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MISCARRIAGE & PCOS
Women with PCOS who conceive either spontaneously or after ovulation induction have a much higher risk of miscarriage. Liddell has shown that polycystic appearing ovaries (on ultrasound) are more frequently seen in women with recurrent pregnancy loss, the presence of PCO on ultrasound did not predict the outcome in subsequent pregnancies. Hypersecretion of LH was thought to cause chromosomally abnormal eggs leading to an increased risk of miscarriage. But a Japanese study found that PCOS was more common in women whose prior loss was associated with normal chromosomes. Others have suggested that high androgen levels may be a contributory factor. Homburg has shown that miscarriage rates after ovulation induction or IVF is decreased when women are pretreated with a GnRH-agonist such as Synarel, Lupron or Zoladex.

Hyperinsulinemia may be a contributing factor in the higher rate of miscarriage. Elevated levels of insulin interfere with the normal balance between factors promoting blood clotting and those promoting breakdown of the clots. Increases in plasminogen activator inhibitor activity (PAI-Fx) associated with high insulin levels may result in increased blood clotting at the interface between the uterine lining (endometrium) and the placenta. This could lead to placental insufficiency and miscarriage.

There are no placebo-controlled clinical trials to indicate whether pregnancy outcomes are improved in pregnancies that result from the use of insulin-lowering medications or whether pregnancy outcomes are better in those who continue metformin throughout the pregnancy or those who discontinue. Coetzee has shown that use of metformin to manage non-insulin dependent diabetes during pregnancy can be accomplished safely. We have initially noted that women who conceive following metformin, Actos or Avandia therapy have an unacceptably high (>30%) risk of miscarriage. Dr. Glueck notes similar increased risk of miscarriage following metformin therapy. He notes that the risk of miscarriage is increased in those patients with a prior history of miscarriage, those with high LH, high androgen levels, hyperinsulinemia or elevated PAI-Fx. Initial findings in a non-ramdomized trial suggest a decreased risk of miscarriage if metformin is continued throughout the pregnancy. At present there is insufficient data to routinely advise continuation of metformin during pregnancy. As an alternative to continuing metformin therapy, those women with increased risk of abnormal blood clotting may benefit from baby aspirin, folate supplementation and low dose heparin therapy. Pregnancy loss is a troubling concern. This information is provided to enable you work with your ob/gyn physician to make an informed decision about your care.

BIBLIOGRAPHY
1. Velazquez EM, Mendosa S, Hamer T, Sosa F, Glucck CJ. Metformin therapy in women with polycystic ovary syndrome reduces hyperinsulinemia, insulin resistance, hyperandrogenemia, and systolic blood pressure, while facilitating menstrual regularity and pregnancy. Metabolism 1994,43:647­655.

2. Nestler JE, Jakubowicz DJ. Decreases in ovarian cytochrome P450cl7alpha activity and serum free testosterone after reduction of insulin secretion in polycystic ovary syndrome. New England J Medicine 1996,335:617­623.

3. Utiger RD. Insulin and the polycystic ovary syndrome. New England J Medicine 1996,335:657­658

4. Dunaif A, Scott D, Finegood D, Quintana ma B, Whitcomb R. The insulin sensitizing agent Troglitazone improves metabolic and reproductive abnormalities in the polycystic ovary syndrome Endocrinol Metab 1996;81:3299­3306

5. Coetzee EJ, Jackson WP. The management of non-insulin-dependent diabets during pregnancy. Diabetes Res Clin Pract 1985-86;1:281-287

6. Homburg R. Polycystic ovary syndrome: induction of ovulation. Ballieres Cllinical Endocrinologys & Metabolism 1996; 10:281-292

7. Glueck CJ, Wang P, Fontaine R, Tracy T, Sieve-Smith L. Metformin-induced resumption of normal menses in 39 of 43 (91%) previously amenorrheic women with polycystic ovary syndrome. Metabolism 1999; 48:1-10.

8. Tulppala M, Stenman UH, Cacciatore B, Ylikorkala O. Polycystic ovaries and levels of gonadotropins and androgens in recurrent miscarriage: preliminary experience of 500 consecutive cases. Hum Reprod 1994;9:1328-32.

For more information on PCOS and other ovulation problems please read Miracle Babies and Other Happy Endings Online Edition




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thankyou very much for taking the time to share that info.