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Background: The pathophysiological mechanism underlying pregnancy complications is not entirely known. Although it is currently impossible to predict the occurrence of redox imbalance, it is possible to identify women with a high or medium risk of developing this disease prior to a negative outcome by non-invasive diagnostic methods. The Aim: This study aimed to examine the possible role of the parameter of oxidative stress (OS) measured in early pregnancy in the screening/treatment of obesity and its complications during pregnancy. Methods: This research was designed as a prospective observational cross-sectional clinical study which included 40 non-obese and 31 obese pregnant women between 11 and 13 g.w. who were managed in the Department of Obstetrics, University Clinical Center Kragujevac in Serbia. We collected anthropometric and clinical indicators, maternal and pregnancy factors, and measured prooxidative parameters from blood samples. Results: We observed significantly increased levels of the superoxide anion radical, hydrogen peroxide and the index of lipid peroxidation in the Obese group in comparison with the Non-Obese group and significantly decreased bioavailability of nitrites in the Obese group in comparison with the Non-Obese group. Conclusions: The determination of systemic parameters of OS in early pregnancy could be a good methodological approach in the screening/treatment of obesity during pregnancy and this approach should be followed for the screening of endothelial dysfunction in pregnancy which needs further monitoring and/or treatment.

BackgroundGallbladder carcinoma (GBC) producing human chorionic gonadotrophin (HCG) is an extremely rare and highly invasive tumor with a poor prognosis. This unfavorable clinical outcome is partly due to the aggressive nature of the tumor and its insensitivity to chemotherapy.Case presentationWe herein report a case of primary GBC producing HCG with liver metastases in a 58-year-old woman. The patient presented with a markedly elevated β-HCG level and a mass in the gallbladder with multiple liver metastases. A definitive diagnosis was obtained after a needle biopsy of the liver metastases, showing poorly differentiated carcinoma with large-scale necrosis and strong positivity of immunostaining for HCG in tumor cells. The patient received chemotherapy (gemcitabine plus capecitabine) combined with carrellizumab, an immune checkpoint inhibitor (ICI). Pathological complete response was achieved after eight courses of combined therapy, which was confirmed by pathological analysis of resected specimens. After surgery, two courses of chemotherapy plus ICIs were adopted again. Complete response remained for approximately 1 year up to the present. Tumor tissue was collected to perform immunostaining of PD-L1, whole-exome sequencing, and RNA-seq. Low-TMB (1.51 mut/Mb), MSS, and high PD-L1 expression (TPS ≥ 50%) were observed in the tumor. Besides, the dominant types of infiltrating immune cells were macrophage and CD4+ T cells. Compared to other gallbladder adenocarcinoma without HCG, the proportion of M1 macrophage was at a higher level and the gene sets of MYC targets v1 and PI3K/AKT/mTOR signaling were highly expressed in our case. To the best of our knowledge, this is the first case report of complete remission of HCG-producing gallbladder carcinoma with liver metastases after chemotherapy combined with an immune checkpoint inhibitor. Furthermore, this is also the first report that described the tumor genetic feature and tumor immune microenvironment atlas of HCG-producing GBC.Conclusionchemotherapy plus an immune checkpoint inhibitor may provide a potentially curative option for gallbladder carcinoma with HCG production.

Primary hepatic carcinomas are a leading cause of cancer deaths worldwide and more so, an important cause in women. Metastases from hepatic carcinomas to the oral cavity are rare. However, those reported are usually the first manifestation of the tumor.We report a case of an oral metastasis from a primary hepatic carcinoma to a rare maxillary location including the hard palate presenting as a manifestation of the disease in a 48-year-old woman with elevated urine β-hCG. A biopsy of the oral lesion revealed nests of epithelial cells with hyperchromatic nuclei suggestive of metastatic hepatocellular carcinoma.A possible route for this metastasis is the Batson's venous plexus. The prognosis after the appearance of oral metastases is usually poor as was observed with the demise of our patient about 12 weeks after the apparition of the oral mass. A multidisciplinary approach towards patients will help in early diagnosis, treatment and reduce morbidities and mortalities associated with this rare pathology.

