Preimplantation Genetic Testing for Chromosomal Abnormalities: Aneuploidy, Mosaicism, and Structural Rearrangements

Abstract

There is a high incidence of chromosomal abnormalities in early human embryos, whether they are generated by natural conception or by assisted reproductive technologies (ART). Cells with chromosomal copy number deviations or chromosome structural rearrangements can compromise the viability of embryos; much of the naturally low human fecundity as well as low success rates of ART can be ascribed to these cytogenetic defects. Chromosomal anomalies are also responsible for a large proportion of miscarriages and congenital disorders. There is therefore tremendous value in methods that identify embryos containing chromosomal abnormalities before intrauterine transfer to a patient being treated for infertility—the goal being the exclusion of affected embryos in order to improve clinical outcomes. This is the rationale behind preimplantation genetic testing for aneuploidy (PGT-A) and structural rearrangements (-SR). Contemporary methods are capable of much more than detecting whole chromosome abnormalities (e.g., monosomy/trisomy). Technical enhancements and increased resolution and sensitivity permit the identification of chromosomal mosaicism (embryos containing a mix of normal and abnormal cells), as well as the detection of sub-chromosomal abnormalities such as segmental deletions and duplications. Earlier approaches to screening for chromosomal abnormalities yielded a binary result of normal versus abnormal, but the new refinements in the system call for new categories, each with specific clinical outcomes and nuances for clinical management. This review intends to give an overview of PGT-A and -SR, emphasizing recent advances and areas of active development.

Preimplantation genetic testing for aneuploidy: A review of published blastocyst reanalysis concordance data

“…Preimplantation genetic testing for aneuploidy (PGT-A) is a proven intervention in the treatment of infertility, with decreased clinical miscarriage risk, increased delivery rates from the first embryo transfer attempt, and reduced risk of multiple gestation without compromising success rates. [1][2][3][4][5] 5 However, the diagnostic predictive value of PGT-A, when considering embryonic mosaicism, [6][7][8] or segmental imbalance 9,10 remains controversial and has involved considerable resources to investigate. mosaic range) and 30% to 70% (2.3-2.7 mosaic range).…”

Aneuploidy and DNA Methylation as Mirrored Features of Early Human Embryo Development

“…Moreover, these studies showed a direct correlation of mosaicism with maternal age [3]. According to the latest estimates, the level of mosaic karyotypes in human preimplantation embryos is significantly lower-from 4% to 22% [20]. The effect of maternal age on the frequency of mosaic embryos is also controversial, since it has not been confirmed in other studies [25,26].…”

“…Approximately half of human preimplantation embryos have aneuploidy, mostly of maternal origin. In addition, the cleavage stage is characterized by mitotic errors that lead to the appearance of mosaic karyotypes [20]. Early studies showed that the frequency of blastocysts with chromosomal mosaicism varied from 17.6% to 95% [3,[21][22][23][24].…”

SARS-CoV-2 Can Infect Human Embryos

“…Ethical approval for this project was obtained through the IRB of the Zouves Foundation for Reproductive Medicine (OHRP IRB00011505). For the RNA-seq experiment, embryos were of various ethnic backgrounds and comprised a mix of euploid and aneuploid samples based on evaluation by pre-implantation genetic testing for aneuploidy (PGT-A) 18 (Suppl. Table 1).…”