A systematic review and meta-analysis of data from controlled trials found that pre-conception use of metformin for polycystic ovary syndrome (PCOS) was not associated with any significant increase (or decrease) in risk of spontaneous abortion or miscarriage.

PCOS is associated with an increased risk of miscarriage and spontaneous abortion, probably through a number of mechanisms. Metformin is widely used for treating the condition, and there is some evidence that it may improve pregnancy outcomes: this is not robust, however. A number of controlled trials have investigated the effects of pre-conceptual metformin on pregnancy rates, and the authors of this analysis have used these to determine whether any objective effect on miscarriage rates could be identified. They carried out a fairly comprehensive literature search up to June 2008 for randomised controlled trials investigating the effect of metformin on reproductive rate in women with PCOS, where data on abortion rates was available either in the published paper or from the original authors. Primary outcome for the meta-analysis was abortion rate, defined as involuntary loss of pregnancy before 20 weeks gestation.

The initial literature search identified 98 possibly relevant studies, of which 37 were retrieved for more detailed evaluation and 17 (n=566) fulfilled the eligibility criteria. Overall, there was no significant effect of metformin on the spontaneous abortion rate (odds ratio [OR] 0.89; 95% CI,0.65 to 1.21; P=.452). Analysis by a number of subgroups found no significant effects according to comparator, nor according to drugs used for ovarian stimulation or for IVF.

Based on their analysis, the authors conclude that pre-conceptual metformin neither increases nor decreases spontaneous abortion risk in women with PCOS. They note that there are two trials ongoing that are investigating the effects of metformin administered to such patients during pregnancy, and that these will provide further evidence on its effects, if any, on pregnancy.