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      Contraceptive Use and the Risk of Ectopic Pregnancy: A Multi-Center Case-Control Study

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          Abstract

          Objective

          To evaluate the association between the risk of ectopic pregnancy (EP) and the use of common contraceptives during the previous and current conception/menstrual cycle.

          Methods

          A multi-center case-control study was conducted in Shanghai. Women diagnosed with EP were recruited as the case group (n = 2,411). Women with intrauterine pregnancy (IUP) (n = 2,416) and non-pregnant women (n = 2,419) were matched as controls at a ratio of 1∶1. Information regarding the previous and current use of contraceptives was collected. Multivariate logistic regression analyses were performed to calculate odds ratios (ORs) and the corresponding 95% confidential intervals (CIs).

          Results

          Previous use of intrauterine devices (IUDs) was associated with a slight risk of ectopic pregnancy (AOR 1 = 1.87 [95% CI: 1.48–2.37]; AOR 2 = 1.84 [1.49–2.27]), and the risk increased with the duration of previous use ( P 1 for trend <10 −4, P 2 for trend <10 −4). The current use of most contraceptives reduced the risk of both unwanted IUP (condom: AOR = 0.04 [0.03–0.05]; withdrawal method: AOR = 0.10 [0.07–0.13]; calendar rhythm method: AOR = 0.54 [0.40–0.73]; oral contraceptive pills [OCPs]: AOR = 0.03 [0.02–0.08]; levonorgestrel emergency contraception [LNG-EC]: AOR = 0.22 [0.16–0.30]; IUDs: AOR = 0.01 [0.005–0.012]; tubal sterilization: AOR = 0.01 [0.001–0.022]) and unwanted EP (condom: AOR 1 = 0.05 [0.04–0.06]; withdrawal method: AOR 1 = 0.13 [0.09–0.19]; calendar rhythm method: AOR 1 = 0.66 [0.48–0.91]; OCPs: AOR 1 = 0.14 [0.07–0.26]; IUDs: AOR 1 = 0.17 [0.13–0.22]; tubal sterilization: AOR 1 = 0.04 [0.02–0.08]). However, when contraception failed and pregnancy occurred, current use of OCPs (AOR 2 = 4.06 [1.64–10.07]), LNG-EC (AOR 2 = 4.87 [3.88–6.10]), IUDs (AOR 2 = 21.08 [13.44–33.07]), and tubal sterilization (AOR 2 = 7.68 [1.69–34.80]) increased the risk of EP compared with the non-use of contraceptives.

          Conclusion

          Current use of most contraceptives reduce the risk of both IUP and EP. However, if the contraceptive method fails, the proportions of EP may be higher than those of non-users. In the case of contraceptive failure in the current cycle, EP cases should be differentiated according to current use of OCPs, LNG-EC, IUDs, and tubal sterilization. In addition, attention should be paid to women with previous long-term use of IUDs.

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          Most cited references58

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          Ectopic pregnancy.

          Ectopic pregnancy is an important cause of morbidity and mortality worldwide. Use of transvaginal ultrasonography and quantitative measurement of the beta subunit of human chorionic gonadotropin (beta-hCG) has led to a reduction in the need for diagnostic laparoscopy. Furthermore, with earlier diagnosis, medical therapy with methotrexate can be offered and surgery avoided in some women, though the best regimen remains unclear. In the surgical management of ectopic pregnancy, the benefits of salpingectomy over salpingostomy are uncertain. Although there have been advances in the management of ectopic pregnancy there are still questions to be answered.
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            Current knowledge of the aetiology of human tubal ectopic pregnancy.

            BACKGROUND An ectopic pregnancy is a pregnancy which occurs outside of the uterine cavity, and over 98% implant in the Fallopian tube. Tubal ectopic pregnancy remains the most common cause of maternal mortality in the first trimester of pregnancy. The epidemiological risk factors for tubal ectopic pregnancy are well established and include: tubal damage as a result of surgery or infection (particularly Chlamydia trachomatis), smoking and in vitro fertilization. This review appraises the data to date researching the aetiology of tubal ectopic pregnancy. METHODS Scientific literature was searched for studies investigating the underlying aetiology of tubal ectopic pregnancy. RESULTS Existing data addressing the underlying cause of tubal ectopic pregnancy are mostly descriptive. There are currently few good animal models of tubal ectopic pregnancy. There are limited data explaining the link between risk factors and tubal implantation. CONCLUSIONS Current evidence supports the hypothesis that tubal ectopic pregnancy is caused by a combination of retention of the embryo within the Fallopian tube due to impaired embryo-tubal transport and alterations in the tubal environment allowing early implantation to occur. Future studies are needed that address the functional consequences of infection and smoking on Fallopian tube physiology. A greater understanding of the aetiology of tubal ectopic pregnancy is critical for the development of improved preventative measures, the advancement of diagnostic screening methods and the development of novel treatments.
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              Ulipristal acetate versus levonorgestrel for emergency contraception: a randomised non-inferiority trial and meta-analysis.

              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. 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. 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). 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. HRA Pharma. Copyright 2010 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                1932-6203
                2014
                10 December 2014
                : 9
                : 12
                : e115031
                Affiliations
                [1 ]Department of Obstetrics and Gynecology, International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200030, China
                [2 ]Department of Obstetrics, Gynecology and Women’s Health, School of Medicine, University of Missouri-Columbia, Columbia, MO, 65212, United States of America
                [3 ]Department of Obstetrics and Gynecology, Songjiang Maternity and Child Health Hospital, Shanghai, 201620, China
                [4 ]Department of Obstetrics and Gynecology, Minhang Central Hospital, Shanghai, 201100, China
                [5 ]Department of Obstetrics and Gynecology, Songjiang Central Hospital, Shanghai, 201600, China
                [6 ]Department of Obstetrics and Gynecology, Shanghai First People’s Hospital, Shanghai Jiaotong University, Shanghai, 200080, China
                State University of Maringá/Universidade Estadual de Maringá, Brazil
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: JZ XCL. Performed the experiments: WHZ HP GJQ SJC XX. Analyzed the data: CL CXM. Contributed reagents/materials/analysis tools: QZ WHZ. Contributed to the writing of the manuscript: CL WHZ.

                Article
                PONE-D-14-36155
                10.1371/journal.pone.0115031
                4262460
                25493939
                99a6ed08-75f7-4cdf-bb78-964ee9a978f4
                Copyright @ 2014

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 24 August 2014
                : 17 November 2014
                Page count
                Pages: 17
                Funding
                This work was supported by Shanghai Scientific and Technical Committee Grants (124119a4802). The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Epidemiology
                Clinical Epidemiology
                Women's Health
                Obstetrics and Gynecology
                Contraception
                Custom metadata
                The authors confirm that all data underlying the findings are fully available without restriction. All relevant data are within the paper and its Supporting Information files.

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