Embryo ploidy outcomes of PGT-M+PGT-A compared with PGT-A alone: a multicenter real-world cohort study

Abstract

Background Given the increasing adoption of concurrent PGT-M + PGT-A from a single biopsy, understanding the baseline embryo ploidy profiles of patients undergoing combined testing compared to standard PGT-A populations is essential, particularly given concerns about embryo attrition. We aimed to compare embryo ploidy outcomes between PGT-M + PGT-A and PGT-A alone across maternal age strata, using PGT-SR cycles as a high-risk reference group. Methods This retrospective multicenter real-world cohort included 15,956 PGT cycles performed between January 2021 and August 2024 and analyzed in a single genetics laboratory serving multiple reproductive centers in China (7,635 PGT-A–only; 5,874 PGT-M + PGT-A; 2,447 PGT-SR). Blastocyst trophectoderm biopsies were assessed by next-generation sequencing and classified as euploid, aneuploid, or mosaic. Primary outcomes were cycle-level counts and proportions of each ploidy category. We used Poisson regression for count outcomes and offset-Poisson regression for proportion outcomes (offset = log total embryos tested per cycle), with models prespecified to adjust for female age and to apply cluster-robust standard errors by center. Analyses were repeated across maternal age strata. Results Patients undergoing PGT-A alone were older than those undergoing PGT-M + PGT-A (median female age 37 vs. 32 years). After adjustment for female age, euploid proportions were similar between PGT-M + PGT-A and PGT-A alone (RR 0.98, 95% CI 0.95–1.01). Mosaic proportions were slightly higher in PGT-M + PGT-A cycles (RR 1.06, 95% CI 1.002–1.13), whereas aneuploid proportions were slightly lower (RR 0.95, 95% CI 0.90–0.999). Across maternal age strata, the probability of obtaining at least one euploid embryo per cycle was slightly lower among women <35 years (RR 0.96), but did not differ significantly from PGT-A alone in the 35–40 years (RR 1.01) and >40 years (RR 0.87) strata. In contrast, PGT-SR cycles consistently showed poorer euploid outcomes and higher aneuploidy rates, and lower mosaic proportions compared with PGT-A alone. Conclusion After adjusting for maternal age, patients undergoing PGT-M + PGT-A exhibited comparable euploid proportions and probabilities of obtaining at least one euploid embryo per cycle to those undergoing PGT-A alone. Because this study assessed embryo ploidy rather than post-transfer outcomes, evaluating the definitive clinical utility of the combined strategy awaits future prospective studies incorporating live birth and miscarriage data.