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

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.