Skip to main content
Log in

Expectant management versus systemic methotrexate in the management of persistent pregnancy of unknown location, a seven-year retrospective analysis

  • General Gynecology
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript



To compare Expectant management to systemic methotrexate in the management of persistent pregnancy of unknown location with beta-hCG levels below the discrimination zone.


A retrospective cohort study was conducted on 71 women with persistent pregnancy of unknown location. They were divided into two groups according to the applied management; Group 1, (n = 40) who were managed expectantly and Group 2 (n = 31) who were given a single dose of methotrexate. Data variables were collected and analyzed to evaluate whether expectant management was as effective as methotrexate.


There was no significant difference between the two groups regarding age, parity, gestational age, body mass index and day seven beta-hCG. Success rates were (32 patients (80%) and 28 patients (90.3%) in expectant management and methotrexate groups, respectively (P > 0.05). The mean values for day zero and day four beta-hCG were significantly higher and the mean duration for complete recovery was statistically shorter in the methotrexate group (P < 0.05). There were no significant differences between the two groups regarding prior ectopic, percentage of beta-hCG level drop on day four and day seven, success rate, occurrence of sequelae and patient satisfaction that area under the curve (AUC) for group 1 (expectant management) is 0.566 at 95% Confidence Interval of (0.388: 0.745).


Expectant management is an effective and safe alternative to single-dose methotrexate for persistent PUL with beta-hCG levels below the discrimination zone.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

Data are available with the corresponding author upon relevant request.

Code availability

Not applicable.


  1. Barnhart KT (2009) Ectopic pregnancy. N Engl J Med 361(4):379–387.

    Article  CAS  PubMed  Google Scholar 

  2. ACOG Practice Bulletin (2018) Tubal ectopic pregnancy. Obstet Gynecol 131(3):e91–e103.

    Article  Google Scholar 

  3. National Institute for Health and Care Excellence (NICE). Ectopic pregnancy and miscarriage: diagnosis and initial management. Updated November 2019. Accessed April 20, 2021.

  4. Barnhart K, van Mello NM, Bourne T et al (2011) Pregnancy of unknown location: a consensus statement of nomenclature, definitions, and outcome. Fertil Steril 95(3):857–866.

    Article  PubMed  Google Scholar 

  5. Parks MA, Barnhart KT, Howard DL (2018) Trends in the management of nonviable pregnancies of unknown location in the United States. Gynecol Obstet Invest 83(6):552–557.

    Article  CAS  PubMed  Google Scholar 

  6. van Mello NM, Mol F, Verhoeve HR et al (2013) Methotrexate or expectant management in women with an ectopic pregnancy or pregnancy of unknown location and low serum hCG concentrations? a randomized comparison. Hum Reprod 28(1):60–67.

    Article  CAS  PubMed  Google Scholar 

  7. Jurkovic D, Memtsa M, Sawyer E et al (2017) Single-dose systemic methotrexate vs expectant management for treatment of tubal ectopic pregnancy: a placebo-controlled randomized trial. Ultrasound Obstet Gynecol 49(2):171–176.

    Article  CAS  PubMed  Google Scholar 

  8. Silva PM, Araujo Júnior E, Cecchino GN, Elito Júnior J, Camano L (2015) Effectiveness of expectant management versus methotrexate in tubal ectopic pregnancy: a double-blind randomized trial. Arch Gynecol Obstet 291(4):939–943.

    Article  CAS  PubMed  Google Scholar 

  9. Mavrelos D, Nicks H, Jamil A, Hoo W, Jauniaux E, Jurkovic D (2013) Efficacy and safety of a clinical protocol for expectant management of selected women diagnosed with a tubal ectopic pregnancy. Ultrasound Obstet Gynecol 42(1):102–107.

    Article  CAS  PubMed  Google Scholar 

  10. Helmy S, Mavrelos D, Sawyer E et al (2015) Serum human chorionic gonadotropin (β-hCG) clearance curves in women with successfully expectantly managed tubal ectopic pregnancies: a retrospective cohort study. PLoS ONE 10(7):e0130598.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Elson J, Tailor A, Banerjee S, Salim R, Hillaby K, Jurkovic D (2004) Expectant management of tubal ectopic pregnancy: prediction of successful outcome using decision tree analysis. Ultrasound Obstet Gynecol 23(6):552–556.

    Article  CAS  PubMed  Google Scholar 

  12. Fridman D, Hawkins E, Dar P et al (2019) Methotrexate administration to patients with presumed ectopic pregnancy leads to methotrexate exposure of intrauterine pregnancies. J Ultrasound Med 38(3):675–684.

    Article  PubMed  Google Scholar 

  13. Barnhart KT, Senapati S, Sammel MD (2021) Declaring a gestation nonviable: when 99% certainty is not enough. Am J Obstet Gynecol 224(2):232–233.

    Article  PubMed  Google Scholar 

  14. Seeber BE, Sammel MD, Guo W, Zhou L, Hummel A, Barnhart KT (2006) Application of redefined human chorionic gonadotropin curves for the diagnosis of women at risk for ectopic pregnancy. Fertil Steril 86(2):454–459.

    Article  PubMed  Google Scholar 

  15. Condous G, Kirk E, Van Calster B, Van Huffel S, Timmerman D, Bourne T (2006) Failing pregnancies of unknown location: a prospective evaluation of the human chorionic gonadotrophin ratio. Br J Obstet Gynaecol 113:521–527

    Article  CAS  Google Scholar 

  16. Barnhart K, Hansen K, Stephenson M, Usadi R, Steiner A, Cedar M et al (2021) Effect of an Active vs Expectant Management Strategy on Successful Resolution of Pregnancy Among Patients With a Persisting Pregnancy of Unknown Location. JAMA 326(5):390–400.

    Article  PubMed  PubMed Central  Google Scholar 

Download references


The authors would like to acknowledge the contribution of the Record keeping and Bio-statistics personnel at King Abdul-Aziz Airbase Hospital for their logistic support.


Not applicable.

Author information

Authors and Affiliations



EE: Project development, Manuscript writing and editing and plagiarism check. YZ: Project development, data collection and revision. FA: Project development, data collection and revision. and MF: Project development, Data collection and data analysis and manuscript editing.

Corresponding author

Correspondence to Elsayed Elshamy.

Ethics declarations

Conflicts of interest


Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Elshamy, E., Zakaria, Y., Alajami, F. et al. Expectant management versus systemic methotrexate in the management of persistent pregnancy of unknown location, a seven-year retrospective analysis. Arch Gynecol Obstet 309, 1035–1041 (2024).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: