Hyperglycosylated Human Chorionic Gonadotropin Research Articles

Predictive value of hyperglycosylated human chorionic gonadotropin for pregnancy outcomes in threatened abortion in first-trimester viable pregnancies.

To investigate the value of a single determination of hyperglycosylated hCG (hCG-H) for predicting the clinical outcome of patients with threatened abortion in the first trimester of pregnancy. Prospective study performed on 86 consecutively selected women with a diagnosis of threatened abortion and viable intrauterine pregnancy in the first trimester of pregnancy, conducted in two tertiary care hospitals. All patients underwent a single blood sample to determine hCG-H and total hCG serum levels and a transvaginal ultrasound 12-24 hours after diagnosis. Patients were monitored to determine whether the outcome was a miscarriage before the 20th week of pregnancy. Forty-three women (50%) had a miscarriage during the follow-up. We observed a very high correlation between hCG-H and total hCG (r?=?0.91, p?<?0.001). Median hCG-H and total hCG from pregnancies with normal outcome was signif-icantly higher than those ending in abortion. hCG-H and total hCG were very similar predictors of pregnancy outcomes (AUC: 0.90 and 0.89, respectively). The ratio hCG-H / total hCG was a poor predictor (AUC: 0.64). A single hCG-H assay is helpful for predicting pregnancy outcomes in women with first trimester threatened abortion and viable or potentially viable pregnancy at the time of presentation. However, hCG-H is not a better predictor than total hCG.

Core 2 β1,6-N-acetylglucosaminyltransferases accelerate the escape of choriocarcinoma from natural killer cell immunity

Hyperglycosylated human chorionic gonadotropin (H-hCG) is secreted from choriocarcinoma and contains a core2 O-glycan formed by core2 β1,6-N-acetylglucosaminyl transferase (C2GnT). Choriocarcinoma is considered immunogenic as it is gestational and contains paternal chromosomal components. Here we examined the function of C2GnT in the evasion of choriocarcinoma cells from natural killer (NK) cell-mediating killing. We determined that C2GnT is highly expressed in malignant gestational trophoblastic neoplasms. C2GnT KO downregulates core2 O-glycan expression in choriocarcinoma cells, which are more efficiently killed by NK cells than control cells. C2GnT KO cell containing tumor necrosis factor-related apoptosis inducing ligand have lower viability than control cells. Additionally, poly-N-acetyllactosamine in core2 branched oligosaccharides on MHC class I-related chain A (MICA) and mucin1 (MUC1) is significantly reduced in C2GnT KO cells. Meanwhile, the cumulative survival rate of nude mice inoculated with C2GnT KO tumors was higher than that of the control group. These findings suggest that choriocarcinoma cells may escape NK cell-mediated killing via glycosylation of MICA and MUC1.

