The role of matching menstrual data with hormonal measurements in evaluating effectiveness of postcoital contraception

doi:10.1016/S0010-7824(99)00090-6

Contraception

Volume 60, Issue 4, October 1999, Pages 243-247

https://doi.org/10.1016/S0010-7824(99)00090-6 Get rights and content

Abstract

The effectiveness of postcoital contraception can only be estimated. The most commonly used method of calculation compares the expected pregnancy rate in the exposed population to the resultant pregnancies after treatment. Estimation of the fertile period and the day of ovulation are critical to calculate the expected pregnancies. The aim of this study was to improve the accuracy of calculations by evaluating the hormonal status on the day of contraceptive treatment. A total of 483 consecutive women requesting postcoital contraception was included in a prospective observational trial. A blood sample was obtained at the moment of consultation to measure serum luteinizing hormone, estradiol, and progesterone concentrations. An ethinylestradiol-levonorgestrel combination (100 μg/500 mg for two doses, 12 h apart) was then prescribed. The fertile period was estimated according to previous hormonal studies in the normal cycling population. Of 483 women, 64 (13.25%) women were excluded because they presented irregular menstrual cycles and 37 (7.6%) women were lost to follow-up. Two pregnancies occurred in the remaining 382 women. Following Wilcox’s and Trussell’s methods, 21.1 and 17.75 pregnancies should be expected, yielding an overall treatment effectiveness of 90.52% (95% confidence interval [CI] 62.58%–97.6%) and 88.73% (95% CI 55.93%–97.12%), respectively. Hormonal data were available in 356 women; 303 of whom presented with regular cycles. Hormonal information in this group restricted the number of exposed cases to 88 women. Of the women included in Trussell’s method of analysis, only 51 (51.5%; p <0.05) were at risk using hormonal data. Fifty-six percent (95% CI 34.9%–75.6%) of women with luteinizing hormone levels >20 IU/L were not between days −1 and +1 of the cycle. Hormonal studies suggest that methods based on pregnancy risk calculated by cycle day do not faithfully reflect the real exposure.

Introduction

Postcoital contraception is a simple and safe method known to significantly decrease the risk of pregnancy after unprotected intercourse or accidental condom rupture.1, 2 However, its real effectiveness remains uncertain.3 Because, for evident ethical reasons, the situation does not allow the implementation of prospective randomized clinical trials against placebo, effectiveness has to be estimated indirectly. In the majority of studies the calculation has been made by comparing the number of pregnancies observed in the treated population to the number of pregnancies to be expected from cases of unprotected intercourse. The results obtained with these methods vary widely from study to study, with effectiveness rates between 57% and 82%.4, 5 This is probably due to the different systems used to evaluate fertility status for the exposure day, despite being based on the day of the cycle with respect to the last menstrual period. As Glasier3 pointed out: “the timing of exposure to the risk of pregnancy in relation to the day of ovulation is, even in these well-documented studies, an educated guess.” The goal of the present study is to increase our knowledge on method efficacy by including objective information. We obtained blood samples at the moment of consultation to allow a more careful estimation of the fertility status. The discordance with the fertile period as estimated from menstrual cycle data casts doubt on previous studies that depend on such data for their calculations of treatment effectiveness.

Section snippets

Materials and methods

This study included all women consecutively attending the emergency room of our Department of Obstetrics and Gynecology and requesting postcoital contraception from July 1, 1997, until May 31, 1998. Exclusion criteria were 1) women asking for advice more than 72 h after unprotected intercourse, 2) those taking drugs able to modify the metabolism of synthetic steroidal hormones, 3) women in the puerperal or postabortion period or lactating, 4) those reporting unprotected intercourse more than

Results

During the study period, 483 women requested postcoital contraception. To calculate effectiveness according to cycle day, 64 (13.25%) women with irregular periods were excluded and 37 (7.6%) were lost to follow-up. From the final sample of 382 women, 119 (39.27%) were between days −5 and +1 and among these only 99 (25.91%) were between day −5 and 0 at the moment of unprotected intercourse. With this sample and according to Trussell et al.’s fertility calculation system, we should expect 17.75

Discussion

The effectiveness of postcoital contraception remains elusive to ascertain.9 At the present time, the most accepted way to evaluate this is by comparing the number of observed pregnancies with the expected according to the fertility status at the day of exposure.10 The puzzling aspect of this calculation is how to establish the expected pregnancy rate. This issue has been approached in two different ways. One simple manner proposed by Tietze11 attributes a constant value of between 1.25 to 1.50

Acknowledgements

We are grateful to Prof. F. Naftolin for his kind review and suggestions on the manuscript.

