Meta-Analysis: Effect of Endometriosis and Intrauterine Device Contraceptive on Ectopic Pregnancy


  • Afifa Intifadha Habibatullah Master's Program in Public Health, Universitas Sebelas Maret
  • Uki Retno Budihastuti Department of Obstetrics and Gynecology, Dr. Moewardi Hospital, Surakarta
  • Vitri Widyaningsih Faculty of Medicine, Universitas Sebelas Maret



Background: Ectopic pregnancy is an early complication of pregnancy with high morbidity and mortality. Several studies have examined a history of endometriosis and Intrauterine Device Contraceptive (IUD) use as risk factors for ectopic pregnancy, but have shown mixed results. This study aims to analyze the influence of a history of endometriosis and IUD use on the incidence of ectopic pregnancy based on previous primary studies.

Subjects and Method: This was a systematic review and meta-analysis conducted with the PRISMA flow diagram guidelines. The article search process was carried out on the PubMed, Google Scholar, Science Direct, SAGE, JSTOR, and Scopus databases, for articles published from 2005 to 2022. The keywords used were: “Endometriosis” AND “Intrauterine Contraceptive Device” OR “Intrauterine Device” OR “IUD” OR “IUCD” AND “Ectopic Pregnancy” OR “Extrauterine Preg­nancy” OR “Tubal Pregnancy” OR “Pregnancy Outcomes” OR “Pregnancy Complications” AND “Multivariate” OR “Multivariable” OR “Adjusted Odds Ratio” OR “aOR ". Analysis was performed with RevMan 5.3 software. Population: pregnant women of reproductive age. Intervention: endo­metriosis, using the IUD. Comparison: no endometriosis, no IUD use. Outcome: ectopic preg­nancy. Inclusion criteria were full-text observational study articles in English and Indonesian, with ectopic pregnancy as the outcome, analyzed multivariately by including adjusted Odds Ratio/aOR. The analysis was carried out using Review Manager 5.3 software.

Results: A total of 11 articles from Asia, Europe, Africa, Australia, and North America were found to meet the criteria and were included in the meta-analysis. The results of the overall analysis of 4 articles consisting of 2 cohort studies and 2 case-control studies were that endometriosis increased the risk of ectopic pregnancy 1.39 times higher than without endometriosis (aOR = 1.39, 95% CI = 1.16-1.68; p < 0.001). The results of the analysis of 7 case-control study articles showed that the use of IUDs increased the risk of ectopic pregnancy 1.35 times compared to not using the IUD and was not statistically significant (aOR = 1.35, 95% CI = 0.45-4.03; p = 0.590).

Conclusion: Endometriosis is a risk factor for ectopic pregnancy. IUD use increased the risk of ectopic pregnancy but was not statistically significant.

Keywords: endometriosis, intrauterine device contraceptive, ectopic pregnancy, meta-analysis.

Correspondence: Afifa Intifadha Habibatullah. Master’s Program in Public Health, Universitas Sebelas Maret. Jl. Ir. Sutami 36A, Surakarta 57126, Central Java, Indonesia. Email: Mobile: +6285375335480.



endometriosis, intrauterine device contraceptive, ectopic pregnancy, meta-analysis


Assouni-Mindjah YA, Essiben F, Foumane P, Dohbit JS, Mboudou ET (2018). Risk factors for ectopic pregnancy in a population of Cameroonian women: A case-control study. PLoS ONE. 13(12): e0207699. doi:

Callahan R, Yacobson I, Halpern V, Nanda K (2015). Ectopic pregnancy with use of progestin-only injectables and contraceptive implants: a systematic review. Contraception. 92(6): 514-522. doi: 10.1016/j.contraception.2015.08.016.

Farland LV, Prescott J, Sasamoto N, Tobias DK, Gaskins AJ, Stuart JJ, Carusi DA, Chavarro JE, Horne AW, Rich-Edwards JW, Missmer SA (2019). Endometriosis and Risk of Adverse Pregnancy Outcomes. Obstet. Gynecol, 134(3): 527–536. doi: 10.1097/AOG.0000000000003410.

Farquhar CM. (2005). Ectopic pregnancy. Lancet. 366(9485): 583–591. Doi: 10.1016/S01406736(05)671036.

Fylstra DL (2012). Ectopic pregnancy not within the (distal) fallopian tube: etiology, diagnosis, and treatment. Am. J. Obstet. Gynecol, 206(4): 289–299. Doi: 10.1016/j.ajog.2011.10.857.

Gabriel ID, Tudorache Ș, Vlădăreanu S, Oprescu ND, Mureșan MC, Cristina-Drăgușin R, Ceaușu I (2017). Birth control and family planning using intrauterine devices (IUDs). In Amarin, Z. O (Ed.), Family Planning. Intech-Open. doi: 10.5772/intechopen.72242.

