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.
"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 . "
[Show abstract][Hide abstract] ABSTRACT: When a competent blastocyst stage embryo finds itself in an unreceptive uterus, it delays development. In around one hundred species representing various orders, this delay is known to be reversible, but this phenomenon - termed embryonic diapause (ED) - is not considered a general characteristic of all mammals.
Recently, however, we demonstrated that a non-diapausing species, the sheep, is capable of ED, suggesting the hypothesis that this is in fact an ancestral trait common to all mammals, including humans.
In spite of the obvious difficulties in testing this idea, we propose a combination of indirect observations on human fertility patients, and direct study of the embryos of non-human primates.
Support for our hypothesis would require revision of obstetric interventions routinely performed when a human pregnancy extends beyond the due date.
"This observation is consistent with results reported by Lohstroh et al. (2005), who found no association between hCG levels on day of detection and pregnancy outcome either in 62 fertile women undergoing artificial insemination or in 10 naturally conceived pregnancies (Lohstroh et al., 2006). There is some evidence, however, that differences in hCG slopes may emerge during the second week, but findings are based on relatively small samples or IVF patients (Lohstroh et al., 2006, "
[Show abstract][Hide abstract] ABSTRACT: Human chorionic gonadotrophin (hCG) is used to monitor pregnancy status. Yet the pattern of hCG excretion in the first week following implantation has not been adequately described. Therefore the aim of this study was to describe the average profile of hCG and its variability during the 7 days following estimated implantation in a population of naturally conceived pregnancies.
We measured daily hCG concentrations in first-morning urine for 142 clinical pregnancies from women with no known fertility problems. Mixed-effects regression models were used to estimate the hCG trajectory and its variability in relation to pregnancy outcomes.
hCG rose 3-fold between the day of detection and the next day (95% CI = 2.7-3.4). The relative rate of rise decreased thereafter, reaching 1.6-fold (95% CI = 1.5-1.8) between days 6 and 7. HCG levels followed a log-quadratic trajectory, and the patterns of rise were unrelated to number of fetuses, risk of spontaneous abortion or sex of the baby. Later implantations (after 10 luteal days) produced slower rates of increase.
Although mean hCG follows a log-quadratic trajectory during the first week of detectability, there is high variability across pregnancies. Later implantation may reflect characteristics of the uterus or conceptus that slow hCG production.
Human Reproduction 03/2008; 23(2):271-7. DOI:10.1093/humrep/dem397 · 4.57 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: To characterize the hourly profiles of hCG secretion in blood during conceptive cycles that ended in successful pregnancy.
University fertility clinic and research laboratories.
Healthy spontaneously ovulating women with regular menses, no history of infertility, and either no male partner or an azospermic partner.
Frequent blood samples were collected daily from 11 spontaneously ovulating women during 11 cycles of artifical insemination with donor semen. The concentrations of hCG, LH, and FSH were measured in the blood by immunoassay.
The concentration of hCG in the frequent blood samples and the rate that the concentration of hCG changed during the period of frequent sampling.
For the conceptive cycles resulting in successful pregnancies analyzed, hourly hCG concentrations were observed to increase in a consistent nonpulsatile manner.
These data provide the first characterization of the hourly secretion profile of hCG in early pregnancy as well as provide further evidence that individual daily blood samples are sufficient for the accurate assessment of pregnancy.
Fertility and sterility 07/2007; 87(6):1413-8. DOI:10.1016/j.fertnstert.2006.11.053 · 4.59 Impact Factor
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