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Optimizations of the gene expression cassette combined with the selection of an appropriate signal peptide are important factors that must be considered to enhance heterologous protein expression in Chinese Hamster Ovary (CHO) cells. In this study, we investigated the effectiveness of different signal peptides on the production of recombinant human chorionic gonadotropin (r-hCG) in CHO-K1 cells. Four optimized expression constructs containing four promising signal peptides were stably transfected into CHO-K1 cells. The generated CHO-K1 stable pool was then evaluated for r-hCG protein production. Interestingly, human serum albumin and human interleukin-2 signal peptides exhibited relatively greater extracellular secretion of the r-hCG with an average yield of (16.59 ± 0.02 µg/ml) and (14.80 ± 0.13 µg/ml) respectively compared to the native and murine IgGκ light chain signal peptides. The stably transfected CHO pool was further used as the cell substrate to develop an optimized upstream process followed by a downstream phase of the r-hCG. Finally, the biological activity of the purified r-hCG was assessed using in vitro bioassays. The combined data highlight that the choice of signal peptide can be imperative to ensure an optimal secretion of a recombinant protein in CHO cells. In addition, the stable pool technology was a viable approach for the production of biologically active r-hCG at a research scale with acceptable bioprocess performances and consistent product quality.
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Gonadotropina Coriónica , Cricetulus , Proteínas Recombinantes , Células CHO , Animales , Proteínas Recombinantes/genética , Proteínas Recombinantes/biosíntesis , Humanos , Gonadotropina Coriónica/genética , Gonadotropina Coriónica/biosíntesis , Gonadotropina Coriónica/farmacología , Cricetinae , Señales de Clasificación de Proteína/genética , Expresión Génica , TransfecciónRESUMEN
OBJECTIVES: Estrogen insensitivity syndrome (EIS) is a rare genetic disorder characterized by an autosomal dominant inheritance pattern. The disease results from a pathogenic variant in the ESR1 (estrogen receptor 1) gene, leading to estrogen resistance in individuals possessing the 46, XX karyotype. The alpha receptor, which is predominant in peripheral tissues, is responsible for estrogen action. As a result, pathogenic variants in the ESR1 gene can cause various disorders, such as changes in secondary sexual characteristics, increased concentrations of estrogen and gonadotropins, and delayed bone maturation. CASE PRESENTATION: Here, the case of a 13-year-old girl, with high estrogen and gonadotropin concentrations, lack of breast development, uterine growth and delayed bone age is described. The patient's parents were related. She was found to have a homozygous pathogenic variant in the ESR1 gene located on chromosome 6q25, which interferes with estrogen signaling. CONCLUSION: This case supports that disruption of ESR1 causes profound estrogen resistance in females.
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Herein, a conjugated conducting polymer-based impedimetric aptasensor has been developed to detect beta-human chorionic gonadotropin (bHCG), the one of the important biomarkers in gynecology, from synthetic human urine samples. In this context, gold electrodes were, firstly coated with pyrrole and pyrrole-3-carboxylic acid to obtain the poly(pyrrole-pyrrole-3-carboxylic acid) [poly(Py-PyCOOH)] conductive copolymer by cyclic voltammetry (CV). Then, bHCG-specific peptide aptamer was covalently linked onto the surface via applying a well-known carbodiimide-succinimide chemistry. The sensor developed was characterized to confirm modification steps via both electrochemical methods including CV, electrochemical impedance spectroscopy (EIS), and chronoamperometry and physico-chemically via attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR), scanning electron microscopy (SEM), energy dispersive X-ray analysis (EDX), atomic force microscope (AFM), and contact angle measurements (CA). The analytical performance of the sensor was evaluated in the concentration range from 1 µg/mL to 100 µg/mL for successful detection of bHCG even in the presence of interference agents. The results have also revealed that the sensor could be classified as a promising alternative to its benchmark commercial clinical methods due its superior properties such as cost-friendliness, easy-to-prepare, stable, robust, and selectivity / sensitivity.
