hCG Concentrations Research Articles

A Label-Free and Ultrasensitive Immunosensor for Detection of Human Chorionic Gonadotrophin Based on Graphene FETs.

We report on a label-free immunosensor based on graphene field effect transistors (G-FETs) for the ultrasensitive detection of Human Chorionic Gonadotrophin (hCG), as an indicator of pregnancy and related disorders, such as actopic pregnancy, choriocarcinoma and orchic teratoma. Pyrene based bioactive ester was non-covalently anchored onto the graphene channel in order to retain the sp2 lattice. The G-FET transfer characteristics showed repeatable and reliable responses in all surface modifying steps using a direct current (DC) readout system. The hCG concentration gradient showed a detection limit of ~1 pg·mL−1. The proposed method facilitates the cost-effective and viable production of graphene point-of-care devices for clinical diagnosis.

Method Validation of Human Chorionic Gonadotropin and α-Fetoprotein in Cerebrospinal Fluid: Aiding the Diagnosis of Intracranial Germ Cell Tumors.

Our study objective was to validate 2 individual methods to measure α-fetoprotein (AFP) and human chorionic gonadotropin (hCG) in cerebrospinal fluid (CSF) on the Roche cobas® 6000 analyzer. A 3-year retrospective chart review of CSF samples analyzed for AFP and hCG was also conducted. Serum samples with high concentrations of AFP or hCG were added to aliquots of pooled CSF. Precision, linearity, detection limit, recovery, carryover, stability, and interference studies of the AFP and hCG+β assays were performed. Within-day and day-to-day assay imprecision for AFP and hCG assays were <5% at all concentrations tested. The linear range of the AFP assay was established as 1.0-1100 μg/L, and limit of quantification (LOQ) was <1.0 μg/L. The linear range of the hCG assay was established as 1.0-9500 IU/L and LOQ 0.7 IU/L. There was no demonstrable matrix effect, and neither assay was affected by the presence of hemolysis or xanthochromia. AFP in CSF was stable at room and refrigerated temperatures for up to 48 h at concentrations of 19 and 306 μg/L but increased by 24 h at a concentration of 908 μg/L. AFP in CSF was stable frozen (-20 °C) for up to 7 days. hCG in CSF at all concentrations tested was stable at room, refrigerated, and frozen temperatures for up to 7 days. The Roche cobas 6000 AFP and hCG+β assays accurately quantify AFP and hCG in CSF, facilitating rapid and accurate diagnosis as well as monitoring of intracranial germ cell tumors.

Thyroid Function and Premature Delivery in TPO Antibody-Negative Women: The Added Value of hCG.

Human chorionic gonadotropin (hCG) stimulates thyroid function during pregnancy. We recently showed that thyroid autoimmunity severely attenuated the thyroidal response to hCG stimulation and that this may underlie the higher risk of premature delivery in thyroperoxidase antibody (TPOAb)-positive women. We hypothesized that a lower thyroidal response to hCG stimulation in TPOAb-negative women is also associated with a higher risk of premature delivery and preterm premature rupture of membranes (pPROM). Thyrotropin (TSH), free thyroxine (FT4), and hCG concentrations were available in 5644 TPOAb-negative women from a prospective cohort. We tested for interaction between TSH or FT4 and hCG in linear regression models for duration of pregnancy and logistic regression models for premature delivery/pPROM. Accordingly, analyses were stratified per TSH percentile (TSH ≥ 85th percentile) and hCG per 10,000 IU/L. Women with high TSH and low hCG concentrations did not have a higher risk of premature delivery or pPROM, with protective effect estimates. In contrast, women with a high TSH concentration despite a high hCG concentration had twofold to 10-fold higher risk of premature delivery (Pdifference = 0.022) and an up to fourfold higher risk of pPROM (Pdifference = 0.079). hCG concentrations were not associated with premature delivery or pPROM. In TPOAb-negative women with high-normal TSH concentrations, only women with high hCG concentrations had a higher risk of premature delivery or pPROM. These results suggest a lower thyroidal response to hCG stimulation is also associated with premature delivery in TPOAb-negative women and that an additional measurement of hCG may improve thyroid-related risk assessments during pregnancy.

