Immunoassay of human chorionic gonadotropin, its free subunits, and metabolites

Multiple hCG-related molecules are present in pregnancy serum and urine samples. These include non-nicked hCG (the hormone), nicked hCG, hyper- and hypoglycosylated hCG, hCG missing the C-terminal extension, free alpha-subunit, large free alpha-subunit, free beta-subunit, nicked free beta-subunit, and beta-core fragment. Over 100 immunoassays are sold for quantifying hCG-related molecules in serum or urine. Each measures nonnicked hCG and one of seven combinations of the other hCG-related molecules. This is the source of interassay discordance in hCG determinations. Whereas minor variations are noted in different kit results in normal pregnancy samples (more than twofold variation), much larger variations may be found in two immunoassay results in irregular gestations (spontaneous abortion, aneuploidy, preeclampsia, cancers, and trophoblast disease). Care is needed in choosing an immunoassay. What the assay measures may be more important than its cost or speed. This article reviews the structure of hCG and related molecules. It examines the stability and degradation of hCG, and recognition of hCG-related molecules by different types of immunoassay. Also reviewed are new assays for specifically detecting these other hCG-related molecules.