-
The Analyst Aug 2021We introduce analyte-dependent exclusion of reporter reagents from restricted-access adsorbents as the basis of an isocratic reporter-exclusion immunoassay for viruses,...
We introduce analyte-dependent exclusion of reporter reagents from restricted-access adsorbents as the basis of an isocratic reporter-exclusion immunoassay for viruses, proteins, and other analytes. Capto™ Core 700 and related resins possess a noninteracting size-selective outer layer surrounding a high-capacity nonspecific mixed-mode capture adsorbent core. In the absence of analyte, antibody-enzyme reporter conjugates can enter the adsorbent and be captured, and their signal is lost. In the presence of large or artificially-expanded analytes, reporter reagents bind to analyte species to form complexes large enough to be excluded from the adsorbent core, allowing their signal to be observed. This assay principle is demonstrated using M13 bacteriophage virus and human chorionic gonadotropin as model analytes. The simple isocratic detection approach described here allows a rapid implementation of immunoassay for detection of a wide range of analytes and uses inexpensive, generally-applicable, and stable column materials instead of costly analyte-specific immunoaffinity adsorbents.
Topics: Bacteriophage M13; Chorionic Gonadotropin; Humans; Immunoassay; Indicators and Reagents
PubMed: 34198311
DOI: 10.1039/d1an00396h -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Jul 2023Tumor markers have been widely used clinically. Detection of serum CA125 is one of the commonly used clinical methods for early screening and early diagnosis of...
OBJECTIVES
Tumor markers have been widely used clinically. Detection of serum CA125 is one of the commonly used clinical methods for early screening and early diagnosis of epithelial ovarian cancer, but it is difficult to diagnose epithelial ovarian cancer with a single specific tumor marker. In this study, the combinatorial tumor marker detection method was used to compare the value of each tumor marker alone and different combinations in the diagnosis of epithelial ovarian cancer.
METHODS
The clinical data of patients with epithelial ovarian cancer (=65) and ovarian benign disease (=29) were collected. Multiple tumor marker protein chip was used to detect cancer antigen 125 (CA125), carbohydrate antigen 242 (CA242), alpha-fetoprotein (AFP), beta-human chorionic gonadotropin (β-HCG), carcinoembryonic antigen (CEA), cancer antigen 199 (CA199), neuron-specific enolase (NSE), Ferritin, cancer antigen 153 (CA153), and human growth hormone (HGH) serum levels, and to compare the differences between the benign and malignant ovarian tumors. The correlation between tumor markers and clinicopathologic features for ovarian epithelial carcinoma was analyzed by χ test. Spearman rank analysis showed the correlation between CA125 expression level and other tumor markers in epithelial ovarian cancer and the correlation between age and the above 10 tumor markers. Sensitivity, specificity, positive predictive value, negative predictive value, Youden index, and diagnostic efficiency were used to evaluate the diagnostic value of single tumor marker and the combination of tumor markers.
RESULTS
The levels of β-HCG, NSE, CA153, and CA125 in the epithelial ovarian cancer group were higher than those in the ovarian benign disease group. The level of NSE in the serum of patients with epithelial ovarian cancer was related to the clinical stage of patients. In addition, the levels of CA242, β-HCG, CEA, NSE, Ferritin, CA153 in the serum of patients with epithelial ovarian cancer were positively correlated with CA125 (=0.497, <0.001; =0.612, <0.001; =0.358, =0.003; =0.680, <0.001; =0.322, =0.009; =0.609, <0.001, respectively), and the levels of β-HCG, Ferritin, CA153 were positively correlated with the patient's age (=0.256, =0.040; =0.325, =0.008; =0.249, =0.046, respectively). In the diagnosis of epithelial ovarian cancer, the sensitivity, Youden index, and diagnostic efficiency of CA125 detection alone were higher than the results of the other 9 separate detections. When CA153, CA199, CA242, Ferritin, and CEA were combined with CA125, the sensitivity of the combined detection of different combinations was higher than that of CA125 alone. The combined detection sensitivities of CA125+CEA and CA125+Ferritin+CEA were 89.2% and 90.8%, respectively, and the diagnostic efficiencies were both 84.1%, which were higher than those of other combinations. The Youden index of CA125+CEA joint detection was 0.616, which was higher than those of other combinations.
