Letrozole versus Clomiphene Citrate for Ovulation Induction in Women with Polycystic Ovary Syndrome: A Randomized Controlled Trial

Abstract

Polycystic ovary syndrome, which was first described by Stein and Leventhal in 1935 is considered the most common endocrine disorder affecting approximately 5% to 15% of women in reproductive age ,constitutes one of the most common causes of female infertility . PCOS has additional metabolic derangements, such as insulin resistance, impaired glucose tolerance and dyslipidemia. The risks of diabetes, cardiovascular disease, hypertension, metabolic syndrome and endometrial cancer among PCOS patients are significantly increased as well. Therefore, PCOS is defined not only as a gynecologic endocrinopathy but also as a kind of metabolic disorder. The diagnostic criteria of the syndrome were revised by the Rotterdam ESHRE/ ASRM-Sponsored PCOS Consensus Workshop Group in 2003 where the following criteria were established: oligoamenorrhea , clinical and biochemical signs of hyperandrogenism, and echographically confirmed polycystic ovary. Two of the three criteria are required for diagnosis. Clomiphene citrate is the oral ovulation induction agent of choice , it blocks estrogen receptors at the level of the hypothalamus, which alters gonadotropin-releasing hormone secretion and leads to an increase in follicle-stimulating hormone and ovulation , It is the only FDA-approved oral ovulation induction agent , but because of its antiestrogenic properties, clomiphene citrate can be detrimental to cervical mucus and endometrial thickness, which may negatively affect conception and implantation.In addition, studies have shown a significant difference between rate of ovulation and pregnancy and a higher abortion rate in patients undergoing clomiphene citrate therapy. Approximately 20% to 30% of women do not ovulate while taking clomiphene citrate. For this group, the addition of metformin may be beneficial , knowing that the third ESHRE/ASRM-Sponsored PCOS Consensus Workshop did not recommend the routine use of metformin in PCOS patients.Thus, the use of a simpler oral drug, as a safe alternative to clomiphene citrate, can produce a new horizon in ovulation induction.