Urine hCG β-subunit core fragment, a sensitive test for ectopic pregnancy

hCG is a glycoprotein hormone composed of 2 dissimilar subunits, α and β, joined non-covalently. hCG and its free β-subunit are the principal hCG β immunoreactivities in pregnancy serum samples, and the same plus β-core fragment (β-subunit residues 6-40 disulfide-linked to residues 55-92) in urine samples. Ectopic or tubal pregnancy is difficult to diagnose in emergency rooms. With the objective of finding better hCG-related assays for differentiating tubal and normal pregnancies, we tested 2 hCG, 1 free β-subunit and 2 β-core fragment immunoassays. Twelve urine samples were collected in the emergency room from women later shown by surgery to have tubal pregnancy. All were 38 to 80 days since last period. A further 36 urine samples were collected from the same period from those with normal intrauterine pregnancies. Using the 2 hCG assays the median level in tubal pregnancy samples was 1/38th and 1/48th of normal pregnancy concentrations. With the free β-subunit assay tubal pregnancy levels were 1/28th of normal levels. Using 2 β-core fragment assays (Ciba-Triton UGP kit and B204-FBT11 scavenger test), however, tubal levels were most different from intrauterine pregnancy, 1/149th and 1/800th of normal levels. A cut-off level of 100 μg/L was considered for the B204-FBT11 β-core fragment test, at which a predictive value of > 98% was suggested for ectopic pregnancy. In an additional patient, levels were measured 15 days prior to the diagnosis of tubal pregnancy. At this time, results from the 2 hCG tests were 1/97th and 1/126th, from the free β-subunit test was 1/8th and the 2 β-core assays were 1/413th and 1/240th of median normal intrauterine pregnancy levels. While hCG levels are reduced in tubal pregnancy, β-core fragment are reduced much further. β-core fragment measurements may offer a major improvement over hCG in diagnosing tubal pregnancy in the Emergency Room, and in screening for this life threatening disease.