Search Results (474)

Objectives: This retrospective single-center cohort study aims to evaluate the impact of dual-trigger therapy (recombinant hCG [rhCG] combined with GnRH agonist) compared to rhCG alone on ART outcomes in women undergoing GnRH antagonist protocols. Methods: Data from 1291 IVF cycles performed between 2016 and 2022 were analyzed. After propensity score matching (PSM) to adjust for confounders, 395 cycles in each group were compared. Primary outcomes included the total number of oocytes retrieved, while secondary outcomes assessed mature oocytes, fertilization rates, and embryo numbers. Results: Dual-trigger therapy yielded significantly more total oocytes (7.50 ± 5.23 vs. 6.12 ± 4.23, p < 0.001) and mature oocytes (5.67 ± 3.87 vs. 5.01 ± 3.13, p = 0.047) compared to rhCG alone. Cycles with no oocytes were fewer in the dual-trigger group (1.3% vs. 3.8%, p = 0.015). Total embryos were also higher with dual trigger therapy (2.43 ± 1.90 vs. 2.00 ± 1.93, p = 0.001). In intracytoplasmic sperm injection (ICSI) cycles, the fertilization rate significantly improved with dual trigger (64.93 ± 33.50% vs. 52.22 ± 34.12%, p = 0.003). No significant differences were noted in fertilization rates for standard IVF (55.14 ± 30.72% vs. 52.29 ± 32.11%, p = 0.18) or maturation rates (72.52 ± 26.91% vs. 71.53 ± 24.75%, p = 0.37). Conclusions: These findings demonstrate that dual-trigger therapy improves ART outcomes by increasing oocyte and embryo yields. Full article

To investigate the impacts of dietary Bacillus-based probiotics and yeast-derived prebiotics on the hepatic transcriptome profile, 500 Hisex White laying hens were randomly allotted into five dietary treatments from 37 to 52 weeks of age: control; control + Bacillus subtilis; control + Bacillus subtilis and Bacillus licheniformis; control + Bacillus coagulans; and control + Saccharomyces cerevisiae yeast cell wall. Transcriptome analysis revealed a substantial number of differentially expressed genes exclusively between the control and prebiotic groups, identifying 2221 genes (FDR ≤ 0.05), with 980 genes upregulated (log₂ fold change 0.69 to 24.62) and 1241 downregulated (log₂ fold change −0.74 to −26.46). The top 10 upregulated KEGG pathways included protein export, glycerophospholipid metabolism, tryptophan metabolism, amino acid biosynthesis, alanine, aspartate, and glutamate metabolism, cofactor biosynthesis, propanoate metabolism, ABC transporters, 2-oxocarboxylic acid metabolism, and protein processing within the endoplasmic reticulum. In contrast, the most prominently downregulated pathways encompassed fructose and mannose metabolism, hedgehog signaling, PPAR signaling, Notch signaling, GnRH signaling, cell adhesion molecules, cytokine–cytokine receptor interactions, apelin signaling, glycosaminoglycan degradation, and RIG-I-like receptor signaling. These findings advance understanding of the hepatic transcriptomic response to yeast-derived prebiotics and identify key molecular pathways that could be targeted to enhance metabolic function in laying hens. Full article

Saline–alkaline water resources are globally widespread, and their rational development offers significant potential to alleviate freshwater scarcity. Saline–alkaline water aquaculture farming not only affects fish growth and survival but also impairs reproductive and developmental functions. Largemouth bass (Micropterus salmoides), an economically important fish, has demonstrated excellent high tolerance to such environments, in order to investigate the effects of alkaline water aquaculture environments on its growth performance, sex hormone levels, gonadal development, and molecular adaptation mechanisms. In this study, largemouth bass were chronically exposed to freshwater (0.55 mmol/L), low alkalinity (10 mmol/L), or high alkalinity (25 mmol/L) and cultured for 80 days. Alkalinity exposure more severely impacted the growth rate of females. High alkalinity significantly increased the hepatosomatic index and decreased the gonadosomatic index in both sexes; moreover, it induced oxidative stress in both sexes, evidenced by reduced superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (TAOC) levels and elevated malondialdehyde (MDA) content. Furthermore, the levels of sex hormones Serum estradiol (E2), 11-ketotestosterone (11-KT), and testosterone were significantly reduced, accompanied by either an elevated ratio of primary oocytes and follicular atresia, or by reduced spermatogenesis. Apoptotic signals appeared in gonadal interstitial cells, with upregulated expression of genes P53, Bax, Casp3, and Casp8. Ultrastructural damage included fewer mitochondria and cristae blurring, further indicating tissue damage causing dysfunction. Transcriptome results showed that oxidative stress damage and energy metabolism imbalance caused by carbonate alkalinity were key to the delayed gonadal development, which was mainly manifested in enrichment of the ECM–receptor interaction and PI3K-Akt signaling pathways in females exposed to low alkalinity, and the GnRH secretion and chemokine signaling pathways in males. Glycosphingolipid biosynthesis and Ferroptosis pathway were enriched in females exposed to high alkalinity, and the Cortisol synthesis and secretion pathway were enriched in males. Overall, high-alkalinity exposure significantly delayed gonadal development in both sexes of largemouth bass, leading to reproductive impairment. Full article