Objective: Human choriogonadotrophin (hCG) treatment of gonadotrophin-deficient infertile men uses hCG of urinary (uhCG) or recombinant (rhCG) origin, but these treatments have not been compared nor are there studies defining rhCG dosing in men., Design: hCG products were studied in randomized cross-over single-dose studies of standard (Study 1, 1500 IU and 62.5 µg, respectively) or high (Study 2, 5000 IU and 250 µg) dose and a multi-dose population pharmacology study of hCG use., Participants: Eight (Study 1) and seven (Study 2) volunteers in cross-over and 52 gonadotrophin-deficient men in the multi-dose study MEASUREMENTS: In cross-over studies, serum testosterone (T), dihydrotestosterone (DHT) and estradiol by liquid chromatography-mass spectrometry (LCMS) and serum hCG, LH, FSH, SHBG and T (observational study) by immunoassays., Results: After standard and high-dose injection, serum hCG and testosterone responses had similar timing and peak concentrations except for a mildly lower early (<48 h) serum testosterone with uhCG. In the multi-dosing study, both hCGs had similar pharmacokinetics (pooled half-life 5.8 days, p < .001), while serum testosterone concentrations were stable after injection and did not differ between hCG products. Bench testing verified that 20% of pens from 4/10 individuals were used inappropriately., Conclusions: Although hCG pharmacokinetics are not formally bioequivalent, the similar pharmacodynamic effects on serum testosterone indicate that at the doses tested both hCGs provide comparable clinical effects. The starting dose of rhCG for treating gonadotrophin-deficient men should be 62.5 µg (6 clicks) of the rhCG pen., (© 2024 Commonwealth of Australia. Clinical Endocrinology published by John Wiley & Sons Ltd.)

Abstract Backgrounds The immunomodulatory properties of human chorionic gonadotrophin (hCG) have been identified to be critical for successful pregnancy. However, the effects of hCG on peripheral γδT cells during early pregnancy have not been reported previously. Methods We cocultured the purified γδT cells and peripheral blood mononuclear cells (PBMCs) with early pregnancy‐relevant hCG concentrations and investigated the changes in the immune functional characteristics of γδT cells via flow cytometry assays. Results The ratios of CD69+ and IL‐10+ γδT cells were increased in early pregnant women compared to nonpregnant women. γδT cells expressed low levels of the mannose receptor (CD206) instead of the classical hCG/LH receptor for hCG. The direct treatment of purified γδT cells with early pregnancy‐relevant hCG concentrations may have no significant effects on their immune functions. Interestingly, when PBMCs were treated with the same broad range of hCG concentrations, the ratios of CD69+ and IL‐10+ γδT cells to total γδT cells were significantly increased. Conclusion Certain early pregnancy‐relevant hCG concentrations could enhance the ratios of peripheral CD69+ and IL‐10+ γδT cells, contributing to the activation of γδT cells and immunological tolerance during early pregnancy. However, these affects may not be strongly mediated by direct ligand–receptor interactions and they may highly depend on immune microenvironment. Our novel observations propose a perspective into the endocrine‐immune dialog that exists between the fetus and maternal immune cells.