CONCLUSIONS
CA125 has a high diagnostic value in the diagnosis of epithelial ovarian cancer. The detection of combined tumor markers in serum has higher sensitivity and specificity in epithelial ovarian cancer.
Topics: Humans; Female; Biomarkers, Tumor; Carcinoembryonic Antigen; Carcinoma, Ovarian Epithelial; Clinical Relevance; Chorionic Gonadotropin, beta Subunit, Human; Ovarian Neoplasms; Ferritins
PubMed: 37724407
DOI: 10.11817/j.issn.1672-7347.2023.230090 -
Frontiers in Endocrinology 2022Infertility is a major global health issue and is associated with significant psychological distress for afflicted couples. fertilisation (IVF) utilises... (Review)
Review
Infertility is a major global health issue and is associated with significant psychological distress for afflicted couples. fertilisation (IVF) utilises supra-physiological doses of stimulatory hormones to induce the growth of multiple ovarian follicles to enable surgical retrieval of several oocytes for subsequent fertilisation and implantation into the maternal endometrium. The supra-physiological degree of ovarian stimulation can lead to potential risks during IVF treatment, including ovarian hyperstimulation syndrome (OHSS) and multiple pregnancy. The choice of oocyte maturation trigger, such as human chorionic gonadotrophin (hCG) or gonadotrophin releasing hormone agonist (GnRHa), can impact both the efficacy of IVF treatment with a bearing on luteal phase hormonal dynamics and thus the degree of luteal phase support required to maintain optimal pregnancy rates, as well as on safety of treatment with particular respect to the risk of OHSS. Kisspeptin regulates gonadotrophin releasing hormone (GnRH) release and is therefore a key regulator of the hypothalamo-pituitary-gonadal (HPG) axis. Kisspeptin has been shown to be requisite for the occurrence of the physiological ovulatory luteinising hormone (LH) surge. In this review, we discuss the potential use of kisspeptin as a novel trigger of oocyte maturation.
Topics: Chorionic Gonadotropin; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Kisspeptins; Luteinizing Hormone; Oocytes; Ovarian Hyperstimulation Syndrome; Pregnancy
PubMed: 36147569
DOI: 10.3389/fendo.2022.972137 -
Experimental Animals Nov 2022This study aimed to develop a more suitable ovarian stimulation procedure for cynomolgus macaques (Macaca fascicularis). Macaques were divided into 4 groups, 7AG, 8AG,...
This study aimed to develop a more suitable ovarian stimulation procedure for cynomolgus macaques (Macaca fascicularis). Macaques were divided into 4 groups, 7AG, 8AG, 7AN, and 8AN, according to the ovarian stimulation procedure administered (i.e., administration of either a gonadotropin-releasing hormone agonist [GnRH-a] or GnRH antagonist [GnRH-ant]) and the number of menstruations (≤ 7 times or ≥ 8 times) in the previous year. In both procedures, oocyte growth and maturation were induced by administration of human follicle-stimulating hormone and human chorionic gonadotropin. The mean numbers of metaphase II mature and metaphase I premature oocytes collected from the 7AG, 8AG, 7AN, and 8AN groups were 12.1 and 10.4, 12.0 and 13.8, 9.1 and 8.3, and 15.5 and 8.8, respectively (P>0.05). The fertilization rates of the 7AN and 8AN groups (85.3% and 74.7%) tended to be higher compared with those in the 7AG and 8AG groups (59.1% and 47.3%; P>0.05). The 8AN group yielded 19.9 zygotes, which was the largest number per macaque, compared with the other three groups. Furthermore, regarding the decreases in body weight between the start of the procedures and the time of oocyte collection, those of the 7AN and 8AN groups were significantly smaller than those of the 7AG and 8AG groups (P<0.05), suggesting that the procedure involving GnRH-ant reduced the burden on the macaques. Thus, controlled ovarian stimulation using a GnRH-ant has some advantages for cynomolgus macaques compared with that using a GnRH-a.
