Comparison of Two Different Protocols of Methotrexate Therapy in Medical Management of Ectopic Pregnancy

Abstract

Background:Ectopic pregnancy (EP) is one of the most dangerous complications of pregnancy and without prompt diagnosis and treatment, it could become a major cause of maternal morbidity and mortality.Objectives:In this randomized controlled study, we compared single and double dose of methotrexate (MTX) therapy in the treatment of ectopic pregnancy.Patients and Methods:This study was performed on 76 patients who were admitted to Obstetrics Ward with primary diagnosis of ectopic pregnancy based on their medical history, physical examination, beta subunit (β-HCG) level, and transvaginal ultrasonography. Using random block allocation, the patients were classified in two groups of single dose and double dose administration of MTX. In single dose group, 50 mg/m2 of MTX was given at day 0 and in double dose group, the patients received two doses of MTX at day 0 and 4. The level of β-HCG was measured at day 0, 4, 7 in both groups. The successful treatment was defined as 15% reduction in β-HCG level between day 4 and 7. The two groups were compared with each other with regard to their need for operation, or extra dose of MTX; duration of hospitalization; and MTX complications.Results:Results showed that the rate of success in double dose method was more than single dose one (79% versus 69%) but the difference was not significant (P = 0.29). Although the need for operation and extra dose of MTX were lower in the double dose group (15.8% vs. 18.8% and 5.26% vs. 13.2%, respectively), these differences were not significant too. Duration of hospitalization was significantly lower in double dose compared to the single dose (11.55 d vs. 14.76 d, P < 0.001).Conclusions:Single dose therapy of MTX has sufficient power and efficacy in the treatment of ectopic pregnancy, however in patients with higher serum level of β-HCG, the successful treatment increases by using double dose method. Using double dose also could decrease the necessity of operation, re-administration of MTX, and duration of hospitalization.

Multiple-dose and double-dose versus single-dose administration of methotrexate for the treatment of ectopic pregnancy: a systematic review and meta-analysis

“…Nine original articles were excluded because three studies were retrospective analyses (Gungorduk et al, 2011;Guven et al, 2007;Mergenthal et al, 2013), one was non-randomized trial (Lipscomb et al, 2005), one lacked the control group (Balci et al, 2010), the data of a conference abstract was not correct (Golmohammadlou et al, 2012), the multipledose regimen was not standard in two studies (Fakheri et al, 2014;Klauser et al, 2005), and in one study, no extractable data were available (Zargar et al, 2008). Therefore, the total number of studies included in the meta-analysis was six (Alleyassin et al, 2006;Guvendag Guven et al, 2010;Hamed et al, 2012;Saadati et al, 2015;Song et al, 2016;Tabatabaii Bafghi et al, 2012). All of the six studies were randomized controlled trials.…”

Systematic review and meta‐analysis of single‐dose and non‐single‐dose methotrexate protocols in the treatment of ectopic pregnancy

“…3). An analysis after exclusion of the study by Hamed et al27 showed similar results (RR 0.71, 95% CI 0.55-0.93; eight trials,18,19,24,25,28,[30][31][32] 777 patients, I 2 =7%).A subgroup analysis comparing the SDP with the multi-dose protocol revealed no significant difference in the adverse effect rate (RR 0.81, 95% CI 0.48-1.38; five trials,18,19,24,25,28 449 patients, I 2 =46%) (Fig. S3).…”

“…S3). However, a subgroup analysis comparing the SDP with the two-dose protocol showed that the adverse effect rate of the two-dose protocol was higher than that of the SDP (RR 0.74, 95% CI 0.54-1.00; four trials, 27,30-32 485 patients, I 2 =0%).Furthermore, a subgroup analysis of ectopic pregnancies with implantation at any site also revealed no significant difference in the adverse effect rate (RR 0.85, 95% CI 0.57-1.27; five trials,18,19,24,30,31 Baseline characteristics of included studies comparing single-dose and multi-dose protocols for MTX administration in the treatment of ectopic pregnancy.…”

“…The 11 included studies were RCTs comparing the SDP with non-SDPs for the treatment of ectopic pregnancy ( Five studies 25,[27][28][29]32 included tubal pregnancies only, whereas six studies 18,19,24,26,30,31 included ectopic pregnancies at any implantation site. The sensitivity analyses are presented in Table S1.…”

“…analysis, the outcomes remained similar (RR 1.00, 95% CI 0.96-1.05; 10 trials,18,19,[24][25][26][28][29][30][31][32] 964 patients, I 2 =23%).A subgroup analysis comparing the SDP with the multi-dose protocol demonstrated no significant difference in the ectopic pregnancy treatment success rate, although the SDP tended to have a higher success rate than the multi-dose protocol (RR 1.02, 95% CI 0.96-1.08; six trials,18,19,24,25,28,29 626 patients, I 2 =43%) (Fig. S1).A subgroup analysis comparing the SDP with the two-dose protocol also showed no significant difference in the success rate (RR 0.96, 95% CI 0.89-1.03; five trials, 23,24,27-29 495 patients, I 2 =0%).Similar results were obtained in a subgroup analysis comparing the SDP with the two-dose protocol with exclusion of the study byHamed et al 27 (RR 0.95, 95% CI 0.88-1.04; four trials, 26,30-32 251 patients, I 2 =0%).A subgroup analysis assessing ectopic pregnancies with implantation at any site revealed no significant differences in treatment success among the groups (RR 1.00, 95% CI 0.93-1.07; six trials,18,19,24,26,30,31 595 patients, I 2 =50%) (Fig. S2).…”