Ibuprofen delays ovulation by several hours – a prospective controlled study in spontaneous cycles with hCG triggered ovulation

Abstract

Research question Does ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), delay ovulation? Design Two-stage proof of concept controlled study, assessing the percentage of non-ovulated follicles 42h after hCG injection in patients taking ibuprofen. The intervention group consisted of women undergoing natural cycle IVF treatment cycles taking ibuprofen 3×400g/day. The control group consisted of women undergoing timed sexual intercourse or intrauterine insemination. The proportion of patients with non-ovulated follicles in the ibuprofen group was first compared against a reference of 50% using a one-sample binomial test, and second against the proportion observed in the control group using an adjusted logistic regression. Results A total of 26 women were recruited in the ibuprofen intervention group. 25 patients were recruited in the control group. The proportion of patients with delayed ovulation observed (22/26, 85%; CI: 65% - 96%) was significantly higher than the reference of 50% (Pvalue = <0.001). In the control group the proportion of patients with delayed ovulation observed was 20% (5/25, 95% CI: 6.8% - 41%). Comparing this proportion to the one observed in the ibuprofen group a significant increase of probability of a delayed ovulation was found in the ibuprofen intervention group (aOR=22.72 [5.77,115], Pval ≤0.001). Of the 22 women with delayed ovulation, oocytes were retrieved in 20 women (91%) and all oocytes were mature (Metaphase II). Conclusions Women trying to conceive should take care to avoid non-selective NSAIDs around time of ovulation. Ibuprofen or other NSAID can be used to delay ovulation for several hours in ART and other infertility treatments if required.