Day 1 to day 4 serum hCG change in predicting single-dose methotrexate treatment failure for tubal ectopic pregnancies

Abstract

Objective: To determine if changes in Day 1 to Day 4 serum human chorionic gonadotropin (hCG) levels can predict treatment failure of single-dose methotrexate (MTX) in medical management of tubal ectopic pregnancies (EP).

Study design: This retrospective cohort study was conducted at a tertiary level hospital. Files were reviewed for all women who received at least one dose of 50 mg/m² intramuscular MTX for treatment of ultrasound-confirmed tubal EPs between 2013 and 2018. "Treatment failure" is defined as needing additional MTX or surgery to manage the EP. The primary purpose is to establish a threshold percentage change in Day 1 to Day 4 (Day 1/4) hCG that best predicts treatment failure, with clinically and statistically significant sensitivity and specificity, based on receiver-operator characteristic (ROC) analysis.

Results: 252 files were reviewed, with 108 included for final analysis. 17% of cases required a second dose of MTX and 12% required surgery to manage the EP. Women in the treatment failure group had significantly higher median hCG levels on Day 1, 4 and 7, but were otherwise similar to women who were successful in age, parity, history of previous EP, and EP size. ROC curve analysis of Day 1/4 hCG demonstrates that ≥5% rise best predicts treatment failure with sensitivity 68% (95% confidence interval [CI] 49-83%), specificity 69% (95%CI 56-78%), and AUC 0.77 (95%CI 0.68-0.86, p < 0.001). The positive predictive value is 46% (95%CI 36-56%) and negative predictive value is 84% (95%CI 75-90%). In comparison, ROC analysis of Day 4 to Day 7 hCG demonstrates that a drop of ≤17% best predicted failure, with sensitivity 83% (95%CI 64-94%), specificity 82% (95%CI 71-90%), and AUC 0.90 (95%CI 0.84-0.96), p < 0.001.

Conclusion: This study suggests that ≥5% rise in Day 1/4 serum hCG levels could potentially predict treatment failure of single-dose MTX for tubal EPs, and that conversely, <5% rise or any drop in Day 1/4 hCG levels can reliably predict treatment success. Clinicians could consider factoring-in Day 1/4 hCG changes during the course of medically managing patients. They must bear in mind, however, that acting on the Day 1/4 hCG change would lead to increased interventions.

Keywords: Ectopic pregnancy; Methotrexate; Prognostic accuracy; Resource allocation; Tubal pregnancy.