Topics: Female; Animals; Humans; Gonadotropin-Releasing Hormone; Macaca fascicularis; Ovulation Induction; Chorionic Gonadotropin; Hormone Antagonists; Oocytes; Fertilization in Vitro
PubMed: 35527012
DOI: 10.1538/expanim.21-0198 -
Reproductive Biology and Endocrinology... Aug 2020It is widely known that luteinising hormone (LH) and human chorionic gonadotrophin (hCG) are integral in the female reproductive lifecycle. Due to the common binding... (Review)
Review
It is widely known that luteinising hormone (LH) and human chorionic gonadotrophin (hCG) are integral in the female reproductive lifecycle. Due to the common binding site and similarity in molecular structure, they were previously thought to have overlapping roles. However, with the development of both purified urinary-derived and recombinant gonadotrophins, the individual characteristics of these molecules have begun to be defined. There is evidence to suggest that LH and hCG preferentially activate different signalling cascades and display different receptor-binding kinetics. The data generated on the two molecules have led to an improved understanding of their distinct physiological functions, resulting in a debate among clinicians regarding the most beneficial use of LH- and hCG-containing products for ovarian stimulation (OS) in assisted reproductive technologies (ARTs). Over the past few decades, a number of trials have generated data supporting the use of hCG for OS in ART. Indeed, the data indicated that hCG plays an important role in folliculogenesis, leads to improved endometrial receptivity and is associated with a higher quality of embryos, while presenting a favourable safety profile. These observations support the increased use of hCG as a method to provide LH bioactivity during OS. This review summarises the molecular and functional differences between hCG and LH, and provides an overview of the clinical trial data surrounding the use of products for OS that contain LH bioactivity, examining their individual effect on outcomes such as endometrial receptivity, oocyte yield and embryo quality, as well as key pregnancy outcomes.
Topics: Chorionic Gonadotropin; Female; Humans; Infertility; Ovulation Induction; Pregnancy; Pregnancy Outcome; Reproductive Techniques, Assisted; Treatment Outcome
PubMed: 32762698
DOI: 10.1186/s12958-020-00639-3 -
Reproductive Toxicology (Elmsford, N.Y.) Jun 2023Perfluorooctane sulfonate (PFOS) is a widespread and persistent chemical in the environment. Reports show that PFOS is a potential endocrine disruptor; however, the...
Perfluorooctane sulfonate (PFOS) is a widespread and persistent chemical in the environment. Reports show that PFOS is a potential endocrine disruptor; however, the possible effects of PFOS on placental endocrine function are unclear. This study aimed to investigate the endocrine-disrupting effects of PFOS on the placenta in pregnant rats and its potential mechanism. Pregnant rats from gestational days 4-20 were exposed to 0, 10, and 50 μg/mL PFOS through drinking water followed by analysis of various biochemical parameters. PFOS dose-dependently decreased fetal and placental weight in both sexes, with a specific decrease in weight of labyrinth but not junctional layer. Plasma progesterone (↑166%), aldosterone (↑201%), corticosterone (↑205%), testosterone (↑45%), luteinizing hormone (↑49%) levels were significantly increased, while estradiol (↓27%), prolactin (↓28%) and hCG (↓62%) levels were reduced in groups exposed to higher doses of PFOS. Real-time quantitative reverse transcriptase-polymerase chain reaction analysis revealed a significant increase in mRNA levels of placental steroid biosynthesis enzymes, including Cyp11A1 and 3β-HSD1 in male placenta and StAR, Cyp11A1, 17β-HSD1 and 17β-HSD3 in female placenta of PFOS dams. Cyp19A1 expression in ovaries was significantly decreased in PFOS dams. mRNA levels for placental steroid metabolism enzyme UGT1A1 increased in male but not in female placenta of PFOS dams. These results suggest that the placenta is a target tissue of PFOS and PFOS-induced dysregulation in steroid hormone production might be related to the altered expression of hormone biosynthesis and metabolism enzyme genes in the placenta. This hormone disruption might affect maternal health and fetal growth.
