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Relationship between blood and urine concentrations of intact human chorionic gonadotropin and its free subunits in early pregnancy.

Paired blood and urine samples were obtained from patients between the sixth and 14th weeks of normal pregnancy. The levels of intact human chorionic gonadotropin (hCG), and of the free alpha and beta subunits, were measured by specific immunoassays. There was a close association between blood and urine levels of intact hCG and of the alpha subunit of hCG, but no relation between the levels of beta subunit in these sites. These findings suggest that the use of "beta subunit" assays may give discrepant results according to the fluid examined. By contrast, measurement of intact hCG appears to give similar results in blood and urine.

Chorionic Gonadotropin↗

Mapping the receptor binding regions of human chorionic gonadotropin (hCG) using disulfide peptides of its beta-subunit: possible involvement of the disulfide bonds Cys(9)-Cys(57) and Cys(23)-Cys(72) in receptor binding of the hormone.

Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone essential for the establishment and maintenance of pregnancy. The alpha- and beta-subunits of hCG are highly cross-linked internally by disulfide bonds which seem to stabilize the tertiary structures required for the noncovalent association of the subunits to generate hormonal activity. The purpose of this study was to delineate the role of the disulfide bonds of hCGbeta in receptor binding of the hormone. Six disulfide peptides incorporating each of the six disulfide bonds of hCGbeta were synthesized and screened, along with their linear counterparts, for their ability to competitively inhibit the binding of [125I] hCG to sheep ovarian corpora luteal LH/CG receptor. Disulfide peptide Cys (9-57) was found to be approximately 4-fold more potent than the most active of its linear counterparts in inhibiting radiolabeled hCG from binding to its receptor. Similarly, disulfide peptide Cys (23-72) exhibited receptor binding inhibition activity, whereas the constituent linear peptides were found to be inactive. The results suggest the involvement of the disulfide bonds Cys(9)-Cys(57) and Cys(23)-Cys(72) of the beta-subunit of hCG in receptor binding of the hormone. This study is the first of its kind to use disulfide peptides rather than linear peptides to map the receptor binding regions of hCG.

Amino Acid Sequence↗

Immunohistochemical study of the expression of human chorionic gonadotropin-beta in oral squamous cell carcinoma.

BACKGROUND: Human chorionic gonadotropin (hCG) is a glycoprotein hormone comprised of two dissimilar subunits (alpha and beta) and normally is synthesized by trophoblastic tissue. Although hCG expression has been identified in a variety of neoplastic tissues, to the authors' knowledge no investigation has centered on tumors of oral origin. METHODS: Oral squamous cell carcinomas (OSCC) were studied in comparison with oral fibromas for the presence of hCGbeta using the avidin-biotin-peroxidase complex immunohistochemical technique. RESULTS: hCGbeta immunoreactivity was identified in 29 of 45 OSCC (64%). The positively staining cells in each tumor specimen were few (range, 0.5-5%) and were scattered throughout the tumor. When tumors were classified according to grade, it was found that hCGbeta staining was positive in 5 of 15 well differentiated OSCC (33%), in 12 of 15 moderately differentiated OSCC (80%), and in 12 of 15 moderately to poorly differentiated OSCC (80%). hCGbeta immunoreactivity could not be demonstrated in any of the oral fibromas. CONCLUSIONS: The presence of hCGbeta positive tumor cells appears potentially to reflect a malignant behavior of OSCC.

Biomarkers, Tumor↗

Beta-core fragment is a major form of immunoreactive urinary chorionic gonadotropin in human pregnancy.

A small mol wt fragment of the beta-subunit of hCG (beta-core fragment) is present in the urine, but not the serum, of pregnant women. We evaluated the relative proportions of this immunoreactive, but biologically inactive, fragment in urine from 15 women at different stages of pregnancy. Freshly voided urine was ultrafiltered and concentrated, and the molecular species of immunoreactive hCG were separated by Sephadex G-100 column chromatography. All urine samples contained the beta-core fragment, which eluted after the alpha-subunit of hCG. This fragment lacked the carboxy-terminal epitope of hCG, was inactive as an in vitro bioassay, and adsorbed to Concanavalin-A. The beta-core fragment was a major form the immunoreactive hCG in urine throughout pregnancy and accounted for over 90% of the immunoreactive hCG in urine from midpregnancy. The excretion pattern of the beta-core fragment can account for the low biological to immunological ratio of urinary hCG that occurs at different stages of pregnancy.

