Women with PCOS are at greater risk for pregnancy complications including impaired fertility gestational diabetes (GDM), pre-eclampsia, preterm delivery, and miscarriage. This paper wraps up two decades of research from Norwegian University of Science and Technology (NTNU). Three controlled studies were carried out between 2000-2017 across 15 different hospitals in Sweden, Norway, and Iceland. Participants of this study were largely Caucasian and University educated.
A combined analysis of the pilot study of 40 women, conducted in 2000-2004, followed by a study of 273 women in 2005-2009, suggested that women with PCOS who received metformin during pregnancy were less likely to have a late miscarriage (miscarriage between week 13 to week 22 and 6 days) or preterm delivery (delivery between week 23 to week 36 and 6 days). Half of the women were given metformin (2000 milligrams daily) from first trimester to delivery, and the other half were given a placebo.
The final study (PreMet2), ran between 2012 and 2017. A randomized cohort of 487 pregnant women with PCOS were given either metformin (500 mg twice daily for 1 week then 1000 mg twice daily) or a placebo from the third trimester until delivery. Late miscarriage and preterm birth occurred in slightly fewer women who received metformin (12 of 238 women, 5%) versus placebo (23 of 240 women, 10%), but was not significant (odds ratio [OR], 0.50; 95% CI, 0.22 - 1.08; P = .08). An analysis of all three trials determined pre-term birth and late miscarriage occurred in significantly fewer women who received metformin (18 of 397 women, 5%) vs. the placebo (40 of 399 women, 10%) (OR, 0.43; 95% CI, 0.23 - 0.79; P = .004).
What came as a surprise was metformin did not reduce the development or severity of gestational diabetes which was present in approximately 25% of this cohort ((60 [25%] of 238 women in the metformin group vs 57 [24%] of 240 women in the placebo group; OR 1·09, 95% CI 0·69–1·66; p=0·75)). However, those taking metformin did experience less weight gain than those taking the placebo. In this study, Metformin also appeared to have no effect on pre-eclampsia, or pregnancy-induced hypertension. There was also no difference between the two groups in adverse effects for the mother or the offspring.
1Tone S Løvvik, et al."Use of metformin to treat pregnant women with polycystic ovary syndrome (PregMet2): a randomised, double-blind, placebo-controlled trial," The Lancet Diabetes & Endocrinology, Volume 7, Issue 4, 2019, Pages 256-266,ISSN 2213-8587, https://doi.org/10.1016/S2213-8587(19)30002-6.
2Hanem LGE, et al. "E. Intrauterine metformin exposure and offspring cardiometabolic risk factors (PedMet study): a 5-10 year follow-up of the PregMet randomised controlled trial." Lancet Child Adolesc Health. 2019 Mar;3(3):166-174. doi: 10.1016/S2352-4642(18)30385-7.
3Vanky E, et al.. Metformin versus placebo from first trimester to delivery in polycystic ovary syndrome: a randomized, controlled multicenter study. J Clin Endocrinol Metab. 2010 Dec;95(12):E448-55. doi: 10.1210/jc.2010-0853.