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

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 is to summarize the major randomized controlled trials (RCTs) and non-selection studies evaluating the benefit of PGT-A to improve live birth rates (LBRs). We argue that LBR per transfer is more relevant to the individual patient than 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 and live birth rates with PGT-A for embryo selection vs. traditional morphology. However, these studies are limited by small sample size and a bias towards good prognosis patients. Further studies using next generation sequencing (NGS) found more variable results but did confirm an improvement in LBRs per transfer in an older population with 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 three blastocysts with a significant reduction in the cumulative clinical pregnancy loss rate in the PGT-A group. Non-selection studies evaluating pregnancy outcomes following 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 non-selection 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. 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 is to summarize the major randomized controlled trials (RCTs) and non-selection studies evaluating the benefit of PGT-A to improve live birth rates (LBRs). We argue that LBR per transfer is more relevant to the individual patient than 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 and live birth rates with PGT-A for embryo selection vs. traditional morphology. However, these studies are limited by small sample size and a bias towards good prognosis patients. Further studies using next generation sequencing (NGS) found more variable results but did confirm an improvement in LBRs per transfer in an older population with 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 three blastocysts with a significant reduction in the cumulative clinical pregnancy loss rate in the PGT-A group. Non-selection studies evaluating pregnancy outcomes following 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 non-selection 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.