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
In brief
Letrozole shows no live-birth advantage for frozen embryo transfers
Across four randomized trials involving 891 women with polyendocrine metabolic ovarian syndrome, letrozole-based preparation did not improve live birth or other key reproductive outcomes compared with programmed-cycle preparation. Programmed cycles were linked to fewer cases of gestational diabetes in two trials, but unusually high rates and limited evidence make that finding preliminary; larger studies are needed to clarify which approach is safer.
- Journal
- Reproductive biomedicine online (Q1)
- Published
- 10 September 2026
- Study design
- Systematic review / meta-analysis of RCTs
- Evidence level
- Level 1, High (CEBM 1a)
- Authors
- Murat Erden, Savci Bekir Telek, Hakan Yarali, Sezcan Mumusoglu
- PMID
- 42810244
- DOI
- 10.1016/j.rbmo.2026.105967
Why clinicians should know about it
- Picked for Neonatology (top studies of the week, 4 October 2026): High-quality evidence in a top journal
- Picked for Obstetrics and Gynecology (top studies of the week, 4 October 2026): RCT meta‑analysis of letrozole vs programmed FET cycles
Abstract
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.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.