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Cotyledonoid-dissecting leiomyoma, a very unusual form of uterine leiomyoma, often leads to misdiagnosis as a malignant tumor. Here, we describe a case of a 45-year-old nulliparous woman who underwent a laparoscopic biopsy of a large pelvic mass consisting of multiple flaps. Histologically, the mass was composed of smooth muscle fascicle nodules separated by hydropic connective tissue, and exhibited extensive stromal hyalinization. The tumor was diagnosed as a cotyledonoid-dissecting leiomyoma based on the laparoscopic, pathological, and image findings. Prior to performing radical laparotomy, two courses of leuprorelin were administered in anticipation of tumor reduction and hypoperfusion, and the tumor size reduced remarkably. We demonstrated the utility of laparoscopic biopsy, considering its minimal invasiveness and diagnostic accuracy. Furthermore, the preoperative use of Gonadotropin-releasing hormone (GnRH) analogs to reduce surgical stress may be useful for treating cotyledonoid-dissecting leiomyomas.
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To evaluate the effect of growth hormone (GH) supplementation on outcomes of in vitro fertilization (IVF) or Intracytoplasmic sperm injection (ICSI) for women with poor ovarian response. Relevant randomized controlled trials (RCTs) were obtained through search in several databases including PubMed, Scopus, Clinicaltrials.gov, Google Scholar, and Cochrane Library. Outcome measures included live birth rate, clinical pregnancy rate, cycle cancelation rate, number of retrieved oocytes, number of transferred embryos, total dose of gonadotropin, duration of gonadotropin treatment, and peak estradiol level. Additionally, a meta-regression analysis was carried out to determine any potential linear relationships between these outcomes and IVF success. After analyzing 18 RCTs comprising of 1870 patients, the study found that GH supplementation improved the number of retrieved oocytes [standardized mean difference (SMD), 0.65; 95% confidence interval (CI), 0.29-1.00] and transferred embryos group (SMD, 0.80, 95% CI, 0.39, 1.21) as well as peak E2 level (SMD, 1.20; 95% CI, 0.59, 1.81). While reduced the total dose and duration of gonadotropin treatment (SMD, -0.82, 95% CI, -1.25, -0.39, and SMD, -0.63, 95% CI, -1.04, -0.22, respectively). The meta-regression analysis found no linear relationship between clinical pregnancy, live birth rate, or cycle cancelation rate and the outcomes measured (p>0.1). Based on the available evidence, GH supplementation appears to improve the outcomes of IVF or ICSI in women with poor response. However, there is a need for further RCTs with larger sample sizes to determine the cost-effectiveness of adding GH to conventional protocols of IVF/ICSI for treating infertility in women with poor ovarian response.
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BACKGROUND: Adenomyosis can lead to infertility and failure of in vitro fertilization. Limited evidence suggests that the use of long-term treatment with gonadotropin-releasing hormone (GnRH) agonists followed by frozen-thawed embryo transfer (FET) may be the preferred approach for women with adenomyosis. OBJECTIVE: The aim of this randomized controlled trial is to compare the efficacy of an ultra-long GnRH agonist with standard downregulation in women with adenomyosis undergoing FET. MATERIALS AND METHODS: This randomized controlled trial enrolled 72 women with adenomyosis diagnosed by sonographic criteria who underwent FET cycles at the Avicenna Infertility Center. These women were randomly assigned to two equal groups: one received GnRH agonist treatment for three months before the FET cycle and the other served as the standard downregulation group. Results were reported as chemical and clinical pregnancy rates. RESULTS: The two groups were similar in age, body mass index, anti-Müllerian hormone levels, number of previous pregnancies and miscarriages, presence of uterine myomas, and endometriosis. However, the total dose of estradiol used until embryo transfer was significantly higher in the ultra-long GnRH agonist group than in the standard group (96.14 mg vs. 80.52 mg, p-value = 0.004). Nevertheless, chemical and clinical pregnancy rates did not differ significantly between the two groups. CONCLUSIONS: Ultra-long GnRH agonist downregulation did not improve the chemical and clinical pregnancy rate in the FET cycle in women with adenomyosis compared with standard GnRH agonist downregulation in the other words, ultra-long GnRH agonist downregulation is not superior to standard protocol. In women with adenomyosis (without history of endometriosis), downregulation of standard GnRH agonists prior to frozen-thawed embryo transfer may be the preferred embryo transfer protocol to gain higher clinical/chemical pregnancy rate. TRIAL REGISTRATION: Clinical trial registry: IRCT20160717028967N9, available at: https://irct.behdasht.gov.ir/trial/36103 .