B-hCG and H-hCG levels in patients with gestational trophoblastic neoplasia

Objective: Gestational trophoblastic disease is a term that encompasses a spectrum of disorders all arising from the placenta. Human chorionic gonadotropin (hCG) hormone has an essential role in the diagnosis and management of gestational trophoblastic neoplasia. Measuring beta-hCG (B-hCG) levels is the only standard method of monitoring treatment response in patients on chemotherapy. Serial B-hCG levels are also helpful in defining the suitable approach and the dosage of chemotherapeutic drugs. Unfortunately, this marker may not be helpful in some cases. Therefore, the present study was conducted to determine the results of the ratio of B-hCG and hyperglycosylated human chorionic gonadotropin (H-hCG) in patients with gestational trophoblastic neoplasia. Materials and methods: This was a cross-sectional study in 22 patients with gestational trophoblastic neoplasia who were referred to an oncology clinic of an academic hospital of Mashhad University of Medical Sciences in Iran from December 2017 to May 2018. Inclusion criteria were plateau level of B-hCG (during 4 weeks) or persistent low level of hCG. After ruling out other etiologies, H-hCG level was measured and the H-hCG/total hCG ratio was evaluated. If the proportion was more than 20%, active gestational trophoblastic neoplasia was diagnosed, and if it was less than 20%, quiescent gestational trophoblastic neoplasia was diagnosed. In patients with active gestational trophoblastic neoplasia, interventional procedures involved a change in the dose intensity or chemotherapy or proposing a surgery. However, only serial follow-up was recommended in patients with quiescent gestational trophoblastic neoplasia. Then, the patients were followed during the therapy and the condition of patients was followed and recorded. Results: The mean age of patients was 31.36 ± 8.01 years. Hydatidiform mole was the most common diagnosis, accounting for approximately 64% (14) of patients. A total of 81% of patients were undergoing chemotherapy. The interval time between the onset of chemotherapy until plateau or persistent low level of hCG was 11.26 ± 4.03 weeks. The mean B-hCG level was 36.6 mIU/mL and the mean H-hCG/total hCG ratio was 6.24%. This proportion was less than 20% in 82% of patients. Among these patients, 14 patients (77.8%) had spontaneously normalized levels of B-hCG during a 6-month follow-up. Two cases underwent chemotherapy due to increased B-hCG. Other patients are still under follow-up without disease progression. Among 4 patients with a H-hCG/total hCG ratio &gt;20%, hysterectomy was recommended to one patient duo to multiparity and the fact that the tumor was localized in the uterus. In the other patients, an increase in the dose of methotrexate or a change of chemotherapy regimen was performed, which caused a decrease in B-hCG level to normal. All patients are still under follow-up without disease progression. Conclusion: The data in this study suggests the use of H-hCG as a tumor marker in patients with persistent low level of B-hCG, which is useful to distinguish between quiescence gestational trophoblastic neoplasia, which does not need treatment, from active gestational trophoblastic neoplasia. However, further studies with larger sample size are needed to confirm and generalize the above findings. Keywords: gestational trophoblastic

Rational Design of Hyper-glycosylated Human Chorionic Gonadotropin Analogs (A Bioinformatics Approach)

Background:Protein pharmaceuticals routinely display a series of intrinsic physicochemical instabilities during their production and administration that can unfavorably affect their therapeutic effectiveness. Glycoengineering is one of the most desirable techniques to improve the attributes of therapeutic proteins. One aspect of glycoengineering is the rational manipulation of the peptide backbone to introduce new N-glycosylation consensus sequences (Asn-X-Ser/Thr, where X is any amino acid except proline).Methods:In this work, the amino acid sequence of human chorionic gonadotropin (hCG) was analyzed to identify suitable positions in order to create new N-glycosylation sites. This survey led to the detection of 46 potential N-glycosylation sites. The N-glycosylation probability of all the potential positions was measured with the NetNGlyc 1.0 server. After theoretical reviews and the removal of unsuitable positions, the five acceptable ones were selected for more analyses. Then, threedimensional (3D) structures of the selected analogs were generated and evaluated by SPDBV software. The molecular stability and flexibility profile of five designed analogs were examined using Molecular Dynamics (MD) simulations.Results:Finally, three analogs with one additional N-glycosylation site (V68T, V79N and R67N) were proposed as the qualified analogs that could be glycosylated at the new sites.Conclusion:According to the results of this study, further experimental investigations could be guided on the three analogs. Therefore, our computational strategy can be a valuable method due to the reduction in the number of the expensive, tiresome and time-consuming experimental studies of hCG analogs.

Unbalanced human embryos secrete more hyperglycosylated human chorionic gonadotrophin (hCG-H) than balanced ones.

The aim of this study was to compare the levels of hyperglycosylated human chorionic gonadotropin (hCG-H) secreted from balanced and unbalanced human embryos. Single-step culture media samples from 155 good quality embryos, derived from 90 good prognosis patients undergoing intracytoplasmic sperm injection (ICSI), were collected on the fifth day of embryo cultivation. All embryos were tested by next-generation sequencing (NGS) technique. The hCG-H levels in the culture media were evaluated by ELISA kit (Cusabio Biotech, CBS-E15803h) according to the manufacturer's instructions. Statistical analysis was performed using SPSS v.21 (IBM Corp., Armonk, NY, USA). The NGS analysis revealed that 36% of the embryos (n = 56) were balanced, and 64% of the embryos were unbalanced (n = 99). The presence of hCG-H was confirmed in all embryo culture media samples but was absent in the negative control. In addition, hCG-H concentration was significantly higher in the culture media from unbalanced embryos compared with the balanced ones (0.72 ± 0.30mIU/ml vs. 0.62 ± 0.12mIU/ml, p = 0.02, respectively). Furthermore, the mean levels of hCG-H were significantly increased in the samples from embryos with multiple abnormalities. Finally, the highest levels of hCG-H were expressed from embryos with monosomy of chromosome 11 (1.28 ± 0.04mIU/ml) and those with trisomies of chromosomes 21 (2.23mIU/ml) and 4 (1.02 ± 0.35mIU/ml). Our results suggest that chromosomal aberrations in human embryos are associated with an increased secretion of hCG-H. However, hCG-H concentration in embryo culture media as a single biomarker is not sufficient for an accurate selection of balanced embryos.

