Two-dose versus single-dose methotrexate for treatment of ectopic pregnancy: a meta-analysis - PubMed (original) (raw)
Meta-Analysis
Two-dose versus single-dose methotrexate for treatment of ectopic pregnancy: a meta-analysis
Snigdha Alur-Gupta et al. Am J Obstet Gynecol. 2019 Aug.
Abstract
Objective: To compare the treatment success and failure rates, as well as side effects and surgery rates, between methotrexate protocols.
Data sources: PubMed, Embase, and the Cochrane library searched up to July 2018.
Study eligibility criteria: Randomized controlled trials that compared women with ectopic pregnancies receiving the single-dose, two-dose, or multi-dose methotrexate protocols.
Study appraisal and synthesis methods: Odds of treatment success, treatment failure, side effects, and surgery for tubal rupture, as well as length of follow-up until treatment success, were compared using random and fixed effects meta-analysis. Sensitivity analyses compared treatment success in the groups with high human chorionic gonadatropin (hCG) values and a large adnexal mass, as defined by individual studies. The Cochrane Collaboration tool was used to assess risk of bias.
Results: The 2-dose protocol was associated with higher treatment success compared to the single-dose protocol (odds ratio [OR], 1.84; 95% CI, 1.13, 3.00). The 2-dose protocol was more successful in women with high hCG (OR, 3.23; 95% CI, 1.53, 6.84) and in women with a large adnexal mass (OR, 2.93; 95% CI, 1.23, 6.9). The odds of surgery for tubal rupture were lower in the 2-dose protocol (OR, 0.65; 95% CI, 0.26, 1.63), but this was not statistically significant. The length of follow-up was 7.9 days shorter for the 2-dose protocol (95% CI, -12.2, -3.5). The odds of side effects were higher in the 2-dose protocol (OR, 1.53; 95% CI, 1.01, 2.30). Compared to the single-dose protocol, the multi-dose protocol was associated with a nonsignificant reduction in treatment failure (OR, 0.56; 95% CI, 0.28, 1.13) and a higher chance of side effects (OR, 2.10; 95% CI, 1.24, 3.54). The odds of surgery for tubal rupture (OR, 1.62; 95% CI, 0.41, 6.49) and time to follow-up (OR, -1.3; 95% CI, -5.4, 2.7) were similar.
Conclusion: The 2-dose methotrexate protocol is superior to the single-dose protocol for the treatment of ectopic pregnancy in terms of treatment success and time to success. Importantly, these findings hold true in patients thought to be at a lower likelihood of responding to medical management, such as those with higher hCGs and a large adnexal mass.
Keywords: doses; ectopic pregnancy; medical management; methotrexate; protocol; tubal pregnancy.
Copyright © 2019 Elsevier Inc. All rights reserved.
Conflict of interest statement
Conflicts of interest:
The authors report no conflict of interest.
Figures
Figure 1:
Flow diagram of study inclusion
Figure 2:
Risk of bias assessment
Figure 3A:
Forest plot: Two versus Single dose-Treatment success
Figure 3B:
Forest plot: Two versus Single dose-Treatment failure
Figure 3C:
Forest plot: Two versus Single dose-Treatment success in high HCG group (defined by individual studies with a range of >3000–5500 mIUmL)
Figure 3D:
Forest plot: Two versus Single dose-Treatment success in large size group (defined by individual studies with a range of >2–3.5cm)
Figure 3E:
Forest plot: Two versus Single dose-Side effects
Figure 3F:
Forest plot: Two versus Single dose-Surgery for ruptured ectopic pregnancy
Figure 3G:
Forest plot: Two versus Single dose-Length of follow-up
Figure 4A:
Forest plot: Multi versus Single dose-Treatment failure
Figure 4B:
Forest plot: Multi versus Single dose-Treatment success in high HCG group (defined by study as >800 IU/L)
Figure 4C:
Forest plot: Multi versus Single dose-Treatment success in large size group (defined by study as >2 cm)
Figure 4D:
Forest plot: Multi versus Single dose-Surgery for ruptured ectopic pregnancy
Figure 4E:
Forest plot: Multi versus Single dose-Length of follow-up
Comment in
- Emphasis on the off-label use of methotrexate for ectopic pregnancy.
Rigopoulos P, Dardalas I, Pourzitaki C. Rigopoulos P, et al. Am J Obstet Gynecol. 2019 Jun;220(6):611-612. doi: 10.1016/j.ajog.2019.02.043. Epub 2019 Feb 23. Am J Obstet Gynecol. 2019. PMID: 30807765 No abstract available. - Two-dose vs single-dose methotrexate for treatment of ectopic pregnancy.
Zhou Y, Huang H. Zhou Y, et al. Am J Obstet Gynecol. 2019 Oct;221(4):368. doi: 10.1016/j.ajog.2019.06.035. Epub 2019 Jun 20. Am J Obstet Gynecol. 2019. PMID: 31229431 No abstract available. - Excerpts From the World Medical Literature.
Ziegler C. Ziegler C. J Obstet Gynaecol Can. 2020 Apr;42(4):397-400. doi: 10.1016/j.jogc.2020.01.013. J Obstet Gynaecol Can. 2020. PMID: 32303291 No abstract available.
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References
- Marion LL, Meeks GR. Ectopic pregnancy: History, incidence, epidemiology, and risk factors. Clin Obstet Gynecol 2012;55:376–86. - PubMed
- ACOG Practice Bulletin No. 193: Tubal Ectopic Pregnancy. Obstet Gynecol 2018;131:e91–e103. - PubMed
- Barnhart KT. Clinical practice. Ectopic pregnancy. N Engl J Med 2009;361:379–87. - PubMed
- Barnhart K, Coutifaris C, Esposito M. The pharmacology of methotrexate. Expert Opin Pharmacother 2001;2:409–17. - PubMed