PURPOSE:The aim of this study is to investigate the clinical predictors of failure of a single dose of methotrexate (MTX) for management of ectopic pregnancy after in vitro fertilization (IVF). METHODS:A retrospective cohort study was performed of women who conceived ectopic pregnancies following fresh or frozen IVF cycles at an academic infertility clinic between 2007 and 2014, and received intramuscular MTX (50 mg/m2). Successful single-dose MTX treatment was defined as a serum beta-human chorionic gonadotropin (hCG) decline ≥15% between days 4 and 7 post-treatment. Logistic regression models adjusted for oocyte age, number of embryos transferred, and prior ectopic pregnancy were used to estimate the adjusted odds ratio (OR) (95% confidence interval [CI]) of failing one dose of MTX. RESULTS:Sixty-four patients with ectopic pregnancies after IVF were included. Forty required only one dose of MTX (62.5%), while 15 required additional MTX alone (up to four total doses, 23.4%), and 9 required surgery (14.1%). By multivariable logistic regression, the highest tertiles of serum hCG at peak (≥499 IU/L, OR = 9.73, CI 1.88-50.25) and at first MTX administration (≥342 IU/L, OR = 4.74, CI 1.11-20.26), fewer embryos transferred (OR = 0.37 per each additional embryo transferred, CI 0.19-0.74), and adnexal mass by ultrasound (OR = 3.65, CI 1.10-12.11) were each correlated with greater odds of requiring additional MTX and/or surgery. CONCLUSION:This is the first study to report that in women with ectopic pregnancies after IVF, higher hCG-though well below treatment failure thresholds previously described in spontaneous pregnancies-fewer embryos transferred, and adnexal masses are associated with greater odds of failing one dose of MTX. These findings can be used to counsel IVF patients regarding the likelihood of success with single-dose MTX.