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Systematic Review

Does levonorgestrel emergency contraceptive have a post-fertilization effect? A review of its mechanism of action

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References

  • The American Congress of Obstetricians and Gynecologist. (ACOG). 2014. Retrieved August 1, 2014 (http://www.acog.org/Resources-And-Publications/Committee-Opinions/Committee-on-Health-Care-for-Underserved-Women/Access-to-Emergency-Contraception).
  • Ahlgren, M. 1975. Sperm transport to and survival in the human fallopian tube. Gynecologic Investigation 6: 206–9. doi: 10.1159/000301517
  • Bahamondes, L., J. Nascimento, M. Munuce, F. Fazano, and A. Faundes. 2003. The in vitro effect of levonorgestrel on the acrosome reaction of human spermatozoa from fertile men. Contraception 68: 55–9. doi: 10.1016/S0010-7824(03)00105-7
  • Borman, S.M., C.L. Chaffin, K.M. Schwinof, R.L. Stouffer, and M.B. Zelinski-Wooten. 2004. Progesterone promotes oocyte maturation, but not ovulation, in nonhuman primate follicles without a gonadotropin surge. Biology of Reproduction 71: 366–73. doi: 10.1095/biolreprod.103.023390
  • Brache, V., L. Cochon, M. Deniaud, and H.B. Croxatto. 2013. Ulipristal acetate prevents ovulation more effectively than levonorgestrel: Analysis of pooled data from three randomized trials of emergency contraception regimens. Contraception 88: 611–8. doi: 10.1016/j.contraception.2013.05.010
  • Brito, K.S., L. Bahamondes, J.A. Nascimento, L. de Santis, and J.M. Munuce. 2005. The in vitro effect of emergency contraception doses of levonorgestrel on the acrosome reaction of human spermatozoa. Contraception 72: 225–32. doi: 10.1016/j.contraception.2005.04.005
  • Cleland, K., E. Raymond, J. Trussell, L. Cheng, and H. Zhu. 2010. Ectopic pregnancy and emergency contraceptive pills. A systematic review. Obstetrics & Gynecology 115: 1263–68. doi: 10.1097/AOG.0b013e3181dd22ef
  • Croxatto, H.B., V. Brache, M. Pavez, L. Cochon, M.L. Forcelledo, and F. Alvarez. 2004. Pituitary-ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 0.75-mg dose given on the days preceding ovulation. Contraception 70: 442–50. doi: 10.1016/j.contraception.2004.05.007
  • Croxatto, H.B., L. Devoto, M. Durand, E. Ezcurra, F. Larrea, C. Nagle, M.E. Ortiz, D. Vantman, M. Vega, and H. von Hertzen. 2001. Mechanism of action of hormonal preparations used for emergency contraception: A review of the literature. Contraception 63: 111–21. doi: 10.1016/S0010-7824(01)00184-6
  • Croxatto, H.B., B. Fuentealba, V. Brache, A.M. Salvatierra, M. Alvarez, and R. Massai. 2002. Effects of the Yuzpe regimen given during the follicular phase on ovarian function. Contraception 65: 121–8. doi: 10.1016/S0010-7824(01)00299-2
  • Crucker, C. and G. Lipford. 1995. The human sperm acrosome reaction: physiology and regulatory mechanisms. An update. Human Reproduction Update 1: 51–62. doi: 10.1093/humupd/1.1.51
  • Cheng, L., A.M. Gülmezoglu, G. Piaggio, E. Ezcurra, and P.F. Van Look. 2008. Interventions for emergency contraception (review). Cochrane Database of Systematic Reviews 2: 1–20.
