Human chorionic gonadotrophin and trisomy 18

Estimation of maternal serum β-CG is used in conjunction with α-fetoprotein (AFP) and estriol (E₃) for estimating the risk of Down syndrome (DS) affected fetuses. However, low hCG levels have not been regarded as having clinical significance. We report on 2 patients with trisomy 18 fetuses in whom antenatal screening showed extremely low hCG levels (0.05 and 0.15 MOM). Low hCG levels might indicate increased risk for trisomy 18 despite low estimated risk for DS.     

Human trophectoderm biopsy and secretion of chorionic gonadotrophin.

We have previously developed a technique of trophectoderm biopsy to obtain cells from human blastocysts for preimplantation genetic diagnosis. To determine whether this technique affects the subsequent development of the blastocyst, 45 manipulated blastocysts were observed from days 3 to 14 in culture, the amount of human chorionic gonadotrophin (HCG) secreted by each embryo was measured and these results were compared with those of 26 non-manipulated controls documented in a previous study. A slit was made in the zona pellucida opposite the inner cell mass in 18 of the 45 blastocysts. This increased the rate of hatching but the other morphological changes up to day 14 were similar to those seen in the non-manipulated controls. There was no difference in the mean cumulative HCG secretion by these zona-slit controls (149.8 +/- 45.7 mIU/ml) compared to the non-manipulated controls (146.2 +/- 23.7 mIU/ml). A slit was also made in the zona pellicida of the other 27 blastocysts. Approximately 12-18 h later, in 18 blastocysts a biopsy of the herniating trophectoderm cells (5-30) was performed. The rate of hatching and adherence to the culture dish was similar to the non-manipulated controls. The mean cumulative HCG secretion decreased significantly (57.5 +/- 16.2 mIU/ml, P less than 0.01) after the biopsy procedure. However, if a small biopsy was performed (less than 10 cells removed) the decrease in HCG secretion (87.6 +/- 24.8 mIU/ml) was not significant, whereas when a large biopsy was performed (greater than 10 cells), HCG levels fell to 19.9 +/- 9.1 mIU/ml.(ABSTRACT TRUNCATED AT 250 WORDS)     

Human chorionic gonadotrophin concentrations in early pregnancy after in-vitro fertilization.

There is increased risk of early pregnancy loss after assisted reproduction. In this study the use of serum human chorionic gonadotrophin (HCG) concentrations on day 12 after in-vitro fertilization (IVF) and embryo transfer was evaluated to predict pregnancy outcome. A total of 417 IVF pregnancies were included. Early pregnancy loss was defined as biochemical pregnancies, ectopic pregnancies and first trimester abortions. Vital pregnancies were defined as delivered singletons, multiple pregnancies and second trimester abortions. On the post embryo transfer day 12, the mean HCG concentration of the vital pregnancy group was significantly higher than in early pregnancy loss outcomes (P < 0.00001). Receiver operating characteristic (ROC) curve analysis was performed to evaluate the cut-off value of HCG giving maximal sensitivity and specificity in order to discriminate early pregnancy losses from vital pregnancies. A patient with a HCG value higher than the calculated cut-off value (55 IU/l) had a 90% chance of having a vital pregnancy after IVF and embryo transfer. It can be concluded that a discriminatory HCG value on day 12 after IVF and embryo transfer cycles may be useful in predicting pregnancy outcome and may guide clinicians in identifying those pregnancies at risk for adverse outcomes and instituting more intensive surveillance in this population.     

