Archives of Gynecology and Obstetrics

, Volume 290, Issue 3, pp 417-423

First online:

Methotrexate for ectopic pregnancy: when and how

  • Gustavo Nardini CecchinoAffiliated withDepartment of Obstetrics, Federal University of São Paulo (UNIFESP)
  • , Edward Araujo JúniorAffiliated withDepartment of Obstetrics, Federal University of São Paulo (UNIFESP) Email author 
  • , Julio Elito JúniorAffiliated withDepartment of Obstetrics, Federal University of São Paulo (UNIFESP)

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Ectopic pregnancy is the leading cause of maternal death in the first trimester of pregnancy. The dosage of beta fraction of human chorionic gonadotropin (beta-hCG) and improvement of the transvaginal ultrasound allowed an earlier diagnosis and a conservative management. Currently, the use of systemic methotrexate (MTX) proved to be a great alternative with similar success rates and completely non-invasive.


We searched for the most relevant articles on the use of MTX in ectopic pregnancy published between 2003 and 2013 in high-impact journals. We performed a strategic search at the Centre for Reviews and Dissemination (CRD), Database of Abstracts of Reviews of Effects (DARE), National Institute for Health Research (NHS), International Prospective Register of Systematic Reviews (PROSPERO), The Cochrane Database of Systematic Reviews (CDSR) and Medical Literature Analysis and Retrieval System Online (MEDLINE) according to the descriptors “pregnancy, ectopic” and “methotrexate”, alone or combined.


Thus, we based this review on 32 studies that were classified following the grades of recommendation and levels of evidence proposed by the Oxford Centre for Evidence-Based Medicine. Additionally, selected papers were used. Scientific evidence points to a growing trend in the choice of conservative treatment for ectopic pregnancies, whereas expectant management still lacks studies for definitive conclusions. Indeed, the well-established protocols which exhibit a greater number of studies are still based on the single-dose treatment.


Considering MTX, it proved to be more effective in cases of low titers of beta-hCG and masses with a small diameter, although there is still no uniformity of these parameters. The choice largely depends on the experience of the medical team and ultimately, on the woman’s reproductive desire.


Ectopic pregnancy Methotrexate Therapeutic Reproductive health