Polycystic ovary syndrome (PCOS) is characterized by oligo/anovulation, clinical or biochemical evidence of hyperandrogenism and polycystic ovaries, with exclusion of other related disorders. It affects 6 percent-10 percent of women of childbearing age and is the most common cause of anovulatory infertility. Insulin resistance and its compensatory hyperinsulinemia play a key pathogenic role in anovulation and infertility associated with PCOS. Evidence indicates that improving insulin resistance increases ovulation, the success of ovulation induction with clomiphene and pregnancy rates. Lifestyle modification, specifically a weight-reducing diet and exercise, is recommended as first-line therapy for all obese women with PCOS Clomiphene citrate is used as first-line therapy to induce ovulation in women with PCOS, followed by gonadotrophin administration for those who failed to respond to clomiphene. A novel therapeutic approach has emerged from the observation that most women with PCOS suffer from hyperinsulinemic insulin resistance and from evidence that strongly suggests that the elevated circulating insulin concentration impedes ovulation. Insulin sensitizing agents (ISA) used for ovulation induction in PCOS are metformin, rosiglitazone, pioglitazone, troglitazone and d-chiro inositol. The last two are not available. Use of rosiglitazone and pioglitazone (Category B drugs) for PCOS have been reported. Their primary mechanism of action is to enhance peripheral insulin sensitivity. Metformin (Category B drug) has been used in most studies on PCOS. Metformins primary mechanism of action is to reduce hepatic glucose production by improving hepatic insulin sensitivity. It is a safe, effective and rational treatment for the metabolic and endocrine abnormalities in PCOS. Kim, et al. recommended institution of ISA only after clomiphene failure induction. ISA are useful in the treatment of obese and non-obese women with PCOS. In a multinational, randomized, single-blind placebo controlled trial, metformin monotherapy yielded a higher rate of ovulation compared to placebo but a head-to-head trial of ISA vs. clomiphene for initial ovulation induction has not been reported. However, substantial evidence exists, including results from randomized clinical trials, that metformin enhances the likelihood of successful ovulation induction with clomiphene. A multicenter, randomized, double-blind, placebo-controlled trial showed a 75 percent ovulation rate with clomiphene-metformin vs. 27 percent in the clomiphene-placebo group. Fifty eight percent conceived in the clomiphene-metformin group vs. 13 percent in the clomiphene-placebo group Metformin treatment may allow a reduced rate of hyperstimulation with FSH therapy and may reduce the risk of multiple gestation. No randomized, double-blind, placebo-controlled trial of ISA as an adjuvant to gonadotrophin ovulation inductionhas been reported In an abstract at the 1999 meeting of the ASRM, it was reported that metformin increased the number of mature oocytes retrieved from women with PCOS undergoing gonadotrophin-stimulated IVF-ET and ICSI. Women with PCOS have a 30 percent-50 percent first trimester pregnancy loss and 36 percent-82 percent of women with recurrent pregnancy loss are reported to have PCOS. Hyperinsulinemia maybe the important factor in the pregnancy losses. A recent pilot study and a preliminary report both reported a 10 fold reduction in miscarriage in women with PCOS treated throughout pregnancy with metformin. No prospective controlled trials have addressed this issue. In PCOS, use of metformin is associated with a 10-fold reduction in gestational diabetes (31 percent to 3 percent). It also reduces insulin resistance and insulin secretion, thus decreasing the secretory demands imposed on pancreatic beta cells by insulin resistance and pregnancy. It is not teratogenic.
POLYCYSTIC OVARY SYNDROME