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Research on New Methods of Emergency Contraception By Helena von Hertzen and Paul F.A.Van Look he term “emergency contraception” no currently available method is effective struation would raise concerns that the refers to specific contraceptive once implantation has commenced—unless method had failed and add to a woman’s methods that can be used as emer- endometrial aspiration is considered a meth- anxiety. Also, the longer the interval tol- T 4 gency measures to prevent pregnancy od of emergency contraception. erated between unprotected intercourse after unprotected intercourse. Emergency Emergency contraception could prevent and administration of the ideal method, contraception is used after coitus but be- many unwanted pregnancies. For exam- the greater would be its practical value. An fore pregnancy has become established; ple, a study carried out among 733 women emergency contraceptive should provide as such, it is considered a back-up meth- requesting pregnancy termination in Ox- full interceptive protection, preferably after od for occasional rather than regular use.1 ford, United Kingdom, found that 410 a single administration. It should also be All methods currently available for women (56%) had had unprotected inter- active in an easily administered form, such emergency use have limitations. That they course or experienced difficulty with the as an oral or vaginal tablet or a nasal spray. can only be administered within a few barrier method used.5 Among these 410 Finally, the method should be affordable: days after intercourse restricts their use- women, 18 used emergency contraception No matter how perfect emergency meth- fulness and disqualifies for treatment without success; the remaining 392 did not ods might be, they will not help people women who cannot meet this deadline. use emergency contraception, mainly be- who cannot afford them. Moreover, the methods, and the hormon- cause they did not know it existed or A thorough knowledge of the physio- al regimens in particular—such as high- where they could get it. logical mechanisms that lead to pregnan- dose estrogen or combined oral contra- Had these 392 women used the Yuzpe cy is indispensable for the development of ceptive tablets (known as the “Yuzpe regimen, about three-quarters of them new compounds or the identification of al- regimen”)—may cause unpleasant side would not have become pregnant.6 Nev- ready existing ones that might be tested for effects, including nausea, vomiting, ertheless, the fact that the Yuzpe regimen their potential as emergency methods. To headaches, dizziness and breast tender- would not have prevented 25% of the con- be effective, a method has to disrupt cru- ness. These side effects can limit compli- ceptions among these women illustrates the cial events in the establishment of preg- ance and, in the case of vomiting, may af- very clear need for new and better methods nancy. While unprotected intercourse may fect the methods’ efficacy. of emergency contraception. In this article, take place at any time during the men- Emergency methods are generally not we first explore what the ideal emergency strual cycle, pregnancy can only result as effective as other contraceptive meth- contraception method would be. We then from intercourse during the fertile phase— ods. For example, even when the Yuzpe review those new methods that are now from about five days before until about 24 regimen is administered within the rec- being tested and, finally, we conclude by hours after ovulation, a period that corre- ommended 72 hours, it fails to prevent outlining the prospects for improving emer- sponds to the life span of sperm in the fe- one-quarter of the pregnancies that would gency contraception in the future. male genital tract and the time during be expected without the therapy.2 And al- which the oocyte is fertilizable. The human though insertion of an IUD after unpro- Ideal Emergency Contraception blastocyst probably starts to penetrate the tected intercourse is more effective and Method Attributes uterine mucosa by the fifth or sixth day can be initiated later than the hormonal The most important requirement of the after fertilization,7 and implantation is regimens (up until the expected start of ideal emergency contraceptive is that it be completed—and pregnancy established— implantation), its usefulness is limited be- highly effective. Women who seek emer- around the time of missed menses.8 cause of the risk of infection, especially in gency contraception definitely want to While these facts are obviously relevant victims of sexual assault or following in- avoid pregnancy. If a method, such as the in considering emergency contraception, tercourse with a new partner. IUD inser- condom, has already failed, there is no clinicians should always prescribe emer- tion is also not usually recommended for place for another failure. Methods of emer- gency contraception after unprotected in- nulliparous women, and such women gency contraception also have to be as safe