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Women's Health Topics 

  Polycystic Ovary Syndrome and Miscarriages

Walter Futterweit, MD, FACS, FACP
Clinical Professor of Medicine, Division of Endocrinology
Mount Sinai School of Medicine, New York, NY 10029

Walter Futterweit, MDPCOS is the leading cause of infertility in the United States. In addition to having difficulty conceiving, women with PCOS have to face the distressing prospect of an increased risk of miscarriage after either a spontaneous or assisted conception. In view of frequent amenorrhea in PCOS, it is almost necessary to obtain a serum b-HCG to insure that the woman is not already pregnant. Symptoms of a miscarriage usually are those of vaginal bleeding and abdominal pain, which is then confirmed by the findings on an ultrasound examination. This is then confirmed with low serum b-HCG level less than 50 IU/liter and confirmed by uterine ultrasonography. Many investigators believe that the miscarriage rate in PCOS women is 3 times higher than that reported for healthy controls (10-15%). The other side of the coin reveals that in analyzing women with recurrent first trimester pregnancy loss, 36-82% is reported to have polycystic ovary syndrome. A number of risk factors may be involved in the increased first trimester miscarriage rate in women with PCOS. These include obesity, elevation of serum androgen levels, and increased insulin levels (hyperinsulinism) which is a result of insulin resistance. A number of clotting disturbances may also be related to the insulin levels which may alter the balance between blood clotting and the breakdown of clots. Reported elevation of plasminogen activator inhibitor (PAI-1) may cause increased blood clotting leading to placental malfunction and miscarriage.

Other possible reported abnormalities may also be related to the increased miscarriage rate in women with PCOS. Data indicate that there may be abnormalities in the endometrial lining of the womb in pregnant PCOS women which affect an adequate embryonic implantation and maintenance of pregnancy. These endometrial changes occur because certain protective proteins, glycodelin and IGF binding protein-1 (IGFBP-1), are not secreted in adequate amounts in the endometrium of women with PCOS who are likely to have a miscarriage. Reduction of these proteins allows maternal potential immune responses to affect the embryo. The reduction of IGFBP-1 reduces the adhesion process which reduces adequate embryonic implantation. Administration of metformin, an insulin sensitizing agent, has been shown to increase these 2 proteins in nonpregnant women with PCOS.

Metformin is recognized by the FDA to be a category B drug. This means that no teratogenic effects have been noted in animal studies. Treatment with metformin, which often facilitates conception in women with PCOS and continuation of the drug during the first trimester of pregnancy, is associated with a significant reduction in early miscarriage rate. The known effects of metformin in decreasing hyperinsulinemic insulin resistance, elevated androgen levels and possibly obesity, and its effect in reducing a clotting tendency due to increased maternal PAI-1 levels, may be important aspects in its reported benefit in women with PCOS who continue to take the drug during the first trimester of pregnancy. A study of PCOS women who continued metformin for the first trimester to prevent recurrent abortion had a normal miscarriage rate (8.8%). PCOS women who did not take metformin during the first trimester and who had a prior miscarriage had a 42% miscarriage rate. In view of the apparent data suggesting that metformin does not cause fetal or birth defects, those with 3 or more miscarriages have been reported to be successfully treated with metformin when taken throughout the pregnancy. Until more long-term follow-up of infants and children born to such mothers, one still must hesitate to use this option, until its long term safety effect on the child is studied.

My view is to discontinue the metformin in a previously non-pregnant woman with PCOS who conceives. Once there is a history of miscarriages, one then has the option of continuing metformin for the first trimester of pregnancy. Furthermore it must be added that some of the studies demonstrating the effect of metformin treated women with PCOS and the control group of non-treated women with PCOS were well matched for important clinical variables. A randomized clinical trial of many women is necessary to make this the best option in women with recurrent miscarriage in PCOS.

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 Email Dr. Futterweit  Email PCOS questions to Dr. Futterweit

 

 

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“A Patients Guide to PCOS”  by Dr. W. Futterweit

Taken in part from the book “A Patients Guide to PCOS” by Dr. Walter Futterweit

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