Biological Assay↗

Rapid and simple immunoassays for measurement of human chorionic gonadotropin using monoclonal antibodies.

Two monoclonal antibodies, designated Gab-35 and Gab-144, were used in competitive radioimmunoassay (RIA) and solid-phase sandwich enzyme immunoassay. By SDS-polyacrylamide gel electrophoresis and protein blot enzyme immunobinding assay, Gab-35 and Gab-144 were shown to react specifically to the alpha-subunit and beta-subunit of human chorionic gonadotropin (hCG), respectively. The immunoglobulin class and subclass of these two monoclonal antibodies were found to be IgG1 by the Ouchterlony double gel immunodiffusion test. The beta-subunit specific monoclonal antibody of Gab-144 was used in competitive RIA for determination of serum hCG in the range of 5-500 mIU/ml. The assay results correlated well with the monoclonal antibody-based RIA system and commercial RIA kits using polyclonal antisera. Moreover, the present competitive RIA system showed a shorter incubation time (1 hour 20 minutes) and a shorter total assay time (1 hour 40 minutes), as compared to those of the commercial RIA kit. A solid-phase sandwich enzyme immunoassay was developed using a combination of the Gab-35 antibody-coated microtiter plate and the beta-subunit specific antibody of Gab-144 conjugated with horseradish peroxidase (HRP). The assay range was 20-200 mIU/ml, and the incubation time was only 30 minutes. In addition, the solid-phase sandwich enzyme immunoassay developed in the present study could also be used as a qualitative hCG assay with a cutoff point of 50 mIU/ml as an early pregnancy test at or just a few days before the missed period.

Animals↗

Purification of beta-core fragment from pregnancy urine and demonstration that its carbohydrate moieties differ from those of native human chorionic gonadotropin-beta.

Pregnancy urine contains large quantities of hCG, free beta-subunit, free alpha-subunit, and a population of fragments of beta-subunit known as beta-core. This beta-core population, which can account for as much as 70% of the total beta-immunoreactivity in pregnancy urine, is of interest as both a normal metabolite of pregnancy and a potential marker for malignancy. We have purified the beta-core fragment from pregnancy urine (P-core) and have characterized it with respect to size and carbohydrate composition. P-Core was purified by chromatography on Sephadex G-100, Concanavalin A (Con A)-Sepharose, DEAE-Sephacel, and Sephadex G-75 (superfine). The purified P-core has an apparent mol wt of 17,500 and 17,000, as determined by gel filtration on Sephadex G-75 (superfine) and sodium dodecyl sulfate-polyacrylamide gel electrophoresis under nonreducing conditions, respectively. The sialic acid content of P-core was assayed chemically and was less than 0.07 mumol sialic acid/mumole P-core. For comparison to P-core, we have prepared a trypsin fragment of beta-subunit that retains the beta-core immunological determinant recognized by SB6 antiserum and lacks the carboxy-terminal immunological determinant. We have designated this beta-core molecule as T-core (tryptic fragment of beta-subunit) to distinguish it from the beta-core molecule that we have purified from pregnancy urine (i.e. P-core). Most of the P-core and T-core molecules bind to Con A (84% and 86%, respectively). The Con A-bound material was used for subsequent characterizations. Neither P-core nor T-core binds to DEAE using conditions under which intact hCG beta binds to DEAE. A variety of agarose-bound lectins were used to further investigate the carbohydrate nature of the Con A-bound P-core and T-core molecules. The lectin binding data indicate that the antennae on P-core do not contain appreciable sialic acid or galactose, in contrast to the antennae on T-core, which contain both. We conclude that P-core, the naturally occurring beta-core fragment in pregnancy, has been processed to a form in which nearly all of the sialic acid and galactose residues are removed, but the Con A-binding site (consisting of the core sugars) and most of the core fucose are retained.

Carbohydrate Conformation↗

Peritoneal trophoblastic implant.

A case of persistent trophoblastic tissue on the pelvic peritoneum is presented. While most cases are secondary to conservative surgery for tubal ectopic pregnancy, primary implantation can also occur as highlighted by this case. A brief pathophysiology of the condition is presented. The importance of monitoring the serum for beta subunit human chorionic gonadotrophin (HCG) is emphasised.

Adult↗

First trimester screening for aneuploidy: serum biochemical markers.

