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Contraception and ectopic pregnancy risk: a prospective observational analysis

Published:October 09, 2020DOI:https://doi.org/10.1016/j.ajog.2020.10.013

      Objective

      This study aimed to estimate the rates of ectopic pregnancy in women stratified by contraceptive method used and compare these rates to participants using no contraceptive method or condoms. We hypothesized that women using highly to moderately effective contraceptive methods (intrauterine device [IUD], implant, injectable contraception, and oral contraceptives [OCs], contraceptive patch, or vaginal ring) would have a lower rate of ectopic pregnancy than women using no method or condoms.

      Study Design

      This is a secondary analysis of the Contraceptive CHOICE Project (CHOICE), a prospective cohort study of 9256 participants who were provided the contraceptive method of their choice at no cost and observed for a duration of 2 to 3 years.
      • Peipert J.F.
      • Madden T.
      • Allsworth J.E.
      • Secura G.M.
      Preventing unintended pregnancies by providing no-cost contraception.
      Reported incidence of ectopic pregnancy during actual use of the contraceptive method was collected during follow-up telephone surveys. We estimated the incidence of ectopic pregnancy by each contraceptive method category: copper IUD, levonorgestrel IUD (LNG-IUD), implant, depot medroxyprogesterone acetate (DMPA), and 1 combined category consisting of OCs, contraceptive patch, and vaginal ring. Our control or referent group included women using no method or condoms. Inclusion and exclusion criteria followed that of the CHOICE Project.
      • Peipert J.F.
      • Madden T.
      • Allsworth J.E.
      • Secura G.M.
      Preventing unintended pregnancies by providing no-cost contraception.
      The percentages of ectopic pregnancies were calculated using number of ectopic pregnancies divided by number of pregnancies (intrauterine and ectopic, method specific) and multiplied by 100. Ectopic pregnancy rates per 1000 women-years were calculated using number of ectopic pregnancies divided by the total length of method use and multiplied by 1000.
      • Van Den Eeden S.K.
      • Shan J.
      • Bruce C.
      • Glasser M.
      Ectopic pregnancy rate and treatment utilization in a large managed care organization.
      Cox proportional hazard models calculated the hazard ratios (HRs) for ectopic pregnancy in each contraceptive method and in the no method or condoms group.

      Results

      Participants provided 20,381 women-years of follow-up with 13 ectopic pregnancies identified. Follow-up rates were 93.5%, 84.1%, and 78.9% at 1, 2, and 3 years, respectively. Crude results are shown in the Table. Seven participants in the no contraception or barrier group had an incidence of ectopic pregnancy. There were 6 contraceptive users who reported an incidence of ectopic pregnancy; 4 LNG-IUD users, 1 copper IUD user, and 1 OC user. Rates of ectopic pregnancy per 1000 women-years were as follows: no contraceptive method or condoms, 6.90; LNG-IUD, 0.50; copper IUD, 0.46; OCs, contraceptive patch, or vaginal ring, 0.22; implant, 0; and DMPA, 0. Use of the LNG-IUD (HR, 0.06; 95% confidence interval [CI], 0.02–0.23), copper IUD (HR, 0.08; 95% CI, 0.01–0.62), and OCs, contraceptive patch, or vaginal ring (HR, 0.04; 95% CI, 0.01–0.37) reduced the risk of ectopic pregnancy compared with no method or condom. Participants choosing implant and DMPA contraception methods had no reported ectopic pregnancies. Given the small number of ectopic events, we reported only the unadjusted HR.
      TableEctopic pregnancies by contraceptive method and Cox proportional HRs
      Method

      Number of pregnancies
      Both intrauterine and ectopic pregnancies are included in the reported number


      Number of ectopic pregnancies

      Percentage of Ectopic pregnancies

      Women-years

      Rate per 1000 women-years
      The denominator includes all pregnancies (intrauterine and ectopic).


      95% CI (rate)HR95% CI (HR)
      No contraceptive method or condom use51071.3710146.902.7814.22Reference
      LNG-IUD5147.8480600.500.141.270.060.020.23
      Copper IUD2414.1721980.460.012.530.080.010.62
      Implant1500.0028860.00
      DMPA3200.0015710.00
      OCs, contraceptive patch, or vaginal ring36310.2846520.220.011.200.040.010.37
      CI, confidence interval; DMPA, depot medroxyprogesterone acetate; HR, hazard ratio; IUD, intrauterine device; LNG, levonorgestrel; OC, oral contraceptive.
      Schultheis. Contraception and ectopic risk. Am J Obstet Gynecol 2021.
      a Both intrauterine and ectopic pregnancies are included in the reported number
      b The denominator includes all pregnancies (intrauterine and ectopic).

      Conclusion

      Women using the LNG-IUD, copper IUD, DMPA, implant, and OCs, contraceptive patch, or vaginal ring had a significantly lower risk of ectopic pregnancy compared with women using no contraception or barrier method of contraception. The CHOICE Project is one of the largest prospective cohort studies to investigate contraceptive use and ectopic pregnancy rates across multiple forms of contraception. Our study covers a wider range of contraceptive methods than previous studies, and the forms of contraception included in our study are more contemporary than currently included in previous literature.
      • Li C.
      • Zhao W.H.
      • Zhu Q.
      • et al.
      Risk factors for ectopic pregnancy: a multi-center case-control study.
      • Furlong L.A.
      Ectopic pregnancy risk when contraception fails. A review.
      • Li C.
      • Zhao W.H.
      • Meng C.X.
      • et al.
      Contraceptive use and the risk of ectopic pregnancy: a multi-center case-control study.
      One limitation of our work is that the incidence of ectopic pregnancy was low across all methods. This is not unexpected with more than 75% of our cohort using a highly effective method and have a low risk of contraceptive failure. In addition, recall bias is a possible limitation in defining ectopic pregnancy by using telephone call follow-up surveys and patient self-report.

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