Serum Human Chorionic Gonadotropin Normogram for the Detection of Gestational Trophoblastic Neoplasia.

The aim of this study was to develop a serum human chorionic gonadotropin (hCG) normogram for both uneventful complete and partial hydatidiform moles in the first-trimester ultrasound era. An hCG normogram for both complete and partial hydatidiform moles was constructed, based on 639 patients with uneventful serum hCG regression after evacuation between 1990 and 2014. Serum hCG was measured by an in-house-developed radioimmunoassay, detecting both intact hCG and free β-subunit. It has been in use for all serum measurements sent to the Dutch Central Registry for Hydatidiform Moles since 1977. Since introduction of routine first-trimester ultrasonography, lower pre-evacuation and follow-up serum hCG concentrations were observed. When compared with complete hydatidiform moles, patients with a partial hydatidiform mole had significantly lower pre-evacuation serum hCG concentration (median, 4400 and 875 ng/mL, respectively; P < 0.001) and earlier hCG normalization (median, 7 and 6 weeks, respectively; P < 0.001) but higher gestational age (mean, 11.5 and 13.0 weeks, respectively; P < 0.001). For both complete and partial hydatidiform moles, 95% of patients reached normal serum hCG concentrations within 14 weeks after evacuation. A normogram for the detection of gestational trophoblastic neoplasia was developed for complete and partial hydatidiform moles. Although interesting from a scientific perspective, the small divergence in hCG regression between complete and partial hydatidiform moles will be of little importance in clinical practice, as actual differences in regression will encompass only days. To promote clarity and unity in daily practice, we therefore propose a combined normogram to be used as a reference guideline for follow-up after evacuation of a hydatidiform mole. This normogram will be compliant with patients in today's clinical practice.

Predictive value of serum HCG concentrations in pregnancies achieved after single fresh or vitrified-warmed blastocyst transfer

Possible differences between serum HCG levels in pregnancies achieved after transfer of a single fresh or a vitrified-warmed blastocyst were evaluated. Out of 1130 single blastocyst transfers resulting in positive HCG results, 789 were single fresh blastocyst transfers and 341 single vitrified-warmed blastocyst transfers. The initial serum HCG levels of 869 clinical intrauterine pregnancies were evaluated, 638 after the transfer of a single fresh blastocysts and 231 after the transfer of a single vitrified-warmed blastocysts. The HCG levels from cycles resulting in a clinical intrauterine pregnancy were significantly higher after the transfer of a single vitrified-warmed blastocyst (383 ± 230 IU/l) versus a fresh transfer (334 ± 192 IU/l; P = 0.01). Threshold values for predicting a clinical pregnancy for a fresh blastocyst were 111 IU/l and for a vitrified-warmed blastocyst 137 IU/l. Our study shows that the overall beta-HCG levels are comparable after the transfer of a fresh or vitrified-warmed blastocyst, suggesting that vitrification most probably does not affect the ability of the embryos to produce beta-HCG. This study further shows that when clinicians counsel patients, they should take into account that higher HCG levels are needed after a vitrified-warmed blastocyst transfer to predict a clinical intrauterine pregnancy.

Nuchal translucency measurement, freeβ-hCG and PAPP-A concentrations in IVF/ICSI pregnancies: systematic review and meta-analysis

So far, data on the effect of assisted reproductive technologies (ART) on the components of first trimester combined screening for Down syndrome are still controversial. A systematic search of the literature was performed in order to identify the effect of ART, particularly in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) with fresh embryo transfer, on the nuchal translucency, free beta-human chorionic gonadotrophin and pregnancy-associated plasma protein-A measurements. Moreover, a meta-analysis and a descriptive graphical representation of the ratios between ART and spontaneous pregnancies (controls) values of median of the multiple of median (m0 MoM) were performed. Free beta-human chorionic gonadotrophin test showed slightly higher values in the ICSI group than controls (RR=1.09, 95%CI: 1.03-1.16) but not in the IVF group (RR=1.03, 95%CI: 0.94-1.12). Pregnancy-associated plasma protein-A values for IVF/ICSI, IVF and ICSI showed lower values in comparison with controls (RR, 95%CI 0.85, 0.80-0.90; 0.82, 0.74-0.89 and 0.83, 0.79-0.86, respectively). The nuchal translucency measurement did not show any statistical differences between study groups (IVF and ICSI) and controls (RR=1.00, 95%CI: 0.94-1.08 and RR=1.01, 95%CI: 0.97-1.05, respectively). These results may be due to alterations in the placentation of ART pregnancies. Differentiating further subgroups of ART pregnancies may explain the differences in biomarker concentrations, in prenatal behavior and in obstetric outcomes between ART and spontaneous pregnancies. © 2017 John Wiley & Sons, Ltd.

