New WHO guidelines on expanding contraceptive options
3.1 Mifepristone for Emergency Contraception (EC)
WHO recommends adding mifepristone to the method mix for EC, as a single dose between 10 and 50 mg.
Remarks: the availability of mifepristone dosage forms may differ across settings and countries. A dose between 10 and 25 mg may be preferred if available. EC pills are taken as soon as possible after unprotected sex and within five days.
Strong recommendation, moderate-certainty evidence
3.1.1 Background
EC remains an important tool for individuals seeking to prevent pregnancy. Unintended pregnancy affects an estimated 121 million people worldwide (9). When individuals are not using a consistent contraceptive method, do not have access to contraception, have a regular method that fails or are victims of sexual violence, EC can be the only option to reduce the risk of becoming pregnant. EC oral methods that are currently used and included in clinical guidelines are ulipristal acetate, LNG and COCs – often referred to as the Yuzpe method (10, 11). The copper intrauterine device (IUD) is also used for EC.
Mifepristone is a norethindrone derivative that strongly binds to progesterone and glucocorticoid receptors, functioning as an antagonist. Mifepristone has been found to delay or prevent ovulation via this progesterone receptor antagonism. Mifepristone as EC is approved and utilized in a few countries including Armenia, China, the Russian Federation and Ukraine (12). The dosing regimen of mifepristone as EC varies, with doses ranging from 10 to 600 mg taken within 120 hours of unprotected intercourse.
The GDG examined the following key question: “Should mifepristone be added to the contraceptive method mix for EC (and at what dose)?”
3.1.2. Balancing desirable and undesirable effects
Evidence from a recent systematic review of 87 randomized controlled trials (RCTs) was included (13). The literature search was performed through December 2024. The review included studies comparing mifepristone to other methods of EC (COCs [Yuzpe method], LNG oral pills, and copper IUDs [as EC]). No studies comparing mifepristone to ulipristal acetate were identified. Studies were included if the population was women seeking EC for the prevention of pregnancy within 120 hours of unprotected intercourse. Results showed that compared with LNG, mid-dose mifepristone (25–50 mg) likely resulted in 12 fewer pregnancies per 1000 women (risk ratio [RR] 0.67, 95% confidence interval [CI]: 0.49 to 0.91). Compared to LNG, low-dose mifepristone (10–25 mg) resulted in 5 fewer pregnancies per 1000 women (RR 0.73, 95% CI: 0.59 to 0.90). Compared with COCs (Yuzpe regimen), any dose of mifepristone assessed was found to likely result in 22 fewer pregnancies per 1000 women (RR 0.14, 95% CI: 0.05 to 0.41). In terms of undesirable effects experienced per 1000 women, there was moderate-certainty evidence. Mid-dose mifepristone, when compared with LNG likely resulted in 91 fewer side effects including nausea, vomiting and spotting (RR 0.55, 95% CI: 0.39 to 0.76) and likely resulted in 31 more delayed menses events (RR 1.29, 95% CI: 1.01 to 1.64).
When low-dose mifepristone was compared with LNG, mifepristone likely reduced side effects (RR 0.26, 95% CI: 0.17 to 0.38) and slightly increased delayed menses (RR 1.52, 95% CI: 1.11 to 2.08). When comparing mifepristone to Yuzpe, mifepristone likely reduced side effects (RR 0.89, 95% CI: 0.83 to 0.95), and increased delayed menses (RR 2.83, 95% CI: 2.31 to 3.47). 3.1.3 Other considerations There is moderate certainty in the results for acceptability: mifepristone was compared with other oral methods (LNG and Yuzpe) and found to probably increase satisfaction (RR 1.09, 95% CI: 1.05 to 1.13). Mifepristone costs can be variable, and it is not currently widely manufactured or available. Because the other primary use of mifepristone is for medical abortion, political and legal contexts in various countries may influence access. The GDG noted that there may be some concerns related to potential for misuse, however these could be overcome by education, packaging or promotion. The GDG discussed the need for programmatic monitoring of the use of mifepristone for EC. Countries may need to determine how to make it available (e.g. over the counter or prescribed) and whether the costs are covered. The GDG also noted that registration and inclusion in essential medicines lists may motivate production and access.
3.1.4 Justification
The GDG made a strong recommendation for the inclusion of mifepristone in the method mix for EC. Overall, there is moderate certainty in the evidence for the effects of mifepristone; mifepristone is likely to be as effective and safe as other emergency contraceptive methods. Providing mifepristone instead of other EC methods may be more cost-effective in contexts where the cost of mifepristone is lower and thereby increase equitable access to EC if made widely available. It is probably as acceptable to women and clinicians as other methods, and probably feasible to provide. As with all emergency contraceptive methods, the provision of quality information for users and health professionals will be necessary to ensure appropriate use when added to the contraceptive method mix.
3.1.5 Implementation considerations
When implementing this recommendation, the GDG underscored the paramount importance of the right to contraceptive choice. Further, the GDG emphasized the imperative of addressing the following overarching issues when adding mifepristone for EC to national programmes.
- Informed consent
- Elements of quality of care
- Essential screening procedures for administering EC pills
- Provider training skills
- Referral and follow-up care for contraceptive use, as appropriate.
In addition, the GDG advised that WHO Member States should specifically consider the following when implementing mifepristone for EC:
- The cost of mifepristone varies depending on the dosage in countries; current estimates range from US$ 0.90–1.00 for 25 mg and US$ 1.20–1.35 for 50 mg.