Can We Identify Women at Risk of Pregnancy Despite Using Emergency Contraception? Data From Randomized Trials of Ulipristal Acetate and Levonorgestrel

Abstract

Levonorgestrel (LNG) is the most widely used emergency contraceptive. It is effective when given orally up to 72 hours after intercourse and prevents at least 50% of pregnancies that would have occurred without its use. Insertion of a copper intrauterine device (IUD) is more effective for emergency contraception (EC) than LNG. Some organizations recommend the IUD as the agent of choice for EC, especially for women who have intercourse midcycle when the pregnancy risk is greatest. Ulipristal acetate (UPA), a selective progesterone receptor modulator, is nearly twice as effective as LNG for EC and longer acting; it can be used up to 120 hours after intercourse. Ulipristal acetate has been marketed in Europe since 2009 and is now available on prescription in the United States. The decision of some women whether to use EC is based on the timing of intercourse; if they have intercourse at a time in the cycle when they believe they are at low risk, they do not use EC. However, the timing of intercourse before using EC is unreliable and does not protect against pregnancy. A number of potential risk factors increase the risk of pregnancy and the likelihood of failure of a less effective method of EC. To identify risk factors that could explain a higher risk of EC failures, data were analyzed from a meta-analysis of 2 randomized controlled trials that compared the efficacy of UPA with LNG. Risk factors examined with both methods were body mass index (BMI), the timing of intercourse before using EC, and further acts of intercourse after treatment. Compared with women with a normal BMI (<25 kg/m2), the risk of pregnancy was more than 3 times greater (odds ratio [OR], 3.60; 95% confidence interval [CI], 1.96–6.53; P < 0.0001) for obese women (BMI >30 kg/m2) regardless of which method of EC was used. Among obese women, however, the risk of pregnancy was greater with use of LNG (OR, 4.41; 95% CI, 2.05–9.44; P = 0.0002) than with use of UPA (OR, 2.62; 95% CI, 0.89–7.00; not statistically significant). Risk of pregnancy was related to the cycle day of intercourse for both LNG and UPA. The likelihood of pregnancy with both methods was increased 4-fold among women who had intercourse the day before estimated day of ovulation (OR, 4.42; 95% CI, 2.33–8.20; P = 0.0001) compared with women who had sex outside the fertile window. With both methods, unprotected intercourse after using EC was associated with a substantially higher risk of pregnancy compared with those who did not (OR, 4.64; 95% CI, 2.22–8.96; P = 0.0002). These findings suggest that women who have intercourse around the time of ovulation should use a copper IUD. Use of UPA or the IUD is more effective for overweight or obese women than LNG. Effective contraception is advisable immediately after use of EC.