Human Chorionic Gonadotropin Concentrations Research Articles

A Customized Microfluidic Paper-Based Platform for Colorimetric Immunosensing: Demonstrated via hCG Assay for Pregnancy Test

Over the past decades, paper-based lateral flow immunoassays (LFIAs) have been extensively developed for rapid, facile, and low-cost detection of a wide array of target analytes in a point-of-care manner. Conventional home pregnancy tests are the most significant example of LFAs, which detect elevated concentrations of human chorionic gonadotrophin (hCG) in body fluids to identify early pregnancy. In this work, we have upgraded these platforms to a higher version by developing a customized microfluidic paper-based analytical device (μPAD), as the new generation of paper-based point-of-care platforms, for colorimetric immunosensing. This will offer a cost-efficient and environmentally friendly alternative platform for paper-based immunosensing, eliminating the need for nitrocellulose (NC) membrane as the substrate material. The performance of the developed platform is demonstrated by detection of hCG (as a model case) in urine samples and subsequently indicating positive or negative pregnancy. A dual-functional silane-based composite was used to treat filter paper in order to enhance the colorimetric signal intensity in the detection zones of μPADs. In addition, microfluidic pathways were designed in a manner to provide the desired regulated fluid flow, generating sufficient incubation time (delays) at the designated detection zones, and consequently enhancing the obtained signal intensity. The presented approaches allow to overcome the existing limitations of μPADs in immunosensing and will broaden their applicability to a wider range of assays. Although, the application of the developed hCG μPAD assay is mainly in qualitative (i.e., positive or negative) detection of pregnancy, the semi-quantitative measurement of hCG was also investigated, indicating the viability of this assay for sensitive detection of the target hCG analyte within the related physiological range (i.e., 10–500 ng/mL) with a LOD value down to 10 ng/mL.

Predictors for single-agent resistance in FIGO score 5 or 6 gestational trophoblastic neoplasia: a multicentre, retrospective, cohort study.

Patients with gestational trophoblastic neoplasia who have an International Federation of Gynaecology and Obstetrics (FIGO) risk score of 5 or 6 usually receive non-toxic single-agent chemotherapy as a first-line treatment. Previous studies suggest that only a third of patients have complete remission, with the remaining patients requiring toxic multiagent chemotherapy to attain remission. As stratification factors are unknown, some centres offer multiagent therapy upfront, resulting in overtreatment of many patients. We aimed to identify predictive factors for resistance to single-agent therapy to inform clinicians on which patients presenting with a FIGO score of 5 or 6 are likely to benefit from upfront multiagent chemotherapy. We did a multicentre, retrospective, cohort study of patients with gestational trophoblastic neoplasia presenting with a FIGO score of 5 or 6, who received treatment at three gestational trophoblastic neoplasia reference centres in the UK, Brazil, and the USA between Jan 1, 1964, and Dec 31, 2018. All patients who had been followed up for at least 12 months after remission were included. Patients were excluded if they had received a non-standard single-agent treatment (eg, etoposide); had been given a previously established first-line multiagent chemotherapy regimen; or had incomplete data for our analyses. Patient data were retrieved from medical records. The primary outcome was the incidence of chemoresistance after first-line or second-line single-agent chemotherapy. Variables associated with chemoresistance to single-agent therapies were identified by logistic regression analysis. In patient subgroups defined by choriocarcinoma histology and metastatic disease status, we did bootstrap modelling to define thresholds of pretreatment human chorionic gonadotropin concentrations and identify groups of patients with a greater than 80% risk (ie, a positive predictive value [PPV] of 0·8) of resistance to single-agent chemotherapy. Of 5025 patients with low-risk gestational trophoblastic neoplasia, we identified 431 patients with gestational trophoblastic neoplasia presenting with a FIGO risk score of 5 or 6. All patients were followed up for a minimum of 2 years. 141 (40%) of 351 patients developed resistance to single-agent treatments and required multiagent chemotherapy to achieve remission. Univariable and multivariable logistic regression revealed metastatic disease status (multivariable logistic regression analysis, odds ratio [OR] 1·9 [95% CI 1·1-3·2], p=0·018), choriocarcinoma histology (3·7 [1·9-7·4], p=0·0002), and pretreatment human chorionic gonadotropin concentration (2·8 [1·9-4·1], p<0·0001) as significant predictors of resistance to single-agent therapies. In patients with no metastatic disease and without choriocarcinoma, a pretreatment human chorionic gonadotropin concentration of 411 000 IU/L or higher yielded a PPV of 0·8, whereas in patients with either metastases or choriocarcinoma, a pretreatment human chorionic gonadotropin concentration of 149 000 IU/L or higher yielded the same PPV for resistance to single-agent therapy. Approximately 60% of women with gestational trophoblastic neoplasia presenting with a FIGO risk score of 5 or 6 achieve remission with single-agent therapy; almost all remaining patients have complete remission with subsequent multiagent chemotherapy. Primary multiagent chemotherapy should only be given to patients with metastatic disease and choriocarcinoma, regardless of pretreatment human chorionic gonadotropin concentration, or to those defined by our new predictors. None. For the Portuguese translation of the abstract see Supplementary Materials section.

