Combined oral contraceptive interference with the ability of ulipristal acetate to delay ovulation: A prospective cohort study

Objective: To determine if a combined oral contraceptive (COC) initiated shortly after ulipristal acetate (UPA) administration interferes with its mechanism of action. Study design: Healthy, reproductive-age women of normal BMI with proven ovulation (serum progesterone >3 ng/ml) were enrolled for three cycles (Cycle 1, UPA only; Cycle 2 washout; Cycle 3 UPA plus COC). During Cycles 1 and 3, subjects were monitored with transvaginal ultrasound and blood sampling for progesterone and LH every other day until a dominant follicle measuring >15 mm was visualized. In both treatment cycles, subjects received UPA (30mg) and were followed daily with similar monitoring for up to 7 days. In Cycle 3 only, subjects initiated a daily COC (0.15 mg levonorgestrel/30 μg ethinyl estradiol) 2 days after UPA. The study had 80% power to detect a 15% difference in the proportion of cycles with at least a 5-day delay in follicle rupture. We assessed follicle rupture as >50% decrease in mean size and adjudicated unclear outcomes with serum hormones. Results: A total of 36 women enrolled and 33 completed all study procedures [age 28.4 years (SD 3.9); BMI 23.4 (SD 2.4)]. Compared to Cycle 1, more subjects demonstrated evidence of follicle rupture in <5 days in Cycle 3 [1/33 (3%) vs. 9/33 (27%), p =.008]. We also included data from 2 subjects who experienced rupture prior to COC dosing in the analysis. Conclusion: UPA's effectiveness is significantly reduced by administering COCs 2 days later. Implications: This study demonstrates that UPA's efficacy as an emergency contraceptive is reduced with early exposure to COCs.