Objectives: Gonadotropin-releasing hormone (GnRH) antagonist protocols are preferred in polycystic ovary syndrome (PCOS) patients undergoing in vitro fertilization (IVF) as they provide the best combination of flexibility, acceptable outcomes, and safety. Numerous studies have compared outcomes between GnRH agonist long protocol and standard flexible antagonist protocol. However, there are scant studies investigating the effectiveness of antagonist administration from day 1 of ovarian stimulation in PCOS patients. Methods: We performed a retrospective cohort study to compare laboratory and clinical outcomes in IVF between standard flexible day 5/day 6 versus day 1 GnRH antagonist protocol in PCOS patients. Results: Our data indicates significantly superior oocyte yield and top-quality embryo proportion in patients with antagonists from day 1. Cumulative clinical pregnancy rates also tended to be superior in this group. Conclusions: Our findings indicate that administration of GnRH antagonists from day 1 of stimulation in PCOS patients undergoing IVF may lead to superior results. Full article

Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder characterized by a clinical and/or biochemical hyperandrogenism. In addition, PCOS is also associated with the presence of ovarian cysts, anovulation, and menstrual abnormalities such as oligomenorrhea or amenorrhea. The aetiology of the syndrome is multifactorial and heterogeneous due to the interaction of genetic, hormonal, metabolic, and environmental factors, as well as the different phenotypes and responses to treatments exhibited by the patients. Considering this complex interaction, it is essential to continue with the research focused on the mechanisms involved in the development and maintenance of the pathology. The alteration in the pulsatile secretion of the gonadotropin-releasing hormone (GnRH) is considered to be one of the main causes that contributes to its onset. In this review, we discuss recent evidence about the role of the rostral periventricular area of the third ventricle (RP3V), the arcuate nucleus (ARC), and the ventromedial nucleus of the hypothalamus (VMH), key hypothalamic regions that regulate GnRH secretion, in the development of PCOS. In addition, we analyse the clinical, metabolic, and endocrine factors that interact in the patients with PCOS, offering a multifactorial perspective to improve our understanding of this disorder. Full article

Orthotopic transplantation of ovarian tissue at one day of age is a promising solution for preserving female genetic material in avian species; using sterile recipients can ensure that all offspring are donor-derived. This study focuses on the suitability of the Mulard duck as a sterile recipient for Pekin duck donors and provides an investigation of the hormonal background. Firstly, native Pekin ovarian tissue was grafted into Mulard duck recipients, resulting in a 40% adhesion rate and follicular development in 50% of the adhered grafts. Secondly, the transplantation of cryopreserved ovarian tissue resulted in a 66% adhesion rate, with 33% of the adhered grafts showing follicular development. Ovulation occurred in 16% of the recipients with adhered grafts, but the eggs did not move into the oviduct. Estrogen levels were elevated in the recipients with adherence but were lower than in the control Pekin group, while progesterone levels remained unchanged. Consequently, recipients received buserelin acetate, a GnRH analogue, to stimulate follicular and oviductal activity. In this group, graft adhesion occurred in 31% of animals, and primordial follicle development in 25%. The hormonal levels of the recipients with adhered ovaries were elevated, but the GnRH analogue treatment did not affect the ovulation process. We conclude that while the Mulard duck shows potential as a sterile recipient in ovarian transplantation, several questions remain unanswered regarding the adequacy of follicular maturation and ovulation. Full article