Improving single-agent chemoresistance risk identification in gestational trophoblastic neoplasia.

In The Lancet Oncology, Antonio Braga and colleagues 1 Braga A Paiva G Ghorani E et al. Predictors for single-agent resistance in FIGO score 5 or 6 gestational trophoblastic neoplasia: a multicentre, retrospective, cohort study. Lancet Oncol. 2021; (published online June 25.)https://doi.org/10.1016/S1470-2045(21)00262-X Summary Full Text Full Text PDF PubMed Scopus (6) Google Scholar report the results of a multicentre, retrospective study involving the largest cohort of patients with gestational trophoblastic neoplasia presenting with an International Federation of Gynaecology and Obstetrics (FIGO) risk score of 5 or 6, in a low risk setting. 2 Kohorn EI Goldstein DP Hancock BW et al. Workshop report: combining the staging system of the International Federation of Gynecology and Obstetrics with the scoring system of the World Health Organization for trophoblastic neoplasia. Report of the Working Committee of the International Society for the Study of Trophoblastic Disease and the International Gynecologic Cancer Society. Int J Gynecol Cancer. 2000; 10: 84-88 Crossref PubMed Scopus (75) Google Scholar , 3 Goldstein DP Ross S Berkowitz RS Horowitz NS Optimal management of low-risk gestational trophoblastic neoplasia. Expert Rev Anticancer Ther. 2015; 15: 1293-1304 Crossref PubMed Scopus (12) Google Scholar Indeed, in so-called low-risk patients (ie, those with stage I or stage II–III disease and a FIGO risk score of 0–6), patients can have heterogeneous outcomes in terms of chemosensitivity to single-agent chemotherapy; in particular, patients with a FIGO risk score of 0–1 have a complete remission rate of 75% compared with approximately 53% in patients with a FIGO risk score of 2–4 and approximately 33% in patients with a FIGO risk score of 5–6. 4 Sita-Lumsden A Short D Lindsay I et al. Treatment outcomes for 618 women with gestational trophoblastic tumours following a molar pregnancy at the Charing Cross Hospital, 2000–2009. Br J Cancer. 2012; 107: 1810-1814 Crossref PubMed Scopus (88) Google Scholar Therefore, whether patients with a FIGO risk score of 5–6 should be treated with a multiagent approach, which is more aggressive than a single-agent approach, is controversial, 5 Winter MC Treatment of low-risk gestational trophoblastic neoplasia. Best Pract Res Clin Obstet Gynaecol. 2021; (published online Feb 2.)https://doi.org/10.1016/j.bpobgyn.2021.01.006 Crossref PubMed Scopus (1) Google Scholar , 6 Lok C van Trommel N Massuger L Golfier F Seckl M Clinical Working Party of the EOTTDPractical clinical guidelines of the EOTTD for treatment and referral of gestational trophoblastic disease. Eur J Cancer. 2020; 130: 228-240 Summary Full Text Full Text PDF PubMed Scopus (21) Google Scholar , 7 Braga A Mora P de Melo AC et al. Challenges in the diagnosis and treatment of gestational trophoblastic neoplasia worldwide. World J Clin Oncol. 2019; 10: 28-37 Crossref PubMed Google Scholar even though most patients who do not respond to first-line single-agent chemotherapy can have complete remission after second-line single-agent chemotherapy. Predictors for single-agent resistance in FIGO score 5 or 6 gestational trophoblastic neoplasia: a multicentre, retrospective, cohort studyApproximately 60% of women with gestational trophoblastic neoplasia presenting with a FIGO risk score of 5 or 6 achieve remission with single-agent therapy; almost all remaining patients have complete remission with subsequent multiagent chemotherapy. Primary multiagent chemotherapy should only be given to patients with metastatic disease and choriocarcinoma, regardless of pretreatment human chorionic gonadotropin concentration, or to those defined by our new predictors. Full-Text PDF

