The effect of nonsteroidal anti-inflammatory drugs on ovulation: a prospective, randomized clinical trial

Abstract

Objective: To assess the effect of ibuprofen, a nonspecific inhibitor of prostaglandin synthesis, on ovulation. Design: Prospective, randomized, double-blind, placebo-controlled cross-over study. Setting: University Medical Center. Patient(s): Twelve normally cycling women between ages 20 and 40. Intervention(s): Subjects were randomized to either oral ibuprofen (800 mg) or placebo three times per day, beginning when the maximum diameter of the leading follicle reached 16 mm by ultrasound, and continuing for 10 days total. The second cycle was a washout period, and in the third cycle, the subjects were crossed over to the alternate regimen from the first cycle. The probability of delayed follicular collapse was determined using the binomial distribution, and changes in P levels were compared using the paired t test. Main Outcome Measure(s): Urinary LH surge, follicular collapse by serial transvaginal ultrasonography, and serum midluteal P levels. Result(s): Eleven of 12 subjects detected an LH surge with both ibuprofen and placebo. Five of 11 women demonstrated a ≥2-day increase in time interval from detection of the LH surge to follicular collapse, and 3 of those 5 had been randomized to ibuprofen. This represents a 27% (3 of 11; 95% confidence limits: 1%, 53%) rate of delay for follicular collapse for ibuprofen. There was no difference in average midluteal P levels for ibuprofen or placebo. Conclusion(s): If ibuprofen inhibits follicular collapse, this effect is seen in a small group of study subjects, and this information should be clinically reassuring to patients who take nonsteroidal anti-inflammatory drugs. Serum midluteal P levels were unaffected by administration of ibuprofen.