Performance of human chorionic gonadotropin curves in women at risk for ectopic pregnancy: exceptions to the rules

Fertil Steril. 2012 Jan;97(1):101-6.e2. doi: 10.1016/j.fertnstert.2011.10.037.


Objective: To investigate the accuracy of serial hCG to predict outcome of a pregnancy of unknown location in an ethnically and geographically diverse setting.

Design: Multisite cohort study.

Setting: University hospital.

Patient(s): Women with a pregnancy of unknown location.

Intervention(s): None.

Main outcome measure(s): Patients were followed until diagnosed with ectopic pregnancy (EP), intrauterine pregnancy (IUP), or miscarriage. To predict outcome, observed hCG level was compared with recommended thresholds to assess deviation from defined normal curves. Predicted outcome was compared with standard of care. Sensitivity, specificity, predictive value, and accuracy were calculated, stratified by diagnosis.

Result(s): The final diagnosis of 1,005 patients included 179 EPs, 259 IUPs, and 567 miscarriages. The optimal balance in sensitivity and specificity used the minimal expected 2-day increase in hCG level of 35%, and the minimal 2-day decrease in hCG level of 36%-47% (depending on the level) achieving 83.2% sensitivity, 70.8% specificity to predict EP. However, 16.8% of EPs and 7.7% of IUPs would be misclassified solely using serial hCG levels. Consideration of a third hCG and early ultrasound decreased IUP misclassification to 2.7%.

Conclusion(s): Solely using serial hCG values can result in misclassification. Clinical judgment should trump prediction rules and continued surveillance with a third hCG may be prudent, especially when initial values are low or when values are near suggested thresholds.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Validation Study

MeSH terms

  • Abortion, Spontaneous / diagnosis
  • Abortion, Spontaneous / epidemiology
  • Abortion, Spontaneous / metabolism
  • Adult
  • Biomarkers / metabolism
  • Chemistry, Clinical / methods*
  • Chemistry, Clinical / standards*
  • Chorionic Gonadotropin / metabolism*
  • Cohort Studies
  • Databases, Factual / statistics & numerical data
  • Diagnostic Errors / prevention & control
  • Female
  • Humans
  • Predictive Value of Tests
  • Pregnancy
  • Pregnancy, Ectopic* / diagnostic imaging
  • Pregnancy, Ectopic* / epidemiology
  • Pregnancy, Ectopic* / metabolism
  • Reference Values
  • Reproducibility of Results
  • Risk Factors
  • Sensitivity and Specificity
  • Ultrasonography, Prenatal
  • Young Adult


  • Biomarkers
  • Chorionic Gonadotropin