Original research article| Volume 70, ISSUE 6, P442-450, December 2004

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Pituitary���ovarian function following the standard levonorgestrel emergency contraceptive dose or a single 0.75-mg dose given on the days preceding ovulation


      We assessed to what extent the standard dose of levonorgestrel (LNG), used for emergency contraception, or a single dose (half dose), given in the follicular phase, affects the ovulatory process during the ensuing 5-day period. Fifty-eight women were divided into three groups according to timing of treatment. Each woman contributed with three treatment cycles separated by resting cycles. All received placebo in one cycle, and standard or single dose in two other cycles, in a randomized order. The diameter of the dominant follicle determined the time of treatment. Each woman had the same diameter assigned for all her treatments. Diameters were grouped into 33 categories: 12���14, 15���17 or 18���20 mm. Follicular rupture failed to occur during the 5-day period in 44%, 50% and 36% of cycles with the standard, half dose and placebo, respectively. Ovulatory dysfunction, characterized by follicular rupture associated with absent, blunted or mistimed gonadotropin surge, occurred in 35%, 36% and 5% of standard, single dose or placebo cycles, respectively. In conclusion, LNG can disrupt the ovulatory process in 93% of cycles treated when the diameter of the dominant follicle is between 12 and 17 mm. It is highly probable that this mode of action fully accounts for the contraceptive efficacy as well as the failure rate of this method. The present data suggest that half the dose may be as effective as the standard dose.


