A unified SNP-based and multi- omics approach to PGT

Session 1. Euploid but No Implantation?Re-evaluating Embryo Competence Beyond PGT-A Rethinking euploidy: Is diploidy sufficient for implantation? A unified SNP-based and multi- omics approach to PGT Taoli Ding, PhD Research Associate Director, Yikon Genomics Preimplantation Genetic Testing for Aneuploidy (PGT-A) aims to improve implantation rates and reduce the risk of miscarriage by selecting euploid embryos for transfer. However, a substantial proportion of euploid embryos still fail to implant or result in miscarriage. This discrepancy underscores inherent limitations of standard PGT-A, including an inability to detect ploidy abnormalities, and insufficient resolution for small copy number variants (CNVs) associated with pathogenic microdeletion/microduplication syndromes. Furthermore, the frequent detection of mosaic CNVs introduces clinical ambiguity and complicates patient counseling. To address these gaps, we developed the PGT-A Upgrade, an advanced platform that augments conventional PGT-A by integrating SNP genotyping data with custom artificial intelligence (AI) algorithms. This approach enables reliable detection of heteroploidy (including uniparental disomy[UPD] and triploidy), identification of 42 clinically relevant CNV syndromes (33 microdeletions, 9 microduplications) below 4 Mb, and refined discrimination of false mosaicism. A retrospective analysis was performed on 40,849 embryos from 77 centers undergoing PGT-A Upgrade. Ploidy abnormalities (UPD or triploidy) were identified in 1.37% (559/40,849) of embryos, of which 63% (354/559) were triploid. These abnormalities, typically leading to implantation failure, are not reported by basic PGT-A. The overall mosaicism rate was 11.98% (4,895/40,849). Leveraging AI algorithms reduced the ambiguous mosaic call rate to approximately 6%, while maintaining a false negative rate below 5% for true mosaic CNVs. In a subset of 131 embryos at risk for CNV syndromes, detection of microdeletions and microduplications (below 4 Mb) achieved 100% sensitivity and specificity. By reducing diagnostic uncertainty and enhancing the identification of truly viable embryos, PGT-A Upgrade represents a significant advancement toward more comprehensive preimplantation genetic assessment and improved reproductive outcomes.