Background/Objectives: GnRH agonists may offer potential benefits when used for luteal phase support in assisted reproductive treatments. This systematic review and meta-analysis of randomized controlled trials evaluates the effect of a single-dose administration of gonadotropin-releasing hormone (GnRH) agonist on the day of frozen-thawed embryo transfer (FET) in artificial cycles, in terms of reproductive outcomes. Methods: A comprehensive literature search was performed using the PubMed and Cochrane databases to identify relevant studies. The outcomes assessed were live birth rate, clinical pregnancy rate, positive pregnancy test, implantation rate, and miscarriage rate. Three randomized controlled trials were included in the analysis. Results: The clinical pregnancy rate (56.5% vs. 47.4%; OR 1.27; 95% CI: 1.01–1.60; p = 0.0426) and live birth rate (34.3% vs. 23.9%; OR 1.71; 95% CI: 1.00–2.91; p = 0.0483) were significantly higher in the treatment group compared to the control group. No statistically significant differences were observed between the groups in terms of positive pregnancy test, implantation rate, or miscarriage rate, although the analysis revealed a trend toward improved outcomes in the intervention group. Conclusions: In summary, although our meta-analysis indicates that a single dose of GnRH agonist in artificial FET cycles may be associated with improved clinical pregnancy and live birth rates, these findings are based on a limited number of available trials. Larger, well-designed randomized controlled trials are urgently needed before any changes to clinical recommendations can be justified. Full article

The activation mechanism of the reproductive axis in Kazakh ewes during the non-breeding season was explored by supplementation with glycerol complex (7% glycerol + tyrosine + vitamin B9). The experiment divided 50 ewes into five groups (n = 10). After 90 days of intervention, it was found that significant changes in serum DL-carnitine, N-methyl-lysine and other differential metabolites were observed in the GLY-Tyr-B9 group (p < 0.05, “p < 0.05” means significant difference, “p < 0.01” means “highly significant difference”). The bile acid metabolic pathway was specifically activated (p < 0.01). The group had a 50% estrus rate, ovaries contained 3–5 immature follicles, and HE staining showed intact granulosa cell structure. Serum E2/P4 fluctuated cyclically (p < 0.01), FSH/LH pulse frequency increased (p < 0.01), peak Glu/INS appeared on day 60 (p < 0.05), and LEP was negatively correlated with body fat percentage (p < 0.01). Molecular mechanisms revealed: upregulation of hypothalamic kiss-1/GPR54 expression (p < 0.01) drove GnRH pulses; ovarian CYP11A1/LHR/VEGF synergistically promoted follicular development (p < 0.05); the HSL of subcutaneous fat was significantly increased (p < 0.05), suggesting involvement of lipolytic supply. Glycerol activates the reproductive axis through a dual pathway—L-carnitine-mediated elevation of mitochondrial β-oxidation efficacy synergizes with kisspeptin/GPR54 signalling enhancement to re-establish HPO axis rhythms. This study reveals the central role of metabolic reprogramming in regulating seasonal reproduction in ruminants. Full article

Background/Objectives: Mitotane is a key component in the treatment of adrenocortical carcinoma (ACC), but its endocrine side effects in children remain under-characterized. Methods: We conducted a retrospective analysis of 11 pediatric patients (6 males, 5 females) diagnosed with ACC and followed between 2000 and 2025. Seven received mitotane therapy. Data included age at diagnosis, treatment duration and dosage, serum mitotane levels, and endocrine complications. Results: The mean age at diagnosis was 6.6 ± 1.45 years, with a mean follow-up of 10.05 ± 2.45 years. Patients received mitotane for an average of 2.5 ± 0.54 years, with a mean daily dose of 2805.5 ± 145.82 mg and a mean serum level of 16.1 ± 5.92 mg/mL. All mitotane-treated patients developed adrenal insufficiency, requiring supraphysiological hydrocortisone replacement. Four also required mineralocorticoid therapy. Five developed precocious puberty; two males presented with prepubertal gynecomastia; three females were managed with GnRH analogs or aromatase inhibitors followed by estrogen receptor antagonists. Four patients developed central hypothyroidism, treated with levothyroxine. A positive correlation was found between mean serum mitotane levels and the onset of precocious puberty (p = 0.04), while mitotane levels correlated negatively with the development of central hypothyroidism (p = 0.001). Conclusions: Mitotane therapy in pediatric ACC is strongly associated with significant endocrine dysfunction. These findings emphasize the need for proactive, multidisciplinary endocrine management throughout treatment. Full article

