Obstet Gynecol Sci.  2017 Jan;60(1):79-86. 10.5468/ogs.2017.60.1.79.

Pretreatment serum human chorionic gonadotropin cutoff value for medical treatment success with single-dose and multi-dose regimen of methotrexate in tubal ectopic pregnancy

• Kim J
• Jung YM
• Lee DY
• Jee BC

• KMID: 2383212
• DOI: http://doi.org/10.5468/ogs.2017.60.1.79

Abstract

OBJECTIVE
To investigate individual pretreatment serum human chorionic gonadotropin (hCG) cutoff value for medical treatment success with single-dose and multi-dose regimen of methotrexate in tubal ectopic pregnancy.
METHODS
Eighty-five women who received methotrexate for the treatment of tubal ectopic pregnancy during 2003 to 2015 were selected. Fifty-three women received a single-dose regimen and 32 women received a multi-dose regimen. Medical treatment failure was defined as necessity of surgical treatment. The medical treatment success rate was estimated in both regimens and the pretreatment serum hCG titer to predict the success was assessed by receiver operating characteristics curve analysis.
RESULTS
Pretreatment clinical and laboratory parameters were similar between group of single-dose regimen and multi-dose regimen. Treatment success rate was 64.2% in the single-dose regimen group and 71.9% in the multi-dose regimen group (P>0.05). Pretreatment serum hCG titer was an independent prognostic factor for treatment success in each regimen. Serum hCG cutoff value to predict the treatment success was 3,026 IU/L in single-dose regimen group and 3,711 IU/L in multi-dose regimen group.
CONCLUSION
We recommend use of single-dose regimen when pretreatment serum hCG <3,026 IU/L but multi-dose regimen may be favored when initial serum hCG level between 3,026 and 3,711 IU/L.

Keyword

Chorionic gonadotropin; Methotrexate; Pregnancy, tubal

MeSH Terms

Chorionic Gonadotropin*
Female
Humans*
Methotrexate*
Pregnancy
Pregnancy, Ectopic*
Pregnancy, Tubal
ROC Curve
Treatment Failure
Chorionic Gonadotropin
Methotrexate

Reference

1. Centers for Disease Control and Prevention (CDC). Ectopic pregnancy mortality: Florida, 2009-2010. MMWR Morb Mortal Wkly Rep. 2012; 61:106–109. PMID: 22337175.

2. Oron G, Tulandi T. A pragmatic and evidence-based management of ectopic pregnancy. J Minim Invasive Gynecol. 2013; 20:446–454. PMID: 23587907.

3. Stovall TG, Ling FW, Gray LA. Single-dose methotrexate for treatment of ectopic pregnancy. Obstet Gynecol. 1991; 77:754–757. PMID: 2014091.

4. Barnhart KT, Gosman G, Ashby R, Sammel M. The medical management of ectopic pregnancy: a meta-analysis comparing “single dose” and “multidose” regimens. Obstet Gynecol. 2003; 101:778–784. PMID: 12681886.

5. Hajenius PJ, Mol F, Mol BW, Bossuyt PM, Ankum WM, van der Veen F. Interventions for tubal ectopic pregnancy. Cochrane Database Syst Rev. 2007; (1):CD000324. PMID: 17253448.

6. Lipscomb GH, Givens VM, Meyer NL, Bran D. Comparison of multidose and single-dose methotrexate protocols for the treatment of ectopic pregnancy. Am J Obstet Gynecol. 2005; 192:1844–1847. PMID: 15970826.

7. Tabatabaii Bafghi A, Zaretezerjani F, Sekhavat L, Dehghani Firouzabadi R, Ramazankhani Z. Fertility outcome after treatment of unruptured ectopic pregnancy with two different methotrexate protocols. Int J Fertil Steril. 2012; 6:189–194. PMID: 24520438.

8. Alleyassin A, Khademi A, Aghahosseini M, Safdarian L, Badenoosh B, Hamed EA. Comparison of success rates in the medical management of ectopic pregnancy with single-dose and multiple-dose administration of methotrexate: a prospective, randomized clinical trial. Fertil Steril. 2006; 85:1661–1666. PMID: 16650421.

9. Guvendag Guven ES, Dilbaz S, Dilbaz B, Aykan Yildirim B, Akdag D, Haberal A. Comparison of single and multiple dose methotrexate therapy for unruptured tubal ectopic pregnancy: a prospective randomized study. Acta Obstet Gynecol Scand. 2010; 89:889–895. PMID: 20583934.