Dynamics of hormonal disorders following unilateral orchiectomy for a testicular tumor

Testicular tumors and their treatment interfere with homeostasis, hormonal status included. The aim of the study was to evaluate hormonal disorders of the pituitary–gonadal axis in men treated for testicular tumors. One hundred twenty-eight men treated for a unilateral testicular tumor at our institution were included. The hormonal status was prospectively evaluated in 62 patients before orchiectomy, 120 patients 1 month after orchiectomy and 110 patients at least 1 year after the treatment. The concentrations of human chorionic gonadotropin (hCG), testosterone (T), estradiol, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and prolactin were measured. The clinically significant testosterone deficiency was defined either as testosterone <2.31 ng/mL or testosterone within the range of 2.31–3.46 ng/mL but simultaneous with T/LH ratio ≤1. Changes in hormone levels were significant: LH and FSH rose in the course of observation, and the concentration of hCG, testosterone, estradiol decreased. PRL concentration was the lowest at 1 month after orchiectomy. In multivariate analysis, the risk of the clinically significant testosterone deficiency was 0.2107 (95% CI 0.1206–0.3419) prior to orchiectomy, 0.3894 (95% CI 0.2983–0.4889) 1 month after surgery and 0.4972 (95% CI 0.3951–0.5995) 1 year after the treatment. The estradiol concentration was elevated in 40% of patients with recently diagnosed testicular cancer and that was correlated with a higher risk of testosterone deficiency after the treatment completion. Hormonal disorders of the pituitary–gonadal axis in men treated for testicular tumors are frequent. The malignant tissue triggers paraneoplastic disorders that additionally disturb the hormonal equilibrium.

Optimal day to thaw day 5 vitrified blastocysts for frozen embryo transfers

Despite blastocyst cryopreservation having become routine practice in embryology labs, the optimal time to thaw a blastocyst has not been well studied in the literature. Practices differ between institutions as day 5 embryos may be thawed the day prior or the day of transfer. The aim of this study was to evaluate if clinical outcomes differ between day 5 blastocyst stage vitrified embryos thawed on the day prior to versus the day of transfer. Design: Retrospective study. Setting: Academic fertility center. Interventions: Blastocysts vitrified and thawed the day prior to transfer (Group 1) were compared to those thawed the day of transfer (Group 2). All embryos were vitrified on the cryolock device and all patients underwent endometrial priming. Pregnancies were initially detected by serum β-human chorionic gonadotropin (hCG) concentrations. Clinical pregnancy and implantation were confirmed by transvaginal ultrasound (US). Exclusion criteria included: donor oocyte, pre-implantation genetic testing, and gestational carrier cycles, as well as cycles that included embryos imported from different centers and cycles with combined day 5 (D5) and day 6 (D6) frozen embryo transfers. Outcome Measures: Positive pregnancy test (serum β-hCG concentration >6 IU/L) per cryothaw cycle, clinical pregnancy (CPR) and implantation rates (number of sacs observed on US over the number of embryos transferred). Statistics: X2-square and t-test were used as appropriate. P<0.05 was considered statistically significant. A total of 112 thawed blastocysts (88 D5, 24 D6) from 94 patients were included in the analysis. Patient characteristics did not differ between the 2 groups of embryos (Table 1). When all blastocyst stage embryos (D5 and D6) were compared between the Group 1 and Group 2, positive pregnancy test (61.7% vs 70.2, p=0.51, respectively), CPR (61.7% vs 62.2%, p=1.00, respectively) and, implantation (85.0% vs 82.4%, p=0.76, respectively) rates did not differ. When the analysis was restricted to D5 embryos, which were the blastocysts affected by the intervention implemented, positive pregnancy test, CPR and implantation rates were similar amongst the groups (Chart 1). According to our findings, thawing D5 blastocysts the day prior to transfer does not impact CPR or implantation rates, thus allowing embryologists some flexibility to the timing of D5 embryo thaw.

