Mosaicism and Preimplantation Genetic Testing for Aneuploidy: diagnostic accuracy and clinical implications

Abstract

The improvement in preimplantation genetic testing for aneuploidy (PGT-A) has given clinicians access to techniques that are able to identify embryos with genetic abnormalities. What started as a way to prevent monosomic disorders or chromosome abnormalities from being transmitted to the offspring is now widely used in clinics worldwide to improve IVF outcomes. After a blastocyst biopsy is done and five to ten trophectoderm cells are removed from the embryo, genetic testing is performed using next generation sequencing (NGS). With the unrestricted access to preimplantation genetic testing for aneuploidy and the increased sensitivity attributed to next generation sequencing, came the steady rise in mosaicism diagnosis, leading to embryos being discarded. Mosaicism is described as the existence of two or more cell lines with different genotypes within the same embryo. It generally derives from post-zygotic errors and is known to be a common phenomenon in embryos in the stages of early development, decreasing as the embryo progresses. The decrease in mosaicism during embryo development paired with the question of whether the biopsied cells are representative of the embryo and the birth of genetically normal offspring after the transfer of mosaic embryos brings into question whether embryos labeled as "mosaic" are being diagnosed and managed correctly. This review aims to summarize the available information on why the reliability and accuracy of the diagnoses made by PGT-A are being questioned and highlight the need for more definitive guidelines regarding the use of PGT-A and the management of embryos diagnosed with mosaicism.