Bioactive to immunoreactive ratio of circulating human chorionic gonadotropin as possible evaluation for the prognosis of threatened abortion

OBJECTIVE: In an effort to evaluate the prognosis of threatened abortion, we established the ratio of serum human chorionic gonadotropin (hCG), as measured by bioassay or radioimmunoassay techniques, of samples from patients with threatened abortion or normal pregnancy. STUDY DESIGN: Peripheral blood samples from patients in their first trimester of pregnancy with threatened abortion (n=24), or normal pregnancy (n=12), were assayed for progesterone (RIA), and for immunoactive (DELFIA) and bioactive (mouse Leydig cell testosterone production assay) hCG. RESULTS: Serum progesterone was not statistically different between the threatened-continuing and the threatened-miscarried groups. The ratio of hCG bioactive/hCG immunoactive (B/I) was significantly lower for the patients of the threatened group that experienced abortion. The B/I ratio for the control and threatened-continuing patients was similar. CONCLUSION: The hCG bioactive/hCG immunoactive ratio could be a good indicator of the prognosis of threatened abortion.     

Disappearance of human chorionic gonadotropin and resumption of ovulation following abortion.

The disappearance of human chorionic gonadotropin (hCG) and resumption of pituitary ovarian function was investigated in 13 patients following first- and second-trimester abortions. First-trimester abortion patients (with suction curettage) had a mean time of 37.5 +/- 6.4 days for the clearance of hCG to a level of 2 mlU/ml. Second trimester abortions (with prostaglandin) had a mean time of 27.4 +/- 4.8 days. Patients undergoing second-trimester hysterectomy had a mean disappearance time of 39.7 +/- 5.3 days and only 12 days if the hysterectomy was initiated with ligation of the uterine and ovarian vessels. No significant difference in clearance time was found when it was compared on the basis of the baseline hCG levels. Based on a concomitant luteinizing hormone (LH) and follicle-stimulating hormone (FSH) peak, nine of 12 patients resumed normal pituitary function. These LH and FSH peaks were seen even though the serum hCG levels were as high as 35 mlU/ml. Based on serum progesterone levels of greater than 3 ng/ml, all these nine patients ovulated as early as 21 days after abortion. In view of these results, the clearance of hCG after pregnancy termination depends mainly upon the type of procedure used. Moreover, in view of the early time of ovulatory recovery, contraception should be instituted within the first 2 weeks following pregnancy termination.     

Choriocarcinoma associated with undetectable levels of human chorionic gonadotropin

A case of choriocarcinoma is presented which developed during close follow-up for hydatidiform mole. Serum levels of beta subunits of human chorionic gonadotropin (beta-HCG) were assessed by radioimmunoassay (RIA) before, during, and after diagnosis of choriocarcinoma and remained below the sensitivity level of the assay. To our knowledge, this is the fourth reported case where choriocarcinoma was not associated with the presence of elevated beta-HCG levels.     

Urinary estrone glucuronide, pregnanediol glucuronide and human chorionic gonadotrophin in threatened abortion

Estimations of urinary estrone glucuronide, pregnanediol glucuronide and human chorionic gonadotrophin were carried out by ELISA to see their potential in predicting an abnormal outcome in cases with vaginal bleeding in early pregnancy. Reference values were set up with samples from women without bleeding in present or past pregnancies and with normal ultrasonic findings. None of the parameters were found to be sensitive enough to predict an abnormal outcome. However, predictability of an abnormal value was found to be 95% for estrone-3-glucuronide (E1G), 93% for pregnanediol glucuronide (PdG) and 87% for human chorionic gonadotrophin (hCG).     

Fibronectin levels in threatened abortion

Studied were 25 healthy gravidae in the first or second trimester of pregnancy and 28 women with threatened abortion (TA). Plasma fibronectin (pFN) was assayed in maternal blood serum and the fetal fibronectin (fFN) was quantified in cervico-vaginal secretion. Patients with imminent abortion had significantly elevated levels of both pFN and fFN as compared with women with uncomplicated pregnancy. Within the TA group of patients, vaginal bleeding and/or trophoblast was associated with significant increase in fibronectin levels.     

