Preimplantation genetic testing (PGT) is a highly advanced technology used to assess the genetic characteristics of preimplantation embryos created through in vitro fertilization (IVF). The term PGT encompasses both preimplantation genetic diagnosis and screening.
Preimplantation genetic diagnosis (PGD) is used to test embryos for specific genetic disorders or chromosomal abnormalities carried by one or both of the genetic parents so that only unaffected embryos may be selected for transfer into the mother’s uterus. It requires that the parents’ carrier status is known ahead of time through either family history or testing of the parents with karyotyping or carrier screening. We use PGD to avoid transmission of heritable diseases, such as cystic fibrosis, Fragile X syndrome, or muscular dystrophy, or to treat recurrent pregnancy loss associated with parental chromosome rearrangements. PGD is now referred to as PGT-M for monogenic (single gene) disorders or PGT-SR for structural chromosome rearrangements.
Preimplantation genetic screening (PGS) is used to screen for aneuploidy, or chromosomal abnormalities, in embryos from infertile couples with no known genetic condition. Chromosome abnormalities in human preimplantation embryos occur commonly in nature and in the IVF laboratory and grow increasingly likely with eggs that are older (especially after age 35). Most chromosomally abnormal embryos will not result in pregnancy or fail to develop properly and lead to miscarriage.
A relatively small proportion of chromosomally abnormal embryos can result in an affected child or fetus. The most commonly known chromosome disorder is Down Syndrome, which results from an extra copy of chromosome 21. PGS, now called PGT-A for aneuploidy screening, is now the most common indication for preimplantation genetic testing and is chosen by a large majority of patients undergoing IVF at Arizona Center for Fertility Studies.
The aim of PGT-A is to help clinicians and patients to avoid the transfer of chromosomally abnormal embryos and to select those offering the best possibility of a healthy live birth for embryo transfer.
Maybe a better question is: who shouldn’t? In the past, PGT was only offered to couples with advanced maternal age (AMA), recurrent pregnancy loss (RPL), repeated implantation failure (RIF), or severe male factor infertility, but it has become widely recognized that PGT-A allows us to better prioritize embryos for transfer, resulting in higher pregnancy rates and live birth rates per embryo transfer than untested embryos for a wider variety of patients.
It is important to note that testing a normal embryo does not make it any healthier or better. It is either normal, or is not. PGT simply allows us to select healthy embryos far more reliably than standard morphology, or embryo grading, alone. Transferring chromosomally normal embryos leads to higher pregnancy rates, lower miscarriage rates, and virtually eliminates the chances of having a child affected by a chromosome disorder.
There are arguments against the use of PGT, including:
Each of these concerns held some validity in the past and may still be true for some IVF centers that do not specialize in the latest IVF/PGT techniques. Let’s address these potential concerns one-by-one:
Misclassification of embryos. Perhaps the most commonly cited concern is the accuracy of PGT results. Again, this was absolutely an issue with an older testing methodology, known as FISH (fluorescent in situ hybridization), which only tested for a subset of the 23 chromosome pairs that are screened for with modern microarray and next generation sequencing techniques and was prone to reliability issues.
While no medical diagnostic test is perfect, PGT is highly reliable at differentiating potentially healthy embryos from those that are much less likely to result in the desired outcome of a healthy live birth. In double-blinded randomized control trial where embryos were tested but FET was performed without knowing the PGT results, no embryos that were classified as abnormal resulted in healthy live births. On the other hand, embryos that were classified as normal resulted pregnancy at a significantly higher rate and only gave rise to chromosomally normal children. Additionally, while there were far more miscarriages with chromosomally abnormal embryos, there were some pregnancies that resulted in miscarriages in both treatment groups.
When chromosome testing was performed on the products of conception, no miscarriages in the PGT-euploid group were found to be chromosomally abnormal. All miscarriages in the PGT-aneuploid group were found to be abnormal. This study proved that PGT was accurate in distinguishing healthy embryos from unhealthy embryos in a clinical research setting.
But what about the stories we’ve all read online about people transferring abnormal embryos and getting healthy babies? There are a few possible explanations for such unusual outcomes. The most likely explanation is a developmental phenomenon called mosaicism, where a portion of the cells in the embryo are normal and a portion of the cells are not. Most embryos with a high percentage of abnormal cells in the mix would have been called “abnormal” on older PGT platforms. With improvements in PGT technologies over the past few years, we have come to recognize that some mosaic embryos may hold the potential for a healthy live birth. However, it is already clear that mosaic embryos implant at a lower rate, miscarry at a higher rate, and have more potential to result in a child affected by a chromosome disorder than an embryo that is classified as normal. These embryos are still avoided for transfer when healthy embryos could possibly be transferred instead.
PGT has revolutionized the way that we approach in vitro fertilization and has created new and almost unbelievable standards for embryo transfer outcomes. It has enabled a shift away from transferring excess embryos to achieve “okay” pregnancy rates to single embryo transfer that works almost four out of five times regardless of the age of the mother. Less than a decade ago, these types of results would have been unheard of. Even so, PGT is not without its shortcomings. While it appears that we may be at the cusp of being able to edit single gene disorders with new technologies, like CRISPR, we are still not able to make chromosomally abnormal embryos become normal. In that regard, we remain at the mercy of age and chance. If we are fortunate enough to retrieve at least one good egg, we are very good at getting that egg to develop into a healthy embryo and can give any patient a solid fighting chance at having a child with her own eggs.
If you want to learn more about preimplantation genetic testing (PGT), call your ACFS fertility team today at (480) 630-0212.