Letrozole-based stimulation versus programmed cycle for frozen embryo transfer in women with polyendocrine metabolic ovarian syndrome: a systematic review and meta-analysis of randomized controlled trials.

This systematic review and meta-analysis compared reproductive, perinatal and neonatal outcomes between letrozole-based endometrial preparation, with or without adjuvant gonadotrophins, and programmed-cycle endometrial preparation for frozen embryo transfer (FET) in women with polyendocrine metabolic ovarian syndrome (PMOS), including only randomized controlled trials (RCTs). MEDLINE, Embase and the Cochrane Central Register of Controlled Trials were searched from inception through September 10, 2025. Four RCTs met inclusion criteria (n = 891). Random-effects models were used to pool risk ratios, risk of bias was assessed with RoB-2 and certainty of evidence was evaluated using Grading of Recommendations, Assessment, Development and Evaluations. No significant difference in live birth rate was observed between the two protocols (RR 0.92, 95% CI 0.79 to 1.07). Similarly, no significant differences were observed in clinical pregnancy, miscarriage, hypertensive disorders of pregnancy or cycle cancellation rates. A lower risk of gestational diabetes mellitus (GDM) was observed with programmed-cycle FET in a meta-analysis of two RCTs (RR 0.33, 95% CI 0.14 to 0.82, P = 0.02); however, this hypothesis-generating finding should be interpreted cautiously because of the unexpectedly high GDM rates and requires confirmation in larger studies. Other perinatal and neonatal outcomes did not differ significantly, although evidence was underpowered. In contrast to observational studies, current RCT evidence does not demonstrate superiority of letrozole-based over programmed-cycle endometrial preparation for reproductive outcomes in women with PMOS.