Predictive value of serum HCG concentrations for outcomes of vitrified-warmed blastocyst transfers in women of different ages

Research questionCan serum human chorionic gonadotrophin (HCG) concentrations on day 10 after single-blastocyst transfer (SBT) in cryopreserved transfer cycles help to predict the cycle outcome in patients of different maternal ages? DesignThe study included 772 vitrified-warmed SBT cycles. The initial maternal serum HCG concentrations measured on day 10 after blastocyst transfer were evaluated using receiver operating characteristic (ROC) curves to predict clinical pregnancy and live birth. Threshold values for predicting a clinical pregnancy were established in three different age groups: group A (21–29 years old, n = 360), group B (30–34 years old, n = 290) and group C (35–47 years old, n = 122). ResultsThe areas under the ROC curves for clinical pregnancy and live birth were 0.986 and 0.922, and the corresponding cut-off values were 113.28 and 146.37 mIU/ml, respectively. The optimal threshold values for clinical pregnancy as indicated by Youden index values for the three age groups were 145.15, 126.25 and 94.44 mIU/ml, respectively. ConclusionsThe study demonstrates that determination of initial serum β-HCG concentrations on day 10 after SBT in cryopreserved transfer cycles can help to predict cycle outcome in women of different ages. The optimal threshold value for clinical pregnancy for patients over 35 years of age was lower than that for the younger age groups.

An enzyme immunoassay to determine human chorionic gonadotropin (HCG) in serum and urine samples using an ultra-microanalytical system

The determination of Human Chorionic Gonadotropin (HCG) in biological fluids is of great interest in the early pregnancy diagnostics, the evaluation of pregnancy disorders, as a tumor marker, as a screening procedure for anti-doping control, and many other purposes. A simple sandwich-type UltraMicro Enzyme-Linked ImmunoSorbent Assay (UMELISA) has been developed for the measurement of HCG in serum and urine samples. Strips coated with a high affinity MAb directed against HCG are used as solid phase, to ensure the specificity of the assay. The HCG assay was completed in 1.5 h, with a measuring range of 0.76–400 mIU/mL. The intra- and inter-assay coefficients of variation were lower than 10 %, depending on the HCG concentrations evaluated. Recovery percentages were 96.43–97.16 % (serum) and 98.10–99.04 % (urine). The assay detected intact HCG, nicked HCG, HCG β, and nicked HCG β, and did not recognize any of the interfering molecules tested. Regression analysis showed a good correlation with Elecsys in serum (n = 1459, r = 0.952, ρc = 0.948) and urine (n = 869, r = 0.988, ρc = 0.978). A good correlation was also found with 84 RIQAS samples analyzed with the kits Elecsys (r = 0.969, ρc = 0.957), Architect (r = 0.982, ρc = 0.970), Dimension (r = 0.989, ρc = 0.977), and Bioscience (r = 0.992, ρc = 0.980), all with a p < 0.01. Comparison with transvaginal ultrasonography in early pregnancy detection showed a specificity and a sensitivity of 100 % (n = 2385, κ = 1). The analytical performance characteristics of UMELISA HCG endorse its use for the quantification of HCG in serum and urine samples. This assay will make a cost-effective diagnostic kit accessible to low-income countries and is now available in the Cuban Public Health System.

The Application of the EP9-A Protocol in the Analysis of the Performance of the Immunofluorescence Assay for HCG Detection.

ObjectiveThe present study aims to evaluate the comparability of the results of two methodologies for detecting human chorionic gonadotropin (HCG) to assess whether the immunofluorescence method for detecting HCG is adequate for clinical applications.MethodsReferring to the protocol requirements of the American Clinical Laboratory Standards Institute (CLSI) EP9-A2 (methodological matching and bias assessment with patient samples), we collected 40 fresh serum specimens from our outpatients and inpatients, including 20 specimens with abnormal HCG concentrations (eight samples with different concentration ranges were selected daily and HCG was measured simultaneously with the two testing systems for five consecutive days). The assays were performed on a Dxl 800 fully automated immunoassay analyzer from Beckman Coulter Inc., USA, as a comparative method and on a Jet-iStar 3000 immunoassay analyzer from Zhonghan Shengtai Inc. as an experimental method. Methodological comparison and bias assessment of the results of the two methods for HCG detection were performed. The OLR regression model was used for calculating bias and regression analysis, and Spearman’s rank correlation coefficient was used for correlation analysis. The correlation and comparability of the two systems were calculated based on the results of the analysis.ResultsA good correlation in HCG results in the range of 5–50,000 U/mL was obtained from the two assay systems (r = 0.998) with the regression equation of y = 1.020x + 12.96. The estimated deviation was within the permissible deviation and acceptable.ConclusionThe results of HCG measurement by the two different assay systems were well correlated and comparable.

