Transfer of the fittest: using preimplantation genetic testing for aneuploidy to select embryo(s) most likely to lead to live birth

Abstract

Preimplantation genetic testing for aneuploidy (PGT-A) was developed to identify euploid embryos from a cohort of embryos with unknown ploidy produced during an in vitro fertilization (IVF) cycle. In recent years, the ability of PGT-A to improve IVF outcomes has come into question. The goal of this review was to summarize the major randomized controlled trials (RCTs) and nonselection studies evaluating the benefit of PGT-A to improve the live birth rates (LBRs). We argue that the LBR per transfer is more relevant to the individual patient than the cumulative LBR as a means to minimize the burden of IVF by reducing futile transfers, pregnancy losses, and ongoing aneuploidy. The early RCTs demonstrate improved implantation rates and LBRs with PGT-A for embryo selection vs. traditional morphology. However, these studies are limited by the small sample size and a bias toward good-prognosis patients. Further studies using next-generation sequencing found more variable results but did confirm an improvement in the LBRs per transfer in an older population with a higher baseline risk of aneuploidy. The largest RCT to date showed similar cumulative LBRs in the PGT-A and control groups after biopsy and sequential transfer of up to 3 blastocysts with a significant reduction in the cumulative clinical pregnancy loss rate in the PGT-A group. Nonselection studies evaluating pregnancy outcomes after transfer of euploid vs. aneuploid embryos demonstrate near-perfect negative predictive value for an aneuploid result to predict live birth. Putative mosaic embryos had similar LBRs compared with euploid embryos. The available RCTs and nonselection studies support the practice of using PGT-A to identify euploid embryos for transfer, especially in an older population, while simultaneously selecting against aneuploid embryos, without negative impact on the total reproductive potential of the cycle.