Anat Hershko Klement1, Robert F Casper. 1. aDivision of Reproductive Sciences, Fran and Lawrence Bloomberg Department of Obstetrics and Gynecology, University of Toronto, The Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital bTCART Fertility Partners, Toronto, Ontario, Canada.
Abstract
PURPOSE OF REVIEW: Approximately 15% of the infertile population faces an ovulatory disorder; most of them classified as WHO class two anovulation [polycystic ovarian syndrome (PCOS) prototype]. Worldwide, this translates into millions of patients and emphasizes the need of a simple, effective and well tolerated method of ovulation induction. In this review, we will revisit letrozole use in the subset of WHO class two ovulatory problems and evaluate the contribution of the last year's literature to its practice. RECENT FINDINGS: In a multicentre, randomized controlled trial comparing letrozole with clomiphene in 750 PCOS patients having regular intercourse, live birth rates were significantly higher for the letrozole group [rate ratio 1.44, 95% confidence interval (95% CI) 1.10-1.87]. In a meta-analysis summarizing clinical trials testing aromatase inhibitors used alone or with other medical therapies for ovulation induction in PCOS patients, live birth rates were again significantly higher when letrozole was compared with clomiphene citrate [odds ratio (OR) 1.64, 95% CI 1.32-2.04]. A retrospective analysis of children born to infertile women assessed the congenital malformation rate after exposure to letrozole in comparison to clomiphene citrate and to natural conceptions. No significant differences in malformation rates were detected between the groups (2.9, 2.5 and 3.9%, respectively). SUMMARY: High-level evidence supports letrozole as the first drug of choice for ovulation induction in the PCOS population. The increasing use of letrozole with pregnancy follow-up provides additional reassurance for foetal safety.
PURPOSE OF REVIEW: Approximately 15% of the infertile population faces an ovulatory disorder; most of them classified as WHO class two anovulation [polycystic ovarian syndrome (PCOS) prototype]. Worldwide, this translates into millions of patients and emphasizes the need of a simple, effective and well tolerated method of ovulation induction. In this review, we will revisit letrozole use in the subset of WHO class two ovulatory problems and evaluate the contribution of the last year's literature to its practice. RECENT FINDINGS: In a multicentre, randomized controlled trial comparing letrozole with clomiphene in 750 PCOSpatients having regular intercourse, live birth rates were significantly higher for the letrozole group [rate ratio 1.44, 95% confidence interval (95% CI) 1.10-1.87]. In a meta-analysis summarizing clinical trials testing aromatase inhibitors used alone or with other medical therapies for ovulation induction in PCOSpatients, live birth rates were again significantly higher when letrozole was compared with clomiphene citrate [odds ratio (OR) 1.64, 95% CI 1.32-2.04]. A retrospective analysis of children born to infertile women assessed the congenital malformation rate after exposure to letrozole in comparison to clomiphene citrate and to natural conceptions. No significant differences in malformation rates were detected between the groups (2.9, 2.5 and 3.9%, respectively). SUMMARY: High-level evidence supports letrozole as the first drug of choice for ovulation induction in the PCOS population. The increasing use of letrozole with pregnancy follow-up provides additional reassurance for foetal safety.