Serum SP1 and hCG beta-subunit (hCG beta) levels in choriocarcinoma, invasive mole, and hydatidiform mole--clinical significance of SP1/hCG beta ratio

Serum SP₁ (pregnancy-specific β₁, glycoprotein) levels in patients with choriocarcinoma, invasive mole, and hydatidiform mole were radioimmunoassayed and compared with simultaneously measured serum hCGβ-subunit (hCGβ) levels in order to evaluate the clinical significance of SP₁ determination. Serum SP₁ levels at the time of admission ranged from 6.4 to 1660 ng/ml in choriocarcinoma patients, 16.3 to 540 ng/ml in invasive mole, and 720 to 58,000 ng/ml in hydatidiform mole. $\text{SP}{}_1\text{hCGβ}$ ratios were under 1.0 in choriocarcinoma (0.3 ± 0.2, mean ± SD), over 1.0 in hydatidiform mole (10.9 ± 8.3), and intermediate in invasive mole (1.5 ± 0.3). In normal pregnancy, the ratio increases as pregnancy progresses, that is, from 15.25 in 7-week gestation to 14,090.90 in 40-week gestation. The mean $\text{SP}{}_1\text{hCGβ}$ ratio differs significantly among choriocarcinoma, invasive mole, and hydatidiform mole. $\text{SP}{}_1\text{hCGβ}$ ratio is likely to represent the degree of differentiation of trophoblastic cells. The $\text{SP}{}_1\text{hCGβ}$ ratio may be useful in differentiating between choriocarcinoma and invasive mole.     

First trimester maternal serum placenta growth factor (PIGF)concentrations in pregnancies with fetal trisomy 21 or trisomy 18

Placenta growth factor (PIGF), an angiogenic factor belonging to the vascular endothelial growth factor family, pregnancy-associated plasma protein A (PAPP-A) and free beta-human chorionic gonadotrophin (beta-hCG) were measured in maternal serum from 45 pregnancies with trisomy 21, 45 with trisomy 18 and 493 normal controls at 10-13 completed weeks of gestation. In the normal pregnancies maternal serum PIGF levels increased exponentially with gestation. The median multiple of the median (MoM) PIGF concentration in the trisomy 21 group (1.26 MoM) was significantly higher (p<0.0001) than in the control group (1.00 MoM). In the trisomy 18 group the median PIGF was lower (0.889 MoM) but this did not quite reach significance (p=0.064). The corresponding median MoM values for PAPP-A were 1.00 MoM for the controls, 0.49 MoM for trisomy 21 and 0.16 MoM for trisomy 18. The median MoM values for free beta-hCG were 1.00 MoM for the controls, 2.05 MoM for trisomy 21 and 0.38 MoM for trisomy 18. In the control group there was a small but significant correlation of PIGF with free beta-hCG (r=+0.1024) and PAPP-A (r=+0.2288). In the trisomy 18 group there was a significant association between PIGF and free beta-hCG (r=+0.2629) but not with PAPP-A (r=+0.0038). In the trisomy 21 group there was a small but significant association with PAPP-A (r=+0.1028) but not with free beta-hCG (r=+0.0339). The separation of affected and unaffected pregnancies in maternal serum PIGF is small, and therefore it is unlikely that measurement of PIGF would improve screening for these abnormalities provided by the combination of fetal nuchal translucency and maternal serum PAPP-A and free beta-hCG.     

Evaluation of pregnancy-associated plasma protein A (PAPP-A) and free beta subunit of human chorionic gonadotropin (beta hCG) levels and sonographic assesement of fetal nuchal translucency (NT) in singleton pregnancies between 11 and 14 weeks of gestation--Polish multi-centre research

Evaluation of pregnancy-associated plasma protein A (PAPP-A) and free beta subunit of human chorionic gonadotropin (beta hCG) levels and sonographic assessment of fetal nuchal translucency (NT) in singleton pregnancies between 11 and 14 weeks of gestation--Poland's multi-centers research. OBJECTIVES: Pregnancy-associated plasma protein A has been reported to be low in Down syndrome affected pregnancies during the first trimester of pregnancy. Enlarged nuchal translucency (NT) is observed in about 80% of fetuses affected with chromosomal abnormalities and congenital heart defects (CHD). MATERIAL AND METHODS: The aim of this study were to determine value and the medians of free beta-human chorionic gonadotropin (beta-hCG) and pregnancy associated plasma protein-A (PAPP-A) and nuchal translucency thickness in the first trimester in a prospective study of a non-selected Polish population. RESULTS: All examinations have been performed according to the Fetal Medicine Foundation (FMF) rules. We have included 800 women between 11 weeks 0 days and 13 weeks 6 days gestation into a biochemical examination. Women booked into the clinic were offered screening, using a combination of maternal serum free beta-hCG and pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency thickness. The maternal serum were measured using the Kryptor analyzer (Brahms Diagnostica). All pregnant women have been divided into 2 groups younger than (first group) and older than (second group) 35 years of age. CONCLUSIONS: Nomogrames for free beta-hCG and PAPP-A levels in physiological pregnancy between 11(+0) and 13(6) weeks were determined in the examined population. A positive correlation between PAPP-A and CRL levels, as well as a weak negative correlation between free beta-hCG and CRL, were demonstrated.     

