One of the most common misuses of terms in the field of Reproductive Genetics is “PGD”. PGD stands for Preimplantation Genetic Diagnosis. This pertains to the genetic testing of embryos for a specific known genetic condition, most commonly single gene disorders. This requires two things: the first is to know what specific condition we are looking for such as cystic fibrosis, BRCA1/2, or sickle cell disease. The other thing that is required is to have a genetic “probe” (specific gene sequence) to test for that specific genetic condition. In most cases, PGD applies only to patients who are carriers of, or affected by that specific genetic condition.
Yet, more often than not, the term “PGD” is applied to any/all genetic testing of embryos. More correctly, when we are testing for chromosomal abnormalities of embryos, the proper term is “PGS” which stands for Preimplantation Genetic Screening. The most common application of this technology is to screen embryos for aneuploidies (abnormal number of chromosomes) that would render an embryo to be either incompatible with life, or result in a child with severe disabilities. As a woman get older, we know her eggs are more likely to yield embryos that will be aneuploid. Therefore, it is important to screen embryos for those capable of developing to the point of a healthy live birth.
There is a great deal of confusion regarding the different types of technologies used to perform preimplantation genetic testing. In recent years there have been tremendous advances; an “explosion” of technology, in fact. We have come from low resolution testing that could give limited information on only a few of the 22 autosomal chromosomes and 2 sex chromosomes to presently being able to determine even sub-chromosomal results. The differences really come down to the level of resolution each test yields. Flourescent in situ Hybridization (FISH) was used for years. Yet, it had a very limited degree of resolution and therefore was inherently flawed in its reported results. Next came array Comparative Genomic Hybridization (aCGH). This test provided much greater resolution, with over 3000 unique data points, and hence, more accurate information.
This brings us to our next controversy: mosaicism. Mosaicism refers to the presence of two or more different cell types within an embryo. Experts disagree as to the actual frequency with which mosaicism occurs, but some estimate it at approximately 15-20% of all embryos. With the current blastocyst (30-200 cell stage embryo) biopsy techniques of the trophectoderm (outer embryo cells destined to become the placenta- not disrupting cells destined to become the baby) we are actually sampling several cells. This helps in identifying those embryos that are mosaic, and thus less likely to implant or lead to a viable pregnancy.
There have been tremendous recent advances in technology that have led to significantly decreased miscarriage rates, and greatly improved chances for a couple to have a healthy, live-born baby. This is what I refer to as “technology done right”. The terminologies and technology can be confusing. Utilizing a fertility specialist who is knowledgeable and collaborates with a reproductive genetic testing laboratory that uses the “latest and greatest” technology is important. Not all PGS/PGD is the same.