Gilbert C et al. (2006) Pregnancy outcome after first-trimester exposure to metformin: a meta-analysis. Fertil Steril 86: 658–663

Metformin has been approved by the FDA for the treatment of type 2 diabetes. Metformin is also used off-label to treat infertility in women with polycystic ovary syndrome (PCOS). There is commonly a delay in the diagnosis of pregnancy in women with PCOS because oligomenorrhea is a common feature of this disorder. It is, therefore, not unusual for women with PCOS to be exposed to metformin during the first trimester of their pregnancy.

Gilbert et al. conducted a systematic review and meta-analysis to determine whether treatment with metformin during pregnancy increases the risk of major fetal malformations. Their analyses included data from eight controlled and five noncontrolled studies that examined metformin use in pregnancy, included a disease-matched control group, and were published on MEDLINE or EMBASE between 1966 and September 2004.

Treatment with metformin during the first trimester was not associated with an increased rate of major fetal malformation. The overall malformation rate in the 496 pregnancies exposed to metformin was 1.01%, compared with 7.50% in the disease-matched control groups.

This meta-analysis included data on only a few pregnancies because there are only a limited number of published studies that have examined the effects of metformin on pregnancy outcomes. The authors, therefore, state that metformin cannot be assumed safe until further studies are carried out that investigate all adverse pregnancy outcomes such as stillbirth, spontaneous abortions, intrauterine growth retardation and minor anomalies.