A review of more than 100 trials compared the effectiveness and safety of levonorgestrel, mifepristone, and the Yuzpe regimen for emergency contraception.
For emergency contraception, levonorgestrel and mifepristone are more effective than the Yuzpe regimen (estradiol-levonorgestrel combination), according to a literature search and review of 115 randomized controlled trials. The review in the Cochrane Database of Systematic Reviews is an update of a review previously published in 2009 and 2012.
“Information on the comparative effectiveness, safety and convenience of these methods is crucial for reproductive healthcare providers and the women they serve,” the Chinese review authors wrote.
The included studies comprised 60,479 women who used emergency contraception after a single act of unprotected intercourse.
The primary review outcome was the observed number of pregnancies. Side effects and changes in menses were secondary outcomes.
The quality of the evidence ranged from moderate to high for the primary outcome, and from very low to high for the other outcomes.
Six studies of 4,750 women total found that levonorgestrel was associated with fewer pregnancies than Yuzpe (RR 0.57; 95% CI: 0.39 to 0.84). In other words, if the chance of pregnancy using Yuzpe is 29 per 1,000 women, the likelihood of pregnancy using levonorgestrel would be between 11 and 24 women per 1,000.
Both mid-dose (25 mg to 50 mg) and low-dose mifepristone (less than 25 mg) also were associated with fewer pregnancies than Yuzpe (RR 0.14; 95% CI: 0.05 to 0.41), according to three studies of 2,144 women total. For example, if the probability of pregnancy following Yuzpe is 25 per 1,000 women, the chance after mifepristone would be between 1 and 10 women per 1,000.
In addition, both low- and mid-dose mifepristone were likely associated with fewer pregnancies than levonorgestrel (RR 0.72; 95% CI: 0.52 to 0.99), according to three studies of 8,752 women total.
This finding suggests that if likelihood of pregnancy following levonorgestrel is 20 per 1,000 women, the chance of pregnancy after low-dose mifepristone would be between 10 and 20 women per 1,000.
Similarly, if the probability of pregnancy following levonorgestrel is 35 per 1,000 women, the chance of pregnancy following mid-dose mifepristone would be between 16 and 29 women per 1,000.
On the other hand, there was no conclusive evidence of a difference in risk of pregnancy between the copper intrauterine device (Cu-IUD) and mifepristone (RR 0.33; 95% CI: 0.04 to 2.74), according to two studies of 395 women total.
Nausea and vomiting are the two main adverse events associated with emergency contraception. Compared to Yuzpe, mifepristone had a lower risk of nausea (RR 0.63; 95% CI: 0.53 to 0.76) or vomiting (RR 0.12; 95% CI: 0.07 to 0.20). Levonorgestrel also had a lower risk of nausea (RR 0.40; 95% CI: 0.36 to 0.44) or vomiting (RR 0.29; 95% CI: 0.24 to 0.35) than Yuzpe. Furthermore, one study of 1,955 women concluded that levonorgestrel users were less likely to have any side effects compared to Yuzpe users (RR 0.80; 95% CI: 0.75 to 0.86).
The medication ulipristal acetate (UPA) was more likely than levonorgestrel to cause resumption of menstruation after the expected date (RR 1.65; 95% CI: 1.42 to 1.92) according to two studies totalling 3,593 women.
“Menstrual delay was more common with mifepristone than with any other intervention and appeared to be dose-related,” the authors wrote.
They also noted that there is low-quality evidence that the Cu-IUD may be linked to higher risks of abdominal pain than mifepristone: 18 events in 95 women using Cu-IUD as opposed to no events in 190 women using mifepristone.
Three review limitations were risk of bias due to poor reporting of methods, imprecision and inconsistency.