Beyond the Embryo: Rethinking the Genetics of Recurrent Implantation Failure in the PGT-A Era

Background/Objectives: Recurrent implantation failure (RIF) affects many women undergoing IVF, but its genetic basis remains poorly defined. Most studies linking genetic or chromosomal factors to RIF were conducted before preimplantation genetic testing for aneuploidy (PGT-A) was widely used, when embryonic aneuploidy could not be reliably excluded. This review asks whether that evidence still holds now that PGT-A allows embryo aneuploidy to be excluded, at least analytically, as the default explanation for failed transfers. Methods: We reviewed the literature on parental karyotype abnormalities, chromosomal microarray findings, thrombophilia-related gene variants, and endometrial receptivity testing in women with RIF, comparing pre-PGT-A and post-PGT-A era studies where available. Results: Most foundational data on RIF genetics predate PGT-A and likely overstate the embryo’s contribution to implantation failure relative to maternal factors. Very few studies have re-evaluated RIF using strict, PGT-A-confirmed criteria for “true” implantation failure. Evidence for thrombophilia gene variants remains inconsistent across populations, and endometrial receptivity testing still lacks well-established genetic correlates. Conclusions: The genetic evidence base for RIF needs updating for the PGT-A era. A clear, PGT-A-confirmed picture of the genetic and chromosomal contributors to true implantation failure is still missing. Closing this gap should be a priority for future research in reproductive genetics.