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JOURNAL OF THE AMERICAN MEDICAL WOMEN S ASSOCIATION. 1998; 53(5 Suppl 2):222-4, 232.During the last decade, the UNDP/UNFPA/WHO/World Bank Special Program of Research, Development, and Research Training in Human Reproduction has been in the forefront of research on new methods of emergency contraception. This research has focused on both levonorgestrel and mifepristone. The results of large clinical studies suggest that both these compounds are better tolerated and even more effective than the Yuzpe regimen. This article, intended for purposes of continuing medical education, summarizes the findings of studies that have compared these three approaches to emergency contraception.
Lancet. 1999 Feb 27; 353(9154):721.A World Health Organization (WHO) study of combined oral contraceptives (Yuzpe regimen) and levonorgestrel alone for emergency contraception found that the effectiveness of both treatments declined with increasing time since unprotected intercourse. An earlier review of primarily observational studies found no such timing effect, however. The authors' reanalysis of the WHO data revealed a consistent linear relationship between efficacy and time from intercourse to treatment. The pregnancy rate rose from 0.5% when treatment was given within 12 hours of treatment to 4.1% when 61-72 hours had elapsed. The odds ratio of pregnancy associated with either treatment at a given time compared with treatment 12 hours earlier was 1.46 (95% confidence interval, 1.20-1.77). This estimate was not affected by adjustment for confounding factors such as age, weight, cycle length, or cycle day in which unprotected intercourse took place. The consistency between the WHO trial and an earlier randomized controlled trial, the statistically significant temporal effect observed with both treatment regimens, and biologic plausibility all suggest that the effect of timing on emergency contraception efficacy is real.
JOURNAL OF FAMILY PRACTICE. 1998 Dec; 47(6):417.A study supported by the World Health Organization's Task Force on Postovulatory Methods of Fertility Control compared the efficacy of the Yuzpe and levonorgestrel-only methods of emergency contraception (EC). Enrolled in this double-blind, randomized trial were 1998 women from 21 centers around the world who requested EC within 72 hours of unprotected intercourse. The pregnancy rate was 1.1% for levonorgestrel alone and 3.2% for the combined ethinyl estradiol-levonorgestrel regimen. The crude relative risk of pregnancy was 0.36 (95% confidence interval, 0.18-0.70) for levonorgestrel compared with the Yuzpe regimen. The former method prevented 85% of expected pregnancies, while the latter prevented only 57%. Finally, side effects such as nausea, vomiting, dizziness, and fatigue were significantly less common in the levonorgestrel group. Although these findings document the superiority of the levonorgestrel regimen for EC, the 0.75 mg tablets are not currently manufactured in the US.
Lancet. 1998 Dec 12; 352(9144):1939-40.In response to concerns raised by both Trussell and Ellertson et al., the authors (members of the WHO Task Force on Postovulatory Methods of Fertility Regulation) investigated the impact of time elapsed since unprotected intercourse on the efficacy of emergency contraception in more detail. Overall, the pregnancy rate increased from 0.5% when treatment was initiated within 24 hours to 4.1% after a time lapse of 61-72 hours. Postponement of the first dose by 12 hours increased the likelihood of pregnancy by almost 50%. A levonorgestrel-only regimen was consistently more effective than the Yuzpe regimen. A comparison of the pregnancy risk associated with levonorgestrel with that of Yuzpe in the 7 studies pooled by Trussell yields a relative risk of 0.3 (95% confidence interval, 0.23-0.97)--similar to that reported in the WHO study with other conception probabilities. Since the Yuzpe regimen has not been updated since 1973, it is time to review and improve emergency contraception options.
Lancet. 1998 Oct 10; 352(9135):1222-3.The World Health Organization (WHO) Task Force on Postovulatory Methods of Fertility Regulation has concluded that the efficacy of emergency contraception regimens decrease progressively with time elapsed since unprotected intercourse. In the WHO study, the efficacy of both the Yuzpe method and the levonorgestrel-only regimen demonstrated a significant downward gradient when treatment was initiated within 24 hours of unprotected sex compared with 49-72 hours. In contrast, an analysis of nine published reports of the efficacy of the Yuzpe regimen indicated that the timing of treatment 1, 2, or 3 days after unprotected intercourse did not affect the method's efficacy. The discrepancy between these two bodies of research requires further attention. An effort should be made to initiate emergency contraceptive use as soon as possible. However, this guideline should not be used to deny women access to the method after 24, 48, or even 72 hours with proper informed consent.
Lancet. 1998 Aug 8; 352(9126):416-7.The World Health Organization (WHO) multicenter, randomized trial reported in this issue of "The Lancet" confirms that levonorgestrel-only (two 750-mcg doses) is significantly more effective in preventing pregnancy after unprotected intercourse than the standard Yuzpe regimen (two doses of 500 mcg levonorgestrel and 100 mcg ethinyl estradiol) and is further associated with significantly less nausea and vomiting. When initiated within 24 hours of coitus, the failure rate was only 0.4% for levonorgestrel compared with 2.0% for the combined hormonal method. A further advantage of a progestogen-only emergency contraceptive method is avoidance of contraindications in women with past proven arterial or venous thrombosis or a current attack of migraine with focal aura. Although only one pharmaceutical company (Gedeon Richter in Budapest, Hungary) currently manufactures 750 mcg of levonorgestrel in a single tablet, others are likely to follow this example given the findings of the WHO study. Strong pressure exists to increase availability of postcoital contraception through trained nurses and retail pharmacists. However, potential users will still require counseling on the importance of selecting a long-term method of contraception and a family planning provider.
Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception.
Lancet. 1998 Aug 8; 352(9126):428-33.A previous study suggested that provision of two 0.75 mg doses of levonorgestrel for emergency contraception caused less nausea and vomiting and was more effective than the Yuzpe regimen of combined oral contraceptives (two doses of 100 mcg of ethinyl estradiol and 0.5 mg of levonorgestrel). These two regimens were evaluated further in a double-blind, randomized World Health Organization study of 1998 women recruited from 21 centers worldwide who requested emergency contraception within 72 hours of unprotected intercourse. Among the 1955 women for whom the outcome was known, the crude pregnancy rate was 1.1% (11/976) in the levonorgestrel group and 3.2% (31/979) in the Yuzpe group. The crude relative risk of pregnancy for levonorgestrel compared with the Yuzpe regimen was 0.36 (95% confidence interval, 0.18-0.70). The proportion of pregnancies prevented was 85% in the former group and 57% in the latter group. Nausea and vomiting occurred significantly less frequently in the levonorgestrel group (23.1% and 5.6%, respectively) than in the Yuzpe regimen group (50.5% and 18.8%, respectively). The efficacy of both treatments declined significantly (p = 0.01) with increasing time since unprotected intercourse. These findings confirm that the levonorgestrel regimen may be more effective and is better tolerated than the current standard in emergency contraception.
Geneva, Switzerland, WHO, Division of Reproductive Health (Technical Support), Family Planning and Population, 1998. 60 p. (WHO/FRH/FPP/98.19)The introduction of emergency contraception into family planning programs and its distribution through both clinical and nonclinical channels have been urged to prevent the serious health and socioeconomic consequences of unwanted pregnancies. The need for emergency contraception is especially high among adolescents, who may become sexually active before they are informed about contraception or have access to appropriate services. The provision of emergency contraceptive methods through official family planning programs should be regarded as key to the long-term international strategy of upgrading reproductive health care. Moreover, when service outlets offer emergency contraception information and care, they can serve as a first contact point where sexually active men, women, and teens can receive other reproductive health services or referrals. This booklet, prepared by the World Health Organization for service delivery personnel, presents information on emergency contraceptive pills, the use of copper-releasing IUDs as emergency contraception, service delivery aspects, the introduction of emergency contraception in reproductive health programs, and information dissemination. An appendix sets forth medical eligibility criteria.
Medical Journal of Australia. 1981 Jan 24; 1(4):55-7.Differences in contraceptive technology available in a developed country (Australia) vs. an underdeveloped country may be as important in explaining a lack of enthusiasm for fertility control as the differences in sociocultural views of children and child worth. In Australia, a large number of women and couples are unhappy with the existing methods of contraception because of potentially lethal side effects (cardiovascular and carcinogenic effects of oral contraceptives and chance of pelvic sepsis with intrauterine forms of fertility control). These anxieties in many women in developed countries who use contraception for child spacing rather than for absolute infertility may outweigh the short term goal of family size choice. New methods are needed. But the recent withdrawal of private funds and the reliance on public funding sources has skewed the types of research and development occurring since the mid-1970s. 1 feasible method was a vaccine against pregnancy (via immunologically controlling either the zona pellucida or sperm); but lack of funds and ethical considerations have effectively halted research into this method. 3 current reviews of contraceptive technology, aimed at the clinical practitioner, have discussed risk-benefit of common contraceptive agents, the possibility of pregnancy interception, and the potential of injectable regimens for women in developed countries. The longest review, by Fraser and Weisberg, explains how taking standard oral contraceptive preparations within 72 hours of unprotected intercourse can intercept a pregnancy without the need for constantly ingesting these preparations.
[Unpublished] 1979 Oct 10-12. Presented at the Annual Scientific Meeting of the Association of Planned Parenthood Physicians, Philadelphia, Pennsylvania, October 10-12, 1979. 16 p.A study was undertaken by Planned Parenthood Federation to discover the effectiveness rate of postcoital Copper-7 IUD (CU-7) insertion in preventing pregnancy. Hence the use of CU-7 postcoitally after unprotected midcycle coitus was assessed in 42 valid candidates (of 80 who were originally enrolled). No pregnancies were documented resulting from the unprotected midcycle coitus in any of the 42 study participants. Fertilization was assumed to have occurred in 5 women (12%), based on positive radioimmunoassay and human chorionic gonadotropin radioreceptorassay on Day 25 of cycle. 4 patients have continued to use the device. Acceptor characteristics of all 42 eligible acceptors and the continuers are presented tabularly. Presumed fertilization occurred in 10 other women, presumed because only chorionic gondotropin assay was positive, which could have been detecting merely luteinizing hormone. 57% of study participants had the IUD in place at the 3rd visit. 14% (n=6) had the IUD removed, preferring another or no contraceptive method. The study seems to confirm the postcoital effect of IUDs.