The article reviews screening for Down syndrome in the first trimester (8-13 gestational weeks) with maternal serum analytes. In the first trimester, 2 serum markers stand out: pregnancy-associated plasma protein-A, a large glycoprotein tetramer, and free beta-human chorionic gonadotropin (beta-hCG), 1 of the 2 subunits of the glycoprotein hormone hCG. Some data indicate that hCG itself may be as effective as free beta-hCG in the first trimester. Maternal serum levels of pregnancy-associated plasma protein-A are low and free beta-hCG are high (consensus multiple of the medians, 0.4 and 1.8, respectively) in Down syndrome pregnancy. The consensus estimate of screening performance by using pregnancy-associated plasma protein-A and free beta-hCG in combination with maternal age is 60% detection rate at a 5% false positive rate. This is similar to the screening performance of second trimester double markers, but not as good as the screening performance of second trimester triple or quad markers. For this reason, first trimester screening with serum markers alone cannot be recommended except in cases in which second trimester screening cannot be done.

Aneuploidy↗

Cloning and sequencing of feline thyrotropin (fTSH): heterodimeric and yoked constructs.

The genes encoding the mature common glycoprotein alpha (CGA) and hormone-specific beta subunits of feline thyroid stimulating hormone (fTSH) were cloned and sequenced. The feline CGA gene was cloned from RNA extracted from the feline pituitary gland by the reverse transcription polymerase chain reaction (RT-PCR). The gene fragment that encodes mature TSHbeta was cloned from feline genomic DNA after direct polymerase chain reaction (PCR). In both cases, primers were based on the consensus sequences from TSH in other species. The resulting 510 bp PCR product for the CGA-subunit included the full coding sequence for the 96 amino acid mature subunit preceded by a 24 amino acid signal peptide. The 850 bp sequence of fTSHbeta genomic DNA consisted of two coding exons, an intron of 418 bp, and a 60 bp signal sequence. The octapeptide immunoaffinity tag FLAG was added to 3' end of the alpha gene to facilitate detection and purification. Both genes were cloned independently downstream from the EF1alpha promoter of the PEAK transfer vector to facilitate co-expression studies in PEAK cells (modified human embryonic kidney (HEK) cells). A single-chain analogue of fTSH termed yoked fTSH (yfTSH) was developed by fusing the nucleotides encoding the C-terminus of the beta-subunit fused to the N-terminus of the alpha-subunit with DNA encoding the C-terminal peptide (CTP) of human chorionic gonadotropin beta-subunit as a linker peptide. The resulting single-chain analogue encoded from N-terminus to C-terminus: beta-CTP-alpha-FLAG. The resulting DNA sequence was cloned, sequenced, ligated and recloned into expression vector PEAK. This report constitutes the first cloning and sequencing of the genes encoding the subunits of feline thyrotropin.

Amino Acid Sequence↗

[Germinoma originating in the basal ganglia--report of 2 cases].

We reported two cases of germinoma originating in the basal ganglia among the 50 cases of intracranial germinoma which were experienced at the Department of Neurosurgery, Hokkaido University Hospital. (Case 1) A 8-year-old boy was admitted to our hospital in October 1977, because of precocious puberty and left hemiparesis. Plain CT showed an irregularly-defined high density lesion in the right basal ganglia, which had several low density spots and was moderately enhanced on contrast CT. Endocrinological examination by radioimmunoassay revealed abnormally high level of serum luteinizing hormone and scanty level of serum follicle stimulating hormone. Beta-subunit of human chorionic gonadotropin (HCG) showed 46.4 ng/ml. Following radiation, the lesion on CT disappeared and beta-subunit turned to be in the normal range. It was concluded that the precocious puberty was due to hypersecretion of HCG by the tumor. About 2 years after the first admission, the tumors were disseminated to the spinal cord, followed several months later by the intracranial recurrence. The neurosurgical exploration was performed to both intracranial and spinal tumor lesions, which were proved to be germinoma by histological examination. Postoperative course was uneventful without recurrent signs. (Case 2) A 10-year-old boy was admitted to our hospital with 6-month history of right hemiparesis in February, 1979. CT at the first admission disclosed a slight high density lesion in the left basal ganglia, which had low density area suggesting cyst formation and was moderately enhanced on contrast CT. CT after one year showed multiple cysts in the tumor and displacement of neighboring structures. In February, 1980, a piece of the tumor was removed under bifrontal craniotomy and histologically diagnosed to be germinoma. Following radiation, the tumor disappeared on CT and his clinical features improved. In August, 1981, no recurrent signs were noted. From our 2 cases and review of the literature, it can be concluded that germinoma originating in the basal ganglia is rare and have high radiosensitivity as well as germinoma arising in the other sites, and common symptoms and signs are hemiparesis in all cases, not accompanied by intracranial hypertension in the early stage.