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Pineal region tumours are rare and mainly arise at a younger age. They can be categorized into various types: germ cell tumours (GCT), pineal parenchymal tumours (PPT), meningiomas, gliomas, pineoblastoma, pineal parenchymal tumours of intermediate differentiation, papillary tumours of the pineal region, and SMARCB1- mutant desmoplastic myxoid tumour. Within GCT, germinomas are the most prevalent, comprising the majority of tumours in this region, while nongerminomatous GCTs are also present. In rare instances, metastases from other sites may manifest. These tumours often lead to obstructive hydrocephalus and commonly exhibit symptoms related to mass effect, including headache, nausea, vomiting, and impaired gait stability. Different subtypes of pineal region tumours exhibit distinct radiological characteristics, thus imaging remains the primary diagnostic tool. Histologic diagnosis necessitates biopsy, unless in cases of germ cell tumours, particularly germinomas, which can be identified through elevated levels of tumour markers like alpha-fetoprotein (AFP) and human chorionic gonadotropin (HCG) in both cerebrospinal fluid (CSF) and serum. While benign tumours might be effectively treated with radical resection alone, malignant tumours demand additional chemotherapy and radiotherapy following surgical removal.
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Neoplasias Encefálicas , Glándula Pineal , Pinealoma , Humanos , Pinealoma/terapia , Pinealoma/diagnóstico , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/diagnóstico , Glándula Pineal/patología , Países en Desarrollo , Neoplasias de Células Germinales y Embrionarias/terapia , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Consenso , Germinoma/terapia , Germinoma/diagnósticoRESUMEN
Background: Nausea and vomiting in pregnancy (NVP), or emesis gravidarum, is a frequent complication of early gestation with unclear causes, suspected to involve genetic, hormonal, and gastrointestinal factors. Our study investigated the association of human chorionic gonadotropin (hCG), histamine, diamine oxidase (DAO), thyroxine and pyridoxine and the severity of NVP symptoms and assessed the efficacy of a vitamin C-containing chewing gum as a potential NVP treatment. Methods: In this prospective, double-blinded, randomized, controlled trial, 111 participants were assigned to receive vitamin C-containing chewing gum, placebo gum, or no treatment at two follow-ups during early pregnancy. Maternal serum levels of hCG, histamine, DAO, thyroxine, and pyridoxine were measured and correlated with NVP severity using the Pregnancy-Unique Quantification of Emesis and Nausea (PUQE-24) score. Results: Elevated maternal hCG levels were significantly associated with an increased PUQE-24 score (p < 0.001), while histamine levels showed no significant correlation (p = 0.68). Maternal DAO levels negatively correlated with NVP symptoms (p < 0.001) and elevated thyroxine (p < 0.001) and pyridoxine levels (p < 0.001) were associated with increased PUQE-24 scores. The vitamin C-containing chewing gum did not demonstrate efficacy in alleviating NVP symptoms compared to placebo gum or no treatment during the first (p = 0.62) and second follow-up visits (p = 0.87). Conclusions: Our study underscores the complexity of factors contributing to NVP, highlighting the significant roles of hCG and DAO, while histamine levels appear unrelated. Maternal thyroxine and pyridoxine levels also significantly correlate with NVP symptoms. Vitamin C-containing chewing gum was not effective as a treatment for NVP. Further large-scale studies are needed to better understand these interactions and develop targeted treatments in the future.
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The gonadotropin-releasing hormone (GnRH) receptor (GnRH-R) is highly expressed in ovarian cancer cells (OCC), and it is an important molecular target for cancer therapeutics. To develop a new class of drugs targeting OCC, we designed and synthesized Con-3 and Con-7 which are novel high-affinity GnRH-R agonists, covalently coupled through a disulfide bond to the DNA synthesis inhibitor mitoxantrone. We hypothesized that Con-3 and Con-7 binding to the GnRH-R of OCC would expose the conjugated mitoxantrone to the cellular thioredoxin, which reduces the disulfide bond of Con-3 and Con-7. The subsequent release of mitoxantrone leads to its intracellular accumulation, thus exerting its cytotoxic effects. To test this hypothesis, we determined the cytotoxic effects of Con-3 and Con-7 using the SKOV-3 human OCC. Treatment with Con-3 and Con-7, but not with their unconjugated GnRH counterparts, resulted in the accumulation of mitoxantrone within the SKOV-3 cells, increased their apoptosis, and reduced their proliferation, in a dose- and time-dependent manner, with half-maximal inhibitory concentrations of 0.6-0.9 µM. It is concluded that Con-3 and Con-7 act as cytotoxic "prodrugs" in which mitoxantrone is delivered in a GnRH-R-specific manner and constitute a new class of lead compounds for use as anticancer drugs targeting ovarian tumors.