Maternal age and blastocyst quality do not influence the embryo production of hyperglycosylated human chorionic gonadotropin

Maternal age and blastocyst quality do not influence the embryo production of hyperglycosylated human chorionic gonadotropin

Hyperglycosylated human chorionic gonadotropin as a predictor of ongoing pregnancy

Hyperglycosylated human chorionic gonadotropin, the predominant human chorionic gonadotropin variant secreted following implantation, is associated with trophoblast invasion. To determine whether the initial serum hyperglycosylated human chorionic gonadotropin differs between ongoing and failed pregnancies, and to compare it to total serum human chorionic gonadotropin as a predictor of ongoing pregnancy. Women undergoing fresh/frozen invitro fertilization cycles at a university-based infertility clinic with an autologous day 5 single embryo transfer resulting in serum human chorionic gonadotropin >3 mIU/mL (n= 115) were included. Human chorionic gonadotropin was measured 11 days after embryo transfer in a single laboratory (coefficient of variation <6%). Surplus frozen serum (-80oC) was shipped to Quest Laboratories for measurement of hyperglycosylated human chorionic gonadotropin (coefficient of variation <9.1%). Linear regression analyses adjusted for oocyte age a priori were used to compare human chorionic gonadotropin and hyperglycosylated human chorionic gonadotropin in ongoing pregnancies (>8 weeks of gestation) and failed pregnancies (clinical pregnancy loss, biochemical and ectopic pregnancies). A total of 85 pregnancies (73.9%) were ongoing. Hyperglycosylated human chorionic gonadotropin and human chorionic gonadotropin values were highly correlated (Pearson correlation coefficient 92.14, P < .0001), and mean values of both were positively correlated with blastocyst expansion score (P value test for trend <.0004). Mean human chorionic gonadotropin and hyperglycosylated human chorionic gonadotropin were significantly higher in ongoing vs failed pregnancies. Among ongoing pregnancies vs clinical losses, mean hyperglycosylated human chorionic gonadotropin, but not human chorionic gonadotropin, was significantly higher (19.0 vs 12.2 ng/mL, β-8.1, 95% confidence interval-13.0 to-3.2), and hyperglycosylated human chorionic gonadotropin comprised a higher proportion of total human chorionic gonadotropin (4.6% vs 4.1%; risk ratio, 0.79; 95% confidence interval, 0.66-0.94). Measured 11 days after single blastocyst transfer, hyperglycosylated human chorionic gonadotropin and human chorionic gonadotropin values were highly correlated, but only mean hyperglycosylated human chorionic gonadotropin and its ratio to total human chorionic gonadotropin were significantly higher in ongoing pregnancies vs clinical pregnancy losses. Further evaluation of hyperglycosylated human chorionic gonadotropin, including in multiple embryo transfers and multiple pregnancy, and using serial measurements, is required.

