PGT-M combined with PGT-A in fertile versus infertile carrier couples at risk of autosomal recessive disorders: greater embryological efficiency and superior reproductive outcomes in fertile couples

To evaluate the clinical and laboratory outcomes of preimplantation genetic testing for monogenic disorders (PGT-M), combined with preimplantation genetic testing for aneuploidy (PGT-A), in fertile and infertile couples at risk of transmitting one autosomal recessive monogenic disorder. Retrospective single-centre cohort study including 128 Sicilian couples (67 fertile, 61 infertile), one cycle per couple. Following controlled ovarian stimulation and intracytoplasmic sperm injection, embryos were cultured to blastocyst stage, trophectoderm biopsied, and analysed by next-generation sequencing–based PGT-M; embryos genetically suitable for transfer after PGT-M (wild-type or carrier) subsequently underwent PGT-A. All embryos were vitrified and single vitrified–warmed embryo transfers were performed. Outcomes were assessed per transfer and cumulatively per couple (intention-to-treat) up to two transfers. Fertile couples had a higher blastocyst-to-test rate than infertile couples (64.6% vs. 51.6%, p < 0.001) and required fewer metaphase II oocytes to obtain one transferable euploid embryo after PGT-M + PGT-A (4.76 vs. 6.25, p < 0.001). Euploidy rates among conclusive PGT-A results were similar (63.2% vs. 63.4%, p > 0.05). Clinical pregnancy rate and live birth rate per embryo transfer were higher in fertile couples (66.3% vs. 50.7% and 62.8% vs. 46.7%, respectively; both p < 0.05). Cumulative live birth per couple after up to two transfers was 76.1% (51/67) versus 54.1% (33/61) ( p < 0.05). In carrier couples undergoing PGT-M with add-on PGT-A, fertility status was associated with greater embryological efficiency, higher live birth per embryo transfer, and higher cumulative live birth rates, providing clinically relevant benchmarks for individualized patient counselling and treatment planning.