Metformin taken by women with polycystic ovary syndrome during the first trimester of pregnancy does not appear to increase the risk of major fetal malformations, and may have a significant protective effect, according to Canadian researchers.

These findings are still preliminary and further studies are needed to confirm the safety of this drug in pregnancy, the researchers stress in their report, published in the September issue of Fertility and Sterility.

Metformin is used, with or without insulin, to treat patients with type 2 diabetes - and it is also used to treat infertility in women with polycystic ovary syndrome. However, the safety of this drug for the fetus has not been established, Dr. Gideon Koren of The Hospital for Sick Children in Toronto, Ontario, and colleagues point out. Furthermore, a similar drug, phenformin, has been shown to cause birth defects.

Polycystic ovary syndrome, the most common hormonal disorder in premenopausal women in the U.S., is caused by the disruption of the reproductive cycle. Features include enlarged ovaries studded with numerous cystic follicles that contain immature eggs; excess hair growth; and obesity. Women with polycystic ovary syndrome have difficulty conceiving and are at risk of diabetes and heart disease.

To further explore the safety of metformin in pregnancy, Koren and colleagues conducted a large review of the medical literature, including eight studies of metformin taken during the first trimester of pregnancy by a total of nearly 500 women with either PCOS or diabetes.

From the pooled data, the malformation rate in the treatment group was 1.7 percent compared with 7.2 percent in disease-matched control subjects who did not receive metformin.

The researchers found that after the data were adjusted for publication bias, metformin had a statistically significant protective effect of 57 percent against major malformations in the fetus.

The investigators caution that the data establishing safety of metformin in pregnancy are still limited. This study considered only major malformations of the fetus. Other studies assessing the incidence of spontaneous abortion, stillbirth, minor abnormalities, intrauterine growth retardation and preterm labor still need to be conducted.

SOURCE: Fertility and Sterility, September 2006.