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Cited by (24)

Contraception d'urgence
2016, Journal of Obstetrics and Gynaecology Canada
Citation Excerpt :
une agression sexuelle, lorsque la victime n’utilise pas déjà un moyen de contraception fiable Puisqu’il est difficile de déterminer avec certitude la période fertile du cycle d’une femme48–50, une CU devrait être offerte à une femme qui entretient des préoccupations au sujet de son risque de connaître une grossesse, et ce, peu importe le jour du cycle au cours duquel l’exposition a eu lieu. Bien que la CU hormonale ne soit pas recommandée à titre de forme régulière de contraception, son utilisation répétée ne pose aucun risque connu pour la santé et une telle utilisation ne devrait pas constituer un motif pour refuser aux femmes l’accès au traitement51.
Analyser les connaissances actuelles au sujet de la contraception d’urgence (CU), y compris les options disponibles, leurs modes d’action, leur efficacité, leur innocuité et l’offre efficace d’une CU en milieu de pratique.
Le schéma posologique combiné estradiol-lévonorgestrel (schéma posologique Yuzpe) et le schéma posologique ne faisant appel qu’au lévonorgestrel, ainsi que l’utilisation postcoïtale de dispositifs intra-utérins de cuivre, font l’objet de notre analyse.
L’efficacité pour ce qui est de la réduction du risque de grossesse, l’innocuité et les effets indésirables des modes de CU et l’effet des moyens d’obtenir accès à la CU sur son utilisation appropriée et l’utilisation d’une contraception systématique.
Les études publiées en anglais entre janvier 1998 et mars 2010 ont été récupérées par l’intermédiaire de recherches menées dans Medline et la base de données Cochrane, au moyen de mots clés appropriés («emergency contraception», «post-coital contraception», «emergency contraceptive pills», «post-coital copper IUD»). Les directives cliniques et les déclarations de principe élaborées par des organisations de santé ou de planification familiale ont également été analysées.
Les études analysées ont été classées en fonction des critères décrits par le Groupe d’étude canadien sur les soins de santé préventifs et les recommandations visant la pratique ont été évaluées en fonction de cette classification (Tableau 1).
La présente directive clinique a pour objectif de contribuer à réduire le nombre de grossesses non souhaitées en accroissant la sensibilisation envers la CU et son utilisation appropriée.
Société des obstétriciens et gynécologues du Canada.
- 1.
  La contraception d’urgence hormonale peut être efficace lorsqu’elle est utilisée jusqu’à cinq jours à la suite de relations sexuelles non protégées. (II-2)
- 2.
  Plus la contraception d’urgence hormonale est utilisée tôt, plus elle est efficace. (II-2)
- 3.
  Un DIU de cuivre peut constituer un moyen de contraception d’urgence efficace, lorsqu’il est utilisé dans les sept jours suivant les relations sexuelles. (II-2)
- 4.
  Les schémas posologiques de contraception d’urgence faisant appel au lévonorgestrel sont plus efficaces et occasionnent moins d’effets indésirables que le schéma posologique Yuzpe. (I)
- 5.
  Le schéma posologique de contraception d’urgence faisant appel à une seule dose de lévonorgestrel (1,5 mg) et celui qui fait appel à deux doses de ce dernier (0,75 mg, à 12 heures d’intervalle) comptent une efficacité semblable et ne présentent aucune différence en matière d’effets indésirables. (I)
- 6.
  Parmi les schémas posologiques de contraception hormonale d’urgence disponibles au Canada, ceux qui ne font appel qu’au lévonorgestrel sont à privilégier. (I)
- 7.
  Les grossesses qui résultent de l’échec de la contraception d’urgence n’ont pas à faire l’objet d’une interruption. (I)
- 1.
  La contraception d’urgence devrait être utilisée dès que possible à la suite des relations sexuelles non protégées. (II-2A)
- 2.
  La contraception d’urgence devrait être offerte aux femmes lorsque les relations sexuelles non protégées ont eu lieu dans les limites de temps requises pour assurer l’efficacité de l’intervention (cinq jours pour les méthodes hormonales et jusqu’à sept jours pour le DIU de cuivre). (II-2B)
- 3.
  Une évaluation visant à déterminer la présence d’une grossesse devrait être menée en l’absence de règles dans les 21 jours suivant le traitement de contraception d’urgence. (III-A)
- 4.
  Au moment de l’examen de santé périodique ou dans le cadre de consultations portant sur des questions de santé génésique, toute femme en âge de procréer n’ayant pas été stérilisée pourrait bénéficier, de façon anticipée, de services de counseling au sujet de la contraception d’urgence et se voir remettre des renseignements détaillés sur la façon et le moment de l’utiliser. (III-C)
Population-based evaluation of the effectiveness of two regimens for emergency contraception
2016, International Journal of Gynecology and Obstetrics
To estimate and compare the effectiveness of the levonorgestrel and Yuzpe regimens for hormonal emergency contraception in routine clinical practice.
