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      Effect of BMI and body weight on pregnancy rates with LNG as emergency contraception: analysis of four WHO HRP studies

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          Abstract

          Objective

          To estimate the effect of increased body weight and body mass index (BMI) on pregnancy rates with levonorgestrel (LNG) 1.5 mg used as emergency contraception (EC).

          Methods

          The study reviewed data from 6873 women in four WHO-HRP randomized trials on EC conducted between 1993 and 2010. Participants took either 1.5 mg of LNG as a single dose or in two doses 12 h apart, up to 120 h of unprotected intercourse. Contraceptive efficacy (pregnancy rates) at different weight and BMI categories was evaluated.

          Results

          Overall pregnancy rate was low at 1.2%. Pregnancy rates were also low in women weighing over 80 kg (0.7%) and who were obese (BMI over 30 kg/m 2) (2.0%). The pooled analyses for pregnancy demonstrated that BMI over 30 kg/m 2 decreased efficacy significantly (odds ratio 8.27, 95% confidence interval = 2.70–25.37) when compared to women in lower BMI categories, mainly influenced by pregnancies in obese women from one study site. Sensitivity analyses excluding that site showed that obesity was no longer a risk factor; however, the other studies included too few obese women in the sample to exclude a substantial decrease in efficacy.

          Conclusions

          Pregnancy rates with use of LNG 1.5 mg for EC were low at less than 3% across different weight and BMI categories. Pooled analyses showed an increase in pregnancy rates among obese women (BMI more than 30 kg/m 2) compared to women with normal BMI levels, influenced by pregnancies all coming from one study site.

          Implications

          Access to LNG as EC should still be promoted to women who need them, and not be restricted in any weight or BMI category, with additional attention for counselling and advice for obese women.

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          Most cited references10

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          Low dose mifepristone and two regimens of levonorgestrel for emergency contraception: a WHO multicentre randomised trial.

          A single 10 mg dose of mifepristone, and two 0.75 mg doses of levonorgestrel 12 h apart, are effective for emergency contraception. Because no studies had compared the efficacies of both compounds, or investigated a single dose of 1.5 mg levonorgestrel, we undertook this three-arm trial. We did a randomised, double-blind trial in 15 family-planning clinics in 10 countries. We randomly assigned 4136 healthy women with regular menstrual cycles, who requested emergency contraception within 120 h of one unprotected coitus, to one of three regimens: 10 mg single-dose mifepristone; 1.5 mg single-dose levonorgestrel; or two doses of 0.75 mg levonorgestrel given 12 h apart. The primary outcome was unintended pregnancy; other outcomes were side-effects and timing of next menstruation. Analysis was by intention to treat, but we did exclude some patients from the final analyses. Of 4071 women with known outcome, pregnancy rates were 1.5% (21/1359) in those given mifepristone, 1.5% (20/1356) in those assigned single-dose levonorgestrel, and 1.8% (24/1356) in women assigned two-dose levonorgestrel. These proportions did not differ significantly (p=0.83). The relative risk of pregnancy for single-dose levonorgestrel compared with two-dose levonorgestrel was 0.83 (95% CI 0.46-1.50), and that for levonorgestrel (the two regimens combined) compared with mifepristone, 1.05 (0.63-1.76). Side-effects were mild and did not differ greatly between groups, and most women menstruated within 2 days of the expected date. Women who took levonorgestrel had earlier menses than did those who took mifepristone. The three regimens studied are very efficacious for emergency contraception and prevent a high proportion of pregnancies if taken within 5 days of unprotected coitus. Mifepristone and levonorgestrel do not differ in efficacy. A 1.5 mg single levonorgestrel dose can substitute two 0.75 mg doses 12 h apart.
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            Can we identify women at risk of pregnancy despite using emergency contraception? Data from randomized trials of ulipristal acetate and levonorgestrel.

            Emergency contraception (EC) does not always work. Clinicians should be aware of potential risk factors for EC failure. 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. 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 25 kg/m(2) should be offered an intrauterine device or UPA. All women should be advised to start effective contraception immediately after EC. Copyright © 2011 Elsevier Inc. All rights reserved.
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              Randomised controlled trial of levonorgestrel versus the Yuzpe regimen of combined oral contraceptives for emergency contraception. Task Force on Postovulatory Methods of Fertility Regulation.

              (1998)
              A previous randomised study suggested that the progestagen, levonorgestrel, given alone in two separate doses each of 0.75 mg caused nausea and vomiting in fewer women and might be more effective than the Yuzpe regimen of combined oral contraceptives for emergency contraception, although the difference was not significant. We compared these two regimens when started within 72 h of unprotected coitus. We enrolled in the double-blind, randomised trial 1998 women at 21 centres worldwide. Women with regular menses, not using hormonal contraception, and requesting emergency contraception after one unprotected coitus, received levonorgestrel (0.75 mg, repeated 12 h later) or the Yuzpe regimen (ethinyloestradiol 100 microg plus levonorgestrel 0.5 mg, repeated 12 h later). Outcome was unknown for 43 women (25 assigned levonorgestrel, 18 assigned Yuzpe regimen). Among the remaining 1955 women, the crude pregnancy rate was 1.1% (11/976) in the levonorgestrel group compared with 3.2% (31/979) in the Yuzpe regimen group. The crude relative risk of pregnancy for levonorgestrel compared with the Yuzpe regimen was 0.36 (95% CI 0.18-0.70). The proportion of pregnancies prevented (compared with the expected number without treatment) was 85% (74-93) with the levonorgestrel regimen and 57% (39-71) with the Yuzpe regimen. Nausea (23.1 vs 50.5%) and vomiting (5.6 vs 18.8%) were significantly less frequent with the levonorgestrel regimen than with the Yuzpe regimen (p<0.01). The efficacy of both treatments declined with increasing time since unprotected coitus (p=0.01). The levonorgestrel regimen was better tolerated and more effective than the current standard in hormonal emergency contraception. With either regimen, the earlier the treatment is given, the more effective it seems to be.
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                Author and article information

                Contributors
                Journal
                Contraception
                Contraception
                Contraception
                Elsevier
                0010-7824
                1879-0518
                1 January 2017
                January 2017
                : 95
                : 1
                : 50-54
                Affiliations
                [a ]Department of Reproductive Health and Research, UNDP – UNFPA- UNICEF – WHO – World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), World Health Organization
                [b ]Aga Khan University Center for Women's Health and Research
                Author notes
                [* ]Corresponding author. Tel.: +41-227913267. festinma@ 123456who.int mfestinmd@ 123456gmail.com
                Article
                S0010-7824(16)30357-2
                10.1016/j.contraception.2016.08.001
                5357708
                27527670
                f44c29e6-a9a8-42ea-94fc-ad1c2d7216e9
                © 2016 Published by Elsevier Inc.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 15 May 2015
                : 29 April 2016
                : 6 August 2016
                Categories
                Short Communication

                emergency contraception,hormonal contraception,levonorgestrel,body weight,body mass index (bmi)

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