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Abstract
Clomiphene citrate (CC) results in estrogen receptor clown-- regulation or depletion, which releases the hypothalamus and/or pituitary from estrogenic negative feedback on gonadotropin secretion. However, CC may also result in adverse endometrial and cervical mucus effects, resulting in pregnancy rates that are lower than expected compared with ovulation rates. Aromatase inhibitors (AIs) decrease estrogen concentrations without direct antiestrogenic effects themselves. We hypothesized that use of an AI in anovulatory women should result in increased gonadotropin secretion and stimulation of ovarian follicle development. In addition, AIs have a relatively short half-life compared with CC. In this study, we present our preliminary experience with the use of the AI letrozole for ovulation induction in anovulatory women with polycystic ovary syndrome (PCOS). Letrozole (2.5 mg from day 3 to day 7 after menses) was administered to 10 patients with PCOS who either failed to ovulate (n = 4) or ovulated with an endometrial thickness =< 5 mm (n = 6) in response to CC administration. Ovulation occurred in 7 of the 10 letrozole-treated cycles (70%), with clinical pregnancy in 2 patients and chemical pregnancy in 1. To our knowledge, this is the first report of the clinical use of an AI for ovulation induction. AIs may have the potential to be a first-line treatment for ovulation induction.
In women with infertility, the treatment of first choice for the induction of ovulation is an antiestrogen, most commonly, clomiphene citrate (CC).1,2 However, 20 to 25% of women are resistant to clomiphene citrate and do not ovulate. In addition, in our previously published experience, about 32% of patients who successfully achieved ovulation with clomiphene citrate had endometrial development below 6 mm in thickness on the day after human chorionic gonadotropin (hCG) administration,3 and, we believe, a markedly reduced chance for implantation and successful pregnancy. Some investigators have attempted to reverse the antiestrogenic effects of clomiphene citrate by adding the potent synthetic estrogen ethinyl estradiol during CC-stimulated cycles.4,5
Other clinical data reveal an apparent discrepancy between ovulation and conception rates during CC treatment and a slightly higher than expected incidence of miscarriage in conception cycles of patients without luteal phase defects.6 Dickey and Holtkamp found that conception rates and preclinical abortions were related to endometrial thickness prior to ovulation.7...