A study of the properties of human chorionic gonadotropin (hCG) from total hydatidiform mole with low hCG immunoactivity

A study was conducted to define biochemical characteristics of human chorionic gonadotropin (hCG) in total hydatidiform mole patients with low serum and urinary hCG levels and to inquire into the reason for its low immunological hCG level by comparing with the hCG of molar patients with a high hCG level. Both hCGs purified from chorionic tissue of molar patients with low and high hCG levels have essentially identical physicochemical, immunological and biological properties. They have low levels of biological activity and practically identical amino acid and carbohydrate compositions. It appears that moles of patients with high levels as well as those with low levels of immunoreactivity produce this purified form of hCG. Extracts of molar tissue from patients with high levels of hCG immunoreactivity also contained other substances with apparent immunoreactivity which can be found in small amounts in tissue extracts from patients who excreted low levels of hCG immunoreactivity. In contrast, extracts of molar tissue and urine from patients with low hCG levels contained hCG-like substances which cannot be detected with the ordinary commercial hCG immunoassay kits. These differences may account for the different levels excreted by these two types of patients.     

Urinary free beta hCG, beta core fragment and total oestriol as markers of Down syndrome in the second trimester of pregnancy

In a study of 69 random urine samples from cases of Down syndrome and 405 samples from unaffected pregnancies, we have assessed the value of various candidate markers that have been proposed as tools for screening for Down syndrome. We found that the marker urine free beta hCG in Down syndrome had a median MoM of 3.53 (95 per cent confidence interval 2.48-4.68) and at a 5 per cent cut-off would have identified 49 per cent (34/69) of cases. Urine beta core had a median MoM of 4.95 (3.87-8.62) and at a 5 per cent cut-off would have identified 39 per cent (27/69) of cases. Total oestriol had a median MoM of 0.65 (0.55-0.80) and at a 5 per cent cut-off would have identified 35 per cent (24/69) of cases. In conjunction with maternal age, the modelled detection rate increased to 55.8 per cent for free beta hCG, 49.8 per cent for beta core and 48.8 per cent for total oestriol. In combination free beta hCG, total oestriol and maternal age would have detected 68 per cent of cases for a 5 per cent false-positive rate. Using analyte ratios to obviate the need to correct for urine dilution in our study (rather than correcting to a fixed creatinine concentration) was not shown to be as effective as correcting using urine creatinine. Urine markers on the whole are unlikely to be of practical screening value considering the 85 per cent to 90 per cent detection rates achievable in the first trimester using a combination of ultrasound and maternal serum biochemistry.     

Human choriogonadotropin (hCG) and placental lactogen (hPL) inhibit interleukin-2 (IL-2) and increase interleukin-1 beta (IL-1 beta), -6 (IL-6) and tumor necrosis factor (TNF-alpha) expression in monocyte cell cultures.

The effect of the human trophoblast hormones chorionic gonadotropin (hCG) and placental lactogen (hPL) on the expression of cytokines in peripheral blood mononuclear cell cultures was followed under a variety of culture conditions, (a) phytohemagglutinin stimulated cells (PHA-MSC), (b) allogenic mixed cells (AMC) and (c) spontaneously proliferating cells (SPC). A dose dependent enhanced release of IL-6, IL-1 beta and TNF-alpha by hCG and hPL was observed under all culture conditions. However, an inhibitory effect on the IL-2 release was seen in PHA-MSC by hPL and in AMC by hPL and hCG. The role of the suppression of IL-2 production/release on cytotoxicity towards trophoblast is discussed. These results suggest a sensitive, dose dependent hormonal control of the modulation of the immune response during pregnancy and strengthen the concept of a distinct regulation of monocytes and lymphocyte subpopulation by trophoblast hormones.     

