DOI: 10.1111/jog.70532 ISSN: 1341-8076

Early β‐ hCG Trajectories After Single‐Dose Methotrexate Treatment and Their Predictive Value for Treatment Failure in Tubal Ectopic Pregnancy: A Retrospective Cohort Study

Juanping Zhang, Yanni Ma

ABSTRACT

Objective

To identify distinct early beta‐human chorionic gonadotropin (β‐hCG) trajectories following single‐dose methotrexate (MTX) treatment for tubal ectopic pregnancy and to evaluate their associations with treatment outcomes and potential value for Day‐7 posttreatment risk stratification.

Methods

This retrospective cohort study included hemodynamically stable patients with confirmed tubal ectopic pregnancy treated with single‐dose MTX. Among 828 patients in the all‐clinical cohort, 373 had quantitative β‐hCG measurements at Day 0, Day 4, and Day 7 and were included in trajectory modeling. Group‐based trajectory modeling was applied to log‐transformed β‐hCG values. Multivariable logistic regression evaluated associations with overall treatment failure and clinical treatment failure, while exploratory Day‐7 risk‐stratification analyses assessed model discrimination, calibration, and net benefit.

Results

Overall treatment failure occurred in 94 of 373 patients (25.2%), and clinical treatment failure occurred in 45 patients. A three‐class quadratic model identified a rapid decline class (56.3%), delayed decline class (28.2%), and persistent elevation/slow decline class (15.5%). Compared with the rapid decline class, the persistent elevation/slow decline class was associated with higher odds of overall treatment failure (adjusted OR [aOR] = 85.42, 95% CI: 25.64–284.55) and clinical treatment failure (aOR = 52.65, 95% CI: 11.22–246.88), although estimates for clinical failure were imprecise. In the exploratory Day‐7 model for overall treatment failure, the apparent AUC increased from 0.775 for the base clinical model to 0.862 after adding trajectory class ( p  < 0.001). Trajectory classes also showed heterogeneity in clinical failure within conventional Day 4–Day 7 β‐hCG response categories.

Conclusion

Early β‐hCG trajectories were associated with treatment outcomes after single‐dose MTX and may complement conventional Day‐7 posttreatment reassessment. Their clinical utility requires prospective multicenter external validation before routine use.

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