Difference in Serum Human Chorionic Gonadotrophin Levels Measured Using the World Health Organization 3rd versus 5th International Standard: A Correlation Study with Reference to Management of Pregnancy of Unknown Location

Abstract

Objective: To evaluate the difference in serum human chorionic gonadotrophin (hCG) level in pregnant women when using assays calibrated against the World Health Organization (WHO) 3rd versus 5th International Standard (IS), and to determine the implications for management of pregnancy of unknown location (PUL).
Methods: 105 samples of serum hCG obtained from pregnant women were tested using assays calibrated against the WHO 3rd IS versus 5th IS. The clinical course, ultrasound findings, final diagnosis, and clinical outcome were evaluated. The optimal cut-off value of ‘discriminatory zone’ for management of PUL was determined using receiver operating characteristic curve analysis.
Results: Both WHO 3rd IS and 5th IS were highly correlated (Pearson’s r=0.996, r2=0.992) but not equivalent. The mean percentage difference was 12.9%. 34 paired samples were included in a diagnostic-validation study, and the cut-off value of ‘discriminatory zone’ was 1500 IU/L for the 3rd IS (sensitivity=50.0%, specificity=87.5%, area under curve=77.9%) and 1745 IU/L for the 5th IS (sensitivity=60.0%, specificity=87.5%, area under curve=79.2%).
Conclusion: Calibration of serum hCG using the WHO 3rd IS and 5th IS was highly correlated but not equivalent. A larger prospective study is required before recommendations can be made with regard to the cut-off value of a new ‘discriminatory zone’.