A poor prognostic metastatic nongestational choriocarcinoma of the ovary: a case report and the literature review

BackgroundPure ovarian choriocarcinoma can be gestational or nongestational in origin. Nongestational pure ovarian choriocarcinoma is extremely rare and the prognosis is thought to be worse than that of the gestational type in patients with metastatic disease. We present a case of metastatic pure ovarian choriocarcinoma with poor prognosis in which the origin was identified as nongestational by DNA short tandem repeat (STR) analysis.Case presentationA nulliparous woman in her thirties with metastatic choriocarcinoma was referred to our hospital after initial treatment proved unsuccessful. Two months earlier, she had undergone brain tumor resection and histological examination confirmed choriocarcinoma. Serum human chorionic gonadotropin (hCG) concentration at initial diagnosis was 5030 IU/L. Two cycles of a combination chemotherapy regimen of methotrexate, etoposide, and actinomycin-D (MEA therapy), which is commonly used for gestational choriocarcinoma, was administered. However, the disease could not be controlled. Imaging modalities at presentation revealed tumor present in the left ovary and left lung, but not in the uterus, which led us think that the choriocarcinoma was nongestational. Bleomycin, etoposide, and cisplatin (BEP therapy) which is commonly used for nongestational choriocarcinoma (malignant germ cell tumor) and surgical resection of the uterus, bilateral ovaries, and an affected part of the left lung led to the nadir level of hCG, but the tumor relapsed and levels of hCG again increased. To investigate the origin of choriocarcinoma, we performed DNA STR analysis of tumor cells and oral mucosal cells. Analysis revealed the origin of the choriocarcinoma as nongestational, as the genotype of tumor cells entirely corresponded with that of oral mucosal cells. BEP therapy and chemotherapy regimens administered for nongestational choriocarcinoma and gestational choriocarcinoma proved ineffective, and the patient died 21 months after diagnosis of metastatic choriocarcinoma.ConclusionMetastaic nongestational pure choriocarcinoma of ovary is an extremely rare and an aggressive disease, frequently resulting in poor outcome.

Efficacy of hormone stimulation on sperm production in an alpine amphibian (Anaxyrus boreas boreas) and the impact of short-term storage on sperm quality

The Southern Rocky Mountain boreal toad (Anaxyrus boreas boreas) has disappeared from much of its range in the alpine regions of Central and Western North America, and restoration efforts are compromised by limited knowledge of this species’ reproductive biology. This study aimed to establish whether assisted reproductive techniques could be used to improve breeding output in captive boreal toads by determining the most effective concentration of human chorionic gonadotropin (hCG) for induction of spermiation and viability of sperm during cold storage. Male toads (n = 21) were treated with a Low (3 IU g-1), Medium (10 IU g-1), or High (15 IU g-1) concentration of hCG and spermic urine samples were collected over 24 hrs. Treatment effectiveness was evaluated by measuring the response rate, Total Motility (TM), Forward Progressive Motility (FPM), Quality of FPM (QFPM), and concentration. For short-term cold storage, spermic urine samples (n = 13) were stored at 4 °C for 14 days and sperm TM and FPM monitored daily. All treatments induced spermiation; however, a greater number of toads produced sperm in the Medium and High treatments compared to the Low. Overall, TM, FPM, QFPM and sperm concentration were similar across all three treatments, but variation existed in the timing and duration of peak sperm production. Sperm motility was maintained for up to 14 days in cold storage, although the quality slowly decreased over time. An effective reproduction strategy for the boreal toad will provide a means to improve captive breeding efforts and increase our understanding of the reproductive physiology of alpine Bufonids.

