PGT-A: Part 2

The field of preimplantation genetic testing (PGT) is evolving fast. It is essential for regulation and standardization of diagnostic testing in PGT. Preimplantation genetics testing of monogenic disorders (PGT-M) has significant effect and meaning in detecting single-gene diseases, but the application of PGT-M still has certain limitations and deficiencies in some cases. There are some factors that restrict the clinical application of PGT-M, such as small families, expand carrier screening, small number of embryos, allele drop-out (ADO), parental mosaicism and so on. It is important to discusses how to the collect DNA samples, establish haplotypes, determine genetic markers and assessment of the risk of positive embryos implantation in above. For example, whether the pathogenic variants themselves are incorporated in the clinical test depends on multiple factors, including the mutant source (familial or de novo), the variant type and the preclinical work-up results. In addition, there are some detailed technical recommendations for the most applied methods. Providing better genetic counseling to couples with single-gene diseases. It can help them make better reproductive choices. In short, we should focus on the pitfalls of PGT-M application, which will promote PGT-M to have broader application prospects.

Embryonic mosaicism is a phenomenon characterized by the presence of karyotypically different cell lines within the same embryo. It is relatively common in human preimplantation embryos and may occur with regard to numerical aberrations and/or structural aneuploidy.
Until recently, mosaic embryos were not transferred because they were considered abnormal. However, recent studies demonstrate that mosaic embryos hold the potential to implant, and result in the birth of healthy babies. Therefore, the transfer of these embryos is now offered as an option for those patients with no euploid embryos available in some clinics.

Due to the limited available data on pregnancy outcome (no more than 300 mosaic embryos have been reported in a single study) and unknown potential risks associated with mosaic embryo some argue that mosaicism should not yet be reported or that embryos classified as mosaic should not be transferred. Recently criticism has been raised about mosaic embryos.

These doubts can only be addressed with larger data-sets than currently published. Here we conducted a multicentric prospective study involving assessment of embryos obtained from 2.685 PGT cycles collected from May 2016-January 2020. We analyzed the outcomes of 1000 mosaic embryos and compared their outcome with that obtained from the transfer of euploid embryos. We also analyzed the outcomes of the different types of mosaic embryos.

The results of this study indicate that mosaic embryos miscarry more often and implant less often than euploid embryos, but that approximately 30% of them can still result in a viable pregnancy. No difference in the clinical outcome between monosomic and trisomic mosaics was reported, but mosaic blastocysts carrying multiple chromosome abnormalities (complex mosaic) had the lowest viability among the mosaic embryos. Complex and single segmental mosaics fared better than all other types.

The study provides the largest dataset of transferred mosaic embryo outcomes reported to date. This compiled analysis conclusively shows that embryos with different pattern of chromosomal mosaicism have a distinct set of clinical outcomes. These findings should be considered for genetic counseling.