Hyperglycosylated hCG in gestational implantation and in choriocarcinoma and testicular germ cell malignancy tumorigenesis.

OBJECTIVE: Hyperglycosylated human chorionic gonadotropin (hCG-H) is a carbohydrate variant of hCG with double-sized oligosaccharide side chains. While hCG-H is produced exclusively by stem cytotrophoblast cells in gestational choriocarcinoma, by pregnancy cytotrophoblast at implantation and by the cytotrophoblast produced in testicular malignancies, regular hCG is produced only by differentiated syncytiotrophoblast cells. STUDY DESIGN: hCG-H was measured using the Nichols Advantage hCG-H assay (Nichols Institute Diagnostics, San Clemente, California). RESULTS: hCG-H has a function separate from regular hCG. hCG-H, but not regular hCG, acts in vivo and in vitro to promote invasion, whether invasion through membranes or tumor formation. Invasion or tumorigenesis is completely blocked by administration of specific antibody to hCG-H. The same hCG-H-modulated invasion mechanisms are observed in early pregnancy, gestational choriocarcinoma and testicular cancers. CONCLUSION: hCG-H is a cytokinelike molecule, produced by cells different from those that make regular hCG and having a completely separate function. It appears to be the modulator of invasion as in implantation of pregnancy, gestational choriocarcinoma and testicular cancer malignancy.

A single serum test for measuring early pregnancy outcome with high predictive value.

OBJECTIVES: Current testing to determine a failing pregnancy requires two separate clinic visits to measure the hCG doubling rate. Diagnosing a failing pregnancy is often done in emergency departments where simplified and accelerated testing methods are needed. Here, we investigated hyperglycosylated hCG (hCG-H) for predicting pregnancy failure. DESIGN AND METHODS: We studied two independent sets of patient samples collected in the early weeks of gestation. One set was urine samples, and the other was serum samples. In all cases, hCG and hCG-H were measured using automated chemiluminescence immunoassays. Concentrations of hCG and hCG-H were plotted on a scattergram, and levels in failing pregnancies were compared to those in continuing pregnancies. RESULTS: Data indicated that a threshold level of hCG-H (13 microg/L) in both serum and urine samples defined the concentration below where pregnancies were likely to fail. This cut-off corresponded to 73% detection of failures at a 2.9% false positive rate using serum and 75% detection at a 15% false positive rate using urine. Using an hCG cut-off that corresponded to the same false positive rates, hCG detected only 42% of failures using serum and 43% of failures using urine. CONCLUSIONS: Our data indicate that hCG-H provides a much more accurate single test than hCG for assessing pregnancy outcome. Compatible with the use of serum or urine samples, a single hCG-H test might provide simpler, faster, and more accurate results for predicting the progress of a pregnancy than standard hCG testing.

Sensitivity of over-the-counter pregnancy tests: comparison of utility and marketing messages.

OBJECTIVE: To determine the sensitivity of seven over-the-counter pregnancy tests (OTC-PTs) using urine containing a mixture of human chorionic gonadotropin (hCG)-related molecules as found on the first day of missed menstrual period. DESIGN: Blinded in vitro sensitivity analysis. SETTING: Medical school laboratory. PARTICIPANTS: None. INTERVENTIONS: Urine was tested with OTC-PT devices at titers of 100, 50, 25, 12.5, 6.3, and 0 mIU/mL hCG immunoreactivity, and laboratory workers rated their confidence in the test result based on whether the test result was a clear, sharp, and unquestionable band in the test window. MAIN OUTCOME MEASURES: Analytical sensitivity, defined as the urine concentration at which all OTC-PTs tested gave a positive result regardless of operator confidence score; clinical sensitivity of OTC-PTs, defined as the proportion of pregnancies likely to be detected on the first day of a missed period and calculated from the analytical sensitivity and a recently published regression curve for total urine hCG immunoreactivity in 25 urine samples from this period of gestation; percentage of tested devices showing a band in the test window at a specific hCG concentration measured devices positive; percentage faulty devices, defined as the proportion of tested devices failing to yield a band in the control window; and confidence score, determined from operator ratings for each device at each concentration of hCG. RESULTS: First Response Early Result had an analytical sensitivity of 6.3 mIU/mL, which was estimated to detect greater than 95% of pregnancies on the day of missed period. The sensitivity of Clearblue Easy Earliest Results was 25 mIU/mL, which indicated detection of 80% of pregnancies. The sensitivity of the five other products was 100 mIU/mL or greater, indicating detection of 16% or less of pregnancies. Three of these last products included faulty devices. CONCLUSION: Universal claims for OTC-PTs of more than 99% laboratory accuracy and use as early as the first day of missed period, while cleared for use by the U.S. Food and Drug Administration, are ambiguous and inappropriate for many products, according to these data. The majority of products tested were found to detect only a small percentage of pregnancies on the first day of a missed menstrual period. Until more data become available on the actual clinical sensitivity of these products, pharmacists should advise consumers to be cautious in interpreting test results.