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Interventions for emergency contraception

RHL Commentary by Mittal S

1. EVIDENCE SUMMARY

With the objective of determining "which emergency contraceptive method following unprotected intercourse is the most effective, safe and convenient" for preventing pregnancy, this review (1) analysed data form 81 trials (70 of them conducted in China) involving 45 842 women. These trials compared different methods of emergency contraception (in varying doses in the case of hormonal methods) with each other and with nothing or a placebo. The methods included high-dose estrogens, the Yuzpe regimen (estrogen plus progestogen), levonorgestrel (progestogen alone), danazol, mifepristone (in varying doses), anordrin, mifepristone with anordrin, misoprostol, tamoxifen, CDB-2914 and the copper-bearing intrauterine device (IUD).

Comparative evaluation of different interventions – analysed independently by two reviewers – found that any form of emergency contraception was better than no intervention or placebo. Mid-dose (25–50 mg) or low-dose (< 25 mg) mifepristone was more effective in preventing pregnancy compared with levonorgestrel, although low-dose mifepristone was less effective than mid-dose mifepristone, with the difference not being significant in high-quality studies. A single dose (1.5 mg) of levonorgestrel was as effective as the standard two doses (0.75 mg) of levonorgestrel administered at a 12-hour interval, with no difference in side-effects except headache, which was slightly more frequent in women taking the single dose. Levonorgestrel and mifepristone were more effective than the Yuzpe regimen, danazol and anordin, and were associated with fewer side-effects. Side-effects such as nausea and vomiting were more frequently associated with estrogen-containing regimens, and there was a dose-related delay in return of menstruation with mifepristone and CBD-1914. Overall, the side-effects of mifepristone were more tolerable than those of levonorgestrel. The Yuzpe regimen, danazol and levonorgestrel had no significant effect on the menstrual cycle. Combining mifepristone with anordrin, tamoxifen, misoprostol, or methotrexate did not have any significant effect on the pregnancy rate, but side-effects and delay in return of menses were more common when mifepristone was combined with anordrin. Administration of a single-dose of the Yuzpe regimen (half the normal dose given once) did not decrease its efficacy, but its side-effect profile improved significantly. Use of the copper IUD for emergency contraception was effective and provided ongoing contraception. IUD efficacy for emergency contraception was higher, the sooner after intercourse the IUD was used. Five cases of ectopic pregnancy were reported, three following mifepristone use and two after split-dose levonorgestrel. Eight healthy infants were reportedly delivered with no adverse effects following the use of levonorgestrel, Yuzpe regimen, danazol and mifepristone.

The review examined randomized controlled and controlled clinical trials comparing different methods of emergency contraception or any method with nothing or placebo, reporting on clinical outcomes, namely efficacy (number of pregnancies) and side-effects, ectopic pregnancy and delay in menses. Studies comparing emergency contraceptives provided in advance, emergency contraceptives available over the counter, or once-a-month methods were not included.

The trials were identified and retrieved: (i) by electronic searches of the Central/Cochrane Controlled Trials Register, PubMed, EMBASE, Popline, CINAHL and LILACS; (ii) from WHO resources; (iii) Emergency Contraception World Wide Web; and (iv) pharmaceutical companies until December 2006. All trials were checked for duplicates, relevance and proper randomization. Altogether, 67 studies were excluded for different reasons. One study was excluded for have more than 20% loss to follow up of study participants. The trials were assessed for their quality (2) and allocation concealment. The treatment results were calculated using relative risk estimates with the 95% confidence interval. The observed number of pregnancies in comparison to expected number of pregnancies – calculated by estimated probability of conception on the day of intercourse in relation to the menstrual cycle – was used to evaluate the efficacy of emergency contraception regimens. Besides comparison of different regimens, other factors affecting the success of emergency contraception (coitus-treatment interval and risk status of women) were also evaluated. The review is unbiased and thorough. The data are clearly tabulated and graphically depicted for different methods taking in consideration all the parameters evaluated.

2. RELEVANCE TO UNDER-RESOURCED SETTINGS

2.1. Magnitude of the problem

Although several contraceptive techniques are available in India, the couple protection rate (41%) continues to be inadequate. Most couples in India do not want to use a contraceptive method on a long-term basis for the fear of side-effects (especially the oral pill and IUDs), or do not like to use a method linked with coitus (barrier methods). Hence, unwanted and unplanned pregnancies are common. According to the National Family Health Survey (1995), 78% pregnancies in India are unplanned and at least 25% of these are unwanted. Each year 11 million abortions take place in the country, and at least half of these are unsafe, contributing to the high maternal morbidity and mortality rates. Annually, approximately 20 000 women die from abortion-related complications (3). A considerable proportion of these abortions can be prevented by the timely use of emergency contraception.

2.2. Applicability of the results

The findings of this review are applicable to all settings.

