Study of Factors Affecting the Failure of Methotrexate Treatment in Patients Diagnosed With Tubal Ectopic Pregnancy

Background: Methotrexate (MTX) is the first-line treatment for stable tubal ectopic pregnancy(EP), but its failure can lead to serious complications. This study aimed to identify predictive factors for methotrexate treatment failure to improve patient selection. Methods: In this retrospective cross-sectional study, ۳۷۱ patients with EP treated with a single-dose methotrexate regimen (۵۰ mg/m²) at Rouhani Hospital, Babol (۲۰۱۳-۲۰۲۴) were analyzed. Demographic, clinical (β-hCG, pain), sonographic (mass size, free fluid), and inflammatory indices (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII)) data were extracted from medical records. Treatment failure was defined as the need for surgery. Univariate and multivariate logistic regression were used to identify independent predictors, with ROC curves assessing their accuracy. Results: The treatment failure rate was ۹.۷% (n=۳۶). Multivariate analysis identified a larger mass size (OR=۱.۳۲; ۹۵%CI:۱.۱۵-۱.۵۲; p<۰.۰۰۱) and a higher systemic immune-inflammation index (SII) (OR=۱.۰۳; ۹۵%CI:۱.۰۰-۱.۰۶; p=۰.۰۳۶) as significant independent predictors of failure. Higher red blood cell count and platelet distribution width were protective factors. ROC analysis demonstrated high predictive accuracy for mass size (AUC=۰.۸۵) and SII (AUC=۰.۸۲) in distinguishing treatment outcomes. Conclusion: Ectopic pregnancy mass size ≥۲۳ mm and elevated SII are strong predictors of methotrexate treatment failure. These readily available parameters can serve as valuable tools for clinical decision-making, suggesting that primary surgery may be a preferable option for patients with these risk factors to avoid the complications of failed medical therapy.

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Keywords: Ectopic pregnancy ، methotrexate ، treatment failure ، inflammatory markers ، NLR