Search Results (162)

The hallmark feature of empty follicle syndrome (EFS) is failure to retrieve oocytes from apparently mature follicles despite adequate ovarian stimulation and appropriate ovulation triggering. Although considered uncommon, with a reported prevalence ranging from 0.2% to 7%, EFS may have a profound clinical and psychological impact and can recur in assisted reproductive technology (ART) cycles. Modern classification systems divide EFS into genuine and false forms. Genuine EFS is potentially associated with intrinsic abnormalities involving luteinizing hormone/choriogonadotropin receptor (LHCGR) signaling, oocyte competence, and cumulus–oocyte interaction, whereas false EFS is primarily attributed to pharmacokinetic or pharmacodynamic factors resulting in inadequate trigger exposure. Borderline EFS represents a third phenotype characterized by incomplete or partial impairment of final oocyte maturation. This review examines the pharmacodynamics of ovulation-triggering agents, including human chorionic gonadotropin (hCG), gonadotropin-releasing hormone (GnRH) agonist protocols, and dual-trigger strategies, and their roles in regulating final oocyte maturation. The molecular aspects of periovulatory signal transduction and the mechanisms of LHCGR activation, epidermal growth factor (EGF)-like pathways, and meiotic resumption in relation to EFS etiopathogenesis will be described. The impact of patient-dependent conditions like obesity, poor ovarian reserve, polycystic ovary syndrome (PCOS), and pituitary response on trigger response will be assessed. New approaches like post-trigger monitoring of hormones and rescue treatment with gonadotropins represent a valuable method for avoiding cycle cancellation in patients at risk. Overall, EFS is increasingly regarded not as a single disorder but as a heterogeneous spectrum of periovulatory dysfunction arising from pharmacological, endocrine, and intrinsic ovarian factors that impair completion of final oocyte maturation. Full article

Cholangiocarcinoma (CCA) in Northeast Thailand is characterized by late diagnosis and poor prognosis, creating a critical need for effective early-detection biomarkers. This study utilized a multi-omics approach to identify novel diagnostic targets and improve CCA screening. Initial serum proteomic and transcriptomic analyses revealed significant upregulation of the luteinizing hormone/choriogonadotropin receptor (LHCGR) in CCA patients, correlating with advanced disease stages. Interaction network analysis subsequently identified its circulating ligand, beta-human chorionic gonadotropin (β-hCG), as a highly translatable clinical target. The protein expression of β-hCG was assessed via immunohistochemistry (IHC) in 100 tissue samples, and serum levels of β-hCG, alongside routine markers (CA19-9, AFP, and CEA), were quantified in a cohort of 405 individuals, including 153 CCA patients. IHC confirmed significantly higher β-hCG expression in tumor tissues compared to adjacent areas (p < 0.0001). Serum β-hCG levels were significantly elevated in CCA patients and correlated with tumor volume and reduced overall survival. Diagnostically, a combined multiparameter panel (β-hCG, carbohydrate antigen 19-9, carcinoembryonic antigen, and alpha-fetoprotein) yielded excellent accuracy in distinguishing CCA from healthy controls (AUC: 0.962) and hepatocellular carcinoma cases (AUC: 0.890). However, discriminatory efficiency was notably lower when differentiating CCA from benign biliary diseases (AUC: 0.680) and liver metastases (AUC: 0.705). In conclusion, activation of the LHCGR signaling axis is a novel pathophysiological feature in CCA. When integrated into a multi-marker blood panel, circulating β-hCG serves as a valuable complementary risk-stratification and prognostic tool, though further optimization is required to overcome limited specificity in the presence of confounding liver pathologies before routine clinical implementation. Full article