Basal Ganglia↗

Identification of restriction-fragment length polymorphisms for the human chorionic gonadotropin-beta/luteinizing hormone-beta gene cluster.

OBJECTIVE: To determine whether restriction fragment length polymorphisms are present using a deoxyribonucleic acid (DNA) probe for human luteinizing hormone beta subunit (hLH-beta). If the gene for hLH-beta is polymorphic, genetic diagnosis of disorders of luteinizing hormone (hLH) and human chorionic gonadotropin (hCG) production could become possible. DESIGN: Study of genomic DNA from controls with a variety of restriction enzymes to identify polymorphisms. SETTING: Laboratories of the Department of Obstetrics and Gynecology, Department of Oral Biology, Medical College of Georgia, Augusta, Georgia. PATIENTS: Unrelated control men and women seen in clinics at the Medical College of Georgia. INTERVENTIONS: Genomic DNA was extracted from patients and digested with eight different restriction enzymes for the study of the hLH-beta gene by Southern analysis. MAIN OUTCOME MEASURE: Fragment (band) sizes on radiographs from Southern blots were compared with those from molecular weight standards. CONCLUSIONS: Restriction fragment length polymorphisms were identified for four of the restriction enzymes, DraI, HincII, MboI, and KpnI. These polymorphisms may be useful in the diagnosis of disorders of hLH and hCG production.

Chorionic Gonadotropin↗

Variability in β-human chorionic gonadotropin concentrations following evacuation of a hydatidiform mole pregnancy: A retrospective cohort study from Vietnam.

BackgroundGestational trophoblastic disease refers to a group of tumors defined by abnormal trophoblastic proliferation. This disease produces a distinct tumor marker, beta-human chorionic gonadotropin, which can be useful for diagnosis and follow-up. The objective of this study was to investigate the variations in serum beta-human chorionic gonadotropin levels after uterine evacuation as well and the progression of gestational trophoblastic neoplasia.Materials and methodsThis retrospective cohort study was conducted at Tu Du Hospital, Vietnam, between January 2019 and December 2020. All patients diagnosed with molar pregnancy were analyzed retrospectively based on serial serum beta-human chorionic gonadotropin levels following uterine evacuation. Post-evacuation outcomes, including relapsed molar pregnancy and gestational trophoblastic neoplasia, were also monitored.ResultsWe enrolled 560 patients with molar pregnancy, including 298 with complete hydatidiform mole and 262 with partial hydatidiform mole. Severe symptoms were more common in those with complete hydatidiform mole. Over the follow-up period, 97 cases of gestational trophoblastic neoplasia were noted. The data show that the median time to gestational trophoblastic neoplasia diagnosis was 8.75&#x2009;&#xb1;&#x2009;4.41 (4-26) weeks. In terms of variations in the serum beta-human chorionic gonadotropin levels, the generalized estimating equation model showed a faster decline in the complete hydatidiform mole group than in the partial hydatidiform mole group. Similarly, regression in serum beta-human chorionic gonadotropin levels was significantly more rapid in patients who progressed to gestational trophoblastic neoplasia than in those with relapsed molar pregnancy (-11,593 vs. -20,651.22 and -12,946.26 vs. -46,329.23 mUI/mL, p&#x2009;<&#x2009;0.001).ConclusionsSurveillance of serum beta-human chorionic gonadotropin levels remains essential for gestational trophoblastic neoplasia monitoring in patients with molar pregnancy following surgical evacuation. The post-evacuation serum beta-human chorionic gonadotropin level regression curve helps distinguish gestational trophoblastic neoplasia from hydatidiform moles. Further evidence is required to strengthen these findings.

Humans↗

Evidence for free beta-subunit secretion in so-called human chorionic gonadotropin-positive seminoma.