Gaskins AJ, Missmer SA, Rich-Edwards JW, Williams PL, Souter I, Chavarro JE. (2018). Demographic, lifestyle, and reproductive risk factors for ectopic pregnancy. Fertil. Steril. 110(7): 1328–1337. doi: 10.1016/j.fertnstert.2018.08.022.

Gatzke N, Johnson L (2014). Ectopic pregnancy: a red flag diagnosis. J. Nurse Pract, 39(12): 42–47. doi: 10.1097/ 01.NPR.0000456394.77661.8e.

Hill CJ, Fakhreldin M, Maclean A, Dobson L, Nancarrow L, Bradfield A, Choi F, Daley D, Tempest N, Hapangama DK (2020). Endometriosis and the Fallopian Tubes: Theories of Origin and Clinical Implications. J. Clin. Med., 9(6): 1905.

Hjordt HMV, Dalsgaard T, Hartwell D, Skovlund CW, Lidegaard Ø (2014). Reproductive prognosis in endometriosis. A national cohort study. Acta Obstet Gynecol Scand. 93(5), 483–489. doi: 10.1111/aogs.12373.

Hwang A, Chou L, Islam MM, Li YC, Syed-Abdul S (2016). Risk factors for ectopic pregnancy in the Taiwanese population: a retrospective observational study. Arch. Gynecol. Obstet. 294(4): 779–783. doi: 10.1007/s0040401641177.

Jasmy ES, Varghese SA, Varghese MA, Yeldhos S, Baby A (2020). Ectopic pregnancy: An Overview. World J. Pharm. Res. 9(50): 400-415. ISSN: 2277-7105.

Kriebs JM, Fahey JO (2006). Ectopic pregnancy. JMWH, 51(6): 431–439.

Mayaningrum YE, Pamungkasari EP, Murti B. (2021). Meta-Analysis the effect of intrauterine device uptake on the risk of ectopic pregnancy in women of reproductive age. JMCH. 06(02): 165-175. doi: 10.26911/thejmch.2021.06.


Mol BW, Ankum WM, Bossuyt PM, Van der Veen F (1995). Contraception and the risk of ectopic pregnancy: a meta-analysis. Contraception. 52(6): 337–341. doi: 10.1016/00107824(95)002219.

Muzaffar U, Rasool S, Ahmad K, Rasool M. (2020) Risk factors for ectopic pregnancy in women: A case control study. Int J Clin Obstet Gynaecol. 4(3): 153-157. doi: 10.33545/gynae.2020.v4.i3c.596.

Saetta A, Magro M, Oliver R, Odejinmi F (2020). Endometriosis and the risk of ectopic pregnancy: 10-year retrospective cohort study. JEPPD, 12(1): 10–15. Doi: 10.1177/2284026519877095.

Saraswat L, Ayansina DT, Cooper KG, Bhattacharya S, Miligkos D, Horne AW, Bhattacharya S (2017). Pregnancy outcomes in women with endometrio-sis: a national record linkage study. BJOG. 124(3): 444–452. doi: 10.1111/14710528.13920.

Taran FA, Kagan KO, Hübner M, Hoopmann M, Wallwiener D, Brucker S. (2015). The Diagnosis and Treatment of Ectopic Pregnancy. Dtsch. Ärztebl. 112(41): 693–705. doi: 10.3238/arztebl.2015.0693.

Vercellini P, Viganò P, Somigliana E, Fedele L (2014). Endometriosis: pathogenesis and treatment. Nat. Rev. Endocrinol, 10(5): 261–275. doi: 10.1038/nrendo.


Xiong X, Buekens P, Wollast E. (1995). IUD use and the risk of ectopic pregnancy: A meta-analysis of case-control studies. Contraception. 52(1): 23-34. doi: 10.1016/00107824(95)00120Y.

Yanuari RR, Pamungkasari EP, Widyaningsih V (2021). Associations between smoking, intrauterine device uptake, and ectopic pregnancy: a meta-analysis. JMCH, 06(03): 388-399. doi: 10.26911/thejmch.2021.06.04.01.

Yong PJ, Matwani S, Brace C, Quaiattini A, Bedaiwy MA, Albert A, Allaire C (2020). Endometriosis and ectopic pregnancy: a meta-analysis. J.Minim. Invasive Gynecol, 27(2): 352–361.e2. doi: 10.1016/j.jmig.2019.09.778.

Załęcka J, Pankiewicz K, Issat T, Laudański P (2022). Molecular mechanisms underlying the association between endometriosis and ectopic pregnancy. Int. J. Mol. Sci, 23(7): 3490. doi: 10.3390/ijms23073490.




How to Cite

Habibatullah, A. I., Budihastuti, U. R., & Widyaningsih, V. (2022). Meta-Analysis: Effect of Endometriosis and Intrauterine Device Contraceptive on Ectopic Pregnancy. Journal of Maternal and Child Health, 7(4), 387–397.