Normogonadotropic azoospermia (NOAN) represents a diagnostic and therapeutic challenge in male infertility, affecting men with normal gonadotropin levels but absent sperm in the ejaculate. Emerging evidence has identified 17-hydroxyprogesterone (17OHP) as a potential biomarker for detecting reduced intratesticular testosterone (ITT) levels, and the presence of round spermatids in ejaculate as an indicator of residual spermatogenic activity. This report synthesizes current evidence on a proposed hypothesis-generating diagnostic framework that utilizes these markers to guide hormonal treatment strategies. Specifically, patients with elevated 17OHP levels (>1.18 ng/mL) and detectable round spermatids may benefit from combined human chorionic gonadotropin (hCG) and follicle-stimulating hormone (FSH) therapy at doses lower than those used for hypogonadotropic hypogonadism. However, this cutoff has not been prospectively validated in NOAN-specific cohorts, and the evidence supporting this approach remains preliminary, derived from small heterogeneous cohorts. Alternative therapeutic strategies, including FSH monotherapy and non-hormonal pharmacological treatments, are also discussed. This framework requires rigorous prospective validation before clinical implementation. Full article

Human follicular development depends on coordinated communication between granulosa cells (GCs) and oocytes through endocrine cues, direct contacts, and extracellular vesicles (EVs). Exosomes are key EV mediators of intrafollicular signaling, but their cargo and functions in gonadotropin-stimulated GCs remain poorly defined. The human granulosa-like tumor cell line KGN was used to investigate exosome secretion and protein composition following human chorionic gonadotropin (hCG) stimulation. Exosomes were isolated by ultracentrifugation, characterized via nanoparticle tracking analysis (NTA), Scanning Electron Microscopy (SEM) and Western blotting, and analyzed using high-resolution mass spectrometry. Comparative proteomics integrating exosomal profiles with the whole secretome were performed, followed by bioinformatic analyses of protein networks, gene ontology, and pathway enrichment. hCG reshaped exosomal cargo, identifying 59 proteins enriched in exosomes, including Integrin α3 (ITGα3), Galectin-3-binding protein (LGALS3BP), tetraspanins (CD63, CD151), and proteasome subunits. Functional enrichment indicated roles in extracellular matrix remodeling, integrin signaling, proteostasis, and steroidogenesis. Comparison with the secretome revealed distinct protein distributions, supporting selective exosomal packaging. Western blot confirmed increased ITGα3 and LGALS3BP levels in exosomes upon hCG treatment. In conclusion, hCG modulates exosome cargo composition in granulosa cells, uncovering a novel mechanism of extracellular regulation. Full article

Successful embryo implantation requires dynamic, bidirectional communication between a developmentally competent blastocyst and a receptive endometrium, integrating hormonal, molecular, and immunologic signals. Increasing evidence indicates that endometrial receptivity is critically dependent on a specialized immune microenvironment that supports trophoblast invasion while maintaining maternal tolerance. This review synthesizes current knowledge on the immunologic regulation of implantation, with emphasis on uterine natural killer (uNK) cells, regulatory T cells (Tregs), macrophages, dendritic cells, and cytokine networks. We further examine intracellular signaling pathways—including JAK/STAT, PI3K/AKT, NF-κB, and MAPK—that integrate immune and decidual responses. The bidirectional embryo–endometrium dialogue is explored through embryo-derived mediators such as human chorionic gonadotropin (hCG), cytokines, growth factors, and extracellular vesicles. The endometrium is increasingly recognized as a biosensor of embryo quality, selectively supporting viable embryos. Disruption of this complex communication network is implicated in recurrent implantation failure and early pregnancy loss. Despite substantial mechanistic advances, clinical translation remains limited. Emerging strategies, including immune profiling, microbiome modulation, and extracellular vesicle-based diagnostics, hold promise for precision reproductive medicine. Full article