Stimulation of Thyroid Function by Human Chorionic Gonadotropin During Pregnancy: A Risk Factor for Thyroid Disease and a Mechanism for Known Risk Factors.

Thyroid autoimmunity is a major risk factor for gestational thyroid disease, and recently various other risk factors have been identified, including maternal age, body mass index (BMI) and parity. Human chorionic gonadotropin (hCG) is an important determinant of gestational thyroid function, yet it is unknown to what extent differences in hCG concentration affect the risk for thyroid disease. We have recently shown that thyroperoxidase antibody positivity impairs the thyroidal response to hCG stimulation, which may suggest that this is a mechanism through which thyroid autoimmunity acts as a risk factor for thyroid disease. The purpose of this study is to determine whether hCG is a risk factor for thyroid disease entities and whether recently identified risk factors for thyroid disease may influence the thyroidal response to hCG stimulation. Human chorionic gonadotropin, thyrotropin (TSH), and free thyroxine (FT4) were measured in 5435 pregnant women participating in a prospective cohort. The association of hCG with thyroid disease entities, and the association of known risk factors with thyroidal response to hCG stimulation were studied using multivariable linear regression models. Higher hCG concentrations were associated with a higher risk of subclinical and overt hyperthyroidism. Lower hCG concentrations were associated with a higher risk of hypothyroxinemia. In contrast, hCG concentrations were not associated with subclinical hypothyroidism. Further analyses showed that in women with hypothyroxinemia, high hCG concentrations still suppressed TSH. However, in women with subclinical hypothyroidism, high hCG concentrations were not associated with higher FT4. Higher BMI, male fetal sex, and maternal parity >2 were associated with a lower thyroidal response to hCG stimulation. Human chorionic gonadotropin is associated with the risk of (subclinical) hyperthyroidism and hypothyroxinemia, but not with the risk of (subclinical) hypothyroidism. Women with hypothyroxinemia have a normal response to thyroidal stimulation by hCG, but this was abnormal in women with subclinical hypothyroidism. Known risk factors for thyroid dysfunction (BMI and parity), and also male fetal sex, are associated with a lower thyroidal response to hCG stimulation.

Human Chorionic Gonadotropin Does Not Correlate with Risk for Maternal Breast Cancer: Results from the Finnish Maternity Cohort.

Human chorionic gonadotropin (hCG) is necessary for the maintenance of early pregnancy and promotes normal breast cell differentiation. Administered hCG reduces risk of carcinogen-induced breast cancer in animal models, and higher circulating hCG concentrations were associated with significantly lower long-term risk of breast cancer in a prior nested case-control study. In this study, we investigated early-pregnancy hCG concentrations and subsequent breast cancer risk. We conducted a nested case-control study with 1,191 cases and 2,257 controls (matched on age and date at blood collection) in the Finnish Maternity Cohort, a cohort with serum samples from 98% of pregnancies registered in Finland since 1983. This study included women with a serum sample collected early (<140 days gestation) in their first pregnancy resulting in a live, term birth. Breast cancer cases were identified via the Finnish Cancer Registry. Age at breast cancer diagnosis ranged from 22 to 58 years (mean: 41 years). hCG was measured using a solid-phase competitive chemiluminescence assay. Odds ratios (OR) were calculated using conditional logistic regression. We observed no association between hCG and breast cancer risk, overall [Quartile 4 vs. 1, OR, 1.14; 95% confidence interval (CI), 0.94-1.39], by estrogen and progesterone receptor status, or by ages at first-term birth or diagnosis. Associations did not differ by time between pregnancy and diagnosis (e.g., <5 years, ORQ4 vs. Q1, 1.10; 95% CI, 0.64-1.89; ≥15 years, ORQ4 vs. Q1, 1.36; 95% CI, 0.86-2.13; pheterogeneity = 0.62). This large prospective study does not support an inverse relationship between early pregnancy serum hCG concentrations and breast cancer risk. Cancer Res; 77(1); 134-41. ©2016 AACR.