10. Menon S, Colins J, Barnhart KT. Establishing a human chorionic gonadotropin cutoff to guide methotrexate treatment of ectopic pregnancy: a systematic review. Fertil Steril. 2007; 87:481–484. PMID: 17173905.

11. Helmy S, Bader Y, Pablik E, Tiringer D, Pils S, Laml T, et al. Cut-off value of initial serum β-hCG level predicting a successful MTX therapy in tubal ectopic pregnancy: a retrospective cohort study. Eur J Obstet Gynecol Reprod Biol. 2014; 179:175–180. PMID: 24956362.

12. Wu J, Ludlow JP, De Vries B, Black K, Beale P. Single-dose methotrexate treatment for ectopic pregnancy and pregnancy of unknown location and progesterone as a predictor of success. Aust N Z J Obstet Gynaecol. 2014; 54:469–474. PMID: 25287564.

13. Orozco EM, Sanchez-Duran MA, Bello-Munoz JC, Sagala J, Carreras E, Roura LC. ß-hCG and prediction of therapeutic success in ectopic pregnancies treated with methotrexate, results from a prospective observational study. J Matern Fetal Neonatal Med. 2015; 28:695–699. PMID: 24871360.

14. Mirbolouk F, Yousefnezhad A, Ghanbari A. Predicting factors of medical treatment success with single dose methotrexate in tubal ectopic pregnancy: a retrospective study. Iran J Reprod Med. 2015; 13:351–354. PMID: 26330849.

15. Hamed HO, Ahmed SR, Alghasham AA. Comparison of double- and single-dose methotrexate protocols for treatment of ectopic pregnancy. Int J Gynaecol Obstet. 2012; 116:67–71. PMID: 22035883.

16. Practice Committee of American Society for Reproductive Medicine. Medical treatment of ectopic pregnancy: a committee opinion. Fertil Steril. 2013; 100:638–644. PMID: 23849842.

17. Nazac A, Gervaise A, Bouyer J, de Tayrac R, Capella-Allouc S, Fernandez H. Predictors of success in methotrexate treatment of women with unruptured tubal pregnancies. Ultrasound Obstet Gynecol. 2003; 21:181–185. PMID: 12601843.

18. Nowak-Markwitz E, Michalak M, Olejnik M, Spaczynski M. Cutoff value of human chorionic gonadotropin in relation to the number of methotrexate cycles in the successful treatment of ectopic pregnancy. Fertil Steril. 2009; 92:1203–1207. PMID: 18851850.

19. Gamzu R, Almog B, Levin Y, Avni A, Jaffa A, Lessing JB, et al. Efficacy of methotrexate treatment in extrauterine pregnancies defined by stable or increasing human chorionic gonadotropin concentrations. Fertil Steril. 2002; 77:761–765. PMID: 11937130.

20. Sagiv R, Debby A, Feit H, Cohen-Sacher B, Keidar R, Golan A. The optimal cutoff serum level of human chorionic gonadotropin for efficacy of methotrexate treatment in women with extrauterine pregnancy. Int J Gynaecol Obstet. 2012; 116:101–104. PMID: 22093497.

21. Tawfiq A, Agameya AF, Claman P. Predictors of treatment failure for ectopic pregnancy treated with single-dose methotrexate. Fertil Steril. 2000; 74:877–880. PMID: 11056225.

22. Helmy S, Koch M, Kolbl H, Grohmann-Izay B, Solomayer E, Bader Y. Correlation of the volume of ectopic pregnancy and MTX therapy outcome: a retrospective cohort study. Eur J Obstet Gynecol Reprod Biol. 2015; 184:108–111. PMID: 25490001.

23. Barnhart K, Hummel AC, Sammel MD, Menon S, Jain J, Chakhtoura N. Use of “2-dose” regimen of methotrexate to treat ectopic pregnancy. Fertil Steril. 2007; 87:250–256. PMID: 17097649.

24. Kim K, Suh DH, Cheong HH, Yoon SH, Lee TS, No JH, et al. Efficacy of methotrexate therapy in patients with tubal pregnancy and a serum human chorionic gonadotropin level above 10,000 IU/L. Clin Exp Reprod Med. 2014; 41:33–36. PMID: 24693496.

25. American College of Obstetricians and Gynecologists. ACOG Practice Bulletin No. 94: medical management of ectopic pregnancy. Obstet Gynecol. 2008; 111:1479–1485. PMID: 18515537.