Elsevier

Contraception

Volume 81, Issue 5, May 2010, Pages 414-420
Contraception

Original research article
Contraceptive efficacy of emergency contraception with levonorgestrel given before or after ovulation

https://doi.org/10.1016/j.contraception.2009.12.015Get rights and content

Abstract

Background

We aimed to evaluate whether emergency contraception with levonorgestrel (LNG-EC) administered after ovulation is equally effective to LNG-EC administered before ovulation.

Study design

We studied a cohort of women attending a family planning clinic for EC. From interview, we recorded menstrual history, time of intercourse and of intake of LNG-EC. On the day of intake of LNG-EC and during 5 days' follow-up, blood samples were taken for examination of luteinizing hormone, estradiol and progesterone concentrations, and vaginal ultrasound examinations were done for size of the leading follicle and/or corpus luteum. Thereafter women were not contacted until next menses or pregnancy occurred.

Results

Of 388 women attending for LNG-EC, 122 women had intercourse on fertile cycle days according to ultrasound and endocrine findings. At the time of LNG-EC intake, 87 women were in Days −5 to −1 and 35 women were in Day 0 (day of ovulation) or beyond. With the use of the probability of clinical pregnancy reported by Wilcox et al. [N Engl J Med 333 (1995) 1517–1521], expected numbers of pregnancies among the 87 and 35 women were 13 and 7, respectively, while 0 and 6 pregnancies, respectively, occurred.

Conclusion

We conclude that LNG-EC prevents pregnancy only when taken before fertilization of the ovum has occurred.

Introduction

Research [1] on how levonorgestrel emergency contraceptive pills (LNG-ECPs) act to prevent pregnancy has studied its effects on the ovulatory process, on sperm physiology in the female genital tract and on endometrial receptivity to embryo implantation. It is established that preovulatory administration of LNG interferes with the ovulatory process [2], [3], [4], [5]. A previous study at our clinic assessed the interference with ovulation of LNG emergency contraception (LNG-EC) given in the follicular phase to women protected from pregnancy by tubal ligation or nonhormonal IUD. The results showed this interference depends on how advanced the follicular phase is when LNG-EC is given and, specifically, whether treatment takes place before or after the onset of the luteinizing hormone (LH) surge [6].

Other studies report that LNG could interfere in vivo with the migration of spermatozoa by altering cervical mucus and uterine environment [7], [8], [9]. This effect could be significant when coitus precedes ovulation for several hours or days but may have less impact when coitus occurs close to ovulation. Direct effects of LNG on spermatozoa in vitro are of dubious relevance since effects are only observed with high dose levels [10], [11]. Studies on the impact of LNG-EC on endometrial parameters involved in endometrial receptivity are not consistent, and current knowledge on cellular and molecular markers of endometrial receptivity in the human is insufficient to resolve this controversy [3], [12], [13], [14]. A recent study of mifepristone and LNG on embryo attachment to endometrial cells in an in vitro endometrial cell culture reported that LNG did not interfere with embryo attachment to endometrial cells, while mifepristone did so [15].

Ethical and logistical constraints prevent performing experiments in humans that directly address what happens to the embryo when women receive LNG-EC. Studies in rats and capuchin monkeys show that LNG given after fertilization does not prevent pregnancy and that, when given before ovulation, it interferes with the ovulatory process as it does in women [16], [17]. Based on these observations, we advanced the hypothesis that LNG-EC contraceptive failure results from taking LNG-EC when it can no longer prevent fertilization. In line with this hypothesis, a study carried out in Australia assessed the contraceptive effectiveness of LNG-EC given before or after ovulation. The day of ovulation and day of intercourse were determined by reproductive hormone levels measured in a blood sample drawn immediately before taking LNG-EC. Results of the study indicate that when LNG-EC was given before ovulation, it was effective in preventing pregnancy, while it had no contraceptive effect when given after ovulation, although the findings were based on small numbers [18]. The current study aims to accrue a sufficient number of women in whom unprotected intercourse occurred during the fertile days of the cycle so as to determine with better statistical power whether or not LNG-EC can prevent pregnancy when it is administered before and after ovulation. Here we report the preliminary results of this ongoing study.

Section snippets

Emergency contraceptive pills

The product used was TACE® produced by Laboratorio Recalcine SA, Santiago, Chile, consisting of two tablets containing 0.75 mg of LNG each.

Subjects

Volunteers were admitted from among women requesting ECP at the family planning clinic of ICMER.

Inclusion criteria were women 18 to 38 years old, being within 120 h of an unprotected sexual intercourse, having regular menstrual cycles of 21 to 35 days and being between Day 5 and Day 25 of the current cycle as calculated from Day 1 of the last menstrual

Characteristics of women

Three hundred eighty-eight women were enrolled of whom 48%, 35% and 17% were 18–21, 22–27 and 28–38 years old, respectively. As to the unprotected intercourse, 51% of the women reported no contraceptive use, and 43% and 6% said they had problems with condom use and coitus interruptus, respectively. The time elapsed from unprotected intercourse to treatment was less than 24 h in 65% of women, 24–47 h in 24% and between 48 and 72 h in 9% of cases; only four women came later than 72 h. Spermatozoa

Discussion

A previous study in our clinic showed that LNG-EC interferes with the ovulatory process [5]. Since those observations were made in previously sterilized women, the findings were suggestive but not conclusive in terms of preventing pregnancy. For some people a potential postfertilization effect of LNG-EC poses an ethical problem because it would compromise embryo viability and it could be claimed that LNG-EC acts as an abortifacient in these situations. The present study evaluated whether or not

Acknowledgments

We thank Olav Meirik for his comments.

References (31)

Cited by (0)

This study has been supported by grants 1060252 and FB0807 from Fondo Nacional de Desarrollo Científico y Tecnológico (FONDECYT) and by grant A 65559 from the World Health Organization, Department of Reproductive Health and Research (WHO/RHR).

1

Current affiliation. Laboratorio de Inmunologia de la Reproduccion, Universidad de Santiago de Chile y Centro para el Desarrollo de Nanociencia y Nanotecnologia (CEDENNA).

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