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Apoptosis , Proliferación Celular , Hormona Liberadora de Gonadotropina , Mitoxantrona , Neoplasias Ováricas , Receptores LHRH , Humanos , Mitoxantrona/farmacología , Mitoxantrona/química , Femenino , Hormona Liberadora de Gonadotropina/farmacología , Hormona Liberadora de Gonadotropina/química , Neoplasias Ováricas/tratamiento farmacológico , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Apoptosis/efectos de los fármacos , Receptores LHRH/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Supervivencia Celular/efectos de los fármacosRESUMEN
Highly purified human menopausal gonadotropin (HP-hMG [Menopur®, Ferring Pharmaceuticals, Saint-Prex, Switzerland]) contains a 1:1 ratio of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). This analysis aimed to assess gonadotropin (FSH, LH and hCG) abundance in HP-hMG and clarify the source of hCG by assessing the presence of sulfated glycans, which are diagnostic for pituitary hCG forms due to their distinct glycosylation patterns. Additionally, the purity of each sample, their specific components, and their oxidation levels were assessed. HP-hMG samples (three of Menopur® and two of Menogon® Ferring Pharmaceuticals, Saint-Prex, Switzerland) were included in the current analyses. Brevactid® (urinary hCG; Ferring Pharmaceuticals, Saint-Prex, Switzerland) and Ovidrel® (recombinant hCG; Merck KGaA, Darmstadt, Germany) were used as control samples. Glycopeptide mapping and analysis of impurities were carried out by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Oxidation was assessed through reducing peptide mapping using LC-MS/MS. The FSH and LH in the HP-hMG samples showed sulfated glycans, while no signals of sulfated glycopeptides were detected on any site of the beta subunit of hCG. HP-hMG test samples presented the same hCG glycan distribution as the control sample (placental hCG, Brevactid®) extracted from the urine of pregnant women, suggesting a non-pituitary source of hCG. Protein impurities were estimated to constitute approximately 20-30% of the entire HP-hMG protein content in the test samples. More than 200 non-gonadotropin proteins were identified in the HP-hMG test samples, of which several were involved in embryonic development or pregnancy. The alpha subunit of the tested samples was strongly oxidized, with a relative abundance of 20% of the total gonadotropin content. Without taking into account all the protein impurities, the beta subunit of LH was detected only in traces (0.9-1.2%) in all tested HP-HMG samples, confirming the data obtained by intact molecule analysis, while high levels of beta hCG (18-47%) were observed. Advanced molecular analysis of HP-hMG indicates a primarily placental origin of hCG, as evidenced by the absence of hCG sulfated glycans and the predominance of placental non-sulfated hCG in LH activity. The analysis revealed 20-30% of protein impurities and a significant presence of oxidized forms in the HP-hMG samples. These findings are critical for understanding the quality, safety, and clinical profile of HP-hMG.
