Immunochemical Measurement of Early Pregnancy Isoforms of hCG: Potential Applications to Fertility Research, Prenatal Diagnosis, and Cancer

Abstract

Human chorionic gonadotropin, the glycoprotein hormone of pregnancy, is found naturally in blood and urine in a variety of isoforms. These variants are related to both peptide bond cleavages (such as the nicked forms of hCG) and the beta core fragment urinary metabolite, as well as the larger variety of species resulting from carbohydrate heterogeneity. We have recently developed immunoassay systems that can measure nicked forms of hCG (antibody B151) as well as particular high carbohydrate variants (hyperglycosylated forms) of hCG (B152), which are associated with cancers producing hCG. Using the assay system for nicked hCG, we found that nicked hCG does not appear to be present as a significant hCG isoform during normal pregnancies if the urine specimens are well preserved. Applying the assay for hyperglycosylated hCG isoforms, we discovered that these forms are prevalent during very early pregnancy and decline rapidly to low concentration after the first 6 weeks of pregnancy. Persistence of these early pregnancy forms does not bode well for the pregnancy. Other investigators report that measurement of such hCG isoforms may aid in diagnosis of Down syndrome pregnancies. In summary, measurement of the hyperglycosylated hCG isoforms are useful for evaluation of healthy progress of normal pregnancy, as an additional detection marker for Down syndrome pregnancies, and as a potential new marker of trophoblastic malignancy. New reference preparations will soon be available for the calibration of assay systems for measurement of many of these hCG variants and metabolites.