  • Chiu, P.C., M.K. Chung, R. Koistinen, M. Seppala, and Pch Ho. 2007. Cumulus oophorus-associated glycodelin-C displaces sperm-bound glycodelin-A and -F and stimulates spermatozoa-zona pellucida binding. Journal of Biological Chemistry 282: 5378–88. doi: 10.1074/jbc.M607482200
  • Daramola, O. and J.S. Rhee. 2011. Rating evidence in medical literature. Virtual Mentor 13(1): 46–51, http://www.cebm.net/oxford-centre-evidence-based-medicine-levels-evidence-march-2009/. doi: 10.1001/virtualmentor.2011.13.1.pfor2-1101
  • do Nascimento, J.A., M. Seppala, A. Perdigao, X. Espejo-Arce, M.J. Munuce, and L. Hautala. 2007. In vivo assessment of the human sperm acrosome reaction and the expression of glycodelin-A in human endometrium after levonorgestrel-emergency contraceptive pill administration. Human Reproduction 22: 2190–5. doi: 10.1093/humrep/dem119
  • Dunson, D., D. Baird, A. Wilcox, and C. Weinberg. 1999. Day specific probabilities of clinical pregnancy based on two studies with imperfect measures of ovulation. Human Reproduction 14: 1835–43. doi: 10.1093/humrep/14.7.1835
  • Durand, M., M. Cravioto, E.G. Raymond, O. Duran-Sanchez, M. Cruz-Hinojosa, A. Castell-Rodriguez, R. Sciavon, and F. Larrea. 2001. On the mechanisms of action of short-term levonorgestrel administration in emergency contraception. Contraception 64: 227–34. doi: 10.1016/S0010-7824(01)00250-5
  • Durand, M., R. Koistinen, M. Chirinos, J.L. Rodriguez, E. Zambrano, M. Seppala, and F. Larrea. 2010. Hormonal evaluation and midcycle detection of intrauterine glycodelin in women treated with levonorgestrel as in emergency contraception. Contraception 82: 526–33. doi: 10.1016/j.contraception.2010.05.015
  • Durand, M., M. Seppala, M. Cravioto, H. Koistinen, R. Koistinen, J. Gonzalez-Macedo, and F. Larrea. 2005. Late follicular phase administration of levonorgestrel as an emergency contraceptive changes the secretory pattern of glycodelin in serum and endometrium during the luteal phase of the menstrual cycle. Contraception 71: 451–7. doi: 10.1016/j.contraception.2005.01.003
  • FIGO. 2011. Mechanism of action: How do levonorgestrel-only emergency contraceptive pills (LNG ECPs) prevent pregnancy? Retrieved October 2013, http://www.figo.org/sites/default/files/uploads/MOA_FINAL_2011_ENG.pdf.
  • Food and Drug Administration (FDA). 2009. Plan B one-step (levonorgestrel) tablet, 1.5 mg, for oral use. Retrieved June 21, 2014, http://www.accessdata.fda.gov/drugsatfda_docs/label/2009/021998lbl.pdf.
  • Gainer, E. Kenfack, B. Mboudou, E. SamaDoh A., and J. Bouyer. 2006. Menstrual bleeding patterns following levonorgestrel emergency contraception. Contraception 74: 118–24. doi: 10.1016/j.contraception.2006.02.009
  • Gainer, E., Méry C., and Ulmann A. 2001. Levonorgestrel-only emergency contraception: Real-world tolerance and efficacy. Contraception 64: 17–21. doi: 10.1016/S0010-7824(01)00220-7
  • Gemzell-Danielsson, K. 2010. Mechanism of action of emergency contraception. Contraception 82: 401–9. doi: 10.1016/j.contraception.2010.05.004
  • Gemzell-Danielsson, K., C. Berger, and P.G.L. Lalitkumar. 2013. Emergency contraception – mechanisms of action. Contraception 87: 300–8. doi: 10.1016/j.contraception.2012.08.021
  • Hapangama, D., A.F. Glasier, and D.T. Baird. 2001. The effects of peri-ovulatory administration of levonorgestrel on the menstrual cycle. Contraception 63: 123–31. doi: 10.1016/S0010-7824(01)00186-X
  • Hermanny, A., M. Bahamondes, F. Fazano, N.M. Marchi, M. Ortiz, and M.H. Genghini. 2012. In vitro assessment of some sperm function following exposure to levonorgestrel in human fallopian tubes. Reproductive Biology and Endocrinology 10: 8. doi: 10.1186/1477-7827-10-8
  • International Federation of Gynecology & Obstetrics (FIGO) and International Consortium for Emergency Contraception (ICEC). 2012. How do levonorgestrel-only emergency contraceptive pills (LNG ECPs) work to prevent pregnancy? http://www.cecinfo.org/custom-content/uploads/2014/01/ICEC_MoA_Statement_3-28-12.pdf.