Background/Objectives: Androgen deprivation therapy (ADT) is the mainstay of prostate cancer treatment, especially in advanced disease. In particular, the gonadotropin-releasing hormone agonists (aGnRH) reduce the production of gonadotropin and, therefore, of testosterone. In about 10% of patients, the non-pulsatile stimulation of GnRH receptor initially causes a surge in LH and testosterone, defined as the “flare-up phenomenon”, leading to increased bone pain, spinal cord compression, bladder outlet obstruction and cardiovascular issues. To mitigate this effect, combining a first-generation antiandrogen agent (FGA) with aGnRH is recommended. However, second-generation anti-androgens, such as apalutamide, bind selectively and irreversibly to the androgen receptor (AR), exhibiting a more efficient inhibition of the AR pathway. Methods: This is a descriptive retrospective study of 27 patients (pts) with mHSPC, treated at a single center (“Santa Maria delle Grazie” Hospital in Pozzuoli, ASL Napoli 2 Nord, Italy) between June 2022 and April 2024. Patients received apalutamide monotherapy for 14 days followed by continuous combination with aGnRH plus apalutamide. Serum PSA and testosterone levels were measured at baseline, at day 14 (after 13 days of apalutamide monotherapy), at day 28 (after an additional 15 days of apalutamide plus a aGnRH), and at day 60. Results: PSA levels decreased from a mean of 45.2 (±63.1) ng/mL at baseline to a mean of 12.6 (±23.4) ng/mL at day 14 and to 3.3 ng/mL (±6.0) at day 28 of treatment. After 14 days of apalutamide monotherapy, 21 patients (77.8%) achieved a >50% PSA reduction and 4 (14.8%) a >90% PSA reduction. The number of patients with undetectable PSA was one (3.7%) at day 14, two (7.4%) at day 28, and nine (33.3%) at day 60. The mean serum testosterone levels were 6.56 (±4.46) ng/mL at baseline, 6.58 (±4.42) ng/mL at day 14, and 2.40 (± 3.38) ng/mL at day 28. No significant difference in PSA and testosterone level reduction during treatment emerged between subgroups of patients with low- vs. high-volume disease. Conclusions: Apalutamide alone is a viable option for mitigating the flare-up phenomenon, avoiding first generation anti-androgen therapy, and it can achieve rapid and deep biochemical control. Full article

Objective: This retrospective observational study evaluated the efficacy and safety of an ovarian stimulation protocol for embryo banking that involves continuous administration of clomiphene citrate (CC) in combination with gonadotropins, without the use of GnRH antagonists. Methods: Conducted at the Serum IVF Clinic in Athens, Greece, the study included 250 women aged 25–45 who underwent IVF for embryo banking. The protocol involved administering 150 mg of CC daily from day 2 of the menstrual cycle until the day before hCG trigger, alongside 150 IU/day of Meriofert. Outcomes assessed included oocyte yield, fertilization rates, incidence of ovarian hyperstimulation syndrome (OHSS), and hormonal correlations. Comparative and regression analyses explored differences between age groups and predictors of success. Results: The protocol demonstrated a favorable safety profile with no cases of OHSS and yielded a mean of 10.25 oocytes per patient. Group analysis showed significantly more oocytes retrieved in women under 40 (mean: 12.5) versus those over 40 (mean: 8.43), while fertilization rates were paradoxically higher in the older cohort (59.16% vs. 30.68%, p < 0.0001). Regression models revealed basal FSH to be a significant inverse predictor of oocyte yield, but it was positively associated with fertilization rate. Continuous CC use effectively suppressed premature LH surges without compromising oocyte or embryo quality, allowing flexible and cost-effective stimulation with minimal monitoring. Conclusions: Continuous administration of clomiphene citrate in combination with gonadotropins presents a promising, antagonist-free ovarian stimulation protocol for embryo banking. The approach is economically efficient, reduces monitoring requirements, and maintains safety and effectiveness and is particularly notable in women over 40. Further studies are warranted to validate these findings and refine protocol mechanisms. Full article

