Double Versus Single Dose Methotrexate Regimens in Management of Undisturbed Ectopic Pregnancy

Abstract

Objective: To assess the effectiveness and safety of double-dose methotrexate in comparing to single-dose methotrexate for management of ectopic pregnancy. Methods:A prospective randomized-controlled trial was conducted on 200 patients with ectopic pregnancy at the Obstetrics and gynecological Departments of Zagazig University, Egypt between June, 20 11 to May 2014. Patients were randomized into two groups, (group 1) who received a single dose 50 mg per meters squared surface area methotrexate (50 mg/m 2 IM on day 1) intramuscularly or (group 2), who received double-dose methotrexate regimen (50 mg/m 2 intramuscularly on days 1 and 4). The outcomes were; success rate, time duration of fall down of b-hcg to < 15 mlU/mL and undesirable effects of methotrexate. Results:In general, there is significant differences between both groups as regard the success rate and the duration of fall down β-hCG. The success rate was better in group 2 than in group 1 (90% versus 78.75%, P=0.01). The duration of fall down β-hCG until < 15 mlU/mL was shorter in group 2 (P=0.01). There was no significant difference between groups in adverse effects.Conclusion: Double-dose methotrexate as one of regimens of medical management of undisturbed ectopic pregnancy had more effectiveness and success rate than that of single-dose regimen with equivalent safety.

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).…”

“…Although the precise reason for this result is unclear, the total methotrexate dose could have had a substantial influence. The time to resolution in the six studies included in the time analysis 18,19,25,27,31,32 ranged from 14 days to 41 days, regardless of the protocol used.…”

“…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.…”

“…In a meta-analysis of the time from initial methotrexate injection to resolution of the pregnancy, a longer time to resolution was observed for the SDP than for the non-SDPs (MD 5.67 days, 95% CI 1.55-9.79 days; six trials, 18,19,25,27,31,32 688 patients, I 2 =91%) ( Fig. 4).…”

“…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).…”