Prospective randomized double-blind trial of the correlation between time of administration and antiestrogenic effects of clomiphene citrate on reproductive end organs

Objective: To investigate whether the timing of administration of clomiphen e citrate (CC) affects hormone levels, follicular recruitment, reproductive end organs, and pregnancy rates. Design: Prospective, randomized, double-blind trial. Setting: Academic center. Patient(s): Twenty-three patients with unexplained infertility. Intervention(s): Twenty-three patients with unexplained infertility underwe nt 45 cycles of CC and IUI. For each cycle, patients were randomized either to receive 100 mg of CC on days 1-5 and placebo on days 5-9 (study group), or placebo on days 1-5 and CC on days 5-9 (control group). Main Outcome Measure(s): The difference in uterine artery PI, number of fol licles, endometrial thickness, and pregnancy rates. Result(s): Gonadotropins and E-2, levels, as well as uterine artery pulsati lity index, were significantly higher in the study group on day 5. In addit ion, in the study group, a longer time interval existed between finishing C C and IUI (8 versus 6 days; MD = 2 days; 95% CI = 1-3) and the pregnancy ra te was higher than in the control group (6 versus 0; OR = 15.1; 95% CI = 1. 1-72.4). Conclusion(s): Clomiphene citrate commenced on day 1 of the menstrual cycle , rather than day 5, results in more rapid follicular growth, a longer CC-f ree period before IUI, and higher pregnancy rates. Although methodologicall y sound, our results should be taken with some degree of caution because th ey are based on a relatively small number of patients. (Fertil Steril(R) 19 99;71:633-8. (C)1999 by American Society for Reproductive Medicine.).