I-17: Should All Women with PCOS-Related Infertility Be Treated with Insulin Sensitizing Drugs?

Interest in the role of insulin sensitizing drugs (ISDs) as a means of reducing compensatory hyperinsulinemia in the hope of improving metabolic and reproductive functions in women with PCOS has grown measurably over the past decade. Metformin is believed to lower fasting serum insulin levels in insulin-resistance. For the management of ovulatory infertility in the nonobese PCOS population (BMI < 30kg/m2), there is moderate- quality evidence demonstrating that metformin monotherapy improves the odds of ovulation and chance of achieving clinical pregnancy. There is moderate-quality evidence demonstrating the absence of reproductive benefit when metformin is combined with CC therapy in the non-obese population of women with PCOS-related subfertility. CC-alone therapy remains the mainstay pharmacological therapy for this group. For obese women (BMI ≥ 30 kg/m2) with PCOS-associated subfertility, there is low-quality evidence showing the failure of metformin monotherapy to improve reproductive endpoints. In view of the considerable side effect profile, metformin monotherapy may not be recommended for fertility management in this group of women. There is moderate-quality evidence to support a beneficial effect of metformin in combination with CC therapy in increasing the likelihood of ovulation and clinical pregnancies. For women with CC-resistant subfertility, there is moderate-quality evidence to support that metformin co-treatment increases ovulation rates. There is also low-quality evidence demonstrating that metformin/CC combination therapy may be associated with higher live births than laparoscopic ovarian drilling. Women with CC-resistant PCOS may be given the benefit of a trial of medical ovulation induction using combination therapy prior to committing to the more invasive and expensive alternative of LOD. For women with PCOS undergoing IVF/ICSI treatments, there is moderate evidence to support the failure of metformin co-administration to improve the clinical outcomes of live births, clinical pregnancies, or miscarriages. There is moderate evidence demonstrating a significant reduction in the risk of OHSS with metformin co-treatment, when hCG is used to trigger final oocyte maturation.