P-467 Early (day 1–4) post-treatment serum hCG level changes predict single-dose methotrexate treatment success in tubal ectopic pregnancy

Abstract Study question How effective is the change between day 1 and 4 post-treatment serum hCG level at predicting single-dose methotrexate treatment success in tubal ectopic pregnancy (tEP)? Summary answer Any fall in day 1–4 serum hCG signifies an 85% (95%CI 76.8–90.6) likelihood of treatment success for tEP managed with single-dose methotrexate. What is known already For those with tEP managed by single-dose methotrexate, current guidelines advocate intervention if day 4–7 hCG fails to fall by ≥ 15%. The trajectory of hCG over day 1–4 has been proposed as an early indicator that predicts treatment success, allowing early reassurance for women. However, almost all prior studies of day 1–4 hCG change have been small or retrospective. Study design, size, duration This was a prospective cohort study of women with tEP (pre-treatment hCG of ≥ 1000 IU/L and ≤5000 IU/L) managed with single-dose methotrexate. The data were derived from a UK multicentre randomised controlled trial of methotrexate and gefitinib versus methotrexate and placebo for treatment of tEP (GEM3). For this analysis, we include data from both treatment arms. Participants/materials, setting, methods Participants were categorised by single-dose methotrexate treatment success or failure. Treatment success for this analysis was defined as complete tEP resolution to serum hCG <30 IU/L following single-dose methotrexate treatment only. Patient characteristics between groups were compared. Changes in day 1–4, 1–7 and 4–7 serum hCG were evaluated as predictors of treatment success through receiver operating characteristic (ROC) curve analysis. Test performance characteristics were calculated for percentage reduction thresholds including optimal thresholds. Main results and the role of chance A total of 322 women with tEP and hCG ≥1000 IU/L and ≤5000 IU/L were treated with single-dose methotrexate. The overall single-dose methotrexate treatment success rate was 59% (n = 189/322). Day 1–4, 1–7 and 4–7 serum hCG change predicted single-dose methotrexate treatment success with ROC area under curve 0.80 (95% CI 0.74–0.85), 0.86 (95% CI 0.81–0.91) and 0.89 (95% CI 0.85–0.93) respectively. Any fall between day 1 and day 4 hCG predicted single-dose methotrexate treatment success with a positive predictive value of 85%, negative predictive value 57%, sensitivity 58%, specificity 84%, positive likelihood ratio 3.6 and negative likelihood ratio 0.5. A less than 18% rise in day 1–4 serum hCG was identified as an optimal classification threshold and predicted treatment success with 82% positive predictive value, 69% negative predictive value, 79% sensitivity, 74% specificity, positive likelihood ratio 3.0 and negative likelihood ratio 0.3. Limitations, reasons for caution Our findings may be limited by intervention bias resulting from existing guidelines which influences evaluation of hCG changes reliant on day 7 serum hCG levels. Wider implications of the findings This large prospective cohort demonstrates the value of day 1–4 serum hCG changes in predicting single-dose methotrexate treatment success in tEP. We recommend clinicians provide early reassurance to women who have fall or modest (<18%) rise in day 1–4 serum hCG that their treatment will likely be effective. Trial registration number This study is a secondary analysis of the GEM3 trial (ISRCTN Registry ISRCTN67795930).