The stimulating effect of thienopyrimidines structurally similar to Org 43553 on adenylate cyclase activity in the testes and on testosterone production in male rats

The functional activity of the luteinizing hormone (LH) receptor can be regulated not only by gonadotropins, but also by its low molecular weight agonists, which, in contrast to gonadotropins, bind to the allosteric site located in the transmembrane channel of the receptor. The most promising low molecular weight agonists are thienopyrimidine derivatives, which are structural analogs of the Org 43553 compound. The purpose of this work was to synthesize novel thienopyrimidine derivatives—5-amino-N-(tert-butyl)-4-(3-(2-methoxynicotinamido)-phenyl)-2-(methylthio)thieno[2,3-d]pyrimidine-6-carboxamide (TP-21), 4-((3-(5-amino-6-(tert-butylcarbamoyl)-2-(methylthio)thieno[2,3-d]pyrimidine-4-yl)phenyl)carbamoyl)pyridine 1-oxide (TP-22), and 5-amino-N-(tert-butyl)-4-(3-(2-chloroxynicotinamido)phenyl)-2-(methylthio)thieno[2,3-d]pyrimidine-6-carboxamide (TP-23)—and to investigate their effects on adenylate cyclase (AC) activity in rat testicular membranes in vitro and on testosterone levels in male rats following intratesticular or intraperitoneal administration in vivo. Compounds TP-21, TP-22, and TP-23 stimulated basal AC activity in rat testicular membranes with EC50 values of 1556, 358, and 372 nM; their efficiency was ordered as follows: TP-23 > TP-21 ≈ TP-22. When thienopyrimidines (10–4 M) were applied in combination with human chorionic gonadotropin (HCG, 10–8 M), the AC-stimulating effect of HCG was maintained, and, at an HCG concentration of 10–10 M, the effects of thienopyrimidines and HCG on AC activity were additive. Intratesticular administration of 10 mg/kg TP-21, TP-22, and TP-23 increased testosterone levels in male rats: in 5 h after treatment, its levels were 32.8, 36.4, and 76.9 nM, respectively, higher than in the control group. Following intraperitoneal administration, TP-21 and TP-22 had little effect on testosterone levels, while TP-23 induced a significant increase in testosterone levels (by 34.8 and 18.9 nM in comparison to control in 1 and 3 h, respectively). These data suggest that compound TP-23 is an active stimulator of testosterone synthesis and secretion and represents a promising basis for development of highly efficient LH receptor agonists.

Serial multilevel urine pregnancy testing to assess medical abortion outcome: a meta-analysis

ObjectivesTo summarize data on the accuracy of a strategy designed to exclude ongoing pregnancy after medical abortion treatment by observing a decline in urine human chorionic gonadotropin (hCG) concentration as estimated by multilevel urine pregnancy tests (MLPTs) performed before and after treatment. Study designWe collated original data from seven studies performed by our organization that evaluated the accuracy of the MLPT strategy for assessment of outcome of medical abortion. Our first analysis included data from the five studies in which each participant was evaluated both with the MLPT strategy and with ultrasound or other clinical assessment. Our second analysis combined data from two randomized trials that compared the MLPT strategy to assessment by ultrasound. Both analyses included only participants treated at ≤63 days of gestation. ResultsIn the first analysis, 1482 (93%) of 1599 participants had a decline in hCG concentration after treatment. Twenty-one (1.3%) had an ongoing pregnancy, none of whom had a decline (predictive value 100%, 95% CI 93.3%, 100%). The remaining 96 women (6.0%) had no decline without an ongoing pregnancy. The second analysis, which included 3762 participants with follow-up, found no significant difference in the rates of ongoing pregnancy ascertained in the randomized groups (RR 0.88; 95% CI 0.50, 1.54). Nearly all of the post-treatment MLPTs in the seven studies (3484/3535; 99%) were performed by the participants themselves. ConclusionsSerial multilevel urine pregnancy testing is a highly reliable and efficient strategy for excluding ongoing pregnancy after medical abortion at≤63 days of gestation. Implications statementSerial urine testing using MLPTs can obviate the need for routine ultrasound or examination after medical abortion treatment and can allow most women to avoid an in-person follow-up visit to the abortion facility.