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Gonadotropina Coriónica , Hormona Luteinizante , Espectrometría de Masas en Tándem , Humanos , Gonadotropina Coriónica/orina , Gonadotropina Coriónica/análisis , Hormona Luteinizante/orina , Hormona Luteinizante/análisis , Espectrometría de Masas en Tándem/métodos , Cromatografía Liquida/métodos , Polisacáridos/análisis , Polisacáridos/química , Polisacáridos/orina , Glicosilación , Femenino , Menotropinas/orina , Menotropinas/análisis , Hormona Folículo Estimulante/orina , Hormona Folículo Estimulante/análisis , Oxidación-Reducción , Glicopéptidos/análisis , Glicopéptidos/química , Glicopéptidos/orinaRESUMEN
BACKGROUND: Maternal gestational diabetes (GDM), small (SGA) and large (LGA) for gestational age neonates are associated with increased morbidity in both mother and child. We studied how different levels of first trimester pregnancy associated plasma protein-A (PAPP-A) and free beta human chorionic gonadotropin (fß-hCG) were associated with SGA and LGA in GDM pregnancies and controls. METHODS: Altogether 23 482 women with singleton pregnancies participated in first trimester combined screening and delivered between 2014 and 2018 in Northern Finland and were included in this retrospective case-control study. Women with GDM (n = 4697) and controls without GDM (n = 18 492) were divided into groups below 5th and 10th or above 90th and 95th percentile (pc) PAPP-A and fß-hCG MoM levels. SGA was defined as a birthweight more than two standard deviations (SD) below and LGA more than two SDs above the sex-specific and gestational age-specific reference mean. Odds ratios were adjusted (aOR) for maternal age, BMI, ethnicity, IVF/ICSI, parity and smoking. RESULTS: In pregnancies with GDM the proportion of SGA was 2.6% and LGA 4.5%, compared to 3.3% (p = 0.011) and 1.8% (p < 0.001) in the control group, respectively. In ≤ 5th and ≤ 10th pc PAPP-A groups, aORs for SGA were 2.7 (95% CI 1.5-4.7) and 2.2 (95% CI 1.4-3.5) in the GDM group and 3.8 (95% CI 3.0-4.9) and 2.8 (95% CI 2.3-3.5) in the reference group, respectively. When considering LGA, there was no difference in aORs in any high PAPP-A groups. In the low ≤ 5 percentile fß-hCG MoM group, aORs for SGA was 2.3 (95% CI 1.8-3.1) in the control group. In fß-hCG groups with GDM there was no association with SGA and the only significant difference was ≥ 90 percentile group, aOR 1.6 (95% CI 1.1-2.5) for LGA. CONCLUSION: Association with low PAPP-A and SGA seems to be present despite GDM status. High PAPP-A levels are not associated with increased LGA risk in women with or without GDM. Low fß-hCG levels are associated with SGA only in non-GDM pregnancies.
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Gonadotropina Coriónica Humana de Subunidad beta , Diabetes Gestacional , Macrosomía Fetal , Recién Nacido Pequeño para la Edad Gestacional , Primer Trimestre del Embarazo , Proteína Plasmática A Asociada al Embarazo , Humanos , Femenino , Embarazo , Proteína Plasmática A Asociada al Embarazo/análisis , Proteína Plasmática A Asociada al Embarazo/metabolismo , Gonadotropina Coriónica Humana de Subunidad beta/sangre , Primer Trimestre del Embarazo/sangre , Adulto , Estudios de Casos y Controles , Estudios Retrospectivos , Diabetes Gestacional/sangre , Diabetes Gestacional/epidemiología , Recién Nacido , Macrosomía Fetal/sangre , Macrosomía Fetal/epidemiología , Finlandia/epidemiología , Factores de Riesgo , Peso al NacerRESUMEN
BACKGROUND: Around 4% of women receive an endometrial cancer diagnosis before turning 40, mainly those without prior childbirth experience and a strong desire to preserve their ability to conceive. Consequently, for young patients diagnosed with atypical endometrial hyperplasia (AEH) or early endometrial carcinoma (EC), a fertility-preserving approach employing high-dose oral progesterone has been adopted. However, previous research has shown a notable relapse rate. Furthermore, the extended use of substantial oral progesterone doses may hinder ovarian function and raise the risk of weight gain, liver issues, blood clotting, and breast cancer. We previously assessed the clinical effectiveness and pregnancy outcomes of gonadotropin-releasing hormone agonist (GnRH-a) based re-treatment for women with EC and AEH who did not respond to oral progestin therapy but achieved favorable treatment results and reproductive outcomes. METHODS: This study will be an open-label, two-armed, randomized, investigator-initiated multicenter trial evaluating the combination of GnRH-a with the levonorgestrel-releasing intrauterine system or the combination of GnRH-a with an aromatase inhibitor (comprising a subcutaneous GnRH-a injection every 4 weeks and daily oral letrozole 2.5 mg). A total of 226 participants will be randomly allocated to one of the two treatment groups in a 1:1 ratio. The primary objective is to determine the effectiveness of GnRH-a-based re-treatment in achieving a complete response (CR) at 24 weeks for patients with AEH or EC. Secondary objectives include assessing the pregnancy rate 12 weeks after treatment, as well as post-treatment pregnancy outcomes and the rate of recurrence. ETHICS AND DISSEMINATION: The protocol received approval from the Institutional Review Board of Peking Union Medical College Hospital and from boards at five other institutions. The trial will adhere to the principles outlined in the World Medical Association's Declaration of Helsinki and follow Good Clinical Practice standards. The trial results will be disseminated through publication in a peer-reviewed journal. CONCLUSIONS: Prospective evidence supporting conservative treatment for EC and AEH is limited. There is a need for new approaches that can achieve higher CR rates with fewer side effects. This trial will assess the effectiveness of GnRH-a-based fertility-sparing treatment in obese women and recurrent patients, offering a promising alternative for patients with EC and AEH. TRIAL REGISTRATION NUMBER: Chinese Clinical Trial Registry ChiCTR2200067099. Registered on December 27, 2022.
