Ulipristal acetate may contribute to contraceptive action by its effects on tubal function

Abstract

OBJECTIVES: Ulipristal acetate (UPA), a selective progesterone receptor modulator, has been shown to be an effective drug for emergency contraception. We hypothesised that it would have modulatory effects on ciliary beat frequency and muscular contraction frequency of human fallopian tube, which might contribute to its contraceptive action. This study aimed at confirming these effects. DESIGN AND METHODS: This was an in-vitro study using human fallopian tubes obtained from six women who underwent hysterectomy for benign gynaecological conditions not involving the tubes. The tubal epithelium and smooth muscle layer of the collected tubes were stripped into small pieces. These tissue strips were cultured overnight in standardised medium containing oestradiol 100 pmol/l and progesterone 10 nmol/l resembling the physiological early luteal phase. The different tissue strips were then treated with UPA (HRA Pharma, France) at graded concentrations of 0, 20, 200 and 2000 ng/ml. These experimental concentrations were chosen based on the peak serum concentration after a pharmacological dose of UPA in human, which is around 200 ng/ml. The ciliary beat frequency of the treated tubal epithelium was measured using the photometric method. Strips of tubal smooth muscle were connected to a force transducer, and the mean contraction frequency was measured after treatment at different UPA concentrations. The different treatment groups were compared by Kruskal-Wallis test. RESULTS: We found an overall dose-dependent suppressive effect of UPA on ciliary beat frequency at all concentrations studied ( p < 0.001 for each treatment group comparing to control (0 ng/ml) and comparing among each other). Muscular contraction frequency after treatment with UPA at 20 ng/ml did not differ from control (0 ng/ml) ( p > 0.05), but was significantly reduced after treatment with UPA at 200 and 2000 ng/ml respectively ( p < 0.05). CONCLUSIONS: UPA treatment inhibits ciliary beat frequency and muscular contraction frequency of human fallopian tube at the pharmacological dose. These may contribute to post-ovulatory mechanisms for its contraceptive action.