The Accuracy Debate: False Negatives and False Positives

The accuracy of Preimplantation Genetic Testing (PGT) is a topic of ongoing discussion and a source of concern for some, particularly regarding the potential for false negative and false positive results. While PGT is a highly sophisticated and generally reliable test, its limitations, especially concerning mosaicism, are crucial to understand.

A false negative occurs when an embryo is reported as chromosomally normal b (false positive) or, less commonly, transferring an embryo that may not result in a healthy embryo is deemed abnormal by PGT, but it is actually chromosomally normal. These inaccuracies can lead to the heartbreaking decision of discarding a potentially viable or live birth (false negative PGT, but in reality, it contains abnormal cells. Conversely, a false positive happens when an positive really contains normal cells).

The primary reason for these discrepancies often lies in the nature of the biopsy and the phenomenon of mosaicism. PGT involves taking a small sample of cells from the  trophectoderm, which is the outer layer of the blastocyst that will eventually form the placenta. The assumption is that these cells are representative of the entire embryo. However, mosaicism means that an embryo can contain a mixture of both chromosomally normal and abnormal cells. If the biopsied sample happens to contain only normal cells from a mosaic embryo, it could lead to a false negative. Conversely, if the sample contains only abnormal cells from an embryo that is largely normal, it could result in a false positive.

Furthermore, the current technology samples only a very small percentage of the total cells in the embryo. This limited sampling means that the test is not analyzing the entire cell population of the embryo, leaving a margin for error. While advancements in PGT technology are continuously improving accuracy and our understanding of mosaicism, these inherent limitations contribute to the ongoing debate and highlight the importance of thorough genetic counseling to help prospective parents understand the nuances and potential outcomes of PGT.