Effects of Metformin on Early Pregnancy Loss in the Polycystic Ovary Syndrome

Abstract

Women secreting large amounts of luteinizing hormone (LH), including those with polycystic ovary syndrome (PCOS), are reportedly at increased risk for miscarriage. In addition, the hyperinsulinemic insulin resistance found in PCOS patients may increase circulating levels of ovarian androgens and impede ovulation. The insulin-sensitizing drug metformin reduces serum androgen levels and promotes ovulation in affected women, and has positive effects on risk factors for miscarriage in PCOS such as insulin resistance and obesity. A study, therefore, was planned to learn whether metformin therapy limits the risk of early pregnancy loss in this setting. The retrospective study included 65 women with PCOS who became pregnant and received metformin in a dose of 1 to 2 gm daily throughout their pregnancies. Another 31 women did not take metformin. A 75-gm oral glucose tolerance test was performed at 4 to 6 weeks' gestation. The metformin-treated women had previously suffered miscarriage in 71% of 75 untreated pregnancies, and the rate for control women was 54%. The metformin-treated and control women had similar baseline hormonal levels. The rate of pregnancy loss in the first 12 weeks was 9% in the women given metformin throughout pregnancy and 42% in control women, a significant difference. Among women in each group with a past history of miscarriage, the rates of early pregnancy loss were 11% in those given metformin and 58% in untreated pregnancies. The areas under both the serum insulin curve and serum glucose curve were significantly lower in the metformin group in the first trimester of pregnancy. Serum free testosterone levels did not differ at baseline, but during the first trimester they were significantly lower in the metformin-treated women. All but one of 62 liveborn infants of metformin-treated mothers were normal and of appropriate size for gestational age; the exception had chondrodysplasia. None of 18 liveborn infants of control women had fetal abnormalities. Pregnant women with PCOS in this study who received metformin throughout pregnancy experienced a marked, statistically significant reduction in early pregnancy loss-even when there was an established history of miscarriage. The findings would seem to warrant a randomized placebo-controlled trial of metformin in women with PCOS.