Is clomifene citrate the best first-line treatment for anovulation?

Abstract

In 1961, Greenblatt et al. were the first to report on the potential use of a novel compound, MRL-41, later known as clomifene citrate, to induce ovulation in anovulatory women. This was a very welcome breakthrough, because until then the only effective treatment available to help anovulatory women conceive was bilateral wedge resection of the ovaries, with the risk of consequent severe abdominal adhesions. Clomifene citrate has since been widely used as firstline treatment for women with hypothalamic–pituitary– ovarian axis dysfunction causing euestrogenic oligo- or anovulation (WHO group II), 80% of whom suffer from polycystic ovary syndrome (PCOS). Clomifene citrate remains an effective medication in treating this group of infertile women and achieves a single live birth rate of approximately 25%. It is acceptable to women, since it is administered orally, and is relatively cheap. Recently, clomifene citrate has also been used in controlled ovarian stimulation in patients with unexplained infertility. Although in this case the results are less exciting, clomifene citrate is being used as a substitute for the more expensive gonadotropin injections for superovulation accompanying intrauterine insemination or in vitro fertilization. For example, the sequential clomifene citrate/human menopausal gonadotropin (hMG) regimen is as effective as hMG alone, with satisfactory pregnancy rates but much reduced costs.