Endometrial carcinoma (EC) with choriocarcinomatous differentiation is an exceptionally rare malignancy for which standardized postoperative treatment strategies are lacking. Herein, we describe two postmenopausal patients with endometrioid carcinoma containing a choriocarcinomatous component. One patient had an EC-dominant tumor with low and rapidly normalized postoperative serum human chorionic gonadotropin (hCG) levels and received paclitaxel plus carboplatin. The other patient had a choriocarcinomatous-dominant tumor with markedly elevated postoperative serum hCG levels and was treated with gestational trophoblastic neoplasia (GTN)-oriented chemotherapy using etoposide, methotrexate, actinomycin D/cyclophosphamide, and vincristine (EMA/CO). Both patients remain disease-free. A review of representative published cases revealed two competing treatment paradigms, EC-oriented and GTN-oriented, applied inconsistently and without unified selection criteria. On the basis of integrated clinicopathological assessment, we propose that postoperative treatment consideration should be guided primarily by dominant tumor biology, rather than the International Federation of Gynecology and Obstetrics stage alone. Tumors with a dominant choriocarcinomatous component accompanied by elevated postoperative serum hCG levels may benefit from GTN-oriented chemotherapy, whereas EC-dominant tumors with low or normalized hCG levels may benefit from EC-oriented regimens. Reassessment of dominant tumor biology using postoperative pathological findings and serum hCG dynamics may provide a pragmatic, decision-support framework for adjuvant treatment consideration in this rare and clinically challenging entity. Full article

The African catfish (Clarias gariepinus) is an important aquaculture species in the Philippines, but it exhibits reproductive dysfunctions in captivity due to the absence of natural spawning cues and culture-induced stress. In hatcheries, sperm collection often requires sacrificing male breeders, limiting breeding program applications, and threatening genetic diversity. This study evaluated and optimized hormonal induction protocols to enhance spermiation and fertilization success in male C. gariepinus. Two experimental trials were conducted under controlled hatchery conditions. In Trial 1, human chorionic gonadotropin combined with a dopamine antagonist (hCG + DA; 5000 IU·kg⁻¹ BW + 5 mg·kg⁻¹ BW) and Ovaprim (1.0 mL·kg⁻¹ BW) significantly increased circulating testosterone and estradiol levels, spermiation index, and fertilization outcomes (embryo viability, hatching, and larval survival). In Trial 2, medium to low doses of hCG + DA (3000–5000 IU·kg⁻¹ BW + 5 mg·kg⁻¹ BW) and Ovaprim (0.75–1.0 mL·kg⁻¹ BW) yielded the best performance in terms of hormone levels, spermiation index, and fertilizing capabilities. The presence of a dopamine antagonist (DA) likely contributed to the efficacy of the treatments, since dopamine suppresses the secretion of gonadotropin-releasing hormone (dopaminergic inhibition), and DA counteracts this effect, increasing LH and FSH levels necessary for gametogenesis. Taken together, these results highlight the potential of optimized hormonal protocols to mitigate reproductive dysfunctions in male C. gariepinus in aquaculture settings. Further studies should refine dose combinations, assess the long-term health of broodstock, and evaluate cost-effectiveness to support sustainable broodstock management and genetic conservation. Full article

Polycystic ovary syndrome (PCOS) is associated with impaired ovarian steroidogenesis and ovulation, which necessitates the development of effective ovulation inducers for PCOS. The aim of the study was to evaluate the effects of allosteric luteinizing hormone receptor agonist TP03 and human chorionic gonadotropin (hCG) on ovarian steroidogenesis, as well as ovulation in prepubertal female rats with dehydroepiandrosterone(DHEA)-induced PCOS. Taking into account differences in progesterone levels, cohorts with high (PCOS(H)) and low (PCOS(L)) progesterone were formed and treated with Follimag and Cetrotide. After 48 h, TP03 (25 mg/kg) or hCG (25 IU/rat) were injected, and hormone levels, gene expression, and ovarian morphology were assessed. The PCOS(H)-cohort exhibited irregular estrous cycles, ovarian cysts, and increased ovarian mass and estradiol levels, but the number of corpora lutea (CL) was maintained. In the PCOS(L)-cohort, ovarian weight was increased, and Star, Cyp11a1, and Adamts1 gene expression as well as the CL number were decreased. In both cohorts, TP03 and hCG increased progesterone levels and the expression of steroidogenesis (Star, Cyp11a1) and ovulation (Cox2, Adamts1, Egr1) genes, as well as inducing CL formation. Thus, TP03, like hCG, stimulates steroidogenesis and ovulation in PCOS-rats with different progesterone levels, which provides the first evidence of the effectiveness of allosteric LHR agonists as ovulation triggers in PCOS. Full article