Molecular interactions during pregnancy: Placental mRNA expression of {alpha} and {beta} human chorionic gonadotrophin in early trisomy 18 pregnancies

The placental expression of human chorionic gonadotrophin (HCG)I- and ß-subunits was investigated in eight pregnanciespresenting with trisomy 18 and in 30 normal pregnancies at 11–15weeks gestation. In the control group, the median densitometricscores of placental ß-HCG and I-HCG mRNA were 1.23and 1.74 respectively. In the trisomy 18 group the median ß-HCGmRNA was significantly lower (0.16, Z = 2.29, P<0.05) but     

Pregnany: Human chorionic gonadotrophin release and tissue viability in placental organ culture

The use of human chorionic gonadotrophin (HCG) secretion asa measure of viability during the organ culture of human firsttrimester placental tissue has become a popular practice. Ithas been suggested that if cultured tissue is releasing largeamounts of this protein hormone, there is a high level of viability.We have found, however, that the cytosolic enzyme L-lactatedehydrogenase is released into the culture supernatant in asimilar daily pattern as HCG, suggesting that tissue disruptionmay be occurring, resulting in some of the observed hormonerelease. In addition, we have shown that the uptake of the fluorescentdye dansyl-L-lysine into the syncytium increases significantlyfrom day 0 to day 4, suggesting a loss of syncytial membraneintegrity. Electron micrographs show further evidence of thesyncytial degeneration at the ultrastructural level, displayingextensive vacuolation and poor micro-villous cover. In contrastto the degenerated state of the syncytiotrophoblast, a highlevel of bromodeoxyuridine incorporation is observed for cytotrophoblastsand, in particular, stromal cells up to 5 days in culture. Overall,the results suggest that the use of HCG release as a determinantof tissue viability in placental organ culture should be treatedwith a degree of caution.     

Abnormal maternal serum levels of human chorionic gonadotropin free subunits in trisomy 18

We have measured maternal serum levels of free alpha and beta subunits of human chorionic gonadotropin between 8 and 12 weeks of gestation in 704 women at increased risk for trisomy. This group was studied because of advanced maternal age or a previous birth with chromosomal abnormality. All sera had been collected prior to chorion villus biopsy for prenatal diagnosis. Serum levels of free alpha and beta hCG were determined by specific monoclonal antibody-based immunoradiometric assays. Analysis of chorionic tissue showed that in 38 of 704 (5.4%) pregnancies the fetus had a chromosome abnormality. There were 8 fetuses with trisomy 18 (1.1%) and 9 (1.3%) with trisomy 21. In all pregnancies carrying a trisomy 18 fetus, we observed either high levels of free alpha hCG or low levels of free beta hCG or both. More importantly, the calculated ratio of free beta hCG/alpha hCG was less than 0.25 multiples of the median (MoM) in 6 of 8 (75%) trisomy 18 cases. Only 21 of 666 mothers (3.2%) carrying a normal fetus had a ratio less than 0.25 MoM (P less than 0.0001). There was no difference between this ratio in trisomy 21 and normal pregnancy. Thus, when adjusted for gestational age, a low free beta hCG/alpha hCG ratio in maternal serum indicates a pregnancy at high risk [RR = 72 (95% CI 32, 162)] for trisomy 18.     

An immunochemical test for chorionic gonadotrophin

An immunochemical procedure for routine laboratory diagnosis of pregnancy utilizing adsorption of human chorionic gonadotrophin onto kaolin and the Ortho pregnancy test reagents is described. The method is suitable for quantitative assay of urinary human chorionic gonadotrophin and can be adapted for use with serum. It was found to compare favourably with the reliability of Galli-Mainini toad tests. It avoids the disadvantages of `biological' tests and is quicker to perform.     

Human prolactin release induced by follicle stimulating hormone, luteinizing hormone and human chorionic gonadotrophin

Plasma prolactin levels rise in stimulated cycles. To clarifythe effects of gonadotrophin on the lactotrophs, three studieswere performed. First, plasma concentrations of prolactin duringclomiphene citrate (CC)-human menopausal gonadotrophin (HMG)-humanchononic gonadotrophin (HCG) treatment of women enrolled forin-vitro fertilization (IYF) were compared with those duringHMG-HCG administration while under pituitary suppression witha gonadotrophin releasing hormone (GnRH) analogue (buserelin).Women suppressed with buserelin had higher basal levels of PRLin plasma (14.4 ± 4.3 nglml versus 6.9 ± 1.4 ng/ml,P<0.001). Only buserelin-suppressed women showed a significantrise in plasma prolactin before HCG administration, while bothpatient groups had marked prolactin peaks after HCG injection.This peak was higher in the buserelin group (71.9 ± 50.7ng/ml versus 52.6 ± 29.7 ng/ml). The second study showedthat plasma levels of prolactin of 6 post- menopausal womenwere significantly increased 48 h after an injection of 5000IU HCG, i.m. (24.9 ± 17.4 ng/ml versus 12.4 ±6.2 ng/ml P<0.05). Third, plasma prolactin was studied in5 women over 30 days after surgical castration. An upward trendwas observed similar to that of endogenous gonadotrophin, withthe change in prolactin values closely correlating with thechange in concentrations of follicule stimulating hormone (P<0.005).All these findings suggest that human gonadotrophins stimulatelactotrophs.     

