Objective: To conduct a systematic review and meta-analysis of pregnancy outcome after metformin use for polycystic ovary syndrome (PCOS), because the efficacy of metformin has been demonstrated in the treatment of infertility caused by PCOS, whereas the fetal safety of metformin has received very little attention, and the few studies addressing this issue are limited by small sample sizes.
Design: Meta-analytic review.
Setting: All pertinent studies in MEDLINE and EMBASE from 1966 to September 2004.
Patient(s): Women with PCOS or diabetes.
Intervention(s): Exposure to metformin in the first trimester of pregnancy.
Main outcome measure(s): Major malformations.
Result(s): Eight studies were included in the meta-analysis, with an odds ratio of 0.50 (95% confidence interval, 0.15, 1.60). After adjustment for publication bias, metformin treatment in the first trimester was associated with a statistically significant 57% protective effect. After pooling the studies, the malformation rate in the disease-matched control group was approximately 7.2%, statistically significantly higher than the rate found in the metformin group (1.7%).
Conclusion(s): On the basis of the limited data available today, there is no evidence of an increased risk for major malformations when metformin is taken during the first trimester of pregnancy. Large studies are needed to corroborate these preliminary results.