  • Kahlenborn, R., R. Peck, and W. Severs. 2015. Mechanism of action of levonorgestrel emergency contraception. Linacre Quarterly 82(1): 18–33. doi: 10.1179/2050854914Y.0000000026
  • Kahlenborn, C., J.B. Stanford, and W.L. Larimore. 2002. Postfertilization effect of hormonal emergency contraception. Annals of Pharmacotherapy 36(3): 465–70. doi: 10.1345/aph.1A344
  • Kesseru, E., F. Garmendia, N. Westphal, and J. Parada. 1974. The hormonal and peripheral effects of dl-norgestrel in postcoital contraception. Contraception 10: 411–24. doi: 10.1016/0010-7824(74)90041-9
  • Kunz, G., D. Beil, H. Deininger, L. Wildt, and G. Leyendecker. 1996. The dynamics of rapid sperm transport through the female genital tract: Evidence from vaginal sonography of uterine peristalsis and hystero-salpingo-scintigraphy. Human Reproduction 11: 627–32. doi: 10.1093/HUMREP/11.3.627
  • Lalitkumar, P.G., S. Lalitkumar, C.X. Meng, A. Stavreus-Evers, F. Hambiliki, U. Bentin-Ley, and K. Gemzell-Danielsson. 2007. Mifepristone, but not levonorgestrel, inhibits human blastocyst attachment to an in vitro endometrial three-dimensional cell culture model. Human Reproduction 22: 3031–7. doi: 10.1093/humrep/dem297
  • Landgren, B.M., E. Johannisson, A.R. Aedo, A. Kumar, and Y. Shi. 1989. The effect of levonorgestrel administered in large doses at different stages of the cycle on ovarian function and endometrial morphology. Contraception 39: 275–89. doi: 10.1016/0010-7824(89)90060-7
  • Lewis, R.A., D. Taylor, M.F. Natavio, A. Melamed, J. Felix, and D.J. Mishell. 2010. Effects of the levonorgestrel-releasing intrauterine system on cervical mucus quality and sperm penetrability. Contraception 82: 491–3. doi: 10.1016/j.contraception.2010.06.006
  • Lo, S. and P.C. Ho. 2012. The profile of women who seek emergency contraception from the family planning service. Hong Kong Medical Journal 4: 299–303.
  • Mahmood, T., E. Saridogan, S. Smutna, A.M. Habib, and O. Djahanbakhch. 1998. The effect of ovarian steroids on epithelial ciliary beat frecuence in the human Fallopian tube. Human Reproduction 13: 2991–4. doi: 10.1093/humrep/13.11.2991
  • Marions, L., S.Z. Cekan, M. Bygdeman, and K. Gemzell-Danielsson. 2004. Effect of emergency contraception with levonorgestrelor mifepristone on ovarian function. Contraception 69: 373–9. doi: 10.1016/j.contraception.2003.11.018
  • Marions, L., K. Hultenby, I. Lindell, X. Sun, B. Stabi, and K. Gemzell-Danielsson. 2002. Emergency contraception with mifepristone and levonorgestrel: Mechanism of action. Obstetrics & Gynecology 100: 65–71.
  • Massai, M.R., M.L. Forcelledo, V. Brache, A.S. Tejada, A.M. Salvatierra, M.V. Reyes, F. Alvarez, A. Faundes and H.B. Croxatto. 2007. Does meloxicam increase the incidence of anovulation induced by single administration of levonorgestrel in emergency contraception? A pilot study. Human Reproduction 22(2): 434–9. doi: 10.1093/humrep/del369
  • Meng, C.X., K.L. Andersson, U. Bentin-Ley, K. Gemzell-Danielsson, and P.G. Lalitkumar. 2009. Effect of levonorgestrel and mifepristone on endometrial receptivity markers in a three-dimensional human endometrial cell culture model. Fertility and Sterility 91: 256–64. doi: 10.1016/j.fertnstert.2007.11.007
  • Meng, C.X., L. Marions, B. Byström, and K. Gemzell-Danielsson. 2010. Effects of oral and vaginal administration of levonorgestrel emergency contraception on markers of endometrial receptivity. Human Reproduction 25: 874–83. doi: 10.1093/humrep/deq007
  • Mikolajczyk, R. and J. Stanford. 2005. A new method for estimating the effectiveness of emergency contraception that accounts for variation in timing of ovulation and previous cycle length. Fertility and Sterility 83: 1764–80. doi: 10.1016/j.fertnstert.2005.01.097
  • Mikolajczyk, R.T., and J.B. Stanford. 2007. Levonorgestrel emergency contraception: A joint analysis of effectiveness and mechanism of action. Fertility and Sterility 88: 565–71. doi: 10.1016/j.fertnstert.2006.11.178
  • Moghissi, K.S., F.N. Syner, and L.C. McBride. 1973. Contraceptive mechanism of microdose norethindrone. Obstetrics & Gynecology 41: 585–90.
