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Purpose: We aim to assess the outcome of the treatment of cesarean scar pregnancy (CSP) with single-dose methotrexate (MTX) versus multiple-dose MTX protocols., Methods: A retrospective cohort study including two tertiary medical centers was conducted. All women diagnosed with CSPs between the years 2011 and 2019 that were initially managed with systemic MTX were included. Single-dose MTX practiced in one medical center was compared to multiple-dose MTX, practiced in the other medical center., Results: The study cohort included 31 women in the single dose and 32 women in the multiple-dose MTX groups. Baseline characteristics did not differ between groups. The primary outcome occurred in 12 (38.7%) of the cases in the single-dose group and in 6 (18.8%) in the multiple-dose group (p = 0.083). The rate of conversion to surgical treatment was similar in both groups (4 vs. 5 in the single vs. multiple-dose groups, respectively, p = 0.758). There was no significant difference between the single- and the multiple-dose groups in the administration of blood products (16.1% vs. 3.1%, respectively, p = 0.104), total days of admission (18 ± 9.3 vs. 17 ± 12.8 days, respectively, p = 0.850), and readmission rate (32.3% vs. 21.9%, respectively, p = 0.353). Data regarding sequential pregnancies were available for 11 women in the single and 13 women in the multiple-dose MTX groups. There were no differences between the groups in rates of term deliveries, CSP recurrence, and abortions., Conclusion: Both single- and multiple-dose MTX treatment protocols offer high success rate with a relatively low complication rate in the treatment of CSP.

The aim of this study was to compare the success rate of methotrexate (MTX) treatment in patients with recurrent ectopic pregnancy (REP) and primary EP (PEP). A retrospective cohort study. The study cohort comprised all patients diagnosed with an EP and treated by intention with single-dose regimen of intramuscular MTX in a tertiary medical centre during 2010-2018. Cases (REP) and controls (PEP) were compared.262 patients had PEP and 32 had a REP. Women with REP had significantly higher gravidity order and higher incidence of previous abortions (5 vs. 3, median, p  < .001, 59.3% vs. 32.8%, p  < .001, respectively). Women with REP had a higher proportion of a history of previous surgery in general, and specifically pelvic surgery (46.8% vs. 20.6%, p  < .001, 24.4% vs. 7.2%, p  < .001, respectively). Treatment success was lower in the REP group (40.6% vs. 66.4%, p  = .006, Odds ratio 0.34, 95% confidence interval 0.16, 0.73). In a logistic regression analysis, the only factor found to be independently associated with treatment failure was REP (adjusted odds ratio 0.30, 95% confidence interval 0.12, 0.77, p  = .01). Our study suggests that medical treatment success with a single-dose regimen of MTX is lower than expected among REP cases, suggesting that different treatment approach should be considered in this setting.Impact statement What is already known on this subject ? There is paucity of data regarding success rate of methotrexate treatment for a recurrent ectopic pregnancy (REP). What do the results of this study add? Medical treatment success with a single-dose regimen of MTX in patients with a REP is lower than expected What are the implications of these findings for future clinical practice and/or further research? As medical treatment success with a single-dose regimen of MTX for women with a REP is lower than expected, different treatment approach should be considered. Further and prospective studies with a larger sample size are needed to confirm our findings.

