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Early prediction for the requirement of second or third dose methotrexate in women with ectopic pregnancy, treated with single-dose regimen

  • General Gynecology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

To investigate the predictive factors for the requirement of additional doses of methotrexate in women with ectopic pregnancy treated with single-dose methotrexate regimen.

Methods

This retrospective cohort study was conducted on women treated with single-dose methotrexate regimen for ectopic pregnancy at a tertiary referral center. Control group included the patients who were treated only with a single dose of methotrexate (n = 131) and study group included the patients who need a second dose or third dose methotrexate (n = 76). The sonographic variables such as size of the ectopic mass, the endometrial thickness and biochemical variables were analyzed via Chi square and student t test. Logistic regression analysis used to determine independent predictors of the additional dose requirement.

Results

The size of the ectopic mass and the endometrial thickness were similar in both groups. However, all human chorionic gonadotropin values on day 1, 4 and 7 were significantly higher in study group than the control group (p = 0.0001). Logistic regression analysis revealed that the human chorionic gonadotropin changes between day 1 and 4 is a predictive factor for requirement of additional doses of methotrexate (area under curve: 0.763, p < 0.001) and the cutoff value for human chorionic gonadotropin change was calculated as 22 %. The probability of the requirement for an additional dose of methotrexate is 6.45 times more in patients who had less than 22 % reduction in human chorionic gonadotropin levels from day 1 to 4 compared to those who had >22 % reduction from day 1 to 4.

Conclusion

Less than 22 % reduction in human chorionic gonadotropin levels from day 1 to 4 can be used as a predictive factor for the requirement of an additional dose of methotrexate in single-dose regimen. This cutoff value can be used for patients to inform about the probable longer resolution time and refer to alternative treatment modalities such as two-dose, multiple-dose regimens or surgery.

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References

  1. Berg CJ, Callaghan WM, Syverson C et al (2010) Pregnancy-related mortality in the US, 1998–2005. Obstet Gynecol 116:1302–1309

    Article  PubMed  Google Scholar 

  2. Shaw JL, Dey SK, Critchley HO, Horne AW (2010) Current knowledge of the aetiology of human tubal ectopic pregnancy. Hum Reprod Update 16:432–444

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  3. Capmas P, Bouyer J, Fernandez H (2014) Treatment of ectopic pregnancies in 2014: new answers to some old questions. Fertil Steril 101:615–620

    Article  PubMed  Google Scholar 

  4. Fernandez H, Capmas P, Lucot JP, Resch B, Panel P, Bouyer J (2013) GROG. Fertility after ectopic pregnancy: the DEMETER randomized trial. Hum Reprod 28:1247–1253

    Article  PubMed  Google Scholar 

  5. Barnhart KT, Gosman G, Ashby R, Sammel M (2003) The medical management of ectopic pregnancy: a meta-analysis comparing ‘single dose’ and ‘multidose’ regimens. Obstet Gynecol 101:778–784

    Article  PubMed  Google Scholar 

  6. Guvendag Guven ES, Dilbaz S, Dilbaz B, Aykan Yıldırım B, Akdag D, Haberal A (2010) Comparison of single dose and multiple dose methotrexate therapy for unruptured tubal ectopic pregnancy: a prospective randomized trial. Acta Obstet Gynecol Scand 89:889–895

    Article  PubMed  Google Scholar 

  7. Lipscomb GH, Bran D, McCord ML et al (1998) Analysis of three hundred fifteen ectopic pregnancies treated with single-dose methotrexate. Am J Obstet Gynecol 178:1354

    Article  CAS  PubMed  Google Scholar 

  8. Potter MB, Lepine LA, Jamieson DJ (2003) Predictors of success with methotrexate treatment of tubal ectopic pregnancy at Grady Memorial Hospital. Am J Obstet Gynecol 188:1192–1194

    Article  CAS  PubMed  Google Scholar 

  9. Elito J Jr, Reichmann AP, Uchiyama MN, Camano L (1999) Predictive score for the systemic treatment of unruptured ectopic pregnancy with a single dose of methotrexate. Int J Gyneacol Obstet 67:75–79