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        • Yuzpe A.A.
        • Thurlow H.J.
        • Ramzy I.
        • Leyshon J.I.
        Post coital contraception: a pilot study.
        J. Reprod. Med. 1974; 13: 53-58
        • Ho P.C.
        • Kwan M.S.
        A prospective randomized comparison of levonorgestrel with the Yuzpe regimen in post-coital contraception.
        Hum. Reprod. 1993; 8: 389-392
        • Task Force on Postovulatory Methods of Fertility Regulation
        Randomized controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception.
        Lancet. 1998; 352: 428-433
      1. Consensus statement of emergency contraception.
        Contraception. 1995; 52: 211-213
        • Wilcox A.J.
        • Weinberg C.R.
        • Baird D.D.
        Timing of sexual intercourse in relation to ovulation. Effects on the probability of conception, survival of the pregnancy and sex of the baby.
        N. Engl. J. Med. 1995; 333: 1517-1521
        • Croxatto H.B.
        • Fuentealba B.
        • Brache V.
        • et al.
        Effects of the Yuzpe regimen, given during the follicular phase, on ovarian function.
        Contraception. 2002; 65: 121-128
        • Croxatto H.B.
        • Devoto L
        • Durand M
        • et al.
        Mechanism of action of hormonal preparations used for emergency contraception: a review of the literature.
        Contraception. 2001; 63: 111-121
        • Croxatto H.B.
        Response to letter from Rafael T Mikolajczyk and Joseph B Stanford.
        Contraception. 2003; 67: 335-337
        • Kerin J.F.
        • Kirby C.
        • Morris D.
        • et al.
        Incidence of the luteinized unruptured follicle phenomenon in cycling women.
        Fertil. Steril. 1983; 40: 620-626
        • Von Hertzen H.
        • Piaggio G.
        • Ding J.
        • et al.
        Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial.
        Lancet. 2002; 360: 1803-1810
        • Arowojolu A.O.
        • Okewole I.A.
        • Adekunle A.O.
        Comparative evaluation of the effectiveness and safety of two regimens of levonorgestrel for emergency contraception in Nigerians.
        Contraception. 2002; 66: 269-273
        • Hapangama D.
        • Glasier A.F.
        • Baird D.T.
        The effects of peri-ovulatory administration of levonorgestrel on the menstrual cycle.
        Contraception. 2001; 63: 123-129
        • Durand M.
        • Cravioto M.C.
        • Raymond E.G.
        • et al.
        On the mechanism of action of short-term levonorgestrel administration in emergency contraception.
        Contraception. 2001; 64: 227-234
        • Marions L.
        • Hultenby K.
        • Lindell I.
        • et al.
        Emergency contraception with mifepristone and levonorgestrel: mechanism of action.
        Obstet. Gynecol. 2002; 100: 65-71
        • Eppig J.
        Regulation of mammmalian oocyte maturation.
        in: Adashi E.Y. Leung P.C.K. The ovary. Raven Press, New York1993: 185-208
        • Salustri A.
        • Hascall V.C.
        • Camaioni A.
        • Yanagishita M.
        Oocyte-granulosa cell interactions.
        in: Adashi E.Y. Leung P.C.K. The ovary. Raven Press, New York1993: 209-225
        • Espey L.L.
        • Lipner H.
        in: Knobil E. Neill J.D. The physiology of reproduction. Raven Press, New York1994: 725-780
        • Downs S.M.
        Ovulation 2: control of the resumption of meiotic maturation in mammalian oocytes.
        in: Grudzinskas J.G. Yovich J.L. Cambridge reviews in human reproduction. Gametes���the oocyte. Cambridge University Press, Cambridge, UK1995: 150-192
        • Tsafriri A.
        • Chun S.-Y.
        in: Adashi E.Y. Rock J.A. Rosenwaks Z. Reproductive endocrinology, surgery and technology. Lippincott-Raven Publishers, Philadelphia1996: 385-402
        • Cohlen B.J.
        • te Velde E.R.
        • Scheffer G.
        • et al.
        The pattern of the luteinizing hormone surge in spontaneous cycles is related to the probability of conception.
        Fertil. Steril. 1993; 60: 413-417
        • Coulam C.B.
        • Bustillo M.
        • Schulman J.D.
        Empty follicle syndrome.
        Fertil. Steril. 1986; 46: 1153-1155
        • Quintans C.J.
        • Donaldson M.J.
        • Blanco L.A.
        • Pasqualini RS.
        Empty follicle syndrome due to human errors: its occurrence in an in-vitro fertilization programme.
        Hum. Reprod. 1998; 13: 2703-2705
        • Zegers-Hochschild F.
        • Fernandez E.
        • Mackenna A.
        • Fabres C.
        • Altieri E.
        • Lopez T.
        The empty follicle syndrome: a pharmaceutical industry syndrome.
        Hum. Reprod. 1995; 10: 2262-2265
        • Ndukwe G.
        • Thornton S.
        • Fishel S.
        • Dowell K.
        • Aloum M.
        • Green S.
        ���Curing��� empty follicle syndrome.
        Hum. Reprod. 1997; 12: 21-23
        • Lok F.
        • Pritchard J.
        • Lashen H.
        Successful treatment of empty follicle syndrome by triggering endogenous LH surge using GnRH agonist in an antagonist down-regulated IVF cycle.
        Hum. Reprod. 2003; 18: 2079-2081
        • Meniru G.I.
        • Craft I.L.
        Evidence from a salvaged treatment cycle supports an aetiology for the empty follicle syndrome that is related to terminal follicular developmental events.
        Hum. Reprod. 1997; 12: 2385-2387
        • Abdalla H.I.
        • Ah-Moye M.
        • Brinsden P.
        • Howe D.L.
        • Okonofua F.
        • Craft I.
        The effect of the dose of human chorionic gonadotropin and the type of gonadotropin stimulation on oocyte recovery rates in an in vitro fertilization program.
        Fertil. Steril. 1987; 48: 958-963
        • Verpoest W.M.
        • Cahill D.J.
        • Harlow C.R.
        • Hull MG.
        Relationship between midcycle luteinizing hormone surge quality and oocyte fertilization.
        Fertil. Steril. 2000; 73: 75-77
        • M��ller A.L.
        • Llados C.M.
        • Croxatto HB.
        Post-coital treatment with levonorgestrel does not disrupt post-fertilization events in the rat.
        Contraception. 2003; 67: 415-419
        • Ortiz M.E.
        • Ortiz R.E.
        • Fuentes M.A.
        • Parraguez V.H.
        • Croxatto H.B.
        Post-coital administration of levonorgestrel does not interfere with post-fertilization events in the new-world monkey Cebus apella.
        Hum. Reprod. 2004; 19: 1352-1356
        • Shi Y.E.
        • Zheng S.H.
        • Zhu Y.H.
        • He C.H.
        • Yu P.P.
        • Fotherby K.
        Pharmacokinetic study of levonorgestrel used as a postcoital agent.
        Contraception. 1988; 37: 359-369
        • He C.H.
        • Shi Y.E.
        • Liao D.L.
        • et al.
        Comparative cross-over pharmacokinetic study on two types of postcoital contraceptive tablets containing levonorgestrel.
        Contraception. 1990; 41: 557-567
        • Tremblay D.
        • Gainer E.
        • Ulmann A.
        The pharmacokinetics of 750 microgram levonorgestrel following administration of one single dose or two doses at 12- or 24-h interval.
        Contraception. 2001; 64: 327-331
        • Kook K.
        • Gabelnick H.
        • Duncan C.
        Pharmacokinetics of levonorgestrel 0.75 tablets.
        Contraception. 2002; 66: 73-76
        • Johansson E.
        • Brache V.
        • Alvarez F.
        • et al.
        Pharmacokinetic study of different dosing regimens of levonorgestrel for emergency contraception in healthy women.
        Hum. Reprod. 2002; 17: 1472-1476