Fertilization and early embryology: Human chorionic gonadotrophin: embryonic secretion is a time-dependent phenomenon

Of 48 spare human pre-embryos achieving the expanded blastocyststage, 22 (45.6%) secreted significant amounts of human chorionicgonadotrophin (HCG) (>5 IU/l/day). Of these, nine remainedintrazonal, seven partially hatched and six fully hatched. Embryonicproduction of HCG in vitro appeared to be time-dependent, startingafter a certain minimum time (160 h post-insemination) and risingexponentially, with maximal HCG production around day 10. Hatchingwas not a prerequisite for HCG secretion, since similar amountswere produced by intrazonal blastocysts. Blastocysts derivedfrom abnormally fertilized oocytes also began secreting HCGexponentially but secretion was delayed and the upper limitof maximum HCG secretion rate was comparatively low. The actualamount of HCG is thought to reflect the number of viable trophectodermcells producing the hormone. HCG doubling times for blastocystsin vitro were rapid when compared to implanting blastocystsof a similar age in vivo, with 19/22 (86.4%) blastocysts havinga doubling time of < 10 h. Provided a pre-embryo can secreteHCG and maintain an adequate doubling time, sufficient HCG shouldbe produced for initial stages of embryonic recognition in vivo.Since intrazonal blastocysts are capable of fulfilling bothof these criteria, the limiting factor in realizing their fullpotential may be escaping from the zona pellucida.     

Human chorionic gonadotrophin and alpha-fetoprotein in testicular germ cell tumours: a retrospective immunohistochemical study

A series of testicular germ cell tumours (46 seminomas and 27 non-seminomas) was studied immunohistochemically with regard to the presence of alpha FP and HCG. In three seminomas, HCG reactive syncitiotrophoblast-like giant cells (STLG) were found. Immunoreactive alpha FP did not occur in seminomas. In differentiated mature teratomas HCG or alpha FP could not be demonstrated. In embryonal carcinomas with or without teratoma (MTI/MTU/MTT) HCG immunoreactivity was found in 83%, usually localized in STLG. In 75% of these tumours alpha FP could be demonstrated. This protein was localized in foci of endodermal sinus or yolk sac differentiation, but also in single cells and cell clusters in areas of embryonal carcinoma. In some cases syncitial cells were present which contained both HCG and alpha FP. Immunostaining of tumour markers appeared not to provide important additional criteria for classification of these tumours in the currently available classifications. The significance of HCG containing STLG in seminomas deserves further investigation. Prospective studies of embryonal carcinoma with or without teratoma (MTI/MTU/MTT) will be necessary to evaluate the possible prognostic importance of the presence of alpha FP or HCG or both.     

外源性hCG对肾组织EGF的影响

目的:探讨外源性绒毛膜促性腺激素(hCG)对肾组 织表皮生长因子(EGF)的影响.方法:300-350克雄性SD 大鼠20只,分为对照组和实验组,每组10只.实验组肌肉注射hCG 200 IU/d,对照组肌肉注射等量生理盐水,连续注射7 d.用免疫组化分析两组大鼠肾脏EGF表达,用荧光定量PCR法检测肾脏组织EGF mRNA相对表达量.结果:免疫组化结果显示hCG干预后,实验组肾脏EGF的阳性率明显高于对照组(P<0. 01).然而荧光定量PCR结果显示EGF mRNA表达量在实验组与对照组间无统计学差异(P>0. 05).结论:外源性hCG在一定剂量范围内促进肾脏EGF的成熟而非合成.     

