Background
The use of single‐dose intramuscular administration of methotrexate in the treatment of ectopic pregnancies (EP) is a well‐established practice. This study evaluates its use at a novel dose of 40 mg/m2 body surface area (BSA).

Objective
To evaluate the efficacy and safety of single‐dose methotrexate treatment 40 mg/m2 for tubal EP and persistent pregnancies of unknown location (PUL) and determine whether serum progesterone is a predictor of treatment success.

Materials and Methods
Retrospective cohort study of patients receiving intramuscular methotrexate 40 mg/m2 for the treatment of EP or PUL at Royal Prince Alfred Hospital over five years.

Results
One hundred and eighteen women received single‐dose methotrexate with an overall success of 84%. Surgical intervention was needed in 16.6%. Pretreatment beta‐hCG level and ectopic diagnosis were independent variables predictive of the need for surgery (P = 0.003 and 0.02, respectively). Serum progesterone level was not predictive of the need for a second dose or surgery. The sensitivity and specificity at pretreatment beta‐hCG of 1202 IU/L were 84% and 74%, respectively. Commonly reported side effects included nausea, abdominal pain and heavy vaginal bleeding. Significant treatment‐related adverse effects were rare.

Conclusion
Single‐dose IM methotrexate at a novel dose of 40 mg/m2 is a safe and effective treatment for selected EP and persistent PUL. The risk of surgery was positively correlated to serum beta‐hCG level and the diagnosis of EP. Progesterone was not a risk factor for surgery. Further studies are required to confirm the efficacy of this dose regimen and explore the safety of expectant management as an alternative to methotrexate treatment.