Prediction of pre-eclampsia and its subtypes in high-risk cohort: hyperglycosylated human chorionic gonadotropin in multivariate models

BackgroundThe proportion of hyperglycosylated human chorionic gonadotropin (hCG-h) to total human chorionic gonadotropin (%hCG-h) during the first trimester is a promising biomarker for prediction of early-onset pre-eclampsia. We wanted to evaluate the performance of clinical risk factors, mean arterial pressure (MAP), %hCG-h, hCGβ, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PlGF) and mean pulsatility index of the uterine artery (Uta-PI) in the first trimester in predicting pre-eclampsia (PE) and its subtypes early-onset, late-onset, severe and non-severe PE in a high-risk cohort.MethodsWe studied a subcohort of 257 high-risk women in the prospectively collected Prediction and Prevention of Pre-eclampsia and Intrauterine Growth Restriction (PREDO) cohort. Multivariate logistic regression was used to construct the prediction models. The first model included background variables and MAP. Additionally, biomarkers were included in the second model and mean Uta-PI was included in the third model. All variables that improved the model fit were included at each step. The area under the curve (AUC) was determined for all models.ResultsWe found that lower levels of serum PlGF concentration were associated with early-onset PE, whereas lower %hCG-h was associated with the late-onset PE. Serum PlGF was lower and hCGβ higher in severe PE, while %hCG-h and serum PAPP-A were lower in non-severe PE. By using multivariate regression analyses the best prediction for all PE was achieved with the third model: AUC was 0.66, and sensitivity 36% at 90% specificity. Third model also gave the highest prediction accuracy for late-onset, severe and non-severe PE: AUC 0.66 with 32% sensitivity, AUC 0.65, 24% sensitivity and AUC 0.60, 22% sensitivity at 90% specificity, respectively. The best prediction for early-onset PE was achieved using the second model: AUC 0.68 and 20% sensitivity at 90% specificity.ConclusionsAlthough the multivariate models did not meet the requirements to be clinically useful screening tools, our results indicate that the biomarker profile in women with risk factors for PE is different according to the subtype of PE. The heterogeneous nature of PE results in difficulty to find new, clinically useful biomarkers for prediction of PE in early pregnancy in high-risk cohorts.Trial registrationInternational Standard Randomised Controlled Trial number ISRCTN14030412, Date of registration 6/09/2007, retrospectively registered.

Hyperglycosylated hCG and Placenta Accreta Spectrum.

We aimed to evaluate the relationship between hyperglycosylated human chorionic gonadotropin (hCG-H) and placenta accreta spectrum (PAS) in the second and third trimesters of pregnancy. This was a case-control study of PAS and controls. hCG-H was measured in the second and third trimesters of pregnancy in women with pathologically confirmed cases of PAS and in gestational age-matched controls without PAS. We compared serum hCG-H levels in cases and controls, calculated summary statistics for diagnostic accuracy, and used receiver operating characteristic (ROC) curves to define an optimal cut-point for diagnosis of PAS using hCG-H. Thirty case samples and 30 control samples were evaluated for hCG-H. Mean hCG-H was lower in the case compared with control group (7.8 ± 5.9 μg/L vs. 11.8 ± 8.8 μg/L, p = 0.03). At an optimal cut-point for hCG-H of ≤7.6 μg/L, the sensitivity, specificity, positive likelihood ratios, negative likelihood ratios, and area under the ROC curve were 66.7%, 69.7%, 2.20%, 0.48%, and 0.68%, respectively. Hyperglycosylated hCG levels in the second and third trimesters of pregnancy were lower in patients with PAS than in controls, but hCG-H showed only modest capability as a diagnostic test for PAS.

Гіперглікозильований хоріонічний гонадотропін – прогностичний критерій розвитку ускладнень вагітності

The objective: to assess the prognostic significance of the level of serum hyperglycosylated human chorionic gonadotropin (gHCG) reative to the development of pregnancy complications that lead to impaired fetal conditions. Materials and methods. 382 pregnant women were examined who were on the register, were hospitalized in case of complications of pregnancy and gave birth to KCMH №2 (Kiev). All pregnant women were evaluated serum gCGG in the period of 8-10 weeks gestation, evaluated the course and result of pregnancy. Results. Reduction in the level of gHCG is a marker of insufficient trophoblast invasion, which is likely to lead to the formation of placental dysfunction and the development of a variety of obstetric pathology complicating the course of pregnancy and a risk factor for antenatal loss and neonatal morbidity. The conclusion. Determination of the level of hyperglycosylated human chorionic gonadotropin in the first trimester of pregnancy will make it possible to identify pregnant women at risk for the formation of placental dysfunction and propose a set of monitoring activities aimed at early detection of violations of pregnancy and their timely removal. This helps prevent the formation of severe pathological conditions during pregnancy in both the mother and the fetus, which corresponds to the current trends in the development of medical care, namely: prediction, prevention and individual approach. Key words: hyperglycosylated chorionic gonadotrophin, complications of pregnancy, disturbed fetal condition.