Objectives: The objective of this study was to collect information on human chorionic gonadotrophin (hCG) laboratory testing and reporting in women with gestational trophoblastic disease (GTD), to assess the associated challenges, and to offer perspectives on hCG testing harmonisation. Design: Information was collected from laboratories by electronic survey (SurveyMonkey) using a questionnaire designed by members of the European Organisation for the Treatment of Trophoblastic Disease (EOTTD) hCG working party. Participants: The questionnaire was distributed by the EOTTD board to member laboratories and their associated scientists who work within the GTD field. Setting: The questionnaire was distributed and accessed via an online platform. Methods: The questionnaire consisted of 5 main sections. These included methods used for hCG testing, quality procedures, reporting of results, laboratory operational aspects, and non-GTD testing capability. In addition to reporting these survey results, examples of case scenarios which illustrate the difficulties faced by laboratories providing hCG measurement for GTD patient management were described. The benefits and challenges of using centralised versus non-centralised hCG testing were discussed alongside the utilisation of regression curves for management of GTD patients. Results: Information from the survey was collated and presented for each section and showed huge variability in responses across laboratories even for those using the same hCG testing platforms. An educational example was presented, highlighting the consequence of using inappropriate hCG assays on clinical patient management (Educational Example A), along with an example of biotin interference (Educational Example B) and an example of high-dose hook effect (Educational Example C), demonstrating the importance of knowing the limitations of hCG tests. The merits of centralised versus non-centralised hCG testing and use of hCG regression curves to aid patient management were discussed. Limitations: To ensure the survey was completed by laboratories providing hCG testing for GTD management, the questionnaire was distributed by the EOTTD board. It was assumed the EOTTD board held the correct laboratory contact, and that the questionnaire was completed by a scientist with in-depth knowledge of laboratory procedures. Conclusions: The hCG survey highlighted a lack of harmonisation of hCG testing across laboratories. Healthcare professionals involved in the management of women with GTD should be aware of this limitation. Further work is needed to ensure an appropriate, quality-assured laboratory service is available for hCG monitoring in women with GTD. [ABSTRACT FROM AUTHOR]

We hypothesized that the hCG modulates the expression of IFNT-pathway and ISGs in bovine endometrium during early pregnancy. The aim of the current study is to evaluate the effect of hCG on IFNT-pathway signals and ISGs expression in endometrial cells. For this, 29 non-lactating cross-bread cows were used in the study and submitted to a 9-day fixed-time artificial insemination (FTAI) protocol. The day of the AI was considered Day 0 (D0), and five days (D5) after the FTAI, the cows were allocated into two groups: Control and hCG group, when a hCG group received a single dose of 2.500UI of hCG. On day 18 after FTAI (D18) cows were slaughtered and endometrial tissue samples were collected. There was no difference between the embryo recovery rate of the cows in C compared to the hCG. The hCG group increased the accessory corpus luteum formation rate. The hCG resulted in greater serum progesterone concentration in the hCG group compared to the C on Day 14. Only the expression of IFNAR2 and STAT1 were upregulated on pregnant cows of the hCG group compared to the C group. The pathway genes (JAK1, STAT2, and IRF9) were not regulated. The mRNA abundance of ISG15, MX1, MX2, and OAS1 was upregulated in pregnant cows for hCG group, compared to C group. The results show that the administration of hCG, 5 days after AI, in addition to increasing the serum progesterone, modulates the expression of IFNT-pathway and ISGs on bovine endometrium on Day 18 of pregnancy., Competing Interests: Conflicts of interest: The authors have no conflict of interest to declare.

