Methotrexate in relatively contraindicated ectopic pregnancies: who benefits from treatment?

This study aimed to evaluate the efficacy of methotrexate (MTX) therapy and identify clinical and laboratory predictors of treatment failure, particularly in relatively contraindicated cases.

This retrospective cohort study included 225 hemodynamically stable patients with ectopic pregnancy treated with MTX between January 2019 and December 2024 at a tertiary university hospital. Relatively contraindicated cases were defined as having one or more of the following: β-hCG ≥ 5000 IU/L, ectopic mass ≥ 4 cm, fetal cardiac activity, or pelvic free fluid ≥ 5 cm. 58 patients met these criteria, while 167 were MTX-indicated. All patients received a single-dose intramuscular MTX protocol (50 mg/m² on day 0), and serum β-hCG levels were measured on days 0, 4, and 7. Treatment success was defined as a decline of β-hCG to < 5 mIU/mL without surgical intervention. Predictive factors for treatment failure were analyzed using logistic regression. Based on the identified independent predictors, a preliminary scoring model was constructed to explore risk stratification.

The overall MTX success rate was 85.8%. Success was significantly higher in the indicated group (92.8%) than in the relatively contraindicated group (65.5%). In the latter, treatment failure was significantly associated with higher baseline β-hCG levels and the pelvic free fluid ≥ 5 cm in the pouch of douglas. Multivariate analysis identified a significant association between these factors and MTX failure (β-hCG: OR 7.44, p < 0.001; free fluid: OR 4.10, p = 0.022). Other parameters, including fetal cardiac activity, yolk sac presence, adnexal mass size, and patient age, did not show a significant relationship in this model. The median time to surgical intervention in failed cases was 7 days.

Single-dose MTX remains a safe and effective option for carefully selected patients with relatively contraindicated ectopic pregnancies, achieving a 65.5% success rate. High baseline β-hCG and pelvic free fluid may serve as predictors of treatment failure, but do not preclude medical management when close monitoring is ensured. The proposed scoring system should be considered exploratory and requires external validation before clinical implementation. Further prospective studies are needed to confirm these findings and better define candidates for MTX therapy in high-risk cases.