In 349 patients with pure seminoma the authors determined human chorionic gonadotropin (HCG) plus the free beta-subunit (HCG-beta) by a polyclonal radioimmunoassay (RIA) and found elevated serum levels in 42 patients (12%). In addition, each HCG and HCG-beta were specifically measured by monoclonal immunoradiometric assays (IRMA) in 19 of these patients. Overall 12 patients were HCG-beta positive and 12 HCG positive. Elevated serum levels of both molecules were found in five patients, whereas seven patients showed elevation only in HCG and another seven patients only in HCG-beta. In serum samples of patients with high HCG-beta and minimally elevated HCG levels the free beta-subunit could be detected by gel filtration and immunoradiometric assays, whereas both HCG-beta and holo-HCG were found in ultrafiltered and concentrated urinary samples. The authors conclude that HCG-beta can be present as the major form in serum even if both HCG-beta and HCG are detectable in urine. When measuring hormone concentration as a tumor marker in seminoma patients, methods which determine both activities, HCG plus HCG-beta, seem to be the most reliable. Whereas 16 patients with Stage I-IIc had HCG-beta levels between 0.1 and 2.8 IU/l and currently have no evidence of disease, two patients with Stage IV had HCG-beta levels of 18 and 37 IU/l and died. Current investigations have to clarify the prognostic significance of beta-subunit secretion.

Adult↗

Evidence for a human chorionic gonadotropin-like material in the rabbit blastocyst.

Extracts from (1) 300 day 6 rabbit blastocysts, (2) 300 day 2 unfertilized ova, and (3) uteri from the nonpregnant does were analyzed in the following assays in order to determine the presence of a chorionic gonadotropin: (1) in vitro bioassay for testosterone production by decapsulated rat testes, (2) in vitro bioassay for progesterone production by porcine granulosa cells, (3) in vitro determination of adenylyl cyclase-stimulating activity in rabbit Graafian follicles, (4) gel filtration in a Sephadex G-150 column and assay of the elutions in a radioimmunoassay (RIA) specific for the beta-subunit of human chorionic gonadotropin (hCG), (5) parallelism with hCG standard preparations in beta-hCG RIA, and (6) concanavalin A-column chromatography. The rabbit blastocyst extracts showed an hCG-like material in all of the systems tested. None of the other two extracts presented hCG-like activity in any of the assay. The immunoreactive material in the beta-hCG RIA of the blastocyst extracts after gel filtration presented a profile different from that of pure hCG; this may represent heterogeneity due to a species difference or a slightly different molecular weight. These results confirmed previous findings of several investigators and those from our laboratory in that the preimplanted rabbit embryo contains a gonadotropin with characteristics similar to hCG.

Adenylyl Cyclases↗

Elevated steroidogenesis, defective reproductive organs, and infertility in transgenic male mice overexpressing human chorionic gonadotropin.

We previously developed a transgenic (TG) mouse model that overexpresses the human chorionic gonadotropin (hCG) beta-subunit under the universal human ubiquitin C promoter, displaying in males a modest 3-fold increase in circulating levels of LH/hCG bioactivity. The males were fertile and presented with a mild reproductive phenotype. To achieve higher levels of hCG, a double TG model was generated by cross-breeding the hCG beta-expressing mice with another TG line harboring a ubiquitin C/common alpha-subunit fusion gene. The double-TG mice expressed excessive levels of dimeric hCG, with 2000-fold elevated circulating LH/hCG bioactivity. These male mice were infertile, primarily due to inability to copulate, and they showed enhanced testicular androgen production despite clear down-regulation of LH/hCG receptors. Their intratesticular inhibin B was unaltered, but serum FSH was markedly reduced. Apparently the chronic hCG hyperstimulation led to focal Leydig cell proliferation/hypertrophy at 6 months of age, but failed to promote testicular tumors. Even though full spermatogenesis occurred in most of the seminiferous tubules, progressive tubule degeneration was apparent as the males grew older. The prostate and seminal vesicles were enlarged by distension of glandular lumina. Functional urethral obstruction was indicated by distension and sperm accumulation in distal vas deferens as well as by dilated urinary bladder and enlarged kidneys. The abnormal function of accessory sex glands and/or lower urinary tract as a consequence of the disturbed sex hormone balance or direct action of hCG may be the main cause of infertility in this model. The present study provides in vivo evidence that exposure of male mice to chronically elevated levels of hCG severely affects their urogenital tract function at multiple sites and causes infertility, but, unlike in LH/hCG overexpressing female mice, it is not tumorigenic.

Animals↗

Differential regulation of hCG alpha and beta subunit mRNAs in JEG-3 choriocarcinoma cells by 8-bromo-cAMP.