Objective: The first trimester combined risk of trisomy 21 is obtained by multiplying the risk related to maternal age by the likelihood ratios of nuchal translucency, free beta‐human chorionic gonadotrophin (β‐hCG) and placenta associated plasma protein‐A. Beyond five multiples of the median (MoM) of β‐hCG, the risk of trisomy 21 is truncated. The objective of the present study was to evaluate the evolution of the first trimester combined risk of trisomy 21 in individuals with first‐trimester free‐β‐hCG levels between 5 and 10 MoM. Methods: We conducted a non‐interventional cohort study from a 6‐year database of combined first‐trimester trisomy 21 screening of all individuals who underwent the screening in a French specialized medical analysis center. We included all pregnant individuals who had a serum‐free β‐hCG between 5 and 10 MoM. Patients for whom the status of the fetus, with or without trisomy 21, was not identified by the outcome of the pregnancy or by a karyotype result were excluded from the study. The discriminatory capacity of free‐β‐hCG above 5 MoM was studied by a receiver operating characteristic curve. We used an orthogonal polynomial regression to represent the evolution of likelihood ratios according to free‐β‐hCG in MoM. Results: Among 413 216 combined first‐trimester screens of trisomy 21, 2239 (0.5%) screens met the inclusion criteria. In the selected population, 801 (35.8%) were excluded from the study because of missing fetal or neonatal status, and 46 (3.2%) fetuses out of 1438 included were diagnosed with trisomy 21. For free β‐hCG values between 5 and 10 MoM, the area under the curve is 0.56 (0.46–0.65). The scatterplot of the likelihood ratio of β‐hCG showed an increasing parabolic pattern: the likelihood of trisomy 21 increases with the free‐β‐hCG threshold. Conclusion: To override the truncated risk of trisomy 21 in case of free β‐hCG values between 5 and 10 MoM, the study has allowed us to estimate the adjusted risk of trisomy 21, enabling health professionals to offer appropriate prenatal counseling. Synopsis: Estimation of the adjusted risk of trisomy 21 in pregnant individuals with a free ß‐hCG level between 5 and 10 multiples of the median in the first trimester. [ABSTRACT FROM AUTHOR]

Adrenocortical tumor (ACT) is a rare malignant tumor which usually present with Cushing syndrome and virilization. Paraneoplastic syndromes (PNS) due to neoplasms can occur with peptides or cytokines secreted by the tumor. Here, we report a 13-month-old-male presented with severe masculinization. He had signs of precocious puberty with enlarged testicles, very high testosterone levels but low levels of gonadotrophins, and elevated β-hCG. He underwent a left nephrectomy. The histopathological evaluation revealed a diagnosis of adrenocortical neoplasm. The levels of androgens and β-hCG normalized after the resection of tumor, and the clinical findings improved within few months. We report the first pediatric patient with peripheral precocious puberty due to an ACT that secretes β-hCG as PNS. A β-hCG secreting ACT can cause severe virilization due to increased gonadal androgens stimulated by β-hCG as well as due to increased adrenal androgens from the tumor. [ABSTRACT FROM AUTHOR]

Objectives: Quantitative human chorionic gonadotropin (hCG) measurements are used to manage women classified with a pregnancy of unknown location (PUL). Two point of care testing (POCT) devices that quantify hCG are commercially available. We verified the i-STAT 1 (Abbott) and the AQT 90 FLEX (Radiometer) prior to use in PUL triage., Methods: Tests for precision, external quality assurance (EQA), correlation, hook effect and recovery were undertaken alongside a POCT usability assessment during this prospective multi-center verification., Results: Coefficients of variation ranged between 4.0 and 5.1 % for the three i-STAT 1 internal quality control (IQC) solutions and between 6.8 and 7.3 % for the two AQT IQC solutions. Symmetric differences in POCT EQA results when compared with laboratory and EQA stock values ranged between 3.2 and 24.5 % for the i-STAT 1 and between 3.3 and 36.9 % for the AQT. Correlation coefficients (i-STAT 1: 0.96, AQT: 0.99) and goodness of fit curves (i-STAT 1: 0.92, AQT: 0.99) were excellent when using suitable whole blood samples. An hCG hook effect was noted with the i-STAT 1 between 572,194 and 799,089 IU/L, lower than the hook effect noted with the AQT, which was between 799,089 and 1,619,309 IU/L. When hematocrit concentration was considered in sample types validated for use with each device, hCG recovery was 108 % with the i-STAT 1 and 98 % with the AQT. The i-STAT 1 scored lower on usability overall (90/130) than the AQT (121/130, p<0.001, Mann-Whitney)., Conclusions: Both hCG POCT devices were verified for use in clinical practice. Practical factors must also be considered when choosing which device to use in each unit., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

