Multiple hCG-related molecules are present in pregnancy serum and urin
e samples. These include nonnicked hCG (the hormone), nicked hCG, hype
r- and hypoglycosylated hCG, hCG missing the C-terminal extension, fre
e alpha-subunit, large free alpha-subunit, free beta-subunit, nicked f
ree beta-subunit, and beta-core fragment. Over 100 immunoassays are so
ld for quantifying hCG-related molecules in serum or urine. Each measu
res nonnicked hCG and one of seven combinations of the other hCG-relat
ed molecules. This is the source of interassay discordance in hCG dete
rminations. Whereas minor variations are noted in different kit result
s in normal pregnancy samples (more than twofold variation), much larg
er variations may be found in two immunoassay results in irregular ges
tations (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 examine
s the stability and degradation of hCG, and recognition of hCG-related
molecules by different types of immunoassay. Also reviewed are new as
says for specifically detecting these other hCG-related molecules.