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The following is a summary of “Preconception and first trimester metformin on pregnancy outcomes in women with polycystic ovary syndrome: a systematic review and meta-analysis,” published in the June 2025 issue of American Journal of Obstetrics & Gynecology by CHESHIRE et al. 

Researchers conducted a retrospective study to analyze the impact of preconception, and first trimester metformin use on pregnancy outcomes in women with polycystic ovary syndrome (PCOS).  

They searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials from database inception to August 1st, 2024. Randomized controlled trials (RCTs) comparing preconception metformin use, continued at least until a positive pregnancy test, with placebo or no treatment in women with PCOS, were included. A systematic review and meta-analysis were conducted. Pooled odds ratios (OR) with 95% CI were calculated for miscarriage (primary outcome) and clinical pregnancy and live birth (secondary outcomes). Study quality was estimated employing the Grading of Recommendations, Assessment, Development and Evaluation and the Cochrane risk-of-bias tool for randomized trials (RoB-2) approach. Indirect comparisons for all key outcomes were done using Bucher’s technique.  

The results showed that 12 reliable studies involving 1,708 women were included in the meta-analysis, with quality rated as low to moderate. Preconception metformin use continued through the first trimester was linked to higher clinical pregnancy rates (OR 1.57, 95%CI 1.11–2.23), a potential decrease in miscarriage (OR 0.64, 95% CI 0.32–1.25), and a possible rise in live birth rates (OR 1.24, 95% CI 0.59–2.61) compared to placebo or no treatment. When metformin was stopped after pregnancy confirmation, clinical pregnancy rates still increased (OR 1.35, 95% CI 1.01–1.80), but there was also a suggested rise in miscarriage (OR 1.46, 95% CI 0.73–2.90). Indirect comparisons between continuation and discontinuation of metformin showed consistent trends in favor of continued use: clinical pregnancy (OR 1.16, 95% CI 0.74–1.83), miscarriage (OR 0.44, 95% CI 0.17–1.16), and live birth (OR 1.14, 95% CI 0.41–3.13).  

Investigators concluded that continuing metformin through the first trimester was associated with lower miscarriage risk and potentially higher live birth rates in women with PCOS. 

Source: ajog.org/article/S0002-9378(25)00365-5/fulltext