Are Laboratories Reporting Serum Quantitative hCG Results Correctly?

Abstract

Background: Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone that exists in multiple forms. Immunoassays commonly used in clinical laboratories measure intact hCG, total β hCG (intact hCG + hCG free β-subunit), and/or hCG free β-subunit. Measurement of serum concentrations of hCG is useful for confirmation and monitoring of pregnancy, diagnosis of trophoblastic diseases and monitoring of the efficacy of treatment, and prenatal screening. Correctly reporting results for the various forms of hCG is clinically important. Method: We prepared samples by addition of intact hCG and hCG free β-subunit to an essentially hCG-free human serum matrix. The samples were analyzed by participant laboratories using various immunoassay methods. Results: We identified errors in participant reporting of intact hCG results as total β hCG (9.3%; 22 of 235 laboratories) and total β hCG as intact hCG (13.1%; 8 of 61 laboratories). Conclusions: Many factors contribute to the erroneous reporting of hCG results, including (a) the complexity of hCG molecule and confusion of nomenclature on the various forms of hCG; (b) laboratory personnel’s lack of awareness of the distinctions of the forms of hCG and failure to recognize the specificity of assays for their measurement; (c) lack of clarity and uniformity in manufacturers’ reagent labeling; and (d) most product inserts’ lack of information on the specificity of each method to the various forms of hCG.

Comparison of the point of care test (POCT), i-CHROMA™ human chorionic gonadotrophin (HCG), leutinzing hormone (LH) and follicle stimulating hormone (FSH) methods with the other laboratory methods in the Randox International Quality Assessment Scheme (RIQAS)

“…This observation is consistent with the findings, which indicate that the Siemens Immulite Series (1000 and 2000) report higher values for total hCG as they detect both intact hCG and free βhCG [12]. Furthermore, the Siemens Immulite method has been described to detect all the hCG structural variants [13] and therefore is not surprising that this method had the greatest difference of -14.88% and -9.85% compared with the i-CHROMA™ hCG method. While the Siemens/DPC Immulite method detects all the hCG variants, the Ortho Vitros ECi method does not detect hCGβcf and poorly detects hCGβ and nicked hCG.…”

Differences in Recognition of the 1st WHO International Reference Reagents for hCG-Related Isoforms by Diagnostic Immunoassays for Human Chorionic Gonadotropin

“…Availability of highly purified IRRs calibrated in substance concentrations (mol) is therefore a major step forward toward improved characterization of hCG assays, which facilitates comparison of results for various forms of hCG and enables calibration of hCG assays in molar units. Universal adoption of the clear and unambiguous IFCC nomenclature (Table 1) is also a critically important prerequisite for improvement (1 ), the adverse consequences of lack of clarity in descriptions of what hCG methods recognize having recently been clearly demonstrated (11 ).…”

Clinical Significance of Serum Biomarkers in Pediatric Solid Mediastinal and Abdominal Tumors

“…For example, some question the validity of differences in hCG concentrations, as the recognition of hCG variants [nonnicked and nicked intact hCG (hCG and hCGn), nonnicked and nicked free β-subunit (hCGβ and hCGnβ), and regular and hyperglycosylated (or large) free hCGα] can cause discordance in hCG immunoassay results. Cao and Rej identified the following factors that contribute to the incorrect reporting of hCG results by laboratories: (a) complexity of the hCG molecule and confusion of nomenclature among various forms of hCG; (b) laboratory personnel’s lack of awareness of the distinctions in the forms of hCG and failure to recognize the specificity of assays for measurement of different forms; (c) lack of clarity and uniformity in manufacturers’ reagent labeling; and (d) lack of information on the specificity of each method for the various forms of hCG in most product inserts [153]. …”