PGS Genetic Testing

Preimplantation Genetic Screening, in theory, helps your doctor select the best embryo to transfer by determining which embryos have the correct number of chromosomes. PGS has supporters and detractors, but its rate of use is speeding ahead. We cover the benefits and risks of PGS, as well as complex subjects like mosaicism.

An Overview of PGS & CCS Genetic Testing

Preimplantation genetic screening (PGS) is a test to determine if an embryo’s cells contain the appropriate number of chromosomes and therefore is fit to transfer. The goal of PGS is to help doctors determine which embryos will lead to a live, healthy birth and to avoid transferring an embryo that will fail to implant, lead to a chemical pregnancy, a miscarriage, or the birth of an unhealthy child.

PGS is in the midst of massive growth, and according to our data is used in upwards of 35% of all IVF cases. While PGS has its share of detractors, it will probably be used in half of all cycles in the near future. And this is despite PGS’s hefty price tag of $3,000 - $7,000, which is paid entirely by the patient, even when a patient’s insurance covers the cost of IVF treatment.

When PGS is performed, an embryo is grown for five or six days in the lab, and then carefully biopsied. A few of the embryo’s cells are then shipped off to an external lab, which uses testing technology to count the number of chromosomes within each cell. Embryos that have the correct number of chromosomes are known as “euploid” and those with an incorrect number are known as “aneuploid.”

The beauty of PGS was that it was meant to provide a clear, black-and-white, determination of whether an embryo was fit for transfer. When embryos were considered euploid, or normal, they went on to provide a healthy pregnancy in two-third of cases. When embryos were considered aneuploid they were seldom transferred, but when they were, they rarely resulted in a healthy pregnancy. While PGS’s predictive power was not perfect, it was certainly considered by many to be good.

PGS’s usefulness has been limited in the last few years as a new technology, known as Next Generation Sequencing, has shown that many embryos are “mosaic,” meaning they possess cells that are both normal and abnormal. Mosaic embryos are not as good at making babies as purely euploid embryos, but certainly better than purely aneuploid embryos.

The mosaic revelation has created angst in the field. For one, it has created concern that many historically-tested PGS embryos have been mischaracterized, and that a lot of embryos with potential were erroneously marked as aneuploid and discarded. As of now, the field is tussling with how common mosaicism is (many believe 20% of embryos are mosaic), our ability to truly detect it, whether patients have the right to be informed when their embryos are mosaic, and whether we should transfer mosaic embryos.

All the same, many of the benefits of PGS are undeniable. When PGS is used, far fewer transfers result in miscarriages. Miscarriages are costly, and for that reason many clinics have completely bought in, using PGS in upwards of 80% of IVF cases. In the minds of many, the cost and mosaicism questions are inconsequential in light of the benefit PGS confers.

PGS is also credited in driving far higher rates of single embryo transfer, meaning doctors and patients elect to transfer one embryo instead of multiple. Multiple embryo transfers dramatically raises the risk of multiple gestations and multiple births, which are high risk for both mothers and the resulting babies, who often spend significant time in the NICU. Single embryo transfer rates are nearly twice as high when PGS is used, as both patients and doctors have a higher level of comfort that they will select a promising embryo. All the same, single embryo transfer only occurs in half of the IVF cases using PGS, so deploying PGS by no means ensures a doctor or patient will decide on a single embryo transfer.

Another debate is around the proper setting to use PGS. While there are certainly camps that argue for “always” and “never,” there are still those who take a more nuanced approach. For instance, some believe PGS is important to use in younger patients because they have more embryos to choose from, so there is risk of repeatedly selecting the wrong embryo. Others suggest PGS is more valuable in older patients, where the proportion of good embryos is lower, doctors have a higher risk of selecting wrong, and where patients cannot afford to lose any more time on a failed transfer.

Finally, we've begun to notice that clinics seeing practically-the-exact-same patients are recording vastly different PGS euploid rates. The implication is that some clinics do a better job (or worse) at helping patients get a higher proportion of chromosomally-normal embryos. If that's indeed true, the likely cause is differing protocols between clinics or differing culture conditions in the laboratory.