The position of the euploid blastocyst in the uterine cavity influences implantation

Research questionDoes the position of the euploid blastocyst in the uterine cavity upon transfer, measured as distance in millimetres (mm) from the fundus (DFF) to the air bubble, influence implantation potential? DesignA total of 507 single/double euploid frozen embryo transfer (FET) cycles at blastocyst stage were included retrospectively between March 2017 and November 2018 at a single centre. The patients were on average 33.3 years old. The FET were performed in natural cycles (n = 151) or hormone replacement therapy cycles (n = 356). ResultsOf the 507 transfers, 370 (73.0%) resulted in a pregnancy, defined as human chorionic gonadotrophin concentration over 15 mIU/ml, and 341 (67.3%) in a clinical pregnancy, with an implantation rate of 62.0% and ongoing pregnancy rate of 59.6% (302/507). When comparing the number of embryos transferred, the pregnancy rate, clinical pregnancy rate and ongoing pregnancy rate were significantly higher after double-embryo transfer (DET) (P = 0.002: P < 0.001 and P = 0.002). The quality of the blastocyst in the single-embryo transfer group had a positive effect on the pregnancy rate (A versus B, P = 0.016; A versus C, P = 0.003) and clinical pregnancy rate (A versus C, P = 0.013). After performing a multivariate logistic regression analysis to consider the effect of all explanatory variables, a negative effect between DFF and pregnancy (P = 0.001), clinical pregnancy (P = 0.001) and ongoing pregnancy (P = 0.030) was found. When all variables remained constant, an increase of 1 mm of DFF changed the odds of pregnancy by 0.882, of clinical pregnancy by 0.891 and of ongoing pregnancy by 0.925. No significant effect of DFF was found on the miscarriage outcome (P = 0.089). ConclusionsThe depth of blastocyst replacement inside the uterine cavity may influence the pregnancy, clinical pregnancy and ongoing pregnancy rates and should be considered as an important factor to improve the success of IVF cycles.

Reference values and the effect of clinical parameters on thyroid hormone levels during early pregnancy.

Objective: Thyroid dysfunction is a common endocrine problem during pregnancy; correct diagnosis and appropriate treatments are essential to avoid adverse pregnancy outcomes. Besides, it is vital to identify and quantify the major risk factors for gestational thyroid dysfunction, including thyroid autoimmunity, human chorionic gonadotropin (HCG) concentration, body mass index (BMI) and parity. The study objective was to establish reference ranges during early pregnancy and to explore the relationship between risk factors and thyroid stimulating hormone (TSH), free thyroxine (FT4) and free triiodothyroxine (FT3).Design, patients and measurements: To establish the reference ranges of thyroid hormone during early pregnancy in China and to identify the risk factors for thyroid dysfunction, woman in the first trimester of pregnancy (4–12 weeks gestation) were recruited. After excluding thyroid peroxidase antibody (TPO-Ab) positive and/or thyroglobulin antibody (TG-Ab) positive women, previous thyroid disease, a lack of iodine intake, reference values were calculated by 2.5th to 97.5th percentiles.Results: After exclusion of TPO-Ab and/or TG-Ab positive women, reference values were as follows: TSH, 0.11–3.67 mIU/l; FT3, 3.19–5.91 pmol/l; FT4 10.95–16.79 pmol/l. Higher BMI was associated with lower FT4 concentrations (P=0.005). In multiple regression analysis, TSH was significantly and positively associated with TG (P=0.03). Maternal parity and maternal age may be risk factors for the abnormal thyroidal response to hCG concentrations.Conclusions: Our study defined first trimester-specific reference ranges for serum TSH, FT4, FT3 in a Chinese population, and demonstrated that BMI ≥23kg/m2, maternal parity ≥3 and maternal age ≥30 years may increase the risk of thyroid dysfunction.

EGR1 Overexpression Inhibits the Occurrence of Preeclampsia by Binding to MicroRNA-574 Promoter and Upregulating GAB1.

Early growth response protein 1 (EGR1) is potent in modulating placental trophoblast cell growth and shows a differential expression in preeclampsia (PE). We aimed to identify the downstream mechanism of EGR1 in PE. RT-qPCR showed EGR1 was significantly decreased in PE placenta. Overexpression of EGR1 facilitated the proliferation and invasion of HTR-8/Svneo cells, and reduced the concentration of human chorionic gonadotrophin (HCG) in the supernatant. Bioinformatics prediction, ChIP, and luciferase reporter experiments revealed that EGR1 inhibited miR-574 expression by binding to miR-574 promoter and that miR-574 targeted GAB1. Furthermore, overexpression of miR-574 inhibited the proliferation and invasion of HTR-8/Svneo cells. GAB1 was downregulated in placenta of PE patients, which was positively correlated with EGR1 and negatively correlated with miR-574. Inhibition of GAB1 attenuated the effect of EGR1 overexpression on the proliferation and invasion of HTR-8/Svneo cells. All in all, EGR1 upregulated GAB1 by inhibiting miR-574, thus contributing to trophoblast cell proliferation and invasion.

