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Ruptured ectopic pregnancies following methotrexate treatment: clinical course and predictors for improving patient counseling

  • General Gynecology: Original Article
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To determine the predictors for tubal rupture among women treated with methotrexate (MTX) for ectopic pregnancy. We performed a retrospective cohort analysis in a tertiary university-affiliated medical center. Medical records of 401 women who were diagnosed with ectopic pregnancy and were treated with MTX between January 2001 and June 2017 were reviewed. Forty-one women were diagnosed with ruptured ectopic pregnancy (study group) and 360 women with non-ruptured ectopic pregnancy (control group). Descriptive data and predictive variables for rupture ectopic pregnancy following MTX treatment were reviewed. Out of 122 women who failed MTX treatment, forty-one women had tubal rupture (33.6%). The median time interval from MTX treatment to tubal rupture was 6 days (1–25). β-hCG percentage change in the 48 h preceding MTX treatment and β-hCG level at day 0 were independent predictors for tubal rupture (odds ratio [OR] = 1.08, 95% confidence interval [CI] = 1.04–1.12, p < 0.001 for every percent change in β-hCG; OR = 1.001, 95% CI = 1.0003–1.002 for every unit change in β-hCG, respectively). In a decision tree analysis model, in women with β-hCG percentage increment >69% in the 48 h preceding methotrexate the probability for tubal rupture was 85%. Risk assessment for tubal rupture should be made before methotrexate treatment according to β-hCG dynamics and level. The absolute risk for tubal rupture in women with β-hCG increment<20% is low.

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Authors and Affiliations



Aviad Cohen - Protocol/project development, Data collection or management, Manuscript writing/editing, data analysis

Shikma Bar-on - Data management, Manuscript writing/editing

Yoni Cohen - Manuscript writing/editing, data and statistical analysis

Ori Sandel - Protocol/project development, Data collection

Yuval Fouks - Manuscript writing/editing data analysis

Tamar Tzur - Protocol/project development, Manuscript writing/editing

Nadav Michaan - data and statistical analysis

Ishai Levin - Protocol/project development, Manuscript writing/editing

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Correspondence to Aviad Cohen.

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This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of Tel-Aviv medical center IRB approval number: 0208–18-TLV.

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The authors have no relevant financial or non-financial interests to disclose.

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Cohen, A., Bar-on, S., Cohen, Y. et al. Ruptured ectopic pregnancies following methotrexate treatment: clinical course and predictors for improving patient counseling. Reprod. Sci. 29, 1209–1214 (2022).

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