Daily Immunoactive and Bioactive Human Chorionic Gonadotropin Profiles in Periimplantation Urine Samples1

Abstract

A need exists for broadly applicable biomarkers of pregnancy outcome in population-based studies that assess environmental hazards to human reproduction. Previous studies have demonstrated that during the periimplantation period, measures of the circulating levels of immunoreactive hCG (IhCG) are not predictive of pregnancy outcome, whereas measurements of the circulating levels of bioactive hCG (BhCG) provide information relating to pregnancy outcome and might provide the basis for an early biomarker of pregnancy outcome. However, for this biomarker to have broad application in population-based studies, it must be adapted to urinary hCG metabolites. The principle objective of the present study was to characterize the periimplantation excretion patterns of urinary hCG metabolites of pregnancies that resulted in live birth (LB), early pregnancy loss (EPL), and recognized clinical abortion (CAB) with an immunoenzymometric assay specific to intact hCG and an LH/chorionic gonadotropin cellular bioassay as the basis for a preliminary comparison between successful (LB) and failing (EPL and CAB) outcome groups. Automated immunoassays for FSH and hCG were used to define each conceptive cycle's implantation window. The timing of first hCG detection was significantly later for the EPL group. Pregnancies that resulted in LB had consistently rising average daily IhCG and BhCG levels, with no significant differences when average daily IhCG and BhCG measurements were compared (Student t-test, P>0.05), whereas pregnancies that resulted in CAB and EFL had lower average daily IhCG and BhCG levels that increased inconsistently. These findings demonstrate that critical information related to pregnancy outcome may be present when multiple urinary hCG isoforms are measured. Further data suggest that the rate of change for the ratio of daily BhCG over IhCG levels might be useful as the basis of a broadly applicable early biomarker for pregnancy outcome.

Hourly human chorionic gonadotropin secretion profiles during the peri-implantation period of successful pregnancies

“…On the other hand, in a subset of samples from the same study, we reported that circulating bioactive hCG concentrations in a 5-day window during the first post-implantation week tend to be lower and rise less steeply in pregnancies that later fail than in pregnancies that survive to term (16). There is now evidence that within the same narrow analysis window, the measure of hCG bioactivity in daily blood and urine samples provides information relating to pregnancy outcome that is not provided by comparable measures of hCG immunoreactivity alone (26). Although development of an early biomarker for pregnancy outcome based on measures of hCG bioactivity may benefit from a more complete characterization of peri-implantation hCG secretion patterns, it is more certain that the additional data reported here will greatly assist in the development of broadly applicable definitions of pregnancy for future population-based studies that rely on urinary hormone measurements.…”

Embryonic diapause in humans: time to consider?

“…Such a situation is less likely to occur in animals, in which once lactation or a season unfavourable for pregnancy progression ends, the embryo develops without further disturbance. Notably, more recent human studies refuted the association of delayed implantation with pregnancy loss [22]. …”

Urinary hCG patterns during the week following implantation

“…Though the mRNA for the hCG subunits has been detected as early as the 6-8-cell stage (Bonduelle et al 1988), the intact protein first becomes detectable in the mother's blood and urine between 6 and 14 days after fertilization both in vitro and in vivo (Hay and Lopata 1988;Lohstroh et al 2006;Wilcox et al 1999). Most research on longitudinal urinary excretion patterns of hCG has been conducted later in pregnancy (6 or more weeks after the last menstrual period (LMP)) (Braunstein et al 1976;Gerhard and Runnebaum 1984;Gol et al 2005;Williams et al 1995).…”