  • Morton, H. 1984. Early pregnancy factor (EPF): A link between fertilization and immunomodulation. Australian Journal of Biological Sciences 37: 393–407.
  • Mozzanega, B., and E. Cosmi. 2011. How do levonorgestrel-only emergency contraceptive pills prevent pregnancy? Some considerations. Gynecological Endocrinology 27: 439–42. doi: 10.3109/09513590.2010.501885
  • Mozzanega, B., S. Gizzo, S. Di Gangi, E. Cosmi, and G. Nardelli. 2014. Ulipristal acetate: critical review about endometrial and ovulatory effects in emergency contraception. Reproductive Sciences 21(6): 678–85. doi: 10.1177/1933719113519178
  • Munuce, M.J., J.A. Nascimento, G. Rosano, A. Faudes, K.S. Brito, and L. Bahamondes. 2005. In vitro effect of levonorgestrel on sperm fertilizing capacity and mouse embryo development. Contraception 72: 71–6. doi: 10.1016/j.contraception.2004.12.003
  • Noé, G., H.B. Croxatto, A.M. Salvatierra, V. Reyes, C. Villarroel, and C. Munoz. 2011. Contraceptive efficacy of emergency contraception with levonorgestrel given before or after ovulation. Contraception 84: 486–92. doi: 10.1016/j.contraception.2011.03.006
  • Norwitz, E., D. Schust, and S. Fisher. 2001. Implantation and the survival of early pregnancy. New England Journal of Medicine 345: 1400–8. doi: 10.1056/NEJMra000763
  • Novikova, N., E. Weisberg, F.Z. Stanczykc, H.B. Croxatto, and I.S. Fraser. 2007. Effectiveness of levonorgestrel emergency contraception given before or after ovulation: A pilot study. Contraception 75(2): 112–8. doi: 10.1016/j.contraception.2006.08.015
  • Odeblad, E. 1978. Cervical factors. Contributions to Gynecology and Obstetrics 4: 132–42.
  • Okewole, I.A., A.O. Arowojolu, O.L. Odusoga, O.A. Oloyede, O.A. Adeleye, J. Salu, and O.A. Dada. 2007. Effect of A single administration of levonorgestrel on the menstrual cycle. Contraception 75: 372–8. doi: 10.1016/j.contraception.2007.01.019
  • Palomino, W.A., P. Kohen, and L. Devoto. 2010. A single midcycle dose of levonorgestrel similar to emergency contraceptive does not alter the expression of the l-selectin ligand or molecular markers of endometrial receptivity. Fertility and Sterility 94: 1589–94. doi: 10.1016/j.fertnstert.2009.09.013
  • Peck, R. and J.R. Velez. 2013. The postovulatory mechanism of action of plan B. The National Catholic Bioethics Quarterly 13(4): 677–716. doi: 10.5840/ncbq201313410
  • Piaggio, G., N. Kapp, and H. von Hertzen. 2011. Effect on pregnancy rates of the delay in the administration of levonorgestrel for emergency contraception: A combined analysis of four WHO trials. Contraception 84: 35–43. doi: 10.1016/j.contraception.2010.11.010
  • Raymond, E.G., A. Goldberg, J. Trussell, M. Hays, E. Roach, and D. Taylor. 2006. Bleeding patterns after use of levonorgestrel emergency contraceptive pills. Contraception 73: 376–81. doi: 10.1016/j.contraception.2005.10.006
  • Settlage, D., N. Motoshima, and D. Tredway. 1973. Sperm transport from the external cervical os to the Fallopian tubes in women: A time and quantitation study. Fertility and Sterility 24: 655–61.