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Hiperplasia Endometrial , Neoplasias Endometriales , Preservación de la Fertilidad , Hormona Liberadora de Gonadotropina , Levonorgestrel , Estudios Multicéntricos como Asunto , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Femenino , Hormona Liberadora de Gonadotropina/agonistas , Hiperplasia Endometrial/tratamiento farmacológico , Hiperplasia Endometrial/complicaciones , Neoplasias Endometriales/tratamiento farmacológico , Preservación de la Fertilidad/métodos , Embarazo , Levonorgestrel/administración & dosificación , Levonorgestrel/efectos adversos , Levonorgestrel/uso terapéutico , Inhibidores de la Aromatasa/uso terapéutico , Inhibidores de la Aromatasa/efectos adversos , Inhibidores de la Aromatasa/administración & dosificación , Dispositivos Intrauterinos Medicados , Resultado del Tratamiento , Adulto , Antineoplásicos Hormonales/uso terapéutico , Antineoplásicos Hormonales/efectos adversos , Antineoplásicos Hormonales/administración & dosificación , Letrozol/administración & dosificación , Letrozol/uso terapéutico , China , Índice de EmbarazoRESUMEN
AIM: Luteinizing hormone (LH) plays an important role in ovarian follicle maturation. Human menopausal gonadotropin (hMG) or low dose human chorionic gonadotropin (hCG) can provide LH supplementation during in vitro fertilization (IVF) ovarian stimulation, though studies directly comparing their impact on IVF outcomes are limited. The aim of the study was to determine whether LH supplementation with hMG versus low dose hCG during IVF stimulation affects live birth rate. METHODS: Fresh and frozen embryo transfers (ET) from 2017 to 2021 after standard long or antagonist protocols supplemented with hMG (75-250 IU) or low dose hCG (50-100 IU) during stimulation cycles in our academic center were included. Statistical analysis was performed with T-tests, Mann-Whitney U tests, Chi-square, and multiple linear and logistic regression. RESULTS: Four hundred and sixty eight unique stimulation cycles resulting in 213 fresh and 412 frozen embryo transfers were analyzed. There was a lower mature oocyte yield (10.9 vs. 11.8, p = 0.044) but similar high-quality blastocyst yield (3.6 vs. 3.9, p = 0.11) for hMG vs low dose hCG. Live birth rates per transfer were comparable for fresh (42% vs. 49%, p = 0.24) and frozen (46% vs. 53%, p = 0.45) embryo transfers. Multiple logistic regressions showed no association between supplemental gonadotropin and live birth for both fresh and frozen embryo transfers. CONCLUSION: Fresh and frozen IVF-ET pregnancy outcomes were comparable after hMG versus low dose hCG supplementation, suggesting flexibility in supplemental LH dosing regimens that may address patient or physician preference or cost concerns.
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Complete and partial molar pregnancies arise from abnormal fertilization with marked proliferation of syncytiotrophoblasts. Earlier diagnosis has reduced the frequency of severe medical complications at presentation; however, the risk of progression to gestational trophoblastic neoplasia (GTN) has remained unchanged. Initial assessment should include serum hCG measurement after physical examination, laboratory testing for organ dysfunction, and Doppler ultrasound. Following uterine evacuation, pathologic assessment can distinguish complete from partial moles or non-molar gestations. Close surveillance is essential for the timely diagnosis of GTN. Cure rates and subsequent obstetrics outcomes are excellent, but all patients should be referred for psychologic support and expert level care.