Topics: Pregnancy; Rats; Female; Male; Animals; Placenta; Cholesterol Side-Chain Cleavage Enzyme; Fluorocarbons; Alkanesulfonic Acids; Estradiol; Steroids
PubMed: 37148813
DOI: 10.1016/j.reprotox.2023.108390 -
Molecular and Cellular Endocrinology Dec 2021Vasoinhibin is an antiangiogenic, profibrinolytic peptide generated by the proteolytic cleavage of the pituitary hormone prolactin by cathepsin D, matrix...
Vasoinhibin is an antiangiogenic, profibrinolytic peptide generated by the proteolytic cleavage of the pituitary hormone prolactin by cathepsin D, matrix metalloproteinases, and bone morphogenetic protein-1. Vasoinhibin can also be generated when placental lactogen or growth hormone are enzymatically cleaved. Here, it is investigated whether plasmin cleaves human prolactin and placental lactogen to generate vasoinhibin-like peptides. Co-incubation of prolactin and placental lactogen with plasmin was performed and analyzed by gel electrophoresis and Western blotting. Mass spectrometric analyses were carried out for sequence validation and precise cleavage site identification. The cleavage sites responsible for the generation of the vasoinhibin-like peptides were located at K170-E171 in prolactin and R160-T161 in placental lactogen. Various genetic variants of the human prolactin and placental lactogen genes are projected to affect proteolytic generation of the vasoinhibin-like peptides. The endogenous counterparts of the vasoinhibin-like peptides generated by plasmin may represent vasoinhibin-isoforms with inhibitory effects on vasculature and coagulation.
Topics: Cell Cycle Proteins; Fibrinolysin; Genetic Variation; HEK293 Cells; Humans; Mass Spectrometry; Peptides; Placental Lactogen; Prolactin; Proteolysis
PubMed: 34601001
DOI: 10.1016/j.mce.2021.111471 -
PloS One 2023In women scheduled for cancer treatment, oocytes cryopreservation is a well-established procedure. Random start protocols have been a substantial improvement in this...
BACKGROUND
In women scheduled for cancer treatment, oocytes cryopreservation is a well-established procedure. Random start protocols have been a substantial improvement in this setting, allowing to prevent delay in the initiation of cancer treatments. However, there is still the need to optimize the regimen of ovarian stimulation, to make treatments more patient-friendly and to reduce costs.
METHODS
This retrospective study compares two periods (2019 and 2020), corresponding to two different ovarian stimulation regimens. In 2019, women were treated with corifollitropin, recombinant FSH and GnRH antagonists. Ovulation was triggered with GnRH agonists. In 2020, the policy changed, and women were treated with a progestin-primed ovarian stimulation (PPOS) protocol with human menopausal gonadotropin (hMG) and dual trigger (GnRH agonist and low dose hCG) Continuous data are reported as median [Interquartile Range]. To overcome expected changes in baseline characteristics of the women, the primary outcome was the ratio between the number of mature oocytes retrieved and serum anti-mullerian hormone (AMH) in ng/ml.
RESULTS
Overall, 124 women were selected, 46 in 2019 and 78 in 2020. The ratio between the number of mature oocytes retrieved and serum AMH in the first and second period was 4.0 [2.3-7.1] and 4.0 [2.7-6.8], respectively (p = 0.80). The number of scans was 3 [3-4] and 3 [2-3], respectively (p<0.001). The total costs of the drugs used for ovarian stimulation were 940 € [774-1,096 €] and 520 € [434-564 €], respectively (p<0.001).
CONCLUSIONS
Random start PPOS with hMG and dual trigger represents an easy and affordable ovarian stimulation protocol for fertility preservation in women with cancer, showing similar efficacy and being more friendly and economical.