The review suggests that mifepristone and levonorgestrel are effective and well-tolerated when used for emergency contraception. Mifepristone mid-dose should be the method of choice for emergency contraception; however, it is not available in several countries. To ensure compliance, a single-dose regimen is preferable over repeated doses. High-quality trails (4, 5) show that a single 1.5-mg dose of levonorgestrel is as efficacious as the split dose. Currently, levonorgestrel is being marketed in several developing countries as a dedicated method of emergency contraception because of its easy availability and lower cost compared with mifepristone. Delay in the onset of menses is a drawback with the use of mifepristone for emergency contraception, as the woman may continue to be anxious until her menses restart. The Yuzpe regimen should be used only when the above two options are not available. A copper-bearing IUD can be offered to a woman requesting long-term contraception. Women should be advised to use an emergency contraception method as early as possible after unprotected intercourse and to abstain from further intercourse or to use alternative methods of contraception. Other methods like anordrin, tamoxifen, danazol and misoprostol have been used mainly for research purposes and offer no advantage.

Earlier, previous history of ectopic pregnancy was considered a relative contraindication for the use of emergency contraception, owing to the high risk of ectopic pregnancy following estrogen use. With the present review reporting only five ectopic pregnancies in 45 842 women, emergency contraception can be considered safe even for women with previous history of ectopic pregnancy.

2.3. Implementation of the intervention

The full potential of emergency contraception can be realized only when people (especially women) are made aware of the existence of these methods and the need to use them within the short time frame of their efficacy. Such awareness is still limited in many developing countries. In India, a survey of 4000 women aged 18–55 years in the state of Delhi revealed very low (3.2%) awareness about emergency contraception (6). Awareness in rural areas was less than 2%. Evaluation of knowledge and views of doctors about emergency contraception revealed poor knowledge among general practitioners (7). Even specialist physicians were not aware about the appropriate dosages, timing of use, and mechanism of action or availability of emergency contraceptives. Thus, the most important step is to increase awareness of emergency contraception in under-resourced settings.

Information about the availability of these methods needs to be provided to both health-care providers and potential users. In 2001, a consortium was organized for national consensus on emergency contraception in India (8). It addressed several issues including, choice of the drug, distribution protocol, client information and counselling and training of health-care providers. Guidelines were formulated and levonorgestrel was introduced in the country as a two-pill pack, each containing 0.75 mg of the drug, to be taken 12 hours apart, within 72 hours of unprotected intercourse. In view of the new research findings reported in this Cochrane review, the guidelines for emergency contraception will need to be revised. A countrywide public awareness campaign would be needed to inform people about the advantages of this intervention. Since 2005, over-the-counter availability of the two-pill levonorgestrel pack has facilitated wider utilization of the method in India, especially in under-resourced settings where availability of doctors for prescribing the method is limited. However, repeated use and misuse of the method may emerge as a new concern with over-the-counter availability of these methods, especially as opportunity for providing counselling for regular contraception is missed.

3. RESEARCH

To help with policy formulation, there is a need to conduct large-scale field trials to determine efficacy and feasibility of the use of emergency contraception at the peripheral level in developing countries. Research is also needed to evaluate levonorgestrel and mifepristone in comparison with IUDs and to evaluate the cost-effectiveness of different efficacious regimens.

Sources of support: None

Acknowledgement: None

References

• Cheng L, Gülmezoglu AM, Piaggio GGP, Ezcurra EE, Van Look PFA. Interventions for emergency contraception. Cochrane Database of Systematic Reviews 2008;Issue 1. Art. No.: CD001324; DOI: 10.1002/14651858.CD001324.pub3.
• Higgins JPT, Green S, Eds. Cochrane handbook for systematic reviews of interventions Version 5.0.0 (updated February 2008). The Cochrane Collaboration, 2008. Available from www.cochrane-handbook.org.
• National family health survey (MCH and family planning), India 1992–1993. Bombay: International Institute for Population Sciences; 1995.
• Arowojolu AO, Okewole LA, Adekunie AO. Comparative evaluation of the effectiveness and safety of two regimens of levonorgestrel for emergency contraception in Nigerians. Contraception 2002;66:269-273.
• von Hertzen H, Piaggio G, Ding J, Chen J, Song S, Bartfai G, et al. for the WHO Research Group on Post-ovulatory Methods of Fertility Regulation. Low dose mifepristone and two regimens of levonorgestrel for emergency contraception. The Lancet 2002;360:1803-1810.
• Mittal S, Lakhatia M, Kumar S, Singh S. Contraceptive awareness and acceptance in Indian Metropolitan city. Consortium on National consensus for Emergency Contraception 2001;91.
• Singh S, Mittal S, Anandalakshmy PN, Goel V. Emergency contraception: knowledge and views of doctors in Delhi. Health and Population – Perspectives and Issues 2002;25:45-54.
• Consortium on National Consensus for Emergency Contraception in India. New Delhi: All India Institute of Medial Sciences; 2001.

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This document should be cited as: Mittal S. Interventions for emergency contraception: RHL commentary (last revised: 1 November 2008). The WHO Reproductive Health Library; Geneva: World Health Organization.

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