Metformin May Improve Pregnancy Outcomes in Polycystic Ovary Syndrome

Metformin treatment during pregnancy may improve outcomes in women with polycystic ovary syndrome, according to a study presented at ENDO 2018: The Endocrine Society Annual Meeting, held March 17 to 20 in Chicago, Illinois.¹

Polycystic ovary syndrome has been associated with increased incidence of preterm delivery and late miscarriage, among other pregnancy complications.^2,3 Pooled data from 2 randomized controlled trials (Clinicaltrials.gov Identifiers: NCT01587378 [n=489] and NCT00159536 [n=257]) deemed “underpowered” by the investigators of the current study, and examining the effects of metformin treatment in women with polycystic ovary syndrome, indicate that the treatment, when given from the first trimester to delivery, leads to reduced incidence of preterm deliveries and late miscarriages compared with placebo.

In this randomized double-blind trial conducted by investigators in Norway, Sweden, and Iceland, 487 women with polycystic ovary syndrome from 14 centers across these 3 countries were enrolled between 2012 and 2016. Six of the study participants were lost to follow-up or protocol violation.

Women were assigned to receive 2 g/day metformin or placebo from the first trimester to delivery. Primary outcome was the combined prevalence of preterm delivery and late miscarriage. Secondary outcomes examined included prevalence of gestational diabetes, neonatal intensive care unit admissions, and maternal hospitalization. Tertiary outcomes included newborn weight, length, and head circumference.

Study drop out (overall rate, 10.2%) occurred mainly after the initial visit (8.3%). A majority of patients remaining in the trial (81%) took ≥70% of their medication. Combined prevalence of preterm delivery and late miscarriage was reduced in women who had taken metformin vs placebo, following “intention to treat” principles (5.83% vs 9.96%, respectively; P =.09; 95% CI, 0.9-3.54), as well as in a per protocol analysis that excluded study dropouts (5.21% vs 10.71%, respectively; P =.04; 95% CI, 1.04-4.57).

Secondary outcomes were comparable in both groups, and weight gain (tertiary outcome) was reduced in women who had taken metformin vs placebo (8.7 vs 11.5 kg, respectively; P <.001; 95% CI, −4.1 to −1.5). Newborn weight and length were similar in both groups, and the head circumference of those in the metformin group was greater compared with newborns in the placebo group (35.4 vs 34.7 cm; P =.03; 95% CI, 0.07-1.2).

“Metformin from [first] trimester to delivery, prevented preterm delivery and late miscarriage if the patients adhered to the treatment,” concluded the study authors.

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References

1. Shetelig Løvvik T, Magnus Carlsen S, Steffensen B, et al. Metformin treatment of pregnant women with polycystic ovary syndrome — a randomized, Nordic multi-center trial. Presented at: ENDO 2018: The Endocrine Society Annual Meeting; Chicago, IL; March 17-20, 2018. Abstract OR33-4.
2. Yamamoto M, Feigenbaum SL, Crites Y, et al. Risk of preterm delivery in non-diabetic women with polycystic ovarian syndrome. J Perinatol. 2012;32(10):770-776.
3. Kamalanathan S, Sahoo JP, Sathyapalan T. Pregnancy in polycystic ovary syndrome. Indian J Endocrinol Metab. 2013;17(1):37-43.