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Background: Human chorionic gonadotropin (hCG) is a polypeptide hormone synthesized during pregnancy and is also upregulated in some pathologic conditions such as certain tumors. Its measurement is essential for diagnosing pregnancy and malignancies. Despite numerous attempts to introduce an accurate method capable of detecting hCG levels, several limitations are found in previous techniques. This study aimed to address the limitations of current hCG assay methods by designing an electrochemical biosensor based on voltammetry for the rapid, selective, inexpensive, and sensitive measurement of hCG levels. Methods: A carbon paste electrode was prepared and functionalized by para-aminobenzoic acid. The primary anti-ß-hCG monoclonal antibody was immobilized on the electrode surface by activating the carboxyl groups with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide solutions. The study also involved optimizing parameters such as the time for primary antibody fixation, the time for hCG attachment, and the pH of the hydrogen peroxide solution to maximize the biosensor response. Different concentrations of hCG hormone were prepared and loaded on the electrode surface, the secondary antibody labeled with HRP enzyme was applied, thionine in phosphate-buffered saline solution was placed on the electrode surface, and the differential pulse electrical signal was recorded. Results: The linear range ranged from 5 to 100 mIU/ml, and the limit of detection was calculated as 0.11 mIU. The relative standard deviation was 3% and 2% for five repeated measurements of commercial standard samples with concentrations of 2 and 20 mIU/mL, respectively. The percent recovery was obtained from 98.3% to 101.5%. Conclusion: The sensor represents a promising advancement in hCG level measurement, offering a potential solution to overcome the existing limitations in current diagnostic strategies. Simple and inexpensive design, detecting hCG in its important clinical range during early pregnancy, and successful measurement of hCG in real serum samples are the advantages of this sensor.
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BACKGROUND: Quantitative and qualitative human chorionic gonadotropin (hCG) tests are obtained in the emergency department (ED) to determine if a female of child-bearing age is pregnant. A positive hCG result is commonly assumed to indicate an intrauterine or other form of pregnancy. However, elevated hCG levels can also result from various other conditions, such as ovarian tumors, pituitary tumors, and thyroid disorders. Intracranial germ cell tumors, rare central nervous system tumors capable of secreting hCG, primarily affect adolescent and young adult females. CASE REPORT: A 16-year-old female student without significant past medical history presented to our ED with a complaint of intermittent bilateral frontal headache for two days. Last menstrual period started two days prior to presentation. The headache was associated with phonophobia, photophobia, nausea, and vomiting. Serum quantitative hCG was elevated. She denied history of sexual activity or sexual assault. Transabdominal ultrasound was negative for intrauterine pregnancy. Obstetrics and gynecology as well as pediatric oncology were consulted. Subsequent investigations, including brain imaging, revealed a 3.5 cm mass in the right caudate nucleus and corpus callosum. The patient was diagnosed with an intracranial nongerminomatous germ cell tumor, necessitating hospitalization and prompt initiation of chemotherapy. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: An elevated quantitative hCG is not always indicative of pregnancy, especially in a young patient without sexual history. In the case of a nonrevealing transabdominal ultrasound, obstetrics and gynecology should be consulted for discussion of further testing and imaging. Emergency physicians should include malignancy high on their differential since prompt initiation of chemotherapy, evaluation by surgical services, and family planning will be required.
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We studied the effect of a high-fat, high-carbohydrate diet (HFHCD) on basal testosterone levels in the blood and testosterone, its precursors, and expression of steroidogenic genes in the testes of rats treated with human chorionic gonadotropin (hCG, 10 IU/rat, subcutaneously, once), gonadotropin-releasing hormone receptor antagonist cetrorelix (75 µg/kg, subcutaneously, 3 days), and their combination. In HFHCD rats, no obvious signs of androgen deficiency were observed and the response of the testes to hCG stimulation was preserved. Unlike control rats (normal diet), the expression of the luteinizing hormone receptor gene in these rats did not change in response to hCG stimulation and cetrorelix administration; they also showed a paradoxical, more pronounced response to hCG administration under conditions of suppression of the gonadotropin secretion by cetrorelix. This suggests that the etiology and pathogenesis of obesity may have different effects on the hormonal status of the male reproductive system.