A rapid, sensitive and specific radioimmunoassay for human chorionic gonadotrophin.

A specific, quantitative assay for human chorionic gonadotrophin (hCG) in plasma has been developed using an hCG-beta antiserum and an assay procedure lasting four hours. It employs a double antibody method and in a procedure prior to assay the two antibodies are pre-incubated in bulk and then stored in ampoules in lyophilised form ready for use. The assay procedure is a dis-equilibrium (sequential saturation) system in which the sample or unlabelled antigen is first incubated with the pre-incubated antisera followed by the addition of the labelled antigen and a further incubation. The antigen-antibody complex is separated from free antigen by vacuum filtration on glass fibre discs. The assay sensitivity is 100-200 picograms hCG/ml (0.68 mIU/ml) and is uninfluenced by normal concentrations of luteinising hormone in the sample.     

Natural history of trisomy 18 and trisomy 13: II. Psychomotor development

Developmental data were abstracted from medical records on 50 trisomy 18 individuals ranging in age from 1 to 232 months and 12 trisomy 13 individuals ranging in age from 1 to 130 months. Data on the age when trisomy 18 and trisomy 13 children achieved developmental skills were collected from a larger group of 62 trisomy 18 individuals and 14 trisomy 13 individuals whose families filled out parent questionnaires. Developmental quotient (DQ), defined as developmental age divided by chronological age, averaged 0.18 for trisomy 18 and 0.25 for trisomy 13. There was a dramatic drop in DQ from infancy to later childhood. The highest DQs and the greatest variation in DQs were in the first 2–3 years of life. Developmental ages in 7 skill areas were significantly different, with daily living and receptive language having the highest values and motor and communication skills having the lowest. When chronological age was taken into account, there was no significant difference in DQs in the same 7 skill areas, although there was a trend that was similar to the pattern of differences with developmental age. Older children could use a walker, understand words and phrases, use a few words and/or signs, crawl, follow simple commands, recognize and interact with others, and play independently. Walking and some toileting skills were also reported for trisomy 13. Although individuals with trisomy 18 and trisomy 13 were clearly functioning in the severe to profound developmentally handicapped range, they did achieve some psychomotor maturation and always continued to learn. © 1994 Wiley-Liss, Inc.     

The ovarian dysgenesis of trisomy 18.

Ovarian abnormalities have been reported as a rare feature of the trisomy 18 syndrome. Gross and histological examination of autopsy material from 13 female infants with this syndrome revealed that ovarian dysgenesis, in varying degrees of severity, is more common than is indicated by the literature. The characteristic changes are reduction in germ cells due to necrobiosis, and the presence of mesothelial clefts and abnormal masses of stromal cells.     

The human blastocyst: morphology and human chorionic gonadotrophin secretion in vitro.

Micromanipulation of human oocytes and embryos has provided new opportunities for both the treatment of infertility and the preimplantation diagnosis of genetic disease. It is important to determine whether manipulated embryos develop normally in vitro, as an indication of their suitability for transfer. However, at present there is little information on the development of non-manipulated embryos in vitro for comparison. We have therefore monitored morphological changes and human chorionic gonadotrophin (HCG) secretion in 36 non-manipulated human embryos, including 26 blastocysts and 10 cavitating morulae, daily from day 3 to day 14 of culture. Hatching was observed in 10 (38.5%) blastocysts and five of these adhered to the culture dish and appeared viable until day 14. The secretion of HCG was first detected on day 8, peaked at day 10 (51.11 +/- 8.7 mIU/ml) and then declined but was still detectable in four blastocysts on day 14. There was no overall difference in HCG secretion by hatched blastocysts and those which remained within the zona. However, those hatched blastocysts which showed adherence had significantly increased (P less than 0.05) HCG secretion. For individual blastocysts, the pattern of HCG secretion correlated well with the assessment of morphology. These data provide the basis for comparative studies of morphological changes and HCG secretion in manipulated embryos.