  • Severi, F.M., C. Bocchi, P. Florio, L. Cobellis, E. Ignacchiti, and F. Petraglia. 2003. Transvaginal ultrasonography in women receiving emergency contraception. Fertility and Sterility 79: 1074–80. doi: 10.1016/S0015-0282(02)04962-2
  • Siqueira, L.C., M.H. Barreta, B. Gasperin, R. Bohrer, J. Tonellotto Santos, and J. Buratini. 2012. Angiotensin II, progesterone, and prostaglandins are sequential steps in the pathway to bovine oocyte nuclear maturation. Theriogenol 77: 1779–87. doi: 10.1016/j.theriogenology.2011.12.022
  • Soules, M.R., D.K. Clifton, N.L. Cohen, W.J. Bremner, and R.A. Steiner. 1989. Luteal phase deficiency: Abnormal gonadotropin and progesterone secretion patterns. Journal of Clinical Endocrinology and Metabolism 69(4): 813–20. doi: 10.1210/jcem-69-4-813
  • Spona, J., K. Matt, and W.H.F. Schneider. 1975. Study on the action of d-norgestrel as a post-coital contraceptive agent. Contraception 11: 31–43. doi: 10.1016/0010-7824(75)90048-7
  • Suarez, S.S. and A.A. Pacey. 2006. Sperm transport in the female reproductive tract. Human Reproduction Update 12: 23–37. doi: 10.1093/humupd/dmi047
  • Tirelli, A., A. Cagnacci, and A. Volpe. 2008. Levonorgestrel administration in emergency contraception: Bleeding pattern and pituitary-ovarian function. Contraception 77: 328–32. doi: 10.1016/j.contraception.2008.01.013
  • Trussell, J. and B. Jordan. 2006. Mechanism of action of emergency contraceptive pills. Contraception 74: 87–9. doi: 10.1016/j.contraception.2006.03.028
  • Ugocsai, G., M. Ròzsa, and P. Ugocsai. 2002. Scanning electron microscopic (SEM) changes of the endometrium in women taking high doses of levonorgestrel as emergency postcoital. Contraception 66: 433–9. doi: 10.1016/S0010-7824(02)00431-6
  • Vargas, M.F., A.A. Tapia-Pizarro, S.P. Henríquez, M. Quezada, A.M. Salvatierra, and G. Noe. 2012. Effect of single post-ovulatory administration of levonorgestrel on gene expression profile during the receptive period of the human endometrium. Journal of Molecular Endocrinology 48: 25–36. doi: 10.1530/JME-11-0094
  • Verpoest, W.M., D.J. Cahill, C.R. Harlow, and M.G. Hull. 2000. Relationship between midcycle luteinizing hormone surge quality and oocyte fertilization. Fertility and Sterility 73: 75–81. doi: 10.1016/S0015-0282(99)00481-1
  • Von Hertzen, H., G. Piaggio, J. Ding, J. Chen, S. Song, G. Bártfai, E. Ng, K. Gemzell-Danielsson, A. Oyunbileg, S. Wu, W. Cheng, F. Ludicke, A. Pretnar-Darovec, R. Kirkman, S. Mittal, A. Khomassuridze, D. Apter and A. Peregoudov. 2002. Low dose mifepristona and two regimens of levonorgestrel for emergency contraception: A WHO multicentre randomized trial. Lancet 360: 1803–10. doi: 10.1016/S0140-6736(02)11767-3
  • Wånggren, K., A. Stavreus-Evers, C. Olsson, E. Andersson, and K. Gemzell-Danielsson. 2008. Regulation of muscular contractions in the human Fallopian tube through prostaglandins and progestagens. Human Reproduction 23: 2359–68. doi: 10.1093/humrep/den260
  • Wilcox, A.J., D.D. Baird, and C.R. Weinberg. 1999. Time of implantation of the conceptus and loss of pregnancy. New England Journal of Medicine 340: 1796–804. doi: 10.1056/NEJM199906103402304
  • Wilcox, A., C. Weinberg, and D. Baird. 1995. Timing of sexual intercourse in relation to ovulation: Effects on the probability of conception, survival of the pregnancy, and sex of the baby. New England Journal of Medicine 333: 1517–37. doi: 10.1056/NEJM199512073332301
  • Yeung, W.S.B., C.N. Chiu, C.H. Wang, Y.Q. Yao, and P. Ho. 2002. The effects of levonorgestrel on various sperm functions. Contraception 66: 453–9. doi: 10.1016/S0010-7824(02)00408-0

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