Peptide aptamer-based biosensor for the detection of human chorionic gonadotropin by converting silver nanoparticles-based colorimetric assay into sensitive electrochemical analysis

We presented an antibody-free electrochemical technique for the determination of human chorionic gonadotropin (hCG) using silver nanoparticles (AgNPs) as the redox reporters and a hCG-specific binding peptide as the receptor. Peptide-induced AgNPs assembly was achieved on the electrode surface that was modified with the same sequence of peptide (recognition element) used in the AgNPs aggregation. As a result, a well-defined linear-sweep voltammetry (LSV) peak was observed. The attachment of hCG on the electrode surface made the peptide probe lose its ability to trigger the in situ formation of the AgNPs-based network architecture on the electrode surface, thus leading to a much attenuated LSV current. The current decreased with the increase of hCG concentration ranging from 1mIU/mL to 0.2IU/mL. Consequently, a detection limit of 0.4mIU/mL was achieved. To demonstrate the amenability of our method, the contents of hCG in human serum/urine samples were determined. The results were consistent with those obtained by the enzyme linked immunosorbent assay (ELISA). Based on the well-defined and amplified electrochemical signal of the AgNPs-based network architecture, our work would also be valuable for the design of novel electrochemical sensors by marrying specific receptors.

First trimester serum placental growth factor and hyperglycosylated human chorionic gonadotropin are associated with pre-eclampsia: a case control study.

BackgroundTo study whether maternal serum hyperglycosylated human chorionic gonadotropin (hCG-h) improves first trimester prediction of pre-eclampsia when combined with placental growth factor (PlGF), pregnancy-associated plasma protein-A (PAPP-A) and maternal risk factors.MethodsGestational-age-adjusted concentrations of hCG, hCG-h, PlGF and PAPP-A were analysed in serum samples by time-resolved immunofluorometric assays at 8–13 weeks of gestation. The case–control study included 98 women who developed pre-eclampsia, 25 who developed gestational hypertension, 41 normotensive women with small-for-gestational-age (SGA) infants and 177 controls.ResultsOf 98 women with pre-eclampsia, 24 women developed preterm pre-eclampsia (diagnosis < 37 weeks of gestation) and 13 of them had early-onset pre-eclampsia (diagnosis < 34 weeks of gestation). They had lower concentrations of PlGF, PAPP-A and proportion of hCG-h to hCG (%hCG-h) than controls. In receiver-operating characteristics (ROC) curve analysis, the area under the curve (AUC) for the combination of PlGF, PAPP-A, %hCG-h, nulliparity and mean arterial blood pressure was 0.805 (95% confidence interval, CI, 0.699–0.912) for preterm pre-eclampsia and 0.870 (95% CI 0.750–0.988) for early-onset pre-eclampsia. Without %hCG-h the AUC values were 0.756 (95% CI 0.651–0.861) and 0.810 (95% CI 0.682–0.938) respectively. For prediction of gestational hypertension, the AUC for %hCG-h was 0.708 (95% CI 0.608–0.808), but for other markers the AUC values were not significant. None of the AUC values were significant for the prediction of SGA infants in normotensive women.ConclusionsFirst trimester maternal serum %hCG-h tended to improve prediction of preterm and early-onset pre-eclampsia when combined with PlGF, PAPP-A and maternal risk factors.

