Predictive Value of Day 1–4 β-hCG Change for Single-Dose Methotrexate Failure in Tubal Ectopic Pregnancy

Day 1–4 β-hCG percentage change can help identify high-risk patients for methotrexate treatment failure in tubal ectopic pregnancy, but further prospective studies are needed to validate its clinical utility.

Summary and findings

This study evaluated the predictive value of day 1–4 β-hCG percentage change for single-dose methotrexate failure in women with tubal ectopic pregnancy. A total of 158 women aged 18–45 years received a single dose of intramuscular methotrexate (50 mg/m²). The study found that treatment failed in 69 out of 158 women (43.7%).

Abstract

<title>Abstract</title> <p>Background Single-dose intramuscular methotrexate (MTX) for tubal ectopic pregnancy fails in 25–30% of women, yet conventional assessment delays risk stratification until day 4–7. Earlier identification of high-risk patients could enable timely treatment intensification. Objective To evaluate whether day 1–4 β-human chorionic gonadotropin (β-hCG) percentage change predicts single-dose MTX failure and to assess independent clinical risk factors. Methods This retrospective cohort study included 158 women aged 18–45 years with tubal ectopic pregnancy treated with single-dose intramuscular MTX (50 mg/m²) between 2019–2025. Treatment failure was defined as need for additional MTX or surgery. Receiver operating characteristic (ROC) curve analysis with Youden index identified optimal day 1–4 β-hCG percentage change threshold. Multivariable logistic regression assessed independent predictors including initial β-hCG, ectopic mass size, previous ectopic pregnancy, and infertility treatment. Results Treatment failed in 69/158 (43.7%) women. Median day 1–4 β-hCG percentage change was + 26.4% (IQR 10.9–50.8) in the failure group versus − 5.9% (IQR − 16.8 to + 6.6) in the success group (P < 0.001). The optimal threshold of > 32.9% showed 47.8% sensitivity and 83.7% specificity with AUC 0.660 (95% CI 0.574–0.746). Day 1–7 and day 4–7 β-hCG changes demonstrated superior discrimination (AUC 0.768 and 0.774, respectively). In multivariable analysis, day 1–4 β-hCG change > 32.9% (adjusted odds ratio [aOR] 6.16, 95% CI 2.60-14.59) and previous ectopic pregnancy (aOR 7.39, 95% CI 1.88–29.03) remained independently associated with treatment failure. Infertility treatment lost statistical significance after adjustment (aOR 2.17, P = 0.100). The multivariable model showed good discrimination with AUC 0.819 (95% CI 0.750–0.888). Conclusion Day 1–4 β-hCG percentage change enables risk stratification 3 days earlier than conventional assessment, potentially allowing timely treatment intensification in high-risk patients. A multivariable prediction model incorporating early β-hCG kinetics and previous ectopic pregnancy demonstrates good discrimination. Prospective validation studies are needed to confirm clinical utility.</p>

Elsewhere in the HCG (Human Chorionic Gonadotropin) corpus