Pregnancy outcomes among women with polycystic ovary syndrome treated with metformin.

BACKGROUND We sought to determine whether metformin, which had facilitated conception in 72 oligoamenorrhoeic women with polycystic ovary syndrome (PCOS), would safely reduce the rate of first trimester spontaneous abortion (SAB) and increase the number of live births without teratogenicity. METHODS Seventy-two oligoamenorrheic women with PCOS conceived on metformin (2.55 g/day). They were prospectively assessed in an outpatient clinical research centre. Outcome measures included number of first trimester SAB, live births, normal ongoing pregnancies >or=13 weeks, gestational diabetes (GD), congenital defects (CD), birthweight and height, as well as weight, height, and motor and social development during the first 6 months of life. RESULTS Of the 84 fetuses, to date there have been 63 normal live births without CD (75%), 14 first trimester SAB (17%), and seven ongoing pregnancies >or=13 weeks with normal sonograms without CD (8%). Previously, without metformin, 40 of the 72 women had 100 pregnancies (100 fetuses) with 34 (34%) live births and 62 (62%) first trimester SAB. In current pregnancies on metformin in these 40 women (46 pregnancies, 47 fetuses), there have been 33 live births (70%), two pregnancies ongoing >/=13 weeks (4%), and 12 SAB (26%) (P < 0.0001). There was no maternal lactic acidosis, and no maternal or neonatal hypoglycaemia. Fasting entry serum insulin was a significant explanatory variable for total (previous and current) first trimester SAB, odds ratio 1.32 (for each 5 micro U/ml rise in insulin), 95% CI 1.09-1.60 (P = 0.005). On metformin, GD developed in 4% of pregnancies versus 26% of previous pregnancies without metformin, P = 0.025. There have been no major CD in the 63 live births or CD by sonography in the seven fetuses <or=13 weeks. In the 63 live births, neither weight nor height differed from the normal neonatal population. At 6 month follow-up, height was greater (P = 0.008) and weight did not differ from the normal paediatric population; motor and social development were normal. CONCLUSIONS Metformin therapy during pregnancy in women with PCOS was safely associated with reduction in SAB and in GD, was not teratogenic, and did not adversely affect birthweight or height, or height, weight, and motor and social development at 3 and 6 months of life.