tercourse, regardless of when it occurs in constitute a sizable proportion of those re- as other methods, even though they are the menstrual cycle. Women’s cycles vary, questing emergency contraception.3 used only occasionally. The ideal method and even the most sophisticated labora- In addition to the drawbacks of these ex- should be free of side effects, although tory techniques cannot determine retro- isting methods, their variety is very limit- women may accept some side effects as the spectively whether intercourse occurred ed; a woman seeking emergency contra- price to be paid for a high effectiveness. in the fertile or infertile phase. ception has few choices at her disposal. Also, Furthermore, side effects caused by an emergency method may not carry the Mechanisms of Action Helena von Hertzen is medical officer and Paul F.A. Van same weight as those caused by regular All emergency methods currently in use Look is associate director of the Special Programme of methods, since an emergency method may act before implantation. Theoretically, this Research, Development and Research Training in Human Reproduction, World Health Organization (WHO), Gene- be needed only once in a lifetime. could be achieved in several ways; in prac- va, Switzerland. The views expressed in this article do The method would ideally not disturb tice, however, the possible modes of ac- not necessarily reflect those of WHO. the menstrual cycle, as a delay in men- tion are more limited, because women re- 62 International Family Planning Perspectives quest emergency contraception at differ- New Hormonal Approaches treated with the Yuzpe regimen.12 About ent times during their menstrual cycle. Scientists have known about the impor- 3% of women in the levonorgestrel group This variability in timing means that com- tance of ovarian hormones in establishing became pregnant, compared with some pounds that work only through disturb- pregnancy since the early 1930s, and most 2% of the women treated with the Yuzpe ing ovulation or some event closely asso- efforts to identify leads for emergency con- method. ciated with it cannot be highly effective as traception have focused on these hor- Because 0.75 mg levonorgestrel tablets emergency methods. mones. In the 1970s, the regular combined are marketed in several countries for oc- Figure 1 depicts how a drug’s mode of oral contraceptive was tested as an emer- casional contraceptive use, the World action influences its potential value as an gency method in what became known as Health Organization (WHO) supported emergency contraceptive compound. A the Yuzpe regimen. More recently, levo- a prospective randomized trial conduct- drug that acts during the follicular phase norgestrel alone was tested as an emer- ed in 1991 that compared the effectiveness only—for example, by interfering with gency method, and a number of studies and side effects of two tablets, each taken oocyte maturation or by blocking ovula- have looked at the efficacy of danazol, a 12 hours apart, with those of the Yuzpe tion—would only be effective at prevent- potent antigonadotropin and progesto- regimen among women requesting emer- ing pregnancies that result from inter- gen. Another approach has been to coun- gency contraception within 48 hours of course in the preovulatory phase, if the teract those hormones presumed or unprotected intercourse.13 A total of 424 treatment is started soon enough before known to be involved in the establishment women were assigned the Yuzpe regimen ovulation (see arrow A in figure). of pregnancy—including estrogens, go- and 410 women were given two 0.75 mg Preventing fertilization rather than ovu- nadotropin-releasing hormone (GnRH) doses of levonorgestrel. lation would be a potentially more useful and progesterone—through the adminis- There were 15 pregnancies (3.5%) in the approach, since the window of activity tration of antihormones. Yuzpe group and 12 pregnancies (2.9%) in would be wider (see arrow B in figure). the levonorgestrel group. After women Such a compound’s duration of action Levonorgestrel who had had further acts of intercourse would need to be sufficiently long to remain Research undertaken mainly in the 1970s during the remainder of the treatment capable of preventing fertilization, even if concluded that progestogens were un- cycle were excluded (18% of the Yuzpe both unprotected intercourse and use of the suitable for regular postcoital use, pri- group and 19% of the levonorgestrel drug take place early in the fertile period. marily because they caused a high degree group), the failure rates were 2.6% and However, if intercourse were to take place of cycle disturbance. However, some stud- 2.4%, respectively. The incidence of nau- late in the fertile period, at about the same ies did indicate levonorgestrel’s potential sea, vomiting and fatigue was signifi- time as or shortly after ovulation, fertiliza- as an occasional method of postcoital con- cantly higher (p<.001) among women tak- tion may not be successfully blocked.

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