Breakthrough in treatment of Polycystic Ovary Syndrome (11/1/02)
Metformin, which reverses endocrinopathy in women with polycystic ovary syndrome and restores fertility, now shown to reduce first trimester miscarriage 3-fold, to reduce development of gestational diabetes 7-fold, to prevent fetal macrosomia (babies >10 pounds), without any adverse effects on mothers or their newborn infants.
Glueck CJ, Wang P, Goldenberg N, Sieve-Smith L. Pregnancy outcomes among women with polycystic ovarian syndrome treated with Metformin. Human Reproduction 2002;17 (#11):2858-2864 .
Background: Without treatment, women with polycystic ovary syndrome (PCOS) usually do not have normal regular menstrual periods, are commonly infertile, and are characterized by severe obesity, extra body hair, increased risk to type 2 diabetes mellitus, and increased risk to endometrial cancer. PCOS is the most common endocrinopathy in women, affecting 7-10% of US women, and is probably the most common cause of infertility. Without Metformin, those women with PCOS who are able to conceive, often requiring extensive fertility treatments, have a 65% likelihood of first trimester miscarriage, and a 40% likelihood of development of gestational diabetes mellitus. Metformin, a safe, effective, insulin sensitizing drug which does not lower blood glucose in women with normal blood glucose, reverses the endocrinopathy of PCOS, facilitating weight loss, reduction of extra body hair, resumption of normal ovulatory menstrual cycles, and pregnancy.
In the November 2002 issue of Human Reproduction, CJ Glueck MD and colleagues from the Jewish Hospital Cholesterol center, studied 72 women with polycystic ovary syndrome (PCOS) with 81 pregnancies and 84 fetuses, to determine whether metformin would safely reduce the rate of 1st trimester spontaneous miscarriage and increase the number of live births without teratogenicity (development of major birth defects). This is by far the largest such study published to date in the medical literature, and is the 5th such study from the Jewish Hospital Cholesterol Center.
Methods: Seventy-two infertile women with PCOS who either had no menses or infrequent menses without metformin conceived on metformin (2.55 g/day). They were prospectively assessed in an outpatient clinical research center at the Jewish Hospital. Outcome measures included number of 1st-trimester miscarriages, live births, normal ongoing pregnancies > 13 weeks, gestational diabetes (GD), congenital defects (CD), birth weight and height, weight, height, and motor and social development during the 1st 6 months of life.
Results: Of the 84 fetuses, to date there have been 63 normal live births without CD (75%), 14 1st trimester miscarriages (17%), and 7 ongoing pregnancies > 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%) 1st trimester miscarriages. In current pregnancies on metformin in these 40 women (46 pregnancies, 47 fetuses), there have been 33 live births (70%), 2 pregnancies ongoing > 13 weeks (4%), and 12 miscarriages (26%). The reduction from 62% 1st trimester miscarriage to 26% was highly significant, p <.0001. There was no maternal lactic acidosis, and no maternal or neonatal hypoglycemia. Fasting entry serum insulin was a significant explanatory variable for total (previous and current) 1st trimester miscarriage. On metformin, GD developed in 4% of pregnancies vs 26% of previous pregnancies without metformin, p= .025. There have been no major CD in the 63 live births or CD by sonography in the 7 fetuses > 13 weeks. In the 63 live births, weight (p = .19) and height (p = .14) did not differ from normal neonatal populations. At 6 month follow-up, height was greater (p =.008) and weight did not differ (p =.26) from normal pediatric populations; motor and social development were normal.
Conclusions: Metformin therapy during pregnancy in women with PCOS was safely associated with reduction in miscarriage and in GD, was not teratogenic, and did not adversely affect birth weight or height, or height, weight, and motor and social development at 3 and 6 months of life.