Reference
Raffone E, Rizzo P, Benedetto V. Insulin sensitiser agents alone and in co-treatment with r-FSH for ovulation induction in PCOS women. Gynecol Endocrinol. 2010;26(4)275-280.
Design
One hundred twenty patients with polycystic ovarian syndrome (PCOS) and 14–16 months of infertility were studied in this randomized, controlled clinical trial. Patients were randomly assigned to receive either 1,500 mg/day metformin or 4 grams of myo-inositol plus 400 mcg folic acid daily. Patients who did not become pregnant underwent ovulation induction with recombinant follicle stimulating hormone (r-FSH, 37.5 units/day) for a maximum of 3 attempts.
Key Findings
Fifty percent of the patients who received metformin restored spontaneous ovulation, and 18.3% of these achieved pregnancy. Sixty-five percent of patients treated with myo-inositol restored spontaneous ovulation, and 30% of these achieved pregnancy. In the remaining patients who did not respond to monotherapy, r-FSH was added. In each of the 2 groups, (metformin plus r-FSH group or myo-inositol, folic acid plus r-FSH group), 11 pregnancies occurred. The total pregnancy rates were 36.6% for patients receiving metformin and 48.4% for patients receiving myo-inositol. The study demonstrated a statistically significant difference in restoration of spontaneous ovulation in patients taking myo-inositol over metformin. There was an overall higher rate of pregnancy in the myo-inositol group, but the effect was not significant.
Practice Implications
One metabolic feature often observed in patients with PCOS is a defect in d-chiro inositol metabolism. D-chiro inositol plays an important role in insulin and glucose metabolism. It accelerates the dephosphorylation of glycogen synthase and pyruvate dehydrogenase, both rate-limiting enzymes of nonoxidative and oxidative glucose disposal.1 Supplying d-chiro inositol or myo-inositol can accelerate glucose disposal and sensitize insulin action. This may decrease the hyperinsulinemic state that can prohibit proper LH secretion.2
Previous studies have demonstrated that myo-inositol is capable of restoring spontaneous ovarian activity, and consequently fertility, in patients with PCOS.3,4 This study is the first to compare the effectiveness of 2 insulin-sensitizing agents—inositol and metformin—in the treatment of chronic anovulation and infertility secondary to PCOS.
In this study, myo-inositol offered a significant advantage over metformin in restoration of spontaneous ovulation in patients with PCOS. This also resulted in a non-significant increase in pregnancy rate. In addition, patients on myo-inositol reported no side effects during the course of treatment. Myo-inositol should be considered as a first-line treatment in patients with PCOS experiencing chronic anovulation or infertility secondary to anovulation.
