O-290 Clinical utility of putative mosaicism detected using concurrent copy-number and genotyping PGT method: outcomes from multisite, prospective, non-selection study including 9828 single embryo transfer cycles

Abstract Study question What is the clinical utility and associated outcomes of mosaic whole chromosome or segmental aneuploidies detected using concurrent copy-number genotyping analysis in PGT-A cycles? Summary answer Although high-level whole-chromosome mosaicism linked to reduced sustained implantation, it has limited significance cycles when co-evaluated with other clinical/ embryological factors known already NGS-based can detect intermediate chromosomal copy number (CN), commonly interpreted as embryos. A prospective non-selection approach most effective way assess reporting putative findings PGT-A, wherein presence not disclosed does influence embryo selection. Conflicting results have been reported previously, possibly due technological limitations assessment retrospective methods. This study reports largest multisite examining predictive value mosaicism, assessed through combined CN data analysis. design, size, duration involving seven IVF clinics was conducted from Feb 2020 Oct 2022, including 6951 patients 9828 single transfers. The involved a approach, where embryos suspected having were negative for non-mosaic aneuploidies. Embryos chosen transfer based solely on standard morphological features. primary outcome implantation rate (SIR) defined pregnancy continuing beyond 8 weeks gestation. Participants/materials, setting, methods In this study, trophectoderm biopsies analyzed custom, targeted NGS assay that examined approximately 5000 loci across genome, providing information support aneuploidy classification. Mosaicism identified by any deviation expected two copies (LogR plots) confirmed corresponding SNP B-allele frequency (BAF) patterns. Confounding factors, such variables, controlled multivariate Main role chance average female age cohort 34.9 years (SD = 4.1), 30% SIR 61.2%. Of transferred, 6.5% (636/9828) (WCM) only; 9.6% (947/9828) (SM) only 1% (83/9829) combination WCM SM. ranged 15%-89%. control group (non-mosaic), SM 62% (5190/8328; 95%CI), 58% (549/947;95%CI) 50.3% (320/636; 95%CI P < 0.01) respectively. logistic model found level SIR, along factors. particular, difference >50% well poor morphology lower (OR 0.5; 95% CI:0.32-0.76), but low-level (<50%) significant (NS). Notably, 0.98; CI:0.97-0.99 per year), BMI (0.98; CI:0.98-0.99) previous ET failures 0.58; CI:0.5-0.68) strongly SIR. model, taking into account all relevant yielded stratification 43% 68%. Given low incidence our prediction (AUC) 0.580 without 0.585 included. Limitations, reasons caution did prenatal post-natal available at time abstract's writing, hence conclusions about these wasn’t possible. Despite large sample specific feasible. Furthermore, study’s platform-specific cannot be translated assays. Wider implications > 50% variation However, minimal overall impact co-evaluating parameters. Decisions criteria must weigh risk discarding potentially viable substantial reproductive potential. Trial registration Not applicable