The coordinate regulation of human chorionic gonadotropin (hCG) subunit synthesis by JEG-3 choriocarcinoma cells was studied at the pretranslational level. The responses of the hCG alpha and beta mRNAs were measured during stimulation with the potent cAMP analog 8-bromo-cAMP (8-Br-cAMP) using 32P-labeled hCG alpha and beta cDNA probes. The hCG alpha mRNA (850 bases) and beta mRNA (1050 bases) from JEG-3 cells were identical in size to that of their respective mRNAs from placenta, by Northern blot analysis. After 48 h of stimulation with 2 mM 8-Br-cAMP, production of immunoreactive alpha and beta subunits increased 25- and 52-fold, respectively; corresponding levels of the alpha and beta mRNAs increased 36- and 43-fold, respectively, in a dot blot hybridization assay. Total cellular protein, DNA content, and messenger RNA pools were not altered by treatment with 8-Br-cAMP. The temporal coordination of the expression of the hCG alpha- and beta-subunit genes was examined by comparing the time course of stimulation of the respective mRNAs and the production of immunoreactive subunits. The kinetic responses of the alpha and beta mRNAs differed: the increase in hCG alpha mRNA preceded the increase in hCG beta mRNA, while levels of free alpha subunit and intact hCG increased in parallel with the increase in beta mRNA. hCG alpha mRNA levels increased rapidly between 8 and 24 h after the addition of 8-Br-cAMP, and approached a plateau by 48 h. The levels of hCG beta mRNA increased steadily throughout the 8-48 h period. These results demonstrate that the cAMP analog 8-Br-cAMP differentially regulates hCG subunit biosynthesis in JEG-3 cells at a pretranslational level, and that the stimulation by 8-Br-cAMP in this system appears to be relatively selective for hCG subunits.

8-Bromo Cyclic Adenosine Monophosphate↗

Cyclic AMP and phorbol esters interact synergistically to regulate expression of the chorionic gonadotropin genes.

Previous studies have shown that activators of the protein kinase A pathway increase transcription of the genes encoding the alpha- and beta-subunits of human chorionic gonadotropin (hCG) in choriocarcinoma cell lines. Here, we show that treatment of choriocarcinoma cells with activators of protein kinase C, such as phorbol myristate acetate (PMA) and dioctanoylglycerol, increases accumulation of the mRNAs for both subunits of hCG by 3-4-fold. In contrast, a phorbol ester which fails to activate protein kinase C, phorbol 12 beta,13 alpha-didecanoate, has no effect on hCG mRNA levels. To test the possibility that these two major intracellular signaling pathways interact, we treated choriocarcinoma cells with PMA, forskolin, or PMA and forskolin together. Treatment with either agent led to a 2-3-fold increase in hCG mRNA levels, whereas treatment with both agents resulted in a 9-fold increase. This synergistic response also occurred when choriocarcinoma cells were treated with PMA and 8-Br-cAMP. Furthermore, PMA did not increase intracellular cAMP levels, suggesting that these two pathways interact subsequent to cAMP generation. PMA also increased transcription of the hCG alpha- and beta-genes by 2-3-fold. Whereas transcription of the alpha subunit gene increases synergistically after treatment with both PMA and forskolin, transcription of the hCG beta-gene was limited to the increase caused by either agent alone. This latter result suggests that regulation of hCG beta mRNA accumulation is more complex than that of alpha-subunit mRNA and probably involves both transcriptional and post-transcriptional components.

8-Bromo Cyclic Adenosine Monophosphate↗

Prenatal screening for Down syndrome with maternal serum human chorionic gonadotropin levels.

Human chorionic gonadotropin levels in midtrimester pregnancies may be predictive of Down syndrome. A commercially available enzyme immunoassay kit was used to measure the beta-subunit of human chorionic gonadotropin in maternal sera from 38 Down syndrome pregnancies and 114 gestational age matched controls. The human chorionic gonadotropin levels were also assayed in 236 normal sera and plasma samples to determine normative values and appropriate individual corrections. Serum and plasma human chorionic gonadotropin levels are closely correlated and are stable at room temperature, during refrigeration, and throughout freeze-thaw cycles. There is no correlation between the human chorionic gonadotropin level and maternal age, weight, or race. However, the human chorionic gonadotropin level decreases with each week of gestation from 15 to 19 weeks. Medians for each week of gestation were established to account for this variable. Up to 63% of the Down syndrome pregnancies were detected with a cutoff of 2.0 multiples of the normal median. A computational combination of human chorionic gonadotropin and maternal serum alpha-fetoprotein testing will detect additional Down syndrome pregnancies and decrease the false-positive rate. The measurement of human chorionic gonadotropin appears to be a valuable addition to maternal serum alpha-fetoprotein screening programs that can significantly increase the proportion of Down syndrome cases diagnosed.

Blood Specimen Collection↗