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Am Fam Physician. 2020;101(11):651-652

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Clinical Question

Which form of emergency contraception is the safest and most effective for preventing pregnancy after a single episode of unprotected intercourse?

Evidence-Based Answer

Oral mifepristone (Mifeprex), ulipristal (Ella), levonorgestrel-releasing emergency contraception (Plan B One-Step), ethinyl estradiol/levonorgestrel, and the copper intrauterine device (IUD; Paragard) are safe and effective for emergency contraception. 1 (Strength of Recommendation [SOR]: B, based on inconsistent or limited-quality patient-oriented evidence.)

In head-to-head comparisons, a one-time dose of mifepristone is more effective than any dose of oral levonorgestrel, with moderate-dose mifepristone (25 to 50 mg) being more effective than low-dose mifepristone (less than 25 mg; relative risk [RR] = 0.61). (SOR: B, based on inconsistent or limited-quality patient-oriented evidence.) All other forms of emergency contraception are more effective than ethinyl estradiol/levonorgestrel (RR = 0.57). (SOR: A, based on consistent, good-quality patient-oriented evidence.) Ulipristal is more effective than oral levonorgestrel alone (RR = 0.59). (SOR: A, based on consistent, good-quality patient-oriented evidence.)

The copper IUD is not inferior to any dose of mifepristone, but no direct comparison has been made between the copper IUD and other types of emergency contraception. (SOR: C, based on consensus, disease-oriented evidence, usual practice, expert opinion, or case series.) Adverse effects most often include nausea and vomiting for oral medications and abdominal pain and menorrhagia for the copper IUD.1

Practice Pointers

Emergency contraception is the use of a medication or device to prevent pregnancy following unprotected intercourse. Although the likelihood of pregnancy after a single episode of unprotected intercourse is highly variable depending on timing and other factors, emergency contraception can be more than 95% effective at preventing pregnancy when used within five days of intercourse. Nearly one-half of pregnancies in the United States are unintended, and they are associated with increased health risks to both mother and fetus.2 The authors of this review sought to identify the safest and most effective emergency contraception.

This Cochrane review included 115 randomized controlled trials, 92 of which were performed in China, and involved 60,479 women who had engaged in a single act of unprotected intercourse.1 Both one-time low-dose (less than 25 mg) and moderate-dose (25 to 50 mg) oral mifepristone were superior when compared with one-time oral levonorgestrel, 1.5 mg (RR for low-dose mifepristone = 0.72; 95% CI, 0.52 to 0.99; n = 8,752; RR for moderate-dose mifepristone = 0.61; 95% CI, 0.45 to 0.83; n = 6,052). For example, if the chance of pregnancy following unprotected intercourse and subsequent treatment with oral levonorgestrel is 20 women per 1,000, the chance following treatment with low-dose mifepristone would be between 10 and 20 women per 1,000. In a different cohort, if the chance of pregnancy following treatment with oral levonorgestrel is 35 women per 1,000, then the chance after taking moderate-dose mifepristone is between 16 and 29 women per 1,000. One study confirmed that oral levonorgestrel can be given as a single dose or as two doses 12 hours apart, but no difference in effectiveness was demonstrated between single and split dosing; other studies compared single-dose regimens.

All one-time doses of oral ulipristal, most often 30 mg, were more effective than oral levonorgestrel alone (RR = 0.59; 95% CI, 0.35 to 0.99; n = 3,448). If the chance of pregnancy following unprotected sex and treatment with oral levonorgestrel is 22 women per 1,000, the chance following treatment with ulipristal is eight to 22 per 1,000.

Ethinyl estradiol/levonorgestrel was found to be inferior to one-time oral levonorgestrel (RR = 0.57; 95% CI, 0.39 to 0.84; n = 4,750) and one-time mifepristone (RR = 0.14; 95% CI, 0.05 to 0.4; n = 2,144). In other words, if the chance of pregnancy following treatment with ethinyl estradiol/levonorgestrel is 29 women per 1,000, then the chance following treatment with oral levonorgestrel is between 11 and 24 women per 1,000. In the mifepristone studies, if the chance of pregnancy after taking ethinyl estradiol/levonorgestrel is 25 women per 1,000, the chance after taking a single dose of mifepristone is one to 10 per 1,000.

A single study comparing the effectiveness of the copper IUD and moderate-dose mifepristone (25 to 50 mg) at preventing pregnancy revealed no significant difference between the two treatments (RR = 0.33; 95% CI, 0.04 to 2.74; n = 395).

No serious adverse effects were reported in any of the studies. Nausea and vomiting were most common in patients taking oral medications, with mifepristone and oral levonorgestrel having lower rates than ethinyl estradiol/levonorgestrel. Menstrual delay occurred most often in those taking mifepristone vs. any other intervention, and this appeared to be dose-dependent. Users of ulipristal were more likely to experience delayed resumption of menses compared with those who took oral levonorgestrel (RR = 1.65; 95% CI, 1.42 to 19.2; n = 3,593). Women who used copper IUDs were at risk of uterine perforation and/or expulsion, abdominal pain, and menorrhagia.3,4

The 2015 American College of Obstetricians and Gynecologists practice bulletin on emergency contraception recommends ulipristal, oral levonorgestrel, and the copper IUD as effective forms of emergency contraception.3 (SOR: A, based on consistent, good-quality patient-oriented evidence.) Because ethinyl estradiol/levonorgestrel is often the only method available, physicians should be familiar with its dosing regimens. They should also be educated on all of the available methods so that they can provide compassionate and timely emergency contraception to their patients.

The practice recommendations in this activity are available at http://www.cochrane.org/CD001324.

The views expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Department of the Navy, Department of Defense, or the U.S. government.

I am a military service member. This work was prepared as part of my official duties. Title 17 U.S.C. 105 provides that “Copyright protection under this title is not available for any work of the United States Government.” Title 17 U.S.C. 101 defines a United States Government work as a work prepared by a military service member or employee of the United States Government as part of that person's official duties.

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