The microstructure and ultrastructure of the sperm of Japanese eel, Anguilla japonica, artificially induced with weekly injections with carp pituitary (CP) and human chorionic gonadotropin (HCG), was studied, and milt from 10 out of 20 mature fish was collected. Two distinct morphological structures of A. japonica sperm had been observed with optical microscopy. The cell nucleus of one type of sperm was round or nearly round, the sperm was smaller in size, with 2.57 ± 0.62 μm of the long diameter of the cell nucleus, 2.11 ± 0.59 μm of the short diameter, and 37.35 ± 7.71 μm of the flagellum length. Another type was the eyebrow-shaped sperm, the sperm was relatively larger in size, with 7.66 ± 1.09 μm of the long axis, 2.54 ± 0.46 μm of the short axis, and 38.26 ± 9.02 μm of the flagellum length. By means of scanning electron microscopy (SEM) and transmission electron microscopy (TEM), the anterior end of the round sperm lacked an acrosomal structure. The implantation fossa was located in the center of the base of the sperm head, and it was in the shape of a channel along the long axis of sperm. The centriolar complex was situated within the implantation fossa. There were 2–3 mitochondria distributed at the basal end of the nucleus. Sperm flagellum prolongated from the sleeve cavity, and the initial part of axoneme connected to the distal end of basal body. The axoneme displayed a typical “9 + 2” pattern. There was a spherical structure in the curving area for eyebrow-shaped sperm, and the axoneme formed a “9 + 0” pattern. The discovery of two different types of sperm in the Japanese eel has provided new perspectives for research on its artificial reproduction. Full article

Background/Objectives: Sufficient preconception vitamin D may promote robust implantation and higher human chorionic gonadotropin (hCG) levels, potentially increasing nausea and vomiting in pregnancy. We assessed associations between maternal serum 25-hydroxyvitamin D (25(OH)D) at both preconception and 8 weeks’ gestation with nausea and vomiting during early pregnancy. We hypothesized that women with sufficient vitamin D status or those who improved their levels in early gestation, would have higher odds of nausea and vomiting compared to women who were deficient or insufficient. Methods: This secondary analysis of the randomized EAGeR Trial included women with 1–2 prior pregnancy losses and 25(OH)D measured at preconception (n = 774) and 8 weeks’ gestation (N = 641). Nausea and vomiting were captured via medical records and daily symptom diaries. 25(OH)D was categorized as deficient (≤20 ng/mL), insufficient (21–29 ng/mL), or sufficient (≥30 ng/mL). Logistic regression and generalized estimating equations (GEE) estimated associations. Results: Women who improved from deficient/insufficient preconception to sufficient by 8 weeks had higher odds of nausea and vomiting in early pregnancy compared to those remaining sufficient (aOR: 1.71; 95% CI: 1.12, 2.61). Conversely, those remaining deficient/insufficient (aOR: 0.34; 95% CI: 0.20, 0.60) or declining to deficiency (aOR: 0.44; 95% CI: 0.22, 0.87) had lower odds. In longitudinal models, deficiency was associated with lower odds of daily vomiting (aOR: 0.54; 95% CI: 0.28, 1.04), though estimates were imprecise. Conclusion: Dynamic changes in vitamin D status from preconception to early pregnancy appear to be associated with nausea and vomiting in early pregnancy. Improvement of sufficiency increased emesis odds, while persistent deficiency correlated with fewer symptoms. These findings suggest vitamin D may be associated with nausea and vomiting through hormonal or placental signaling mechanisms in early gestation. Full article