A retrospective population-based study included women who accessed emergency contraceptives for immediate use prescribed by community pharmacists in British Columbia, Canada, between December 2000 and December 2002. Linked administrative healthcare data were used to discern the timings of menses, unprotected intercourse, and any pregnancy-related health services. A panel of experts evaluated the compatibility of observed pregnancies with the timing of events. The two regimens were compared with statistical adjustments for potential confounding.
Among 7493 women in the cohort, 4470 (59.7%) received levonorgestrel and 3023 (40.3%) the Yuzpe regimen. There were 99 (2.2%) compatible pregnancies in the levonorgestrel group and 94 (3.1%) in the Yuzpe group (P = 0.017). The estimated odds ratio for levonorgestrel compared with the Yuzpe regimen after adjusting for potential confounders was 0.64 (95% confidence interval 0.47–0.87). Against an expected pregnancy rate of approximately 5%, the relative and absolute risk reductions were 56.0% and 2.8%, respectively, for levonorgestrel and 36.7% and 1.8% for the Yuzpe regimen.
The levonorgestrel regimen is more effective than the Yuzpe regimen in routine use. The data suggest that both regimens are less effective than has been observed in randomized trials.
Ulipristal acetate prevents ovulation more effectively than levonorgestrel: Analysis of pooled data from three randomized trials of emergency contraception regimens
2013, Contraception
Citation Excerpt :
In recent trials in western populations, LNG prevented fewer than 70% of expected pregnancies [5,6] while in two earlier World Health Organization-sponsored studies, the estimate was closer to 80–85% [7,8]. However, the precision of the methodology to obtain these estimates has been questioned [9–11]. The primary mechanism of action of oral EC is to interfere with the ovulatory process by preventing or delaying ovulation.
The days just prior to ovulation are the most crucial for emergency contraception (EC) efficacy. Ulipristal acetate (UPA) and levonorgestrel's (LNG) capacity to inhibit follicular rupture have never been compared directly at this time of the cycle.
Raw data from three pharmacodynamics studies with similar methodology were pooled to allow direct comparison of UPA, LNG and LNG+meloxicam's ability to prevent ovulation when administered orally in the advanced follicular phase, with a leading follicle of ≥18 mm.
Forty eight LNG-treated (1.5 mg) cycles, 31 LNG (1.5 mg) + meloxicam (15 mg), 34 UPA (30 mg) cycles and 50 placebo cycles were compared. Follicle rupture was delayed for at least 5 days in 14.6%, 38.7%, 58.8% and 4% of the LNG-, LNG+meloxicam-, UPA- and placebo-treated cycles, respectively. UPA was more effective than LNG and placebo in inhibiting follicular rupture (p=.0001), while LNG, when administered at this time of the cycle, was not different than placebo. The addition of meloxicam improved the efficacy of LNG in preventing follicular rupture (p=.0292 vs. LNG; p=.0001 vs. placebo; non-significant vs. UPA). UPA was effective in preventing rupture in the 5 days following treatment, even when administered at the time of the luteinizing hormone (LH) surge (UPA 79%, LNG 14% and placebo 10%). None of the treatments were effective when administered on the day of the LH peak. The median time from treatment to rupture was 6 days during the ulipristal cycles and 2 days in the placebo and LNG/LNG+meloxicam cycles (p=.0015).
Although no EC treatment is 100% effective in inhibiting follicular rupture when administered in the late follicular phase, UPA is the most effective treatment, delaying ovulation for at least 5 days in 59% of the cycles. LNG is not different from placebo in inhibiting follicular rupture at this advanced phase of the cycle. No treatment was effective in postponing rupture when administered on the day of LH peak.
Emergency contraception: No. 280 (Replaces No. 131, August 2003)
2013, International Journal of Gynecology and Obstetrics
To review current knowledge about emergency contraception (EC), including available options, their modes of action, efficacy, safety, and the effective provision of EC within a practice setting.
The combined estradiol-levonorgestrel (Yuzpe regimen) and the levonorgestrel-only regimen, as well as post-coital use of copper intrauterine devices, are reviewed.
Efficacy in terms of reduction in risk of pregnancy, safety, and side effects of methods for EC and the effect of the means of access to EC on its appropriate use and the use of consistent contraception.
Studies published in English between January 1998 and March 2010 were retrieved though searches of Medline and the Cochrane Database, using appropriate key words (emergency contraception, post-coital contraception, emergency contraceptive pills, post-coital copper IUD). Clinical guidelines and position papers developed by health or family planning organizations were also reviewed.