Hyperglycosylated human chorionic gonadotropin as an early predictor of pregnancy outcomes after in vitro fertilization

To determine whether serum hyperglycosylated human chorionic gonadotropin (hhCG) measured as early as 9 days after egg retrieval can predict ongoing pregnancies after in vitro fertilization and fresh embryo transfer (IVF-ET). Cohort Academic assisted reproduction center. Consecutive patients undergoing IVF-ET INTERVENTION(S): Serum hhCG and hCG levels measured 9 (D9) and 16 (D16) days after egg retrieval Ongoing pregnancy beyond 9 weeks of gestation. Ongoing pregnancy (62 of 112 participants) was associated with higher D9 levels of hhCG and hCG. However, hhCG was detectable in all D9 OP samples, while hCG was detectable in only 22%. A D9 hhCG level of >110 pg/mL was 96% specific for an ongoing pregnancy, yielding a positive predictive value of 94%. Compared with the D9 hCG levels, hhCG was more sensitive and had a larger area under the curve (0.87 vs. 0.67, respectively). The diagnostic test characteristics were similar between the D16 hhCG and hCG levels. In patients undergoing assisted reproduction, a test to detect pregnancy early and predict outcomes is highly desirable, and hhCG is detectable in serum 9 days after egg retrieval IVF-ET cycles. In this early assessment, hhCG was superior to traditional hCG and highly predictive of ongoing pregnancies.

First‐trimester hyperglycosylated human chorionic gonadotropin and development of hypertension

This study aimed to determine whether urine levels of hyperglycosylated human chorionic gonadotropin (HhCG) in the first trimester are predictive of subsequent development of hypertension during pregnancy This prospective cohort study consisted of women seeking care before 12 weeks gestation. A clean catch urine was obtained at the first prenatal visit and tested for HhCG and creatinine levels. The median HhCG levels and multiples of the median (MoM) by gestational age were compared between the groups that either developed hypertension or did not. Urine HhCG were determined for 204 women between 4 weeks 4 days to 11 weeks 6 days. The median HhCG of those who developed gestational hypertension (n = 7) or preeclampsia (n = 15) did not differ from the group that did not (median: 284 ng/mg creatinine vs 365 ng/mg; p = 0.55). If the MoM of HhCG for the no hypertension group was 1.00, the MoM of HhCG for the hypertension group was 0.93 (p = 0.93). A possible association was observed after 10 weeks between low HhCG levels and the development of late-onset hypertension (≥34 weeks). Prenatal screening for subsequent hypertension is unreliable with a single measurement of maternal urine HhCG at 10 weeks or less.

Hyperglycosylated human chorionic gonadotropin (HhCG): a novel finding in seminal plasma

OBJECTIVE: Human chorionic gonadotropin (hCG) is present in seminal plasma (SP) and its concentration correlates with semen analysis (SA) results. We recently confirmed the presence of hCG receptors (hCGR) on sperm and found a correlation with sperm concentration suggesting a role in spermatogenesis. HhCG is an isoform of hCG associated with early embryo implantation and has a longer half-life due to an increased number of glucose residues. It is unknown if this translates into more biological activity.

Serum Hyperglycosylated Human Chorionic Gonadotropin to Predict the Gestational Outcome in in vitro Fertilization/Intracytoplasmic Sperm Injection Pregnancies

Hyperglycosylated human chorionic gonadotropin (H-hCG) is secreted by the placenta in early pregnancy. Decreased H-hCG levels have been associated with abortion in spontaneous pregnancy. We retrospectively measured H-hCG and dimeric hCG in the sera of 87 in vitro fertilization patients obtained in the 3 weeks following embryo transfer and set the results in relation to pregnancy outcome. H-hCG and dimeric hCG were correlated (r² = 0.89), and were significantly decreased in biochemical pregnancy (2 µg/l and 18 IU/l, respectively) compared to early pregnancy loss (22 µg/l and 331 IU/l) and ongoing pregnancy (32 µg/l and 353 IU/l). Only H-hCG tended to discriminate between these last two groups.