Serum markers in quadruple screening associated with adverse pregnancy outcomes: A case–control study in China

BackgroundWe assessed whether the results of quadruple screening during pregnancy are associated with an increased risk of adverse pregnancy outcomes. MethodsWe measured serum marker concentrations using quadruple screening in the second trimester of pregnancy and analyzed the relationship between adverse perinatal outcomes and serum markers in 12,124 pregnant women. A multivariate logistic regression analysis was used to evaluate the relative risk of quadruple screening and adverse pregnancy outcomes. ResultsCompared with the control group, increased concentrations of alpha-fetoprotein (AFP) and inhibin A were risk factors for preeclampsia and preterm delivery; low concentrations of unconjugated estriol and high inhibin A were risk factors for pregnancy hypertension; an increased concentration of human chorionic gonadotropin (hCG) was a risk factor for gestational diabetes mellitus; high AFP, low hCG, and high inhibin A were risk factors for low birth weight; and low AFP and high hCG were risk factors for macrosomia. ConclusionsQuadruple screening in the second trimester of pregnancy can provide early warning signs for maternal and fetal adverse pregnancy outcomes.

Growth differentiation factor 9 (gdf9) and bone morphogenetic protein 15 (bmp15) are potential intraovarian regulators of steroidogenesis in Japanese flounder (Paralichthys olivaceus)

Members of transforming growth factor-β (TGF-β) superfamily are vital regulators during the development of fish ovary. However, its intraovarian functions in teleost are still unclear. As members of the TGF-β superfamily, gdf9 and bmp15 are necessary for follicle formation and granulosa cell proliferation. Here in Japanese flounder, quantitative real-time polymerase chain reaction (qRT-PCR) and in situ hybridization (ISH) analysis showed that gdf9 and bmp15 were mainly expressed in oogonia and oocytes, whereas weakly expressed in non-ovarian tissues. Overexpression of single gdf9 and the co-overexpression with bmp15 could up-regulate the expression of most steroidogenic genes, while the overexpression of single bmp15 could down-regulate the expression of most steroidogenic genes. These findings demonstrate that single gdf9 and the combination with bmp15 may act as “activator”, while single bmp15 may act as “inhibitor” in the process of steroidogenesis in flounder. This was also verified in negative feedback regulation of gdf9 and bmp15 during hormone treatment. High concentration of human chorionic gonadotropin (hCG) could down-regulate gdf9 and up-regulate bmp15, which were beneficial for the homeostasis of hCG hormone. Besides, knockdown of either gdf9 or bmp15 could significantly down-regulate most steroidogenic genes. This indicated that heterodimer of GDF9:BMP15 might be the most bioactive ligand in gonad development of flounder. Taken together, our study provided a novel recognition that gdf9 and bmp15 could regulate steroidogenesis in teleost through mechanism different from that in mammals.

A smartphone-based rapid quantitative detection platform for lateral flow strip of human chorionic gonadotropin with optimized image algorithm

Colloidal gold immunochromatographic test strip has been widely used as a rapid, simple and low-cost correct detection technology. However, its detection is often qualitative or semi-quantitative, which limits its clinical application to some extent. Herein, a portable test strip quantitative detection device based on smartphone to detect human chorionic gonadotropin (HCG) is developed. In experiment, a colloidal gold HCG detection strip based on antigen antibody immune response is constructed, and the quantitative results of three different image processing methods on the same strip detection are compared, including the threshold processing algorithm based on location information, the RGB color component extraction algorithm and the grayscale projection value processing algorithm, the results show that the last algorithm can realize the best recognition of the region of interest of strip. The mobile phone application software (App) based on this design shows that the detection limit of constructed colloidal gold HCG strip is 3 ng/mL with a linear range of 6–300 ng/mL. The detection result of real urine sample is consistent with the spiked concentration (R2 = 0.988), indicating that the concentration of HCG can be accurately measured in urine with this method, presenting the potential for instant diagnosis.