Prenatal evaluation of fetal renal function based on serum beta(2)-microglobulin assessment

The relationship between fetal renal function (FRF) and fetal serum beta(2)-microglobulin (B2MG) was investigated by comparing its value in 112 unaffected fetuses with that of 23 fetuses presenting with urinary tract malformations (UTM). Fetal serum level of B2MG was totally unrelated to gestational age; its value increased in cases of severe impairment of FRF but was similar to controls in all mild uropathies (p<0.05). Evaluating serum B2MG could be beneficial in fetuses with severe renal damage, but is of no use in unilateral UTM since only the global FRF is tested and not the function of each single kidney.     

Risk assessment of trisomy 21 by maternal age and fetal nuchal translucency thickness in 7,096 unselected pregnancies in Slovenia

AIM: To evaluate the screening for trisomy 21 by maternal age and nuchal translucency in a low-risk population. METHODS: Screening was performed in 7,096 singleton pregnancies. The estimated risk for trisomy 21, the detection rate (DR), false positive rate (FPR) and the cut-off nuchal translucency thickness to obtain a 5% FPR were calculated. RESULTS: The median maternal age was 28.6 years. The estimated risk for trisomy 21 was 1 in 300 or greater in 2.4% (171 of 7,096) of all pregnancies and in 75% (9 of 12) of trisomy 21 pregnancies. The DR for all aneuploidies was 83.3%, and 75% for trisomy 21. The estimated FPR at risk 1 in 300 for the whole population in 2004 was 3.8%. It is predicted to remain below 4% at least until 2007; to achieve a 5% FPR in 2007 the risk limit 1 in 400 is proposed. CONCLUSIONS: Screening for trisomy 21 in a low-risk population in Slovenia gives comparable results to those in other countries. The only result that varies is the percentage of screen positive patients at the risk limit 1 in 300. We believe the risk limit should be specifically estimated for each country based on its population distribution of maternal age.     

Ultrasonographic assessment of fetal growth: Comparison between human and ovin fetus

OBJECTIVE: Our purpose was to evaluate the rate of ovine fetal growth for several body parameters by serial ultrasonographic measurements and to compare them with analogous data in the human fetus.STUDY DESIGN: Forty-three ewes with singleton gestations were studied. Four parameters were measured: biparietal diameter, abdominal circumference, femur length, and tibia length. Ultrasonographic examinations were performed weekly from 50 to 138 days of gestation (term 147 days). Quadratic regression analysis was used to describe each data set.RESULTS: The biparietal diameter showed a significant deceleration of its growth rate. The abdominal circumference showed a linear growth pattern. Both femur and tibia revealed a significant acceleration of the growth rate.CONCLUSION: The ovine fetal growth pattern is different from that observed in the human fetus, in which all four parameters show deceleration of the growth rate in late gestation. In comparison to the ovine, the human fetus reaches similar abdominal circumference and femur length values at term, but in a gestational period that is twice as long. In sharp contrast to abdominal circumference and femur length growth, the biparietal diameter has a similar growth rate in both species. Thus the human fetus has a slower rate of somatic growth and its greater biparietal diameter at term results from the longer gestational period.     

The influence of fetal sex in screening for trisomy 21 by fetal nuchal translucency, maternal serum free beta-hCG and PAPP-A at 10-14 weeks of gestation

In a study of 2923 normal pregnancies and 203 pregnancies affected by trisomy 21 we have shown a significant difference in the median MoM of the markers: fetal nuchal translucency, maternal serum free beta-hCG and PAPP-A in the presence of a female fetus compared with a male fetus. For maternal serum free beta-hCG levels are higher by 15% if the fetus is chromosomally normal and by 11% if the fetus has trisomy 21. For maternal serum PAPP-A the levels in chromosomally normal fetuses are 10% higher in the presence of a female fetus and 13% higher if the fetus has trisomy 21. In contrast, fetal nuchal translucency is 3-4% lower in both chromosomally normal and trisomy 21 female fetuses. The consequence of such changes when screening for trisomy 21 will be a reduction in the detection rate in female fetuses by a factor of 1-2%. Correction of risk algorithms for fetal sex, however, is probably not feasible, since ultrasound detection of fetal sex is only 70-90% accurate in the 10-14 week period.     

Prenatal diagnosis of trisomy 21 by i(21q): a rare case of fetoplacental chromosomal discrepancy

OBJECTIVE: A study was conducted to explain the mechanism of an unusual discrepancy between short- and long-term culture examination methods of chorionic villus sampling (CVS). METHOD: In a 29-year-old Caucasian woman, transabdominal CVS was carried out at 12 weeks of gestation. Non-mosaic karyotype 46,XX,i(21q) was found on long-term CVS culture but number and morphology of chromosomes were normal on short-term culture, amniocyte culture, hygroma colli fluid and fetal fibroblast. RESULTS: Chromosomal aberration probably appeared after the trophoblast cell line differentiation, four days after fertilization, by means of a 21 centromere misdivision and formation of a i(21q) with secondary positive selection of the 46,XX,i(21q) cell line and loss of the 46,XX in the fetus. CONCLUSION: The restricted number of cases with this type of discrepancy limits the possibility of drawing generalised conclusions. In case of discrepancy, we recommend confirmation by amniocentesis or by fetal blood combined with sonographic examination to provide a more definitive diagnosis.     

