Safety of repeated use of emergency contraceptive pills in the same menstrual cycle: a systematic review.

backgroundEmergency contraception refers to contraceptive methods used following unprotected sexual intercourse.

objectiveTo review the literature on safety of repeated use of emergency contraceptive pills (ECPs) in the same menstrual cycle.

methodsWe searched multiple databases from inception through February 2024 for articles on repeated ECP use. We assessed the risk of bias for each study and certainty of evidence for all outcomes.

resultsFrom 4565 articles identified, six met the inclusion criteria. Four studies of repeated levonorgestrel (LNG)-ECP use provided very low certainty evidence. Among women who became pregnant after at least one use of LNG-ECP in the conception cycle, women with ectopic pregnancy had increased odds of repeated LNG-ECP use in the conception cycle compared with women with intrauterine pregnancy (adjusted OR (aOR) 2.5, 95% CI 1.0 to 6.2). One non-comparative study reported few serious adverse events with repeated pericoital use of LNG-ECP, and two cohort studies of LNG-ECP failure found no differences in pregnancy, fetal/neonatal, infant or child outcomes comparing higher (2.25-9 mg LNG) and lower (0.75-1.5 mg LNG) doses in the conception cycle. Two studies of repeated ulipristal acetate (UPA) use provided very low certainty evidence. One non-comparative study observed no serious adverse events, no abnormal laboratory results and normal endometrial biopsies with UPA (30 mg, 4-6 doses/month). One randomised controlled trial in a clinical setting observed no serious adverse events with UPA (10 mg, 20 mg or 50 mg for 10 days) compared with placebo.

conclusionEvidence on the safety of repeated ECP use is limited and of very low certainty, but overall does not suggest safety concerns.