Exclusion of pregnancy in dialysis patients: diagnostic performance of human chorionic gonadotropin

BackgroundA positive pregnancy test in acute or chronically ill patients has implications for the use of potentially mutagenic or teratogenic products in urgent medical therapies such as the use of chemotherapies or therapies with immunosuppressants, for anesthesia, and for time-sensitive indications like urgent surgery or organ Transplantation.Despite a lack of evidence, it is currently believed that human chorionic gonadotropin serum concentrations are always elevated in female dialysis patients even without pregnancy. It is also believed that human chorionic gonadotropin cannot be used to confirm or exclude pregnancy.MethodsHuman chorionic gonadotropin was examined in female dialysis patients (18–50 years of age), and was classified as positive above 5 mlU/ml. In addition, fertility status was determined. For an enhanced index test, the cut-off of 5 mIU/ml was used for potentially fertile patients and 14 mIU/ml for infertile patients to calculate diagnostic test accuracy. The ideal cut-off for human chorionic gonadotropin was estimated using Liu’s method with bootstrapped 95% confidence intervals. Predictors of human chorionic gonadotropin increase were analyzed using multivariable linear regression.ResultsAmong 71 women, two (2.8%) were pregnant, 46 (64.8%) potentially fertile, and 23 (32.4%) infertile. We observed human chorionic gonadotropin concentrations > 5 mIU/ml in 10 patients, which had a sensitivity of 100% (95% confidence interval: 100 to 100), a specificity of 86% (95% confidence interval: 77 to 94), a positive predictive value of 17% (95% confidence interval: 8 to 25) and a negative predictive value of 100% (95% confidence interval: 100 to 100) for the diagnosis of pregnancy. Using a cut-off > 14 mIU/ml for infertile patients or the exclusion of infertile patients increased specificity to 93% or 98%, respectively. The ideal cut-off was 25 mIU/ml (95% confidence interval: 17 to 33). Pregnancy and potential fertility, but not age, were independent predictors of human chorionic gonadotropin.ConclusionHuman chorionic gonadotropin is elevated > 5mIU/ml in 14.5% of non-pregnant dialysis patients of child-bearing age. In potentially fertile women, this cut-off can be used to exclude pregnancy. In case of an unknown fertility status, the ideal human chorionic gonadotropin cut-off was 25 mIU/ml.

Tumor maligno mixto de células germinales de ovario. Reporte de caso

Los tumores malignos de células germinales del ovario, aunque poco frecuentes, son el tipo más común de neoplasias ováricas malignas en niñas y adolescentes; aproximadamente dos tercios de ellas menores de 20 años. Representan 2% a 5% de todos los tumores ováricos de origen germinal. Los tumores comprenden dos o más tipos de componentes de células germinales, e incluyen al disgerminoma acompañado de tumores del seno endodérmico, carcinoma de células embrionarias, teratoma maduro o inmaduro y/o coriocarcinoma. Existen pocos informes de casos de tumores de células germinales mixtas con diferentes combinaciones de componentes malignos. La alfafetoproteína y la gonadotropina coriónica humana son los marcadores tumorales más característicos. Los hallazgos inmunohistoquímicos son importantes para el diagnóstico. La cirugía más quimioterapia adyuvante es la primera opción para preservar la fertilidad en cualquier niña o adolescente que presente con un tumor pélvico en rápido crecimiento. Se presenta un caso de tumor maligno mixto de células germinales de ovario.

Melatonin on hypothyroidism and gonadal development in rats: a review.

We evaluated the evidence in research on the effects of melatonin on hypothyroidism and gonadal development. According to the World Health Organization, thyroid disorders due to iodine deficiency affect about 740 million people worldwide. Hypothyroidism is a thyroid dysfunction characterized by hypometabolism of the gland, with reduced or physiologically normal T3 and T4 serum levels, and high TSH level. This disorder occurs mainly in adult women in the reproductive phase, with a prevalence of 2% among the world's female population, with profound repercussions on gestation and fetal formation. During the gestational period, the thyroid is initially stimulated by high concentrations of human chorionic gonadotrophin; thus, maintaining maternal euthyroidism during pregnancy and lactation is fundamental for fetal growth and development. Besides, the hormones produced by this gland are involved in the formation of various organs, such as the skin, brain and gonads. Hypothyroidism is associated with several menstrual abnormalities, anovulation and hyperprolactinemia, resulting in a high rate of abortions, premature births, placental rupture, and weight-related neonatal deficits. In addition, there are studies showing that hypothyroidism can affect ovarian morphology (number of ovarian follicles) and testicular morphology (changes in the testicular-lumen epithelium). Melatonin is a hormone known to modulate the estrous cycle and pregnancy, and studies show that the exogenous application of melatonin increased T4 levels in female rats and controlled the decrease in T3 serum levels, reverting the sigs of hypothyroidism.

