Fertility Care and Severe Polycystic Ovarian Syndrome (PCOS)

Objectives: In women with severe clomiphene-resistant PCOS, we proposed that
the insulin-lowering agent troglitazone (Rezulin®) could have a positive impact on the ovarian microenvironment by supporting normal follicular growth, ovulation, and successful pregnancy.

Design: Observational and prospective, in an academic-affiliated subspecialty private practice.

Methods: Clomiphene-resistant women (n=22) were referred by their gynecologists for subspecialty fertility care, with a desire to avoid gonadotropin therapy. All women were evaluated in detail for objective evidence of anovulation, polycystic ovaries, insulin resistance, androgen excess, and dyslipidemias, and written informed consent was obtained prior to prescribing troglitazone.

Results: Of 22 patients, 21 (95%) had documented ovulatory cycles, and 19 continued in active treatment beyond one cycle. Of 16/19 women continuing with troglitazone ± clomiphene, 13/16 (81%) achieved a pregnancy within 6 months; 10/16 (62%) had healthy ongoing gestations (9 singletons, 1 twin); 4/16 (25%) had spontaneous losses, but one subsequently achieved a normal pregnancy. Of the 3/19 patients who ovulated with troglitazone ± clomiphene but didn't conceive, 2 pursued IVF (both singletons) and 1 patient had gonadotropins in conjunction with troglitazone (singleton).

Conclusions: A high percentage of women with clomiphene-resistant PCOS manifest treatable insulin resistance and hyperinsulinemia. For many of these women, the insulin-lowering agent troglitazone is effective in supporting ovulatory function, leading to ongoing pregnancies. Beneficially, the risks and costs associated with gonadotropin use in these women can potentially be avoided.