Meta-Analysis
Am J Obstet Gynecol
. 2019 Aug;221(2):95-108.e2.
doi: 10.1016/j.ajog.2019.01.002. Epub 2019 Jan 7.
Two-dose versus single-dose methotrexate for treatment of ectopic pregnancy: a meta-analysis
Snigdha Alur-Gupta 1 , Laura G Cooney 2 , Suneeta Senapati 2 , Mary D Sammel 3 , Kurt T Barnhart 2
Affiliations
PMID: 30629908 PMCID: PMC6612469 DOI: 10.1016/j.ajog.2019.01.002
Free PMC article
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
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Flow diagram of study inclusion
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Risk of bias assessment
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Forest plot: Two versus Single…
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Figure 3B:
Forest plot: Two versus Single…
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Figure 3C:
Forest plot: Two versus Single…
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Forest plot: Two versus Single…
Comment in
Emphasis on the off-label use of methotrexate for ectopic pregnancy.
Rigopoulos P, Dardalas I, Pourzitaki C. Am J Obstet Gynecol. 2019 Jun;220(6):611-612. doi: 10.1016/j.ajog.2019.02.043. Epub 2019 Feb 23. PMID: 30807765 No abstract available.
Two-dose vs single-dose methotrexate for treatment of ectopic pregnancy.
Zhou Y, Huang H. Am J Obstet Gynecol. 2019 Oct;221(4):368. doi: 10.1016/j.ajog.2019.06.035. Epub 2019 Jun 20. PMID: 31229431 No abstract available.
Excerpts From the World Medical Literature.
Ziegler C. J Obstet Gynaecol Can. 2020 Apr;42(4):397-400. doi: 10.1016/j.jogc.2020.01.013. PMID: 32303291 No abstract available.
2 doses of methotrexate for ectopic pregnancy?