The studies reviewed were classified according to criteria described by the Canadian Task Force on Preventive Health Care, and the recommendations for practice were ranked according to this classification (Table 1).
These guidelines are intended to help reduce unintended pregnancies by increasing awareness and appropriate use of EC.
The Society of Obstetricians and Gynecologists of Canada.
Emergency Contraception
2012, Journal of Obstetrics and Gynaecology Canada
To review current knowledge about emergency contraception (EC), including available options, their modes of action, efficacy, safety, and the effective provision of EC within a practice setting.
The combined estradiol-levonorgestrel (Yuzpe regimen) and the levonorgestrel-only regimen, as well as post-coital use of copper intrauterine devices, are reviewed.
Efficacy in terms of reduction in risk of pregnancy, safety, and side effects of methods for EC and the effect of the means of access to EC on its appropriate use and the use of consistent contraception.
Studies published in English between January 1998 and March 2010 were retrieved though searches of Medline and the Cochrane Database, using appropriate key words (emergency contraception, post-coital contraception, emergency contraceptive pills, post-coital copper IUD). Clinical guidelines and position papers developed by health or family planning organizations were also reviewed.
The studies reviewed were classified according to criteria described by the Canadian Task Force on Preventive Health Care, and the recommendations for practice were ranked according to this classification (Table 1).
These guidelines are intended to help reduce unintended pregnancies by increasing awareness and appropriate use of EC.
The Society of Obstetricians and Gynaecologists of Canada.
- 1.
  Hormonal emergency contraception may be effective if used up to 5 days after unprotected intercourse. (II-2)
- 2.
  The earlier hormonal emergency contraception is used, the more effective it is. (II-2)
- 3.
  A copper IUD can be effective emergency contraception if used within 7 days after intercourse. (II-2)
- 4.
  Levonorgestrel emergency contraception regimens are more effective and cause fewer side effects than the Yuzpe regimen. (I)
- 5.
  Levonorgestrel emergency contraception single dose (1.5 mg) and the 2-dose levonorgestrel regimen (0.75 mg 12 hours apart) have similar efficacy with no difference in side effects. (I)
- 6.
  Of the hormonal emergency contraception regimens available in Canada, levonorgestrel-only is the drug of choice. (I)
- 7.
  A pregnancy that results from failure of emergency contraception need not be terminated (I)
- 1.
  Emergency contraception should be used as soon as possible after unprotected sexual intercourse. (II-2A)
- 2.
  Emergency contraception should be offered to women if unprotected intercourse has occurred within the time it is known to be effective (5 days for hormonal methods and up to 7 days for a copper IUD). (II-2B)
- 3.
  Women should be evaluated for pregnancy if menses have not begun within 21 days following emergency contraception treatment. (III-A)
- 4.
  During physician visits for periodic health examinations or reproductive health concerns, any woman in the reproductive age group who has not been sterilized may be counselled about emergency contraception in advance with detailed information about how and when to use it. (III-C)
Contraceptive efficacy of emergency contraception with levonorgestrel given before or after ovulation
2011, Contraception
Citation Excerpt :
The pregnancy assigned to a treatment in the preovulatory period corresponded to a woman who had a CL and postovulatory hormone levels on the day she took LNG-EC. Previous studies attempting to verify the coincidence between estimated ovulatory day using historical menstrual data versus objective parameters of the current cycle also revealed an important degree of discrepancy [26,27]. In conclusion, LNG-EC is highly effective for preventing unintended pregnancy when it is used before ovulation, but when used after ovulation, it is completely unable to prevent pregnancy because it has no effect on subsequent reproductive processes, including implantation of the embryo.
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.
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.
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 (p<.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.
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.

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Original Research ArticlesThe role of matching menstrual data with hormonal measurements in evaluating effectiveness of postcoital contraception

Abstract

Introduction

Section snippets

Materials and methods

Results

Discussion

Acknowledgements

Lancet

Fertil Steril

Contraception

Lancet

Fertil Steril

Lancet

Emergency contraception

BMJ

Emergency postcoital contraception

N Engl J Med

Original Research Articles
The role of matching menstrual data with hormonal measurements in evaluating effectiveness of postcoital contraception