Immunocytochemistry of human chorionic gonadotropin in human chorionic villi

The immunocytochemical localization of human chorionic gonadotropin was investigated in chorionic villi from the seventh to twelfth week of gestation. By the light microscopic peroxidase-antiperoxidase technique, positive reactions of human chorionic gonadotropin were found exclusively in the syncytiotrophoblast. Immunoelectron microscopy by means of the protein A-gold technique reveals localization of the immunoreactive gold particles in two kinds of membrane-bound granular inclusions in this cell; one type is granules of 200 to 300 nm in diameter with moderate electron density and the other is large electron-dense bodies of 500 to 1000 nm. The former seems to be Golgi-derived secretory granules that play a role in the release of human chorionic gonadotropin from the syncytiotrophoblast. Although the origin of the latter is still uncertain, a certain amount of this hormone might be stored or treated by lysosomal digestion in the large bodies during these stages.     

Hyperglycosylated human chorionic gonadotropin and human chorionic gonadotropin free beta-subunit: tumor markers and tumor promoters

Human chorionic gonadotropin (hCG) is a heterogeneous glycoprotein hormone comprising an alpha-subunit and beta-subunit that can vary in peptide and carbohydrate structure. After conception, hCG produced by early trophoblast cells acts on luteinizing hormone (LH)/hCG receptor corpus luteum cells to promote progesterone production and establish maternal recognition of pregnancy. hCG is not simply 1 molecule, and 2 variants of hCG appear to have independent activities in promoting tumor cell growth, invasion and malignancy. Hyperglycosylated hCG (H-hCG), produced by cytotrophoblast cells, is a marker for cytotrophoblast cells and tumor marker for gestational trophoblastic diseases. H-hCG promotes growth and invasion in these cells during pregnancy implantation, and growth in varying degrees by many nontrophoblastic neoplasms. beta-hCG is a marker of poor prognosis shown to promote growth and invasion in vitro, suggesting autocrine growth factor properties. Vaccines to beta-hCG have been successfully demonstrated, suggesting a potential adjuvant therapy in cancer treatment. Although sufficiently distinct in both structure and occurrence, similarities have been observed between H-hCG and beta-hCG as promoters of cell growth, invasion and malignancy. It is somewhat irregular for 2 structural variants of a molecule to have independent actions, actions very different to the gonadotropic function of the established hormone hCG.     

Suppression of human chorionic gonadotropin by progestational steroids

The dynamics of the secretion of human chorionic gonadotropin (hCG) were studied by culturing explants of normal term placentas for as long as 144 hours. A significant accumulation of immunoreactive hCG (beta-subunit) was first detected at 48 to 72 hours, and a sixfold increase in hCG was observed in control culture medium at 144 hours. Compared to control cultures, progesterone (P < 0.001) in physiologic tissue levels of 5 to 20 micrograms/ml, pregnenolone (P < 0.001), 20 micrograms/ml, and 20 alpha-dihydroprogesterone (P < 0.001), 20 micrograms/ml, suppressed the secretion of hCG throughout the study period. Progesterone decreased the secretion of hCG in a dose-response manner (r = -0.8S87, P < 0.1). No suppression of hCG was observed in the presence of cortisol, testosterone, dihydrotestosterone, 17 beta-estradiol, or estriol. The secretion of human chorionic somatomammotropin was unchanged in the presence of progesterone. The augmented hCG response in the presence of dibutyl cAMP (P < 0.001) was significantly, but not completely, suppressed by progesterone 20 micrograms/ml culture medium (P < 0.01). Under these conditions progestational steroids or their immediate metabolites suppress the secretion of hCG, and they may be responsible for the decline in the levels of hCG during pregnancy.