Hyperglycosylated human chorionic gonadotropin and the source of pregnancy failures

To investigate the proportion of hyperglycosylated human chorionic gonadotropin (hCG-H) produced at the time of implantation as a predictor of pregnancy success. Measuring daily urine hCG and hCG-H on the day of implantation. The time of implantation was assumed to be the first day of hCG detection (total hCG >1 mIU/mL). Urine samples were collected at volunteers' homes throughout city of Albuquerque. 110 women attempting to conceive spontaneously; 62 achieved pregnancies (42 to term and 20 failed). None. Measurements of the total hCG and hCG-H, and calculations of the proportion of hCG-H. In all 42 term pregnancies, the proportion of hCG-H on the day of implantation was >50%. This was also true for 7 of the 20 failures. Statistically significant lower proportions of hCG-H (<50%) were observed in 13 of 20 pregnancies that eventually failed. The predictive values of proportion of hCG-H, concentration of hCG-H, total hCG, and regular hCG alone for detecting failures were 100%, 59%, 41%, and 21%, respectively. Hyperglycosylated is produced by cytotrophoblast cells in early pregnancy at the time of implantation. Effective proportions of hCG-H (>50%) are required for successful growth and invasion by cytotrophoblasts at the time of implantation. Low proportions of hCG-H at implantation predict failure and are likely to be the root of many pregnancy failures. The 7 of 20 failures with normal proportions of hCG-H were likely due to genetic, immune, or maternal causes. Measurement of a proportion of hCG-H <50% on the day of implantation absolutely indicates a failing pregnancy.

Determination of hyperglycosylated human chorionic gonadotropin produced by malignant gestational trophoblastic neoplasias and male germ cell tumors using a lectin-based immunoassay and surface plasmon resonance

The ability to reliably detect aberrant glycosylation of human chorionic gonadotropin (hCG) may have profound implications for the diagnosis and monitoring of malignant gestational trophoblastic neoplasia, germ cell tumors, other malignancies, and pregnancy complications. To become a clinically useful assay, however, this discrimination of glycoforms should be possible on minimally treated biological specimens. Towards this end, we have developed a lectin-based sandwich-type immunoassay to compare the glycosylation patterns of hCG among urine specimens from patients presenting with a normal pregnancy, invasive mole, choriocarcinoma, and male germ cell tumors using carbohydrate-free antibody fragments as capture reagents and a panel of eight lectins, five recognizing neutral sugars and three recognizing sialic acid. There was no significant difference in the binding of any of the lectins to hCG in the urine of women over the gestational range of 6–38 weeks. Three lectins, however, exhibited differential binding to urinary hCG derived from these normal pregnant controls and that from patients with malignant forms of gestational trophoblastic disease and male germ cell tumors. Galanthus nivalis agglutinin and Maackia amurensis lectin, which bind terminal mannose and α(2-3)sialic acid, respectively, preferentially bound pregnancy-derived hCG, whereas the lectin, wheat germ agglutinin, which binds sialic acid and β(1-4)N-acetylglucosamine, exhibited decreased binding to pregnancy-derived hCG compared to that from patients with male germ cell tumors and malignant gestational trophoblastic neoplasia. The differential binding observed with these three promising lectins is most encouraging and warrants further examination. The experimental paradigm also holds promise for the development of comparable assays for other glycosylated tumor markers.

P-904: The clinical utility of the measurement of hyperglycosylated human chorionic gonadotropin during early pregnancy following assisted reproductive technology

P-904: The clinical utility of the measurement of hyperglycosylated human chorionic gonadotropin during early pregnancy following assisted reproductive technology

Fully automated chemiluminometric assay for hyperglycosylated human chorionic gonadotropin (invasive trophoblast antigen).

