Embryo and reproductive outcomes in thalassemia-related PGT-M with concurrent PGT-A versus PGT-A alone: a retrospective cohort study

Introduction Concurrent preimplantation genetic testing for monogenic disorders and aneuploidy (PGT-M+PGT-A) assesses monogenic disease status and chromosomal ploidy, but disease-specific outcome data remain limited. Methods This retrospective cohort study included 2,028 cycles from 1,750 patients during 2018–2024: 723 thalassemia-related PGT-M+PGT-A cycles and 1,305 PGT-A-alone cycles in couples without thalassemia-associated pathogenic variants. Reproductive outcomes were evaluated after 1,157 first frozen euploid embryo transfers. Results Women in the combined-testing cohort were younger (median age at biopsy, 32 versus 39 years). The combined-testing cohort had higher adjusted euploid embryo counts (adjusted ratio 1.14, 95% confidence interval [CI] 1.02–1.26; P = .016) and proportions (1.09, 95% CI 1.01–1.16; P = .021). Overall aneuploid and mosaic outcomes did not differ significantly, although the mosaic proportion was higher at ages 38–40 (1.62, 95% CI 1.23–2.13; P<.001). The probability of obtaining at least one usable embryo per cycle was lower at ages 35–40 (adjusted relative risk [aRR] 0.88, 95% CI 0.79–0.99; P = .028). The adjusted live-birth difference after first euploid embryo transfer was not statistically significant (aRR 1.10, 95% CI 0.99–1.24; P = .084). Discussion These findings may inform individualized counseling on embryo availability and outcomes after euploid embryo transfer in thalassemia-related PGT-M.