Original research article Contraceptive efficacy of emergency contraception with levonorgestrel given before or after ovulation Gabriela Noé a, ⁎ , Horacio B. Croxatto b , Ana María Salvatierra a , Verónica Reyes a , Claudio Villarroel a , Carla Muñoz a , Gabriela Morales a , Anita Retamales a a Instituto Chileno de Medicina Reproductiva, Santiago, Chile b Laboratorio de Inmunología de la Reproducción, y Centro para el Desarrollo de Nanociencia y Nanotecnología, Universidad de Santiago de Chile, Santiago, Chile Received 22 October 2010; revised 7 March 2011; accepted 9 March 2011 Abstract Background: The contraceptive efficacy of emergency contraceptive pills containing levonorgestrel (LNG-EC) has been estimated in most previous studies by judging the day of ovulation from presumptive menstrual cycle data, thus providing poorly reliable estimates. Methods: In the present study, the efficacy of LNG-EC was determined in 393 cycles by dating ovulation on the basis of reliable hormonal and ovarian parameters validated by a database constructed in a separate study. In addition, the efficacy was determined separately for cycles in which LNG-EC was given before or after ovulation. Results: For the 148 women who had sexual intercourse during the fertile days, the overall accumulated probability of pregnancy was 24.7, while altogether 8 pregnancies were observed. Thus, the overall contraceptive efficacy of LNG-EC was 68%. Among the 103 women who took LNG-EC before ovulation (days -5 to -1), 16 pregnancies were expected and no pregnancy occurred (pb.0001). Among the 45 women who took LNG-EC on the day of ovulation (day 0) or thereafter, 8 pregnancies occurred and 8.7 were expected (p=1.00). These findings are incompatible with the inhibition of implantation by LNG-EC in women. The same cases were also analyzed using the presumptive menstrual cycle data, and important discrepancies were detected between the two methods. Conclusion: The efficacy of LNG-EC has been overestimated in studies using presumptive menstrual cycle data. Our results confirm previous similar studies and demonstrate that LNG-EC does not prevent embryo implantation and therefore cannot be labeled as abortifacient. © 2011 Elsevier Inc. All rights reserved. Keywords: Emergency contraception; Levonorgestrel; Contraceptive efficacy 1. Introduction We recently published interim results from our study on contraceptive efficacy of levonorgestrel emergency contra- ception (LNG-EC) [1]. That report was based on results from 388 women treated with LNG-EC; here we report the completion of the study with a total of 450 enrolled women as well as data on hormonal and ultrasonic measurements from more than 100 normal cycles that were used in the current study to more accurately determine date of ovulation. We postulate that contraceptive failures of LNG-EC take place when it no longer can prevent fertilization. This hypothesis is sustained by human and animals studies in which pregnancies were not prevented when treatment was given after ovulation [2–4]. Other potential mechanisms of action of LNG-EC were widely analyzed previously [1]. Recent publications add new findings supporting our hypothesis: a study investigating possible actions of LNG on the endometrium demonstrates no effect on endometrial markers of human implantation after oral or vaginal administration of LNG [5], confirming previous findings of the same group [6,7]. Cleland et al. [8] did an extended review of the literature on the rate of ectopic pregnancy after using LNG-EC. They found that in pregnancies in which LNG-EC had failed, there was no increase in the rate of ectopic pregnancy, suggesting that alterations of oviductal transport, which could prevent proper timing for implantation, is an unlikely mechanism for LNG-EC pre- vention of pregnancy. Contraception 84 (2011) 486 – 492 ⁎ Corresponding author. Tel.: +56 2 6649393; fax: +56 2 6336204. E-mail address: gnoe@icmer.org (G. Noé). 0010-7824/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.contraception.2011.03.006