Hyperglycosylated human chorionic gonadotropin (HhCG) is a glycoprotein hormone secreted during embryonic implantation and trophoblast invasion of the uterine wall and is an early marker of pregnancy (1). Relative to hCG, HhCG has a higher molecular mass (38.5–40 kDa, depending on the amount of carbohydrate) and a higher number of asparagine (N)-linked triantennary carbohydrates and serine (O)-linked tetrasaccharide core structures in the β-subunit (2). Although both are secreted from the placenta and choriocarcinoma, HhCG is produced by mononucleated cytotrophoblasts, and hCG is produced by syncytiotrophoblast cells (3)(4)(5)(6). Because the cytotrophoblasts are primitive and invasive in nature, HhCG is also called invasive trophoblast antigen (ITA) (5). Birken et al. (7) described a monoclonal antibody (B152) specific for the β-subunit C-terminal peptide and the O-linked oligosaccharide of HhCG. Although the epitope for this antibody does not require sialic acid, the presence of the O-linked tetrasaccharide core structure is essential (1). Using IRMAs and ELISAs, investigators showed that (a) HhCG rapidly increases in early pregnancy, attaining substantially higher concentrations and decreasing earlier than hCG (1)(8); (b) HhCG is increased in Down syndrome-affected pregnancies in both the first and second trimesters (9)(10)(11); and (c) the HhCG:hCG ratio appears to be higher in those with invasive vs noninvasive trophoblastic disease (12). The above HhCG assays were performed manually using large sample volumes (200 μL) and long incubation …

Maternal circulating biomarkers associated with placenta accreta spectrum disorders.

Maternal circulating biomarkers associated with placenta accreta spectrum disorders.

Comparison of urinary hyperglycosylated human chorionic gonadotropin concentration with the serum triple screen for Down syndrome detection in high-risk pregnancies

Objective: Both modest screening performance and declining patient and physician acceptance have stimulated interest in alternative markers to the triple screen for the detection of Down syndrome. Our purpose was to compare the concentration of a single urinary analyte, hyperglycosylated human chorionic gonadotropin, with the serum triple screen (α-fetoprotein, human chorionic gonadotropin, and unconjugated estriol concentrations combined with age) for second-trimester Down syndrome detection. Study Design: Urine and blood were obtained from pregnant women in the second trimester undergoing genetic amniocentesis. Urinary hyperglycosylated human chorionic gonadotropin concentration and serum triple-screen values were measured. Individuals undergoing amniocentesis because of abnormal triple-screen results were excluded. Individual Down syndrome risks on the basis of urinary hyperglycosylated human chorionic gonadotropin concentration plus maternal age and on the basis of the triple-screen results were calculated. For each algorithm the sensitivity and false-positive rate for Down syndrome detection at different risk thresholds were determined. From these values receiver operating characteristic curves were constructed, and the area under the curve was determined for each algorithm. Finally, the performance of a new combination in which urinary hyperglycosylated human chorionic gonadotropin concentration replaced serum human chorionic gonadotropin concentration in the triple screen was ascertained. Results: We studied 24 pregnancies complicated by Down syndrome and 500 unaffected pregnancies between 14 and 22 weeks’ gestation in a mostly white (93.5%) population undergoing amniocentesis primarily because of advanced maternal age. The sensitivity and false-positive rate for urinary hyperglycosylated human chorionic gonadotropin concentration were 75.0% and 5.6%, respectively, whereas those for the triple screen were 75.0% and 33.2%, respectively. Urinary hyperglycosylated human chorionic gonadotropin concentration was superior to the triple screen (area under the curve, 0.9337 vs 0.7887; P =.02). The substitution of urinary hyperglycosylated human chorionic gonadotropin concentration for serum human chorionic gonadotropin concentration in the triple screen resulted in a 91.7% sensitivity at a 10.0% false-positive rate, versus a 54.2% sensitivity for the traditional triple screen at the same false-positive rate. Conclusion: The performance of urinary hyperglycosylated human chorionic gonadotropin concentration was statistically superior to that of the serum triple screen in a high-risk population. The use of urinary hyperglycosylated human chorionic gonadotropin concentration as an alternative test or substitution of this measurement for serum human chorionic gonadotropin concentration in the triple screen would improve diagnostic accuracy and address many current concerns related to the triple screen. (Am J Obstet Gynecol 2000;183:1114-8.)