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15. Developing Assays of Biologic Markers for Epidemiologic Studies: Experience with a Marker of Pregnancy and Early Loss
Pages 187-196

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From page 187...
... Its principal known role is to act at the ovarian corpus luteum to stimulate further secretion of progestins to support endometrial growth. Blood and urinary hCG concentrations rise rapidly and peak approximately 12 weeks after onset of the last menstrual period; thereafter, they slowly decline until the fetus and placenta are delivered.
From page 188...
... FEAL9LE REPRODUCTIVE TOXICOLOaY of degradation products. Nonetheless, this assay method was used to develop nonradioisotopic home-testing kits for hCG in urine specimens to detect pregnancy with moderate reliability (Doshi, 1986)
From page 189...
... When this is spun down, amounts of radioactivity bound to the solid phase indicate quantities of hCG attached to the capture antibody. The assay permits hCG detection at concentrations approaching 0.01 ng/ml (highly purified reference preparations of hCG have a bioassay value of approximately 13,000 IU/mg)
From page 190...
... In the first study, 30 women collected daily urine specimens from the time they stopped contraception until they became pregnant or for 6 months if no pregnancy occurred (Wilcox et al., 1985~. The study showed the feasibility of the epidemiologic design and permitted investigators to detect several cycles with early fetal loss that would not have been detected with other available methods.
From page 191...
... The ectopic secretion of hCG by some tumors and its slight increase in postmenopausal urine specimens (Armstrong et al., 1984; Kuida et al., 1988) are unlikely to diminish its epidemiologic value as the biologic marker of pregnancy in healthy women of reproductive age because the character~st~c pregnancy-related changes in hCG concentration are not observed from tumor secretions.
From page 192...
... Only urine specimens with positive screening tests that suggest an episode of fetal loss would be shipped to a central assay laboratory. New Monoclonal Antibodies for hCG Detection In the quest for an improved assay for the urinary products of hCG, new antibodies with high affinities for the various forms of urinary hCG will be important.
From page 193...
... In epidemiologic studies of reproductive function, improved markers of ovulation need to be developed in easily collected biologic specimens—saliva or urine. These improvements are needed to develop better methods to detect the various forms of the pituitary gonadotropins and also to detect various estrogen and progesterone derivatives throughout the menstrual cycle, to estimate the time of ovulation, and to document the formation of a corpus luteum.
From page 194...
... Assays that- use antisera raised against antigens derived from postmenopausal or male sources might not be optimal for assays on normally cycling women and might have contributed to the primary lack of sensitivity in ovulation detection. Recent work documented that urinary FSH patterns closely resemble those found in serum FSH patterns when measured by granulosa cell aromatase bioassay (Dahl et al., 1987~.
From page 195...
... The study of luteal phase characteristics has become feasible with the development of direct assays for urinary estrogen and progestin metabolites using nonradioisotopic assay systems. Postmenopausal women have a strong stimulus for pituitary gonadotropin secretion; to some extent, this appears to stimulate a minute degree of hCG synthesis and 195 secretion as well (Robertson et al., 1978; Armstrong et al., 1984~.


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