This study determined the accuracy of first-trimester serum human chorionic gonadotrophin (hCG) for estimating gestational age (GA). We included 273 584 singleton live births that had a first-trimester ultrasound and measured serum hCG at 4-12 weeks gestation in Ontario from 2012 to 2018. We estimated hCG accuracy compared to known GA, within a boundary of ± 1 week. Between 4 to 8 weeks gestation, sensitivity of hCG was over 88% and specificity over 51%. However, at 9-12 weeks gestation, sensitivity declined from 72% to 0%, and specificity rose from 86% to 100%. At all GA, the positive predictive value was consistently under 42%, while negative predictive values were over 96%. Within epidemiological studies in which GA is otherwise unknown, first-trimester serum hCG may aid somewhat in estimating GA between 4 to 6 weeks gestation, but much less so thereafter. Thus, there remains an ongoing need for an accurate method for estimating missing GA within large datasets., (Copyright © 2023 The Society of Obstetricians and Gynaecologists of Canada/La Société des obstétriciens et gynécologues du Canada. Published by Elsevier Inc. All rights reserved.)

Background: Urothelial carcinomais the most common urological malignancy and following prostate and lung cancer, it is the third most common carcinoma in male population. Objective: The main aim of this study was to determine the expression of beta hCG in different grades of human urothelial carcinoma in our population. Methods: The study was conducted in Pathology Department of Faisalabad Medical University, Faisalabad, between 2018-2020.Sections were taken on frosted slides for H& E, and on lysine coated slides for IHC.H& E and IHC were performed according to protocols. Results: Out of the 65 tumor studied, 35(54%) were graded as low and 30(46%) were graded as high. In 35 low grade tumors 4(11%) were muscle invasive and 31(89%) were non-invasive and in 30 high grade tumors, 24(80%) were found to be muscle invasive and only 6(20) were non muscle invasive. Out of 65 specimens, 52 (80%) cases were found to be positive for beta hCG while only 13(20%) were found to be negative of 35 low grade tumors, 27(77%) tumors were stained positive for beta hCG and 8(23%) were negative. Of 30 high grade tumors 25(83%) tumors were stained positive for beta hCG and 5 (17%) were negative. Chi-square test was applied showed that there was no significant association between tumor grade and beta hCG expression. Conclusion: The immunohistochemical expression of beta hCG is positive in majority of low and high grade urothelial carcinoma but it may not be utilized as a marker for prognostic determination. [ABSTRACT FROM AUTHOR]

Serum samples are generally used for the measurement of human chorionic gonadotrophin (hCG) to calculate second-trimester maternal screening results. Lower hCG concentrations correlate with a lower calculated risk of Down syndrome (DS). Hence, erroneously low hCG results due to fibrin clot may lead to misinterpretation. We present a 23-year-old woman with a pregnancy of 17+3 weeks. Blood was taken into the Becton-Dickinson (BD) vacutainer SST-II Advance tube (Ref: 367955). The hCG test was performed on Immulite 2000 XPi analyser (Siemens Healthcare Diagnostics Inc, Tarrytown, USA) with original reagents. The results of the same sample were found as 2566 U/L, 18,153 U/L, and 7748 U/L. Three consecutive results after removal of the small fibrin clot and recentrifugation were 18,878, 20,255, and 22,339 U/L. The risk of DS and MoM for the concentration of 2556 U/L hCG was < 1/10,000 and 0.14, respectively. For a hCG concentration of 20,255 U/L, these values were 1/5632 and 1.13, respectively. Laboratory professionals and technicians should be aware that erroneously low hCG results can be measured with the Immulite 2000 XPi due to interference from small fibrin clots. Falsely underestimated hCG values reduce the MoM values and thus the calculated risk of DS., Competing Interests: Potential conflict of interest None declared., (Croatian Society of Medical Biochemistry and Laboratory Medicine.)