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.
metformin throughout pregnancy PCOS spontaneous abortion reduction, Glueck metformin PCOS pregnancy pilot study, metformin first trimester miscarriage prevention polycystic ovary, PCOS metformin pregnancy safety teratogenicity, metformin continuation pregnancy recurrent miscarriage PCOS, polycystic ovary syndrome insulin resistance pregnancy loss metformin, metformin plasminogen activator inhibitor PCOS pregnancy, PCOS oligoamenorrhea metformin live birth rate, insulin sensitizer pregnancy spontaneous abortion prospective study, metformin safety first trimester PCOS nondiabetic women
PMID 11163815 11163815 DOI 10.1016/s0015-0282(00)01666-6 10.1016/s0015-0282(00)01666-6
Keywords
Abnormalities, Drug-Induced/epidemiology, Abortion, Spontaneous/prevention & Control, Adult, Birth Weight, Female, Health Status Indicators, Humans, Hypoglycemic Agents/adverse Effects/therapeutic Use, Insulin/blood, Metformin/adverse Effects/therapeutic Use, Oligomenorrhea/complications, Pilot Projects, Plasminogen Activator Inhibitor 1/genetics, Plasminogen Inactivators/blood/genetics, Polycystic Ovary Syndrome/complications/drug Therapy, Pregnancy, Pregnancy Trimester, First, Serine Proteinase Inhibitors/blood/genetics, Hypoglycemic Agents, Insulin, Plasminogen Activator Inhibitor 1, Plasminogen Inactivators, Serine Proteinase Inhibitors, Metformin