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Background: Surgical rescue of methotrexate-treated ectopic pregnancy is necessary when tubal rupture or medical therapy failure is detected during post-therapeutic monitoring. It is known that an increased beta human chorionic gonadotropin (beta-hCG) concentration is the most important factor associated with treatment failure. Therefore, we suggested that relative changes in serum beta-hCG could predict a successful result of medical treatment, leading to facilitation of the decision to forgo the prospect of possible surgical rescue. Methods: A retrospective observational study of 115 patients with an ectopic pregnancy who were treated with a single dosage protocol of 50 mg/m(2) of methotrexate injected intramuscularly was performed at Puerta de Hierro University Hospital and Gregorio Maranon University General Hospital. Standard statistical tests were applied in order to evaluate the relative changes in beta-hCG concentration between the 1st and the 4th days following methotrexate injection. Results: Methotrexate treatment has a 95% probability to be successful if the relative change of beta-hCG from the 1st to the 4th day of monitoring is within the following interval: [-1.02; 0.15]. Moreover, if the values of beta-hCG-relative change from 1st to 4th day of monitoring are within [0.54; 1.2], it assures a negative result of treatment with 95% probability. Therefore, the value 0.15 (15%) of beta-hCG relative change can be considered a cut-off value for a positive result to treatment. Conclusions: Our data support that negative beta-hCG relative changes on the 4th day of treatment likely predict a successful result of methotrexate therapy, with a cut-off point of 0.15. Expectant management should be carried out in these cases if no clinical indications of surgery are presented. (C) 2016 Elsevier Ireland Ltd. All rights reserved.