Basics for Genetics of Infertility: PGT Synopsis
Preimplantation genetic testing (PGT) is a powerful tool that to help screen embryos for genetic abnormalities. An embryo is what is formed after an egg cell is fertilized by a sperm cell. There are several types of PGT that we can perform. I will address them briefly, but the discussion will focus on PGT-A, or testing of the embryos for aneuploidy. This means, we are looking to make sure the embryo has 23 pairs of chromosomes – no more and no less.
Before we really focus on PGT-A, what are some of the other kinds of PGT we can do on embryos? Well, if someone has a “monogenic disorder”, meaning there is one gene which is associated with a specific disease state or condition, we can test the embryo prior to embryo transfer to make sure the embryo we transfer back are not affected by the disease that is trying to be avoided. In this way, we can help prevent passing on conditions that can cause cancer, severe disorders in metabolism, neuromuscular conditions and many more. This testing is highly accurate, but accuracy is relative to the disease which we are screening for and should be address on an individual basis.
Patient can also have “structural rearrangements” of their chromosomes. This is when a portion of one chromosome travels to another or change their orientation (like part of chromosome 22 moving over to chromosome 21 or the genes changes to “face forwards or backwards”). This can make it more difficult for DNA to be separated evenly when the cells divide. We can do PGT-SR to identify embryos with such conditions. This is an oversimplification, but there are a lot of variables that go into such a condition make it difficult to address from a bird’s eye view past this description.
PGT-A is used to identify embryos which have an abnormal number of chromosomes or an abnormal number of just part of a chromosome, but the entire chromosome is not duplicated or deleted (termed segmental aneuploidy). This is a powerful tool that can help avoid complications and adverse outcomes for certain populations. PGT-A has not been shown to provide improved outcomes (such as decreased miscarriage rates or decreased time to pregnancy) in all populations. Additionally, PGT, is exactly what it says. It is a test. NONE, of our tests in medicine are 100% accurate or we would call them “diagnostic”. Because aneuploidies increase with age, it is likely that PGT-A is more accurate in patients who are at a higher risk of aneuploidy (patients over 40 years of age). There is also a chance we are wrong in the opposite direction, and we tell you an embryo is abnormal when it is normal.
You need to understand what the test is doing to appreciate the complications with interpretation. At the time of testing, the embryo has ~200-300 cells. We are looking at ~6-8 of these cells and using that to draw conclusions about the rest of the embryo. Also, important to note is that we are looking at cells that will eventually become the placenta, not cells that will become the baby (see image). This is good as there is less likely to be damage to the developing embryo, but the negative is we are not sampling the cells that will be the fetus and the reliability of the testing is likely to be lower as a result. Our field is constantly growing and changing, and the reliability of our genetic testing is improving each day with advancing technology. We are here to help interpret this data in a useful way to help you make the appropriate decisions for you and your family building.