Maternal serum pregnancy-associated plasma protein A (PAPP-A) but not pregnancy-specific beta1-glycoprotein (SP1) is a useful second-trimester marker for fetal trisomy 18.

The usefulness of early second-trimester serum determinations of pregnancy-associated plasma protein A (PAPP-A) and pregnancy-specific beta1-glycoprotein (SP1) in suspected cases of fetal trisomy 18 was examined in a retrospective, cross-sectional study. Maternal serum PAPP-A and SP1 in 20 cases of fetal trisomy 18 between 15 and 20 weeks of pregnancy, and in 40 controls matched for gestational age and storage time were determined and compared with hCG and free oestriol (uE3). In trisomy 18, the reduction in serum concentration was found to be more pronounced for PAPP-A than for hCG and free oestriol. While none of the 40 control sera had a MoM below 0.2 for either PAPP-A, hCG or uE3, in the trisomy 18 group (20 cases) 17 (85 per cent) of the PAPP-A but only 5 (25 per cent) of the hCG and 4 (20 per cent) of the uE3 results were below the 0.2 MoM threshold. SP1 did not distinguish between controls and trisomy 18. This chromosomal abnormality is too rare a condition to justify maternal serum PAPP-A determination in the second trimester as a routine procedure, but such a test can play a useful role whenever the risk of trisomy 18 is found to be only marginally increased after hCG and uE3 measurements.     

In vitro activity of human chorionic gonadotropin (hCG) on myometrium contractility

LH/hCG receptor has been found in extragonadal tissues in human and animals. The myometrium presents such receptors but their functional role is still not clear. Aim of our study was to test the activity of human chorionic gonadotropin (hCG) on bovine uterine contractility. Uterine strips from cows both during follicular and luteal phases were mounted in an organ bath and then exposed to increased doses of hCG. The amplitude of the myometrium contractions were significantly decreased in the follicular and luteal phase but the frequency was not affected.

These findings prove a relaxing effect of hCG in the bovine uterus, as already shown in the sow and human, and its possible functional role in modulating uterine contractility.     

Amniotic fluid beta 2-microglobulin (beta 2-m) as an index of fetal maturity

Amniotic fluid beta 2 microglobulin (beta 2-m) levels were measured by radioimmunoassay in 78 pregnant women between the 14th and the 42nd week of gestation. 62 were healthy subjects, while eight were affected by EPH gestosis, seven by diabetes (cl. B-F) associated with Rh immunization in one case, one by hydramnios. There was no significant correlation either between beta 2-m and creatinine (n = 18), or between beta 2-m and lecithin sphingomyelin ratio (L/S) (n = 16), although low concentrations of beta 2-m were usually observed after the 35th week of gestation. It is noteworthy that only in one case out of seven with amniotic levels less than 5 microgram/ml L/S ratio was less than 2.     

Assessment of expression of luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor (LH/hCGR) and hCG protein in ovarian cancer tissues

OBJECTIVES: Ovarian cancers still remain a significant worldwide epidemiological problem. The vast majority of newly diagnosed cases are in advanced clinical stages, and the five-year survival rate in all clinical stages amounts up to less than fifty percent. A better understanding of the biology of ovarian cancer can bring us closer to successful treatment and recovery. The aim of this study was to evaluate the expression of luteinizing hormone (LH)/human chorionic gonadotropin (hCG) receptor (LH/hCGR) and the expression of hCG protein in the ovarian cancer tissue. MATERIALS: Histologically proven primary ovarian cancer samples (n=20) were obtained from women undergoing gynecologic surgery. Frozen sections of ovarian cancer tissues were evaluated by means of indirect immunofluorescence. RESULTS: The expression of hCG protein was ubiquitous throughout all samples, while LH/hCGR was detected in only sixty percent of samples. Co-expression of LH/hCGR and hCG protein was detected in some individual cells in tumor tissue. Some cancer cells expressed only hCG protein, but not LH/hCGR. CONCLUSIONS: Expression of LH/hCG receptor is a characteristic feature of various histological types of ovarian cancer. Co-expression of LH/hCGR and hCG protein in individual cancer cells may point to an autocrine or paracrine mechanism of _hCG activity in the tumor microenvironment. Further studies are needed to evaluate LH/hCGR and hCG protein function in the course of neoplastic development.