Topics: Humans; Female; Progestins; Fertility Preservation; Chorionic Gonadotropin; Retrospective Studies; Infertility, Female; Ovulation Induction; Steroids; Neoplasms; Gonadotropin-Releasing Hormone; Fertilization in Vitro
PubMed: 36976781
DOI: 10.1371/journal.pone.0280238 -
Acta Obstetricia Et Gynecologica... Sep 2023Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Ectopic pregnancy is an important health condition which affects up to 1 in 100 women. Women who present with mild symptoms and low serum human chorionic gonadotrophin (hCG) are often treated with methotrexate (MTX), but expectant management with close monitoring is a feasible alternative. Studies comparing the two treatments have not shown a statistically significant difference in uneventful resolution of ectopic pregnancy, but these studies were too small to define whether certain subgroups could benefit more from either treatment.
MATERIAL AND METHODS
We performed a systematic review and individual participant data meta-analysis (IPD-MA) of randomized controlled trials comparing systemic MTX and expectant management in women with tubal ectopic pregnancy and low hCG (<2000 IU/L). A one-stage IPD-MA was performed to assess overall treatment effects of MTX and expectant management to generate a pooled intervention effect. Subgroup analyses and exploratory multivariable analyses were undertaken according to baseline serum hCG and progesterone levels. Primary outcome was treatment success, defined as resolution of clinical symptoms and decline in level of serum hCG to <20 IU/L, or a negative urine pregnancy test by the initial intervention strategy, without any additional treatment. Secondary outcomes were need for blood transfusion, surgical intervention, additional MTX side-effects and hCG resolution times.
TRIAL REGISTRATION NUMBER
PROSPERO: CRD42021214093.
RESULTS
1547 studies reviewed and 821 remained after duplicates removed. Five studies screened for eligibility and three IPD requested. Two randomized controlled trials supplied IPD, leading to 153 participants for analysis. Treatment success rate was 65/82 (79.3%) after MTX and 48/70 (68.6%) after expectant management (IPD risk ratio [RR] 1.16, 95% confidence interval [CI] 0.95-1.40). Surgical intervention rates were not significantly different: 8/82 (9.8%) vs 13/70 (18.6%) (RR 0.65, 95% CI 0.23-1.14). Mean time to success was 19.7 days (95% CI 17.4-22.3) after MTX and 21.2 days (95% CI 17.8-25.2) after expectant management (P = 0.25). MTX specific side-effects were reported in 33 MTX compared to four in the expectant group.
CONCLUSIONS
Our IPD-MA showed no statistically significant difference in treatment efficacy between MTX and expectant management in women with tubal ectopic pregnancy with low hCG. Initial expectant management could be the preferred strategy due to fewer side-effects.
Topics: Pregnancy; Humans; Female; Methotrexate; Watchful Waiting; Pregnancy, Tubal; Pregnancy, Ectopic; Chorionic Gonadotropin; Abortifacient Agents, Nonsteroidal; Retrospective Studies
PubMed: 37345445
DOI: 10.1111/aogs.14617 -
Molecular and Cellular Endocrinology Sep 2020Progesterone, a critical hormone in reproduction, is a key sex steroid in the establishment and maintenance of early pregnancy and serves as an intermediary for... (Review)
Review
Progesterone, a critical hormone in reproduction, is a key sex steroid in the establishment and maintenance of early pregnancy and serves as an intermediary for synthesis of other steroid hormones. Progesterone production from the corpus luteum is a tightly regulated process which is stimulated and maintained by multiple factors, both systemic and local. Multiple regulatory systems, including classic mediators of gonadotropin stimulation such as the cAMP/PKA pathway and TGFβ-mediated signaling pathways, as well as local production of hormonal factors, exist to promote granulosa cell function and physiological fine-tuning of progesterone levels. In this manuscript, we provide an updated narrative review of the known mediators of human luteal progesterone and highlight new observations regarding this important process, focusing on studies published within the last five years. We will also review recent evidence suggesting that this complex system of progesterone production is sensitive to disruption by exogenous environmental chemicals that can mimic or interfere with the activities of endogenous hormones.
Topics: Animals; Chorionic Gonadotropin; Corpus Luteum; Female; Granulosa Cells; Humans; Progesterone
PubMed: 32610113
DOI: 10.1016/j.mce.2020.110930