Research Question: Caesarean scar pregnancy (CSP) is an increasing concern in modern obstetrics. Early diagnosis and management are of utmost importance. The optimal management approach for CSP is not well established, with various treatment modalities reported. The role of conservative management of CSP has been previously reported, with conflicting results. This study aimed to further evaluate its role and better delineate the subsequent reproductive outcomes., Design: A retrospective cohort study including all patients diagnosed with a CSP and treated by intention of conservative management with systemic methotrexate (MTX). Maternal and gestation characteristics were compared between treatment success and failure groups., Results: Thirty-six cases of CSP were encountered. Overall, 29/36 (80.6%) were treated by systemic injection of MTX while the other 19.4% had combined systemic and local (i.e. intra-sac) MTX treatment. Invasive intervention was needed in five (13.9%) cases (failure group). Among those successfully treated with MTX, the median time to resolution was 22 (interquartile range 13-37) days. Cases who were converted to surgical treatment had a higher number of previous Caesarean deliveries (median 4 versus 2, P = 0.002). In logistic regression modelling, the number of previous Caesarean deliveries was the only factor independently associated with conversion to surgical management (odds ratio 2.02, 95% confidence interval 1.03-3.94). The majority of future pregnancies ended at term pregnancy with only one preterm delivery due to severe intrauterine growth restriction., Conclusions: Systemic MTX therapy is a safe and effective strategy for the treatment of CSP, with favourable subsequent reproductive results and a low conversion rate to surgical management., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

Objective: Our study aimed to investigate the predisposing factors for recurrence of an ectopic pregnancy (EP) following single-dose methotrexate (MTX) treatment for a primary EP. Methods: This was a retrospective cohort study performed in a tertiary care medical centre including all patients diagnosed with primary EP and treated with a single-dose regimen of intramuscular MTX. EPs with future recurrence were compared with first time only EPs, to identify risk factors for recurrent EP. Forward stepwise multivariate logistic regression analyses were subsequently carried out. Results: The study included 272 women. Of those, 22 (8.1%) had a recurrent EP. Women in the recurrent EP group had a higher rate of abortions (45.5% vs 32.7%; p  = 0.02), previous pelvic surgery (45.5% vs 6.5%; p  < 0.001) and both pelvic and uterine surgery (4.5% vs 1.6%; p  < 0.001). Conception by assisted reproductive technology (ART) was more common among the non-recurrent EP group (23.0% vs 4.5%; p  = 0.04). Success of single-dose MTX treatment was lower in the recurrent EP group compared with the non-recurrent EP group (36.4% vs 65.7%; p  = 0.006). A history of pelvic surgery was independently associated with recurrent EP (adjusted odds ratio [OR] 17.6; 95% confidence interval [CI] 4.9, 63.2; p  = 0.001). Treatment success of single-dose MTX was independently protective for recurrent EP (adjusted OR 0.25; 95% CI 0.08, 0.76; p  = 0.02). Conclusions: Among women with an EP, attention should be paid to those with previous pelvic surgery. Efforts should be made to achieve medical treatment success to prevent recurrent EP.

Research Question: Several studies have tried to identify early markers of treatment outcome after methotrexate (MTX) treatment for ectopic pregnancy, including pretreatment and day 4 human chorionic gonadotrophin (HCG) concentrations and their corresponding changes, and the increment in HCG during the initial 24 h after treatment. There have, however, been conflicting results. This study aimed to re-evaluate the role of these markers in the earlier identification of treatment success in a large cohort of women., Design: This was a retrospective cohort study including women diagnosed with an ectopic pregnancy and treated with a regimen of a single dose of MTX. A comparison of maternal and gestation characteristics was made between groups in whom treatment was successful or failed., Results: A total of 292 women treated with single-dose intramuscular MTX for ectopic pregnancy were included in this study. In the overall cohort, the treatment success rate with a single dose of MTX was 62.7% (183/292). Only two independent determinants were significantly associated with treatment success: the initial 24-h percentage increase in HCG (adjusted odds ratio [OR] 1.82, 95% confidence interval [CI] 1.26-2.63; P < 0.001) and the percentage change in HCG from day 1 to day 4 (adjusted OR 1.12, 95% CI 1.04-1.21; P < 0.001). The optimal cut-off points for prediction of treatment success were an increment of less than 17% in the 24 h before treatment and a decrease of more than 22% between the day 1 and day 4 HCG concentrations., Conclusions: A small increase in HCG concentration 24 h before treatment with MTX, alongside a decline in HCG concentration from day 1 to day 4, may predict the success of medical treatment for an ectopic pregnancy., (Copyright © 2019 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)