” meaning they have the correct number of chromosomes, and which are “aneuploid,” having the incorrect number, so that by transferring only euploid embryos a patient has the best chances of getting pregnant, staying pregnant, and delivering a healthy child.
For almost any patient at a fertility clinic, it’s an unfortunate reality that the majority of their embryos will be abnormal. As women age, the problem becomes worse, and the chance that any given egg will combine with sperm to create a normal embryo goes down dramatically. The bottom line: there are probably lots of bad embryos we’d rather avoid transferring at any age, and especially the older we get. This is the purpose PGS is trying to serve.
The increasing rate of aneuploidy is hypothesized to be the number one driver of the age related fertility decline. As you can see in the chart below, PGS reveals a drastically decreasing number of normal embryos at every increasing age bracket. This closely mirrors what we see in IVF success rates.
PGS advocates claim PGS has “positive predictive value” meaning that when an embryo is considered by PGS-testing to be “euploid” it’s much more likely to lead to a live birth. The extent to which PGS is actually predictive depends on your clinic’s ability to capture a useful sample of the embryo and your reference laboratory’s ability to make an accurate determination. For instance, at one clinic & laboratory combination in New Jersey, 69% of embryos they considered “euploid” actually led to a live birth. At another clinic in New York, which sends its biopsies to a reference laboratory, 48% of “euploid” embryos led to a live birth. So there is very much a range in PGS’s abilities depending upon who is doing it.
And if neither of those sound very “predictive” bear in mind that when clinics make their best guess of which embryos to transfer without PGS, live birth rates per transfer range from 4% to 40%, depending on the patient’s age.
We cover the benefits of PGS, and their magnitude. We dissect the subject of mosaicism and how it helps to construct a hierarchy of which embryos to transfer. We train patients to ask the relevant questions of their clinic, clinic’s laboratory, and reference laboratory before signing on to do PGS. Finally, we address the risk around damage during biopsy, how often useful embryos are being discarded, and how the investment in PGS looks for women of different ages.