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

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          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.


          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).


          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.


          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 references 58

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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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              Estimates of contraceptive failure from the 2002 National Survey of Family Growth.

              In 2001, the US government's "Healthy People 2010" initiative set a goal of reducing contraceptive failure during the first year of use from 13% in 1995 to 7% by 2010. We provide updated estimates of contraceptive failure for the most commonly used reversible methods in the United States, as well as an assessment of changes in failure rates from 1995 to 2002. Estimates are obtained using the 2002 National Survey of Family Growth (NSFG), a nationally representative sample of US women containing information on their characteristics, pregnancies and contraceptive use. We also use the 2001 Abortion Patient Survey to correct for underreporting of abortion in the NSFG. We measure trends in contraceptive failure between 1995 and 2002, provide new estimates for several population subgroups, examine changes in subgroup differences since 1995 and identify socioeconomic characteristics associated with elevated risks of failure for three commonly used reversible contraceptive methods in the United States: the pill, male condom and withdrawal. In 2002, 12.4% of all episodes of contraceptive use ended with a failure within 12 months after initiation of use. Injectable and oral contraceptives remain the most effective reversible methods used by women in the United States, with probabilities of failure during the first 12 months of use of 7% and 9%, respectively. The probabilities of failure for withdrawal (18%) and the condom (17%) are similar. Reliance on fertility-awareness-based methods results in the highest probability of failure (25%). Population subgroups experience different probabilities of failure, but the characteristics of users that may predict elevated risks are not the same for all methods. There was no clear improvement in contraceptive effectiveness between 1995 and 2002. Failure rates remain high for users of the condom, withdrawal and fertility-awareness methods, but for all methods, the risk of failure is greatly affected by socioeconomic characteristics of the users.

                Author and article information

                [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.

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                10 December 2014
                : 9
                : 12
                25493939 4262460 PONE-D-14-36155 10.1371/journal.pone.0115031

                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.

                Pages: 17
                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.
                Research Article
                Medicine and Health Sciences
                Clinical Epidemiology
                Women's Health
                Obstetrics and Gynecology
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                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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