    Article  CAS  Google Scholar 

  10. Krissi H, Peled Y, Eitan R, Bishara A, Goldchmit C, Ben-Haroush A (2013) Single-dose methotrexate injection for treatment of ectopic pregnancy in women with relatively low levels of human chorionic gonadotropin. Int J Gynaecol Obstet 121:141–143

    Article  CAS  PubMed  Google Scholar 

  11. Sagiv R, Debby A, Feit H, Cohen-Sacher B, Keidar R, Golan A (2012) The optimal cutoff serum level of human chorionic gonadotropin for efficacy of methotrexate treatment in women with extrauterine pregnancy. Int J Gynaecol Obstet 116:101–104

    Article  CAS  PubMed  Google Scholar 

  12. Nowak-Markwitz E, Michalak M, Olejnik M, Spaczynski M (2009) Cutoff value of human chorionic gonadotropin in relation to the number of methotrexate cycles in the successful treatment of ectopic pregnancy. Fertil Steril 92:1203–1207

    Article  CAS  PubMed  Google Scholar 

  13. Nazac A, Gervaise A, Bouyer J, de Tayrac R, Capella-Allouc S, Fernandez H (2003) Predictors of success in methotrexate treatment of women with unruptured tubal pregnancies. Ultrasound Obstet Gynecol 21:181–185

    Article  CAS  PubMed  Google Scholar 

  14. Natale A, Busacca M, Candiani M, Gruft L, Izzo S, Felicetta I, Vignali M (2002) Human chorionic gonadotropin patterns after a single dose of methotrexate fpr ectopic pregnancy. Eur J Obstet Gynecol Reprod Biol 100:227–230

    Article  CAS  PubMed  Google Scholar 

  15. Practice Committee of American Society for Reproductive Medicine (2013) Medical treatment of ectopic pregnancy: a committee opinion. Fertil Steril 100(3):638–644

    Article  Google Scholar 

  16. Menon S, Colins J, Barnhart KT (2007) Establishing a human chorionic gonadotropin cutoff to guide methotrexate treatment of ectopic pregnancy: a systematic review. Fertil Steril 87:481–484

    Article  CAS  PubMed  Google Scholar 

  17. Lipscomb GH, McCord ML, Stovall TG, Huff G, Portera SG, Ling FW (1999) Predictors of success of methotrexate treatment in women with tubal ectopic pregnancies. N Engl J Med 341:1974–1978

    Article  CAS  PubMed  Google Scholar 

  18. Agostini A, Blanc K, Ronda I, Romain F, Capelle M, Blanc B (2007) Prognostic value of human chorionic gonadotropin changes after methotrexate injection for ectopic pregnancy. Fertil Steril 88:504–506

    Article  CAS  PubMed  Google Scholar 

  19. Ustunyurt E, Duran M, Coskun E, Ustunyurt B, Simsek H (2013) Role of initial and day 4 human chorionic gonadotropin levels in predicting the outcome of single-dose methotrexate treatment in women with tubal ectopic pregnancy. Arch Gynecol Obstet 288:1149–1152

    Article  CAS  PubMed  Google Scholar 

  20. Bottin P, Gnisci A, Crochet P, Butzbach P, Cravello L, Gamerre M, Agostini A (2014) Prognostic value of early hCG changes after methotrexate injection for ectopic pregnancy. Gynecol Obstet Fertil 42:3–7

    Article  CAS  PubMed  Google Scholar 

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Conflict of interest

A. Y, D. A. C, M. A, O. G do not have any financial disclosure or conflict of interest.

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Authors and Affiliations

  1. Etlik Zubeyde Hanım Women’s Health Education and Research Hospital, Yeni Etlik Caddesi No: 55 Kecioren, Ankara, Turkey

    Aysegul Yıldırım, Derya Akdağ Cırık, Metin Altay & Orhan Gelisen

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  1. Aysegul Yıldırım
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  2. Derya Akdağ Cırık
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  3. Metin Altay
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  4. Orhan Gelisen
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Correspondence to Derya Akdağ Cırık.

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Yıldırım, A., Cırık, D.A., Altay, M. et al. Early prediction for the requirement of second or third dose methotrexate in women with ectopic pregnancy, treated with single-dose regimen. Arch Gynecol Obstet 291, 1327–1332 (2015). https://doi.org/10.1007/s00404-014-3593-x

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  • DOI: https://doi.org/10.1007/s00404-014-3593-x

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