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Background and Objectives: Polycystic ovarian syndrome (PCOS) is a widespread endocrine disorder affecting 5-18% of females in their childbearing age. The aim of this study is to assess the efficacy of combining a low dosage of human chorionic gonadotropin (HCG) along with clomiphene citrate (CC) for stimulating ovulation in infertile women diagnosed with CC-resistant PCOS. Materials and Methods: A randomized controlled trial was carried out on 300 infertile CC-resistant PCOS women. All participants were assigned to two groups: the CC-HCG group and the CC-Placebo group. Subjects in the CC-HCG group were given CC (150 mg/day for 5 days starting on the 2nd day of the cycle) and HCG (200 IU/day SC starting on the 7th day of the cycle). Subjects in the CC-Placebo group were given CC and a placebo. The number of ovarian follicles > 18 mm, cycle cancellation rate, endometrial thickness, ovulation rate, clinical pregnancy rate, and occurrence of early ovarian hyper-stimulation syndrome were all outcome variables in the primary research. Results: Data from 138 individuals in the CC-HCG group and 131 participants in the CC-Placebo group were subjected to final analysis. In comparison to the CC-Placebo group, the cycle cancellation rate in the CC-HCG group was considerably lower. The CC-HCG group exhibited a substantial increase in ovarian follicles reaching > 18 mm, endometrial thickness, and ovulation rate. The clinical pregnancy rate was higher in the CC-HCG group (7.2% vs. 2.3%; CC-HCG vs. CC-Placebo). Upon adjusting for BMI and age, the findings of our study revealed that individuals in the CC-HCG group who had serum prolactin levels below 20 (ng/mL), secondary infertility, infertility duration less than 4 years, baseline LH/FSH ratios below 1.5, and serum AMH levels more than 4 (ng/mL) had a higher likelihood of achieving pregnancy. In the CC-Placebo group, there was a greater prediction of clinical pregnancy for those with serum AMH (<4), primary infertility, serum prolactin ≤ 20 (ng/mL), baseline LH/FSH < 1.5, and infertility duration < 4 years. Conclusions: The use of a small dose of HCG along with CC appeared to be an effective treatment in reducing cycle cancelation, improving the clinical pregnancy rate and ovulation rate in CC-resistant PCOS patients. The trial was registered with Clinical Trials.gov, identifier NCT02436226.
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Gonadotropina Coriónica , Clomifeno , Infertilidad Femenina , Inducción de la Ovulación , Síndrome del Ovario Poliquístico , Humanos , Femenino , Clomifeno/uso terapéutico , Clomifeno/administración & dosificación , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Síndrome del Ovario Poliquístico/complicaciones , Síndrome del Ovario Poliquístico/fisiopatología , Inducción de la Ovulación/métodos , Gonadotropina Coriónica/administración & dosificación , Gonadotropina Coriónica/uso terapéutico , Gonadotropina Coriónica/sangre , Adulto , Embarazo , Infertilidad Femenina/tratamiento farmacológico , Infertilidad Femenina/etiología , Fármacos para la Fertilidad Femenina/uso terapéutico , Fármacos para la Fertilidad Femenina/administración & dosificación , Índice de Embarazo , Resultado del TratamientoRESUMEN
Objective: This study aimed to investigate the effects of the presence of subchorionic hematoma (SH) in early pregnancies with threatened miscarriage (TM) on levels of first-trimester maternal serum markers, pregnancy-associated plasma protein-A (PAPP-A), and free ß-human chorionic gonadotropin (ß-hCG) levels. Methods: The data of TM cases with SH in the first trimester between 2015 and 2021 were evaluated retrospectively. The data of age and gestational age-matched TM cases without SH were also assessed to constitute a control group. Demographic characteristics, obstetric histories, ultrasonographic findings, and free ß-hCG and PAPP-A levels of the groups were compared. Results: There were 119 cases in the study group and 153 cases in the control group. The median vertical and longitudinal lengths of the SH were 31 mm and 16 mm. The median age of both groups was similar (p=0.422). The MoM value of PAPP-A was 0.088 (.93) in the study group and 0.9 (0.63) in the control group (p=0.519). Similarly, the MoM value of free ß-hCG was 1.04 (0.78) in the study group and 0.99 (0.86) in the control group (p=0.66). No significant relationship was found in the multivariate analysis between free ß-hCG MoM, PAPP-A MoM, age, gravida, and vertical and longitudinal lengths of the hematoma (p>0.05). Conclusion: The level of PAPP-A and free ß-hCG were not affected by the SH. Therefore, these markers can be used reliably in TM cases with SH for the first-trimester fetal aneuploidy screening test.