Background/Objectives: Hypogonadotropic hypogonadism (HH) is an uncommon but treatable cause of non-obstructive azoospermia (NOA). Fertility can often be restored with gonadotropin therapy. This study evaluated spermatogenic and reproductive outcomes in men with HH-related NOA managed by stepwise gonadotropin therapy, microdissection testicular sperm extraction (microTESE) for persistent azoospermia, and assisted reproduction when indicated. Methods: A retrospective cohort study included 35 men treated between 2010 and 2022. Human chorionic gonadotropin (hCG), with or without follicle-stimulating hormone (FSH), was administered to induce spermatogenesis. Outcomes included sperm appearance in the ejaculate, microTESE sperm retrieval rate in persistent azoospermia, and pregnancy and live birth outcomes after natural conception or in vitro fertilization with intracytoplasmic sperm injection (IVF-ICSI) when required. Results: Mean gonadotropin therapy duration was 12.0 months (range 6–24). Sperm appeared in the ejaculate in 27/35 men (77%). The remaining 8/35 (23%) underwent microTESE, with sperm retrieved in 7/8 (88%). Seven couples proceeded to IVF-ICSI, undergoing 11 cycles that yielded 6 clinical pregnancies (55% per cycle) and 5 live birth deliveries, including 2 twin pregnancies. Among responders, 13 natural pregnancies occurred, resulting in 13 live birth deliveries, including 2 twin pregnancies. Overall, 18/35 men (51%) achieved biological fatherhood, corresponding to 18 live birth delivery events (4 twin and 14 singleton deliveries) and 22 newborns. Conclusions: In men with HH-related NOA, exogenous gonadotropin therapy is expected to induce spermatogenesis in most patients. MicroTESE provides high sperm retrieval rates for those without ejaculatory sperm. Through an integrated approach of hormonal induction, microsurgical sperm retrieval, and assisted reproduction, approximately half of patients may ultimately achieve biological fatherhood in longer-term follow-up, depending on baseline severity and partner factors. Full article

Background: Following gonadotropin-releasing hormone (GnRH) agonist trigger and “freeze all” in order to prevent ovarian hyper-stimulation syndrome (OHSS), patients are usually anxious to continue immediately with a frozen embryo transfer (FET). Currently, the preferred FET protocol in based on natural or induced ovulation. Objectives: Do ovarian stimulation and GnRH-a, used to trigger final oocyte maturation, affect the reproductive axis in the next natural cycle? Design: An observational case series of 100 subsequent in vitro fertilization (IVF) patients to whom GnRH-a (Triptorelin 0.2 mg) was given for final oocyte maturation in the context of ovarian hyper-stimulation syndrome prevention, followed by embryos “freeze all”. Methods: In the next natural cycle, patients were followed to detect a dominant follicle (≥17 mm), at which time ovulation was triggered with human chorionic gonadotropin (hCG, 250 µg), and FET was scheduled according to embryo’s age on freezing day. Results: Whereas natural ovulation according to pre-IVF treatment was predicted to be on cycle day 14, the actual hCG-scheduled ovulation in our patients was on day 21. In eight patients, follicular activity was not detected after 15–28 days; therefore, the natural cycle frozen embryo transfer approach was abandoned. Conclusions: Ovarian stimulation and GnRH-a used to trigger final oocyte maturation in IVF patients inhibits the reproductive axis for days. Therefore, natural ovulation in the subsequent cycle may be deferred for about one week relative to the patient’s pre-IVF menstrual cycle pattern. This may help schedule clinic visits to optimize monitoring efficiency. Full article

