PGD (PGS) refers to obtaining information about the genetic and chromosomal make-up of an embryo or egg prior to implantation. The goals of testing include improvement of the chances of pregnancy within an embryo transfer cycle, lowering the risk of having a miscarriage and increasing the likelihood of having a healthy baby. PGD can test for numerical chromosomal abnormalities such as Down’s syndrome, trisomies (having an extra chromosome), sex chromosomal abnormalities, monosomies (missing a chromosome) and single gene disorders such as cystic fibrosis, sickle cell disease and many others. PGD can also identify the gender of the embryo.
PGD does not test for all genetic disorders, syndromes, autism, developmental problems or birth defects. It also does not guarantee the health of the embryo, implantation, clinical pregnancy or a live birth.
The main benefit PGD in In Vitro Fertilization (IVF) practices is its ability to diagnose any numerical abnormalities (aneuploidy) in the embryos because it analyses all 23 pairs (46 chromosomes). The pregnancy rates achieved with this technology appears to be very high and often reported to be over 50% per transferred embryo based on recent literature. It is also interesting that the miscarriage rate is very low (~5%) based on our published study. This is because most miscarriages are due to chromosomal abnormalities of the embryos which can be diagnosed by PGD and only chromosomally normal embryos can be transferred into the uterus.
PGD can also be used to screen eggs for chromosomal problems prior to fertilization or egg freezing for the purpose of fertility preservation. The egg releases half of its chromosomes to accommodate the chromosomes coming from sperm at the time of fertilization. The excessive chromosomes are expelled from the egg at the time of ovulation in the form of a chromosome bundle called the “polar body”. Polar bodies can be removed at the time of egg freezing and tested for chromosomal problems, which would then provide genetic information about the egg. This way when the eggs are frozen for later use, normal eggs can be identified and if there are not enough normal eggs in one egg freezing cycle, more eggs can be frozen while there are still eggs that can be harvested. Based on Dr. Bayrak and colleagues’ publication, up to 75% live birth rates can be accomplished with genetically tested frozen eggs using PGD technology.
Over the years many methods have been used for the purpose of PGD including the FISH method, array CGH or SNP approach, quantitative PCR analysis and most recently NGS technique. Whereas most of these latter technologies yield similar results, NGS appears to be the most efficient and reliable method with quicker turnaround time. Typically, whole genome (DNA) is amplified and compared to a normal standard and any deviation is the detected and reported as abnormal. Only normal embryos/eggs are used and transferred to accomplish a healthy pregnancy.
Routine prenatal care and prenatal genetic screening is still recommended in cases where genetic testing was done on the eggs or embryos, including 1st trimester chorionic villus sampling (CVS) and/or 2nd trimester amniocentesis. More recently, non-invasive first trimester screening called NIPT has been implemented into prenatal care and may be a helpful tool. Ultrasound evaluation of the fetus, routine prenatal care and risk assessment are always recommended. Currently, none of the preimplantation genetic screening tests is 100% reliable or accurate, therefore additional testing may be necessary based on risk assessment and evaluation.