Asymmetrical tapered SMS fiber coupler for simultaneous measurement of temperature and refractive index and its application for biosensing

An asymmetrical tapered singlemode–multimode–singlemode (SMS) fiber coupler based on two parallel physical contact SMS fiber structures was proposed. Since the coupler includes modes both from fiber core and cladding, two dips of the transmission spectrum exhibit different sensing characteristics to the surrounding temperature and refractive index (RI) change, which allows the use of the standard matrix inversion method to determine temperature and RI simultaneously. The temperature sensitivities of 0.0498 and 0.0324 nm/°C and RI sensitivities of 1151.76 and 1325.66 nm/RIU have been achieved, respectively. For biosensing application, with the functionalized fiber coupler sensor, a human chorionic gonadotropin concentration of 0.05 mIU/mL has been detected for a wavelength shift of 0.2 nm with good stability and excellent selectivity. The developed tapered SMS fiber coupler structure has advantages of simultaneous measurement of two independent parameters, simple configuration, low cost, and good repeatability that offer a great potential for medical diagnostics.

Regulation of Embryonic Signal on Talin1 in Mouse Endometrium.

Embryonic signals can affect the spatiotemporal-specific expression of the uterus to establish a successful pregnancy. Our previous study has found that talin1 underwent dynamic changes in the mouse endometrium during peri-implantation period. However, whether talin1 is affected by the embryo signals is not clear. In order to investigate the effect of embryonic signals, especially human chorionic gonadotropin (HCG) on talin1, we have designed mouse models of pseudopregnancy, delayed implantation and activation, and HCG treatment. Using these models, the expression of talin1 in the mouse endometrium was determined by immunohistochemistry and Western blotting. In the pseudopregnancy model, an increased expression of talin1 was found from day 3 to day 5, whereas the talin1 protein was decreased on day 5 in the normal pregnant mice. In the delayed implantation model, a strong cytoplasmic staining of talin1 was found, especially in stromal cells. However, after activation of the implantation, the expression of talin1 decreased (P < .05). Furthermore, a significantly lower expression of talin1 was found at the implantation site when compared to the interimplantation sites (P < .05). In the HCG treatment model, an intrauterine perfusion of 10u HCG significantly reduced the expression of talin1 in both stromal and epithelial cells in pseudopregnant mice (P < .05), although further increase in the HCG concentration did not have additional effect on expression of talin1. Taken together, our data suggest that the presence of embryos can affect expression of talin1 in the mouse endometrium, and a certain concentration of HCG can regulate its expression.

Colorimetric immunoassay for human chorionic gonadotropin by using peroxidase-mimickingMnO2 nanorods immobilized in microplate wells.

A colorimetric immunoassay is described for the pregnancy marker human chorionic gonadotropin (HCG). The assay is based on the use of MnO2 nanorods acting as a peroxidase mimic. The nanorods were prepared by a hydrothermal method using EDTA as a template. They exhibit excellent peroxidase-like activity and stability. The nanorods were immobilized in a chitosan matrix in the wells of a BSA-modified microplate which then were further modified with streptavidin and biotinylated capture antibodies. The specific recognition between HCG and the antibodies in wells inhibit the peroxidase-like activity of the nanorods. Hence, the substrate 3,3',5,5'-tetramethylbenzidine is less efficiently catalytically oxidized by H2O2 to form a blue colored product. This results in a decrease in the absorbance at 652nm. Response is linear in the 0.5 to 400 mIU·mL-1 HCG concentration range, and the detection limit is 0.36 mIU·mL-1 under optimized conditions. The method is highly specific, acceptably reproducible and stable. It was applied to the determination of HCG concentration in serum samples, and results were in good agreement with data obtained by the reference method." Graphical abstract Schematic presentation of colorimetric immunoassay for human chorionic gonadotropin (HCG) by using MnO2 nanorods with peroxidase-like activity immobilized in microplate wells. The specific recognition between HCG and the antibodies in wells inhibits the peroxidase-like activity of the nanorods. TMB: 3,3',5,5'-tetramethylbenzidine.