Miscarriage Rate in PCOS Falls to 12% With Metformin.
ARLINGTON, VA. -- Metformin, a drug that allows women with polycystic ovary syndrome to ovulate normally and conceive, should be continued throughout their pregnancies because it also prevents miscarriage, Dr. Charles J. Glueck reported at the Clinical Research 2001 meeting.
Interim results of the ongoing study of 156 women with polycystic ovary syndrome (PCOS) who have received metformin throughout pregnancy showed 54 normal live births, 19 first trimester miscarriages, 2 tubal pregnancies, and 81 women with ongoing pregnancies that appear normal on sonography at 13 weeks or more of gestation.
"So 87% have had a favorable outcome to date, and the rate of first-trimester miscarriage has been cut to 12%--which is about the national average in 'normal' women who have no endocrine disorders," said Dr. Glueck of the cholesterol center at Jewish Hospital, Cincinnati.
In fact, in a series of 183 pregnancies at his institution in which women with PCOS were not treated with metformin, the first-trimester miscarriage rate was a striking 64%, and the live birth rate was only 35%, he said at the meeting, sponsored by the American Federation for Medical Research.
Dr. Glueck speculated that the high miscarriage rate in PCOS is probably due to high levels of plasminogen activator inhibitor, which are markedly reduced by metformin therapy.
Dr. Glueck has also done "long-distance follow-up" on a separate group of 135 pregnancies in which the women were treated with metformin at his hospital to conceive, then returned to their distant homes and their regular physicians for pregnancy management.
Physicians for 29 of these women stopped the metformin therapy as soon as pregnancy was confirmed, and 6 of them (21%) had first-trimester miscarriages. In contrast, of the 106 women whose physicians continued metformin therapy throughout pregnancy, only 13 (12%) have had a first-trimester miscarriage.
The drug has not produced any adverse effects on either the mother or fetus. "The overwhelming majority of the live births have occurred at 37 weeks or later," and the infants' weight and height distribution matches the national average almost exactly he noted.
Once metformin, an insulin-sensitizing agent, was found to induce normal menses and facilitate pregnancy in women with PCOS, attention turned to the out come of those pregnancies.
In the question-and-answer session following his presentation, Dr. Glueck noted that metformin also may be preventing the development of gestational diabetes in these patients.
The average weight in the cohort of 156 women with PCOS was 226 pounds at conception, and most of the women were extremely insulin resistant. Yet the rate of gestational diabetes was only 4%. "Com pare that with a rate of 58% seen in untreated women with PCOS, and it's clear that metformin drastically reduces gestational diabetes," he said.
The average weight gain in treated women was 11 pounds, and "many ended pregnancy thinner than when they started. In this patient population, that is a good thing," Dr. Glueck said.