Comparing four different methods for the management of ectopic pregnancy: A cross-sectional study


Background: Ectopic pregnancy (EP) is one of the major causes of maternal mortality during the first trimester of pregnancy.

Objective: Four treatment methods for EP including single-dose methotrexate (SD-MTX), double-dose methotrexate, expectant and surgical management were considered.

Materials and Methods: In this cross-sectional study, the clinical characteristics of 365 women aged 15-44 yr who had been diagnosed with EP were reviewed from March 2017 to March 2019 in hospitals affiliated to Shiraz University of Medical Sciences, Shiraz, Iran. Receiver operating characteristics curves were plotted to determine the cut-off points for size of ectopic mass and beta-human chorionic gonadotropin (β- hCG) that suitably discriminated between double-dose methotrexate and surgery management.

Results: The most common site of EP was adnexa. According to the receiver operating characteristics analysis, surgery was the best plan for the women with an ectopic mass > 34.50 mm in diameter or with an initial β-hCG level > 6419 mIU/ml. The β-hCG levels in the women successfully treated with SD-MTX were significantly lower than in those with failed treatment (p = 0.02). The SD-MTX group had a higher success rate and significantly shorter duration of hospitalization, and so this was a more effective medical treatment in comparison with the double-dose protocol.

Conclusion: Surgery is proposed as the best option for the cases with large ectopic mass or high β-hCG level. SD-MTX had a higher success rate and shorter hospital stay than the double-dose protocol, and so was found to be an efficient and safe alternative. Further randomized clinical trials with larger sample sizes are recommended to validate the current results.

Key words: Ectopic pregnancy, Methotrexate,

[1] Tas EE, Akcay GFY, Avsar AF. Single-dose methotrexate for the treatment of ectopic pregnancy: Our experience from 2010 to 2015. Pak J Med Sci 2017; 33: 13–17.

[2] Shrestha J, Saha R. Comparison of laparoscopy and laparotomy in the surgical management of ectopic pregnancy. J Coll Physicians Surg Pak 2012; 22: 760–764.

[3] Guven ESG, Dilbaz S, Dilbaz B, Ozdemir DS, Akdag D, Haberal A. Comparison of the effect of single-dose and multiple-dose methotrexate therapy on tubal patency. Fertil Steril 2007; 88: 1288–1292.

[4] Sendy F, AlShehri E, AlAjmi A, Bamanie E, Appani S, Shams T. Failure rate of single dose methotrexate in managment of ectopic pregnancy. Obstet Gynecol Int 2015; 2015: 902426.

[5] Karasu Y, Akselim B. Feasibility of single-incision laparoscopy for ruptured ectopic pregnancies with hemoperitoneum. Minim Invasive Ther Allied Technol 2019; 28: 46–50.

[6] Mol F, Mol BW, Ankum WM, VAN DER Veen F, Hajenius PJ. Current evidence on surgery, systemic methotrexate and expectant management in the treatment of tubal ectopic pregnancy: A systematic review and meta-analysis. Hum Reprod Update 2008; 14: 309–319.

[7] Cheng X, Tian X, Yan Zh, Jia M, Deng J, Wang Y, et al. Comparison of the fertility outcome of salpingotomy and salpingectomy in women with tubal pregnancy: A systematic review and meta-analysis. PLoS One 2016; 11: e0152343.

[8] Snyman L, Makulana T, Makin JD. A randomised trial comparing laparoscopy with laparotomy in the management of women with ruptured ectopic pregnancy. S Afr Med J 2017; 107: 258–263.

[9] Ozyuncu O, Tanacan A, Duru SA, Beksac MS. Methotrexate therapy for ectopic pregnancies: A tertiary center experience. Rev Bras Ginecol Obstet 2018; 40: 680–685.

[10] Boey O, Van Hooland S, Woestenburg A, Van der Niepen P, Verbeelen D. Methotrexate should not be used for patients with end-stage kidney disease. Acta Clin Belg 2006; 61: 166–169.

[11] Pulatoglu C, Dogan O, Basbug A, Kaya AE, Yildiz A, Temizkan O. Predictive factors of methotrexate treatment success in ectopic pregnancy: A single-center tertiary study. North Clin Istanb 2018; 5: 227–231.

[12] Inal ZO, Inal HA. Comparison of four methods of treating ectopic pregnancy: A retrospective cohort study. Geburtshilfe Frauenheilkd 2018; 78: 70–77.

[13] Nadim B, Leonardi M, Infante F, Lattouf I, Reid Sh, Condous G. Rationalizing the management of pregnancies of unknown location: Diagnostic accuracy of human chorionic gonadotropin ratio-based decision tree compared with the risk prediction model M4. Acta Obstet Gynecol Scand 2020; 99: 381–390.

[14] Athanasiou AI, Athanasiou A, Spandorfer SD. Review of ectopic pregnancy treatment for IVF patients. J Immunol Sci 2020; 4: 1–5.

[15] Hakim H, Yaich R, Halouani S, Jouou S, Arfaoudi R, Rachdi R. Non-surgical management of ectopic pregnancies. J Gynecol Oncol 2019; 2: 1013.

[16] Leonardi M, Allison E, Lu Ch, Nadim B, Condous G. Prognostic accuracy of a novel methotrexate protocol for the resolution of tubal ectopic pregnancies. Eur J Obstet Gynecol Reprod Biol 2020; 247: 186–190.

[17] Alsammani MA, Moona NA. Predictors of success of a single-dose methotrexate in the treatment of ectopic pregnancy. J Obstet Gynaecol India 2016; 66: 233–238.

[18] Song T, Kim MK, Kim ML, Lung YW, Yun BS, Seong SJ. Single-dose versus two-dose administration of methotrexate for the treatment of ectopic pregnancy: A randomized controlled trial. Hum Reprod 2015; 31: 332–338.

[19] Brincat M, Bryant-Smith A, Holland TK. The diagnosis and management of interstitial ectopic pregnancies: A review. Gynecol Surg 2019; 16: 2.

[20] Alsammani MA, Moona NA. Predictors of success of a single-dose methotrexate in the treatment of ectopic pregnancy. J Obstet Gynecol India 2016; 66: 233–238.

[21] Kimiaei P, Khani Z, Marefian A, Gholampour Ghavamabadi M, Salimnejad M. The importance of gestational sac size of ectopic pregnancy in response to single-dose methotrexate. ISRN Obstet Gynecol 2013; 2013: 269425.

[22] Sowter MC, Farquhar CM, Petrie KJ, Gudex G. A randomised trial comparing single dose systemic methotrexate and laparoscopic surgery for the treatment of unruptured tubal pregnancy. BJOG 2001; 108: 192–203.

[23] Song T, Kim MK, Kim ML, Jung YW, Yun BS, Seong SJ. Single-dose versus two-dose administration of methotrexate for the treatment of ectopic pregnancy: A randomized controlled trial. Hum Reprod 2016; 31: 332–338.

[24] Alur-Gupta S, Cooney LG, Senapati S, Sammel MD, Barnhart KT. Two-dose versus single-dose methotrexate for treatment of ectopic pregnancy: A meta-analysis. Am J Obstet Gynecol 2019; 221: 95–108.