On the reproductive capabilities of aneuploid human preimplantation embryos

Abstract

In IVF cycles, the application of aneuploidy testing at the blastocyst stage is quickly growing, and the latest reports estimate almost half of cycles in the US undergo preimplantation genetic testing for aneuploidies (PGT-A). Following PGT-A cycles, understanding the predictive value of an aneuploidy result is paramount for making informed decisions about the embryo's fate and utilization. Compelling evidence from non-selection trials strongly supports that embryos diagnosed with a uniform whole-chromosome aneuploidy very rarely result in the live birth of a healthy baby, while their transfer exposes women to significant risks of miscarriage and chromosomally abnormal pregnancy. On the other hand, embryos displaying low range mosaicism for whole chromosomes have shown reproductive capabilities somewhat equivalent to uniformly euploid embryos, and they have comparable clinical outcomes and gestational risks. Therefore, given their clearly distinct biological origin and clinical consequences, careful differentiation between uniform and mosaic aneuploidy is critical in both the clinical setting when counseling individuals and in the research setting when presenting aneuploidy studies in human embryology. Here, we focus on the evidence gathered so far on PGT-A diagnostic predictive values and reproductive outcomes observed across the broad spectrum of whole-chromosome aneuploidies detected at the blastocyst stage to obtain evidence-based conclusions on the clinical management of aneuploid embryos in the quickly growing PGT-A clinical setting.

Keywords: IVF; aneuploidy; meiosis; mosaicism; preimplantation genetic testing.

Figure 1

Main differences between retrospective, RCT, and non-selection studies when assessing predictive values of PGT-A findings in the broad spectrum of aneuploidies During the enrollment phase, intervention is performed prior to group assignment (cohort study), after group assignment (RCT), or not performed (non-selection). Outcome measure for RCTs is limited to the clinical utility of the intervention as sufficiently powered post-intervention randomization requires a prohibitive large population. A robust evaluation of embryo’s reproductive potential in cohort studies is prevented by several uncontrolled factors and covariates that affect treatment’s prognosis independently from embryo’s chromosomal status. Non-selection trials offer the possibility to evaluate the predictive value of different types of chromosomal abnormalities including uniform and mosaic aneuploidies. ET, embryo transfer.