Establishing reference intervals for hCG in postmenopausal women

BackgroundPlasma concentrations of human chorionic gonadotropin (hCG) have been shown to increase with age due to pituitary secretion. We previously recommended that an hCG cutoff of 14.0IU/L be used for women ≥55years of age. However, it remains unknown whether concentrations >14.0IU/L can be expected in women with advanced age. Our objectives were to establish plasma hCG reference intervals and correlate follicle stimulating hormone (FSH) and hCG concentrations in postmenopausal females ≥55years. MethodsResidual plasma samples from 798 women ≥55years were utilized with 303, 269, and 226 samples belonging to the age groups 55–69, 70–84, and ≥85years, respectively. FSH and hCG were measured using the Abbott ARCHITECT. All positive hCG samples (hCG ≥5IU/L) were analyzed for potential heterophile antibody interference and 3 were excluded. Electronic medical records were reviewed and patients with malignancy were excluded. Results8% (56/666) of women age≥55years had plasma hCG ≥5IU/L. There were 19, 16, and 21 patients with hCG ≥5IU/L in the age groups 55–69, 70–84, and ≥85years, respectively. The highest hCG concentrations observed in each age group were: 55–69years maximum=11.7IU/L and 97.5th percentile=9.6IU/L; 70–84years maximum=18.09IU/L, 97.5th percentile=6.2IU/L; ≥85years maximum=11.1IU/L and 97.5th percentile=10.0IU/L, and the overall 97.5th percentile=8.5IU/L for all women ≥55years of age. Neither hCG nor FSH concentrations continued to increase with age in women ≥55years. ConclusionsThe prevalence of positive hCG in women ≥55years is 8%. This study confirms our previously recommended cutoff of 14IU/L for women ≥55years of age. In women ≥55years of age, FSH concentrations do not predict hCG concentrations.

Persistently Elevated Human Chorionic Gonadotropin in a Menopausal Woman.

A sexually active 50-year-old woman with a history of hypothyroidism and a family history remarkable for cancer presented to her primary care physician with complaints of constipation and abdominal cramping. The patient had been amenorrheic for 28 months and, although some intermittent spot bleeding had occured, was assumed menopausal. Because of ovarian cancer concerns, quantitative serum human chorionic gonadotropin (hCG)5 and α-fetoprotein tests were performed; liver function, steroid hormones, and pituitary gonadotropins were also evaluated (Table 1). The increased hCG (16 IU/L; reference interval: <3 IU/L) was concerning and the laboratory was consulted. Analysis of the hCG concentration on a different manufacturer's assay and platform produced consistent results (Table 2). In addition, 1 month before this presentation, the patient's hCG concentration, measured by a different laboratory on a third manufacturer assay/platform, was 13 IU/L. The hCG concentration recovered linearly after a 2-fold dilution and was not affected by treatment with a heterophile blocking tube. Urine …

Thyroid Autoimmunity Impairs the Thyroidal Response to Human Chorionic Gonadotropin: Two Population-Based Prospective Cohort Studies.

Thyroperoxidase antibody (TPOAb) positivity is the main risk factor for thyroid dysfunction during pregnancy and is consistently associated with premature delivery. However, the underlying mechanism is currently unknown. We hypothesized that TPOAb positivity may interfere with gestational thyroid stimulation induced by the pregnancy hormone human chorionic gonadotropin (hCG). Thyrotropin (TSH), free thyroxine (FT4), TPOAbs, and/or hCG concentrations were measured in early and late pregnancy of 7587 pregnant women from 2 Dutch population-based prospective cohorts (n = 5924, Generation R study; n = 1663, Holistic Approach to Pregnancy and the First Postpartum Year study). None. Thyroidal response to hCG stimulation, premature delivery. In TPOAb-negative women, hCG was positively associated with FT4 and negatively with TSH in both cohorts (P < 0.0001). In contrast, in TPOAb-positive women, hCG was not associated with FT4 or TSH in either cohort (all P > 0.40; P for interaction TPOAb positive vs negative ≤ 0.05). Overall, TPOAb positivity was associated with a 1.7-fold higher risk of premature delivery. TPOAb-positive women with an adequate response of FT4 to hCG (high FT4 concentration with high hCG concentration) did not have a higher risk of premature delivery. In contrast, TPOAb-positive women with an inadequate FT4 response to hCG (low FT4 concentration with high hCG concentration) had a 2.2- to 2.8-fold higher risk of premature delivery. TPOAb-positive women display an impaired thyroidal response to hCG and this may explain the higher risk of premature delivery in these women. This abnormal response in TPOAb-positive women might suggest that these women require a different treatment approach than TPOAb-negative women.

A Graphene Oxide-Based Fluorescent Method for the Detection of Human Chorionic Gonadotropin.

