Effect of body weight and BMI on the efficacy of levonorgestrel emergency contraception.

OBJECTIVES: To further evaluate the effect of weight and body mass index (BMI) on the efficacy of levonorgestrel emergency contraception. METHODS: Data from two large, multicenter, randomized controlled trials designed to assess emergency contraceptive efficacy were pooled to evaluate the effect of weight and BMI on pregnancy rates among women who received levonorgestrel. Descriptive methods (comparison of means and distributions according to pregnancy status and pregnancy rates across weight and BMI categories) as well as cubic spline modeling were used to describe the relationship between pregnancy risk and weight/BMI. RESULTS: The analysis population comprised 1731 women, among whom 38 pregnancies were reported. Women for whom levonorgestrel was not effective in preventing pregnancy had a significantly higher mean body weight and BMI than women who did not become pregnant (76.7 vs. 66.4 kg, p<.0001; 28.1 vs. 24.6 kg/m², p<.0001). The estimated pregnancy rate increased significantly from 1.4% [95% confidence interval (CI): 0.5%-3.0%] among the group of women weighing 65-75 kg to 6.4% (95% CI: 3.1%-11.5%) and 5.7% (95% CI: 2.9%-10.0%) in the 75-85 kg and >85 kg groups, respectively. Statistical modeling demonstrated a steep increase in pregnancy risk starting from a weight near 70-75 kg to reach a risk of pregnancy of 6% or greater around 80 kg. Similar results were obtained for statistical modeling of BMI as well as when the two studies were analyzed individually. CONCLUSIONS: All analyses showed a significant drop in the efficacy of levonorgestrel emergency contraception with increasing body weight, with pregnancy risk in the higher weight categories similar to expected rates in the absence of contraception. Like body weight, increasing BMI was highly correlated with increased pregnancy risk.

Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel.

BACKGROUND: Emergency contraception (EC) does not always work. Clinicians should be aware of potential risk factors for EC failure. STUDY DESIGN: Data from a meta-analysis of two randomized controlled trials comparing the efficacy of ulipristal acetate (UPA) with levonorgestrel were analyzed to identify factors associated with EC failure. RESULTS: The risk of pregnancy was more than threefold greater for obese women compared with women with normal body mass index (odds ratio (OR), 3.60; 95% confidence interval (CI), 1.96-6.53; p<.0001), whichever EC was taken. However, for obese women, the risk was greater for those taking levonorgestrel (OR, 4.41; 95% CI, 2.05-9.44, p=.0002) than for UPA users (OR, 2.62; 95% CI, 0.89-7.00; ns). For both ECs, pregnancy risk was related to the cycle day of intercourse. Women who had intercourse the day before estimated day of ovulation had a fourfold increased risk of pregnancy (OR, 4.42; 95% CI, 2.33-8.20; p<.0001) compared with women having sex outside the fertile window. For both methods, women who had unprotected intercourse after using EC were more likely to get pregnant than those who did not (OR, 4.64; 95% CI, 2.22-8.96; p=.0002). CONCLUSIONS: Women who have intercourse around ovulation should ideally be offered a copper intrauterine device. Women with body mass index >25 kg/m(2) should be offered an intrauterine device or UPA. All women should be advised to start effective contraception immediately after EC.

Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and meta-analysis.

BACKGROUND: Emergency contraception can prevent unintended pregnancies, but current methods are only effective if used as soon as possible after sexual intercourse and before ovulation. We compared the efficacy and safety of ulipristal acetate with levonorgestrel for emergency contraception. METHODS: Women with regular menstrual cycles who presented to a participating family planning clinic requesting emergency contraception within 5 days of unprotected sexual intercourse were eligible for enrolment in this randomised, multicentre, non-inferiority trial. 2221 women were randomly assigned to receive a single, supervised dose of 30 mg ulipristal acetate (n=1104) or 1.5 mg levonorgestrel (n=1117) orally. Allocation was by block randomisation stratified by centre and time from unprotected sexual intercourse to treatment, with allocation concealment by identical opaque boxes labelled with a unique treatment number. Participants were masked to treatment assignment whereas investigators were not. Follow-up was done 5-7 days after expected onset of next menses. The primary endpoint was pregnancy rate in women who received emergency contraception within 72 h of unprotected sexual intercourse, with a non-inferiority margin of 1% point difference between groups (limit of 1.6 for odds ratio). Analysis was done on the efficacy-evaluable population, which excluded women lost to follow-up, those aged over 35 years, women with unknown follow-up pregnancy status, and those who had re-enrolled in the study. Additionally, we undertook a meta-analysis of our trial and an earlier study to assess the efficacy of ulipristal acetate compared with levonorgestrel. This trial is registered with ClinicalTrials.gov, number NCT00551616. FINDINGS: In the efficacy-evaluable population, 1696 women received emergency contraception within 72 h of sexual intercourse (ulipristal acetate, n=844; levonorgestrel, n=852). There were 15 pregnancies in the ulipristal acetate group (1.8%, 95% CI 1.0-3.0) and 22 in the levonorgestrel group (2.6%, 1.7-3.9; odds ratio [OR] 0.68, 95% CI 0.35-1.31). In 203 women who received emergency contraception between 72 h and 120 h after sexual intercourse, there were three pregnancies, all of which were in the levonorgestrel group. The most frequent adverse event was headache (ulipristal acetate, 213 events [19.3%] in 1104 women; levonorgestrel, 211 events [18.9%] in 1117 women). Two serious adverse events were judged possibly related to use of emergency contraception; a case of dizziness in the ulipristal acetate group and a molar pregnancy in the levonorgestrel group. In the meta-analysis (0-72 h), there were 22 (1.4%) pregnancies in 1617 women in the ulipristal acetate group and 35 (2.2%) in 1625 women in the levonorgestrel group (OR 0.58, 0.33-0.99; p=0.046). INTERPRETATION: Ulipristal acetate provides women and health-care providers with an effective alternative for emergency contraception that can be used up to 5 days after unprotected sexual intercourse. FUNDING: HRA Pharma.

Ulipristal acetate taken 48-120 hours after intercourse for emergency contraception.

OBJECTIVE: To evaluate the efficacy and safety of ulipristal acetate as emergency contraception in women presenting 48-120 hours after receiving ulipristal acetate for unprotected intercourse. METHODS: Women aged 18 years or older with regular cycles who presented for emergency contraception 48 to 120 hours after unprotected intercourse were enrolled in 45 Planned Parenthood clinics and treated with a single dose of 30 mg ulipristal acetate. Pregnancy status was determined by high-sensitivity urinary human chorionic gonadotropin testing and return of menses. RESULTS: A total of 1,241 women were evaluated for efficacy. Twenty-six were pregnant at follow-up, for a pregnancy rate of 2.1% (95% confidence interval 1.4-3.1%). These results satisfy the protocol-defined statistical criteria for success because the pregnancy rate was lower than both the estimated expected pregnancy rate and a predefined clinical irrelevance threshold. In addition, efficacy did not decrease over time: pregnancy rates were 2.3% (1.4-3.8%), 2.1% (1.0-4.1%), and 1.3% (0.1-4.8%) for intervals of 48 to 72 hours, more than 72 to 96 hours, and more than 96 to 120 hours, respectively. Adverse events were mainly mild or moderate, the most frequent being headache, nausea, and abdominal pain. Cycle length increased a mean of 2.8 days, whereas the duration of menstrual bleeding did not change. CONCLUSION: Ulipristal acetate is effective and well-tolerated for emergency contraception 48-120 hours after unprotected intercourse. LEVEL OF EVIDENCE: II.