Continuing Metformin Throughout Pregnancy in Women With Polycystic Ovary Syndrome Appears to Safely Reduce First-Trimester Spontaneous Abortion: A Pilot Study

Fertil Steril. 2001 Jan;75(1):46-52. doi: 10.1016/s0015-0282(00)01666-6.

Abstract

Objective: To determine whether metformin would safely reduce the rate of first-trimester spontaneous abortion without teratogenicity in 19 women with the polycystic ovary syndrome (PCOS).

Design: Prospective pilot study.

Setting: Outpatient.

Patient(s): Twenty-two previously oligoamenorrheic, nondiabetic women with PCOS; 125 women with PCOS who were not currently pregnant and who had > or = 1 previous pregnancy while they were not receiving metformin.

Intervention(s): Metformin, 1.5-2.55 g/day, throughout pregnancy.

Main outcome measure(s): Rates of first-trimester spontaneous abortion and teratogenicity.

Result(s): Before metformin, 10 women had 22 previous pregnancies with 16 first-trimester spontaneous abortions (73%). While receiving metformin, these 10 women had 6 normal live births (60%), 1 spontaneous abortion (10%), and 3 normal ongoing pregnancies (30%) (all > or = 13 weeks; median gestation, 23 weeks). Among women receiving metformin, including those with live births and normal pregnancy for at least the first trimester, 1 of 10 (10%) had first-trimester spontaneous abortion compared with 73% in 22 previous pregnancies without metformin (P<.002). To date, the 19 women receiving metformin have had no adverse maternal side effects, and no birth defects have occurred; 9 (47%) had normal term live births, 2 (11%) had normal and appropriate for gestational age births (one at 33 and one at 35 weeks), 6 (32%) have ongoing normal pregnancies lasting longer than the first trimester, and 2 (10.5%) had first-trimester spontaneous abortions. Sonography showed normal fetal development without congenital defects in the 6 ongoing pregnancies (median gestation, 23 weeks). Among women who received metformin before conception, reductions in insulin and plasminogen activator inhibitor activity were correlated (r=0.65, P=.04).

Conclusion(s): Metformin therapy throughout pregnancy in women with PCOS reduces the otherwise high rate of first-trimester spontaneous abortion seen among women not receiving metformin and does not appear to be teratogenic.

Publication types

  • Clinical Trial

MeSH terms

  • Abnormalities, Drug-Induced / epidemiology
  • Abortion, Spontaneous / prevention & control*
  • Adult
  • Birth Weight
  • Female
  • Health Status Indicators
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Insulin / blood
  • Metformin / adverse effects
  • Metformin / therapeutic use*
  • Oligomenorrhea / complications
  • Pilot Projects
  • Plasminogen Activator Inhibitor 1 / genetics
  • Plasminogen Inactivators / blood
  • Plasminogen Inactivators / genetics
  • Polycystic Ovary Syndrome / complications
  • Polycystic Ovary Syndrome / drug therapy*
  • Pregnancy
  • Pregnancy Trimester, First
  • Serine Proteinase Inhibitors / blood
  • Serine Proteinase Inhibitors / genetics

Substances

  • Hypoglycemic Agents
  • Insulin
  • Plasminogen Activator Inhibitor 1
  • Plasminogen Inactivators
  • Serine Proteinase Inhibitors
  • Metformin