Human chorionic gonadotropin (hCG) has been regarded as a biomarker for the diagnosis of pregnancy and some cancers. Because the currently used methods (e.g., disposable Point of Care Testing (POCT) device) for hCG detection require the use of many less stable antibodies, simple and cost-effective methods for the sensitive and selective detection of hCG have always been desired. In this work, we have developed a graphene oxide (GO)-based fluorescent platform for the detection of hCG using a fluorescein isothiocyanate (FITC)-labeled hCG-specific binding peptide aptamer (denoted as FITC-PPLRINRHILTR) as the probe, which can be manufactured cheaply and consistently. Specifically, FITC-PPLRINRHILTR adsorbed onto the surface of GO via electrostatic interaction showed a poor fluorescence signal. The specific binding of hCG to FITC-PPLRINRHILTR resulted in the release of the peptide from the GO surface. As a result, an enhanced fluorescence signal was observed. The fluorescence intensity was directly proportional to the hCG concentration in the range of 0.05–20 IU/mL. The detection limit was found to be 20 mIU/mL. The amenability of the strategy to hCG analysis in biological fluids was demonstrated by assaying hCG in the urine samples.

Human chorionic gonadotropin (hCG) concentrations during the late first trimester are associated with fetal growth in a fetal sex-specific manner

Human chorionic gonadotropin (hCG) is a pregnancy-specific hormone that regulates placental development. hCG concentrations vary widely throughout gestation and differ based on fetal sex. Abnormal hCG concentrations are associated with adverse pregnancy outcomes including fetal growth restriction. We studied the association of hCG concentrations with fetal growth and birth weight. In addition, we investigated effect modification by gestational age of hCG measurement and fetal sex. Total serum hCG (median 14.4 weeks, 95 % range 10.1–26.2), estimated fetal weight (measured by ultrasound during 18–25th weeks and >25th weeks) and birth weight were measured in 7987 mother–child pairs from the Generation R cohort and used to establish fetal growth. Small for gestational age (SGA) was defined as a standardized birth weight lower than the 10th percentile of the study population. There was a non-linear association of hCG with birth weight (P = 0.009). However, only low hCG concentrations measured during the late first trimester (11th and 12th week) were associated with birth weight and SGA. Low hCG concentrations measured in the late first trimester were also associated with decreased fetal growth (P = 0.0002). This was the case for both male and female fetuses. In contrast, high hCG concentrations during the late first trimester were associated with increased fetal growth amongst female, but not male fetuses. Low hCG in the late first trimester is associated with lower birth weight due to a decrease in fetal growth. Fetal sex differences exist in the association of hCG concentrations with fetal growth.

Urinary human chorionic gonadotropin isoform concentrations in doping control samples.

Anti-doping laboratories routinely use immunoassays to measure urinary concentrations of human chorionic gonadotropin (hCG). To minimize immunoassay differences and false positive screen results from inactive isoforms (free β-subunit (hCGβ), β-subunit core fragment (hCGβcf)) laboratories now use intact hCG instead of total hCG immunoassays to measure hCG. To determine the distribution of hCG isoforms in urine, we determined the concentrations of intact hCG, hCGβ, and hCGβcf in male urine samples based on immunoassay total hCG concentrations using a sequential immunoextraction and a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method. hCG was isolated using antibody-conjugated magnetic beads and unique tryptic peptides were quantified by LC-MS/MS. Negative samples with detectable but low total hCG concentrations (1.2-3.5 pmol/L) had intact and hCGβ concentrations <1.2 pmol/L, and hCGβcf concentrations <2.3 pmol/L by LC-MS/MS. Urine samples from an athlete receiving hCG had intact hCG concentrations ranging from 18.8 to 57.6 pmol/L, hCGβ concentrations <0.7 pmol/L, and hCGβcf concentrations ranging from 94 to 243% of the intact hCG concentration. In 27 atypical samples with total hCG concentrations ranging from 16.7 to 412.7 pmol/L with intact hCG <2.7 pmol/L by immunoassay, all samples had intact hCG concentrations <3.8 pmol/L and hCGβ concentrations <6.2 pmol/L by LC-MS/MS. hCGβcf concentrations by LC-MS/MS varied widely and ranged from 1.03 to 21.9 pmol/L. In summary, total hCG immunoassays significantly overestimate hCG concentrations and can produce false positive results. Although the intact hCG immunoassay slightly overestimates hCG concentrations compared to LC-MS/MS, it can distinguish between cases of hCG use and atypical cases with elevated total hCG concentrations. Copyright © 2016 John Wiley & Sons, Ltd.