Effective luteal support is crucial for successful pregnancy following embryo transfer in dromedary camels, highlighting the importance of maintaining adequate luteal function. This study compared three luteal support protocols for pregnancy rates after embryo transfer (ET) in dromedary camels. Recipients with a single ovarian follicle (14~16 mm) were assigned into: (1) untreated control, (2) Phenylbutazone (PBZ) at 3.7 mg/kg IV prior to ET, or (3) human chorionic gonadotropin (hCG) 2000 IU plus 3.7 mg/kg IV PBZ prior to ET. Recipients that showed ovarian inactivity were treated with an injection of 1800 IU of equine chorionic gonadotropin (eCG) after progesterone (P₄) priming. Pregnancy was assessed on days 10 (P₄ assay) and 60 (transrectal ultrasonography) post-ET. Pregnancy rates on day 10 were higher in the hCG + PBZ (73.3%) and eCG (68.0%) groups than in the PBZ (44.0%) and control (35.0%) groups (p < 0.05). By day 60, the hCG + PBZ group exhibited the highest pregnancy maintenance rate (81.8%) and the lowest embryonic loss rate (18.2%), compared with eCG (53.0%; 47.0%), PBZ (54.5%; 45.5%), and control (57.1%; 42.9%) groups, respectively (p < 0.05). However, there was no significant difference among the eCG, PBZ, and control groups in embryonic loss rates. In conclusion, hCG synergizes with PBZ to enhance corpus luteum function, uterine receptivity, and pregnancy maintenance more effectively than PBZ or eCG. Full article

Background/Objectives: Ectopic pregnancy (EP) remains a major cause of maternal morbidity. This study aimed to describe the clinical, ultrasonographic and histopathological features of EP, including changes following methotrexate (MTX) therapy. Methods: A retrospective analysis was conducted on 60 patients diagnosed with EP between 2018 and 2024. Clinical characteristics, serum β-hCG (beta-human chorionic gonadotropin) dynamics, treatment type, site-specific ultrasonographic features, and histopathological aspects were evaluated. Results: Extrauterine EPs accounted for 63.3% of cases, predominantly tubal ectopic pregnancy (T-EP), while uterine ectopic pregnancy represented 33.3%, including cesarean scar pregnancy (CSP) in 20%. Heterotopic pregnancy was identified in 3.3%. T-EP most frequently required surgical management, whereas MTX was effective in selected T-EP and CSP cases, as demonstrated by a ≥ 15% decline in serum β-hCG levels at 7 days. Transvaginal ultrasonography (TVUS) enabled accurate site-specific localization of ectopic implantation. Histopathological evaluation confirmed ectopic implantation and MTX-related changes in treated cases. Conclusions: Integrating clinical findings, β-hCG dynamics, and targeted TVUS allows accurate diagnosis and individualized management of EP, with histopathology providing definitive confirmation and insight into treatment-related changes. Full article

A limited period of endometrial receptivity is defined by molecular interactions between the embryo and maternal tissues, which are crucial for successful implantation. The results of clinical studies assessing intrauterine human chorionic gonadotropin (hCG) as an endometrial priming agent in in vitro fertilisation (IVF) have been inconsistent, markedly affected by dose, timing, and cycle context. This narrative review summarises molecular data demonstrating that hCG modulates immunological, stromal, endothelial, and epithelial compartments in a coordinated manner, affecting essential endometrial processes. hCG promotes adhesion competence and proliferation in the epithelium via a microRNA-regulated signalling axis (miR-126-3p–PIK3R2–PI3K/Akt). Intrauterine hCG promotes controlled apposition and invasion at the vascular interface by selectively strengthening endothelial junctional cohesion via VE-cadherin and CD146, without promoting angiogenesis. hCG collaborates with ERK/mTOR signalling to regulate autophagy and apoptosis, alters steroid–receptor networks in the stroma, initiates early decidual and survival markers (ACTA2, NOTCH1, complement C3), and enhances stress resistance. hCG modifies the immunological milieu by enhancing the activity of regulatory T cells and altering the distribution of uterine natural killer cells. This facilitates immunological tolerance and the remodelling of spiral arteries. These pleiotropic effects together enhance biomarkers and provide a scientific justification for context-dependent clinical responses, including patient-chosen, directed methods for the delivery of intrauterine hCG during IVF. Full article