IVF PRE-EMBRYO GENETIC TESTING/MOSAICISM
Pre-embryo genetic testing (PGT) is an exceptionally powerful tool increasing in vitro fertilization pregnancy rates, decreasing the risk of a multiple pregnancy, miscarriage and minimizing the number of babies born with genetic anomalies. To understand this technology it is important to understand how the process is performed. Blastocyst (day 5, 6 and 7) embryos derived from IVF typically contain anywhere from 200-400 cells. The embryo consists of an outer trophoblastic layer destined to develop into the placenta as well as an inner cell mass destined to develop into the fetus. Biopsying the inner cell mass would give us the most direct information about the fetus, but poses a risk of injury. For that reason the outer cell mass is sampled. Biopsy of the outer cell mass is limited to 4-10 cells to minimize the chance of embryo damage – herein lies one of the sources of potential sampling error, i.e., only a small percentage of the total cells are tested. The cells of the outer cell mass have a high degree of concordance with the inner cell mass, but not 100% – a second potential source of sampling error. It is believed that often subsets of abnormal cells are destroyed by healthier more rapidly replicating normal cells – a third potential source of sampling error.
Based on statistical models if the number of abnormal cells is greater than 80%, genetic experts throughout the world agree that this represents an abnormal embryo, an aneuploid. Aneuploid embryos have little or no chance of leading to a healthy pregnancy. If the percentage of abnormal cells is less than 20% this represents a normal embryo, a euploid. Euploid embryos have a high chance of leading to a healthy pregnancy, but not 100%. If the percentage of abnormal cells is between 20 and 80% this represents a mosaic embryo. There are a myriad of different potential mosaic embryos, some with a chance of leading to a healthy pregnancy others with very little. Mosaic embryos overall are less likely to lead to pregnancy, have a higher risk of miscarriage and theoretically a higher chance of developing into a live born with developmental abnormalities. It is recommended that mosaic embryos only be transferred as a last resort when there is no possibility of transferring a euploid embryo. Transfer should only occur after formal genetic counseling. If a mosaic embryo is transferred followup genetic testing in the form of amniocentesis is recommended.
Kevin L. Winslow, M.D.
Director for Florida Institute for Reproductive Medicine