Background: Uterine fibroids (UFs) and endometriosis are gynecological conditions that significantly increase morbidity among women of reproductive age. Relugolix, a novel gonadotropin-releasing hormone receptor antagonist, is approved in combined therapy for the management of symptoms related to these disorders. However, its potential impact on bone mineral density (BMD) and osteoporosis risk should be considered when using a gonadotropin-releasing hormone (GnRH) antagonist. This systematic review aims to evaluate the effects of daily relugolix intake in monotherapy and combination therapy on BMD, ensuring safe long-term management. Methods: A systematic literature review was conducted following PRISMA 2020 guidelines. Searches were performed in PubMed, Medline, and the Cochrane Library. Relevant clinical guidelines from international societies were also reviewed. Studies assessing the impact of relugolix on BMD were selected, and data on treatment efficacy, adverse effects, and bone health outcomes were synthesized. Results: Relugolix monotherapy has been associated with significant BMD loss due to its potent estrogen-suppressing effect. To mitigate this, combination therapy with estradiol and norethisterone acetate has been developed. Although initial monotherapy before transitioning to combination therapy results in transient BMD reduction, clinical trials have demonstrated that relugolix combination therapy maintains BMD over two years while effectively reducing endometriosis- and UF-related symptoms. Conclusions: Relugolix combination therapy is an effective and well-tolerated treatment for UFs and endometriosis, minimizing the risk of hypoestrogenism-related bone loss while maintaining clinical benefits. Although monotherapy may lead to transient BMD reduction, combination therapy appears to stabilize bone health. Full article

Chemotherapeutic agents and radiotherapy are highly effective in treating malignancies. However, they carry a significant risk of harming the gonads and may lead to endocrine dysfunction and reproductive issues. This review outlines the molecular mechanisms of gonadotoxic therapies, focusing on radiation, alkylating agents, and platinum compounds. It discusses the loss of PMFs due to gonadotoxic exposure, including DNA double-strand breaks, oxidative stress, and dysregulated signaling pathways like PI3K/PTEN/Akt/mTOR and TAp63-mediated apoptosis. Furthermore, it explores strategies to mitigate gonadal damage, including GnRH agonists, AMH, imatinib, melatonin, sphingolipid metabolites, G-CSF, mTOR inhibitors, AS101, and LH. These therapies, paired with existing fertility preservation methods, could safeguard reproductive and hormonal functions and improve the quality of life for young cancer patients. Despite the progress made in recent years in understanding gonadotoxic mechanisms, gaps remain due to questionable reliance on mouse models and the lack of models replicating human ovarian dynamics. Long-term studies are vital for wider analyses and exploration of protective strategies based on various animal models and clinical trials. It is essential to verify that these substances do not hinder the anti-cancer effectiveness of treatments or cause lasting DNA changes in granulosa cells, raising the risk of miscarriages and infertility. Full article

Objectives: Research on the immunocastration vaccine is of great significance for animal management. In this study, the gonadotropin-releasing hormone (GnRH) ferritin nanoparticle vaccine was constructed using Spy Catcher-Spy Tag (SC-ST) as a delivery system; Methods: The Spy Catcher was constructed to fuse with the expression vector pET-30a-SF of ferritin nanoparticles. Two polypeptides, STG1: Spy Tag-GnRH I-PADRE and STG2: Spy Tag-GnRH I-GnRH II, coupled to SF in vitro to form two nanoparticles, were designed and synthesized to detect castration effects in mice. We mixed them with the adjuvant MONTANIDE ISA 206 VG to explore the adjuvant’s effect on immunogenicity; Results: All immunized groups produced anti-GnRH specific antibodies after the second immunization, which was significantly higher in the immunized group and the combined adjuvant group than in the control group, and the immune response could still be detected at the 12th week. The concentrations of testosterone, follicle-stimulating hormone, and luteinizing hormone in serum were significantly decreased. The number of sperm in the epididymis of mice in each immune group was significantly reduced, and the rate of sperm deformity was high; Conclusions: The two ferritin-based GnRH nanoparticles developed in this study can significantly cause testicular atrophy, decreased gonadal hormone concentration, decreased sperm count, and increased deformity rate in male mice. These findings provide experimental evidence supporting their potential application in animal immunocastration. Full article

Long-term storage may induce lipid oxidation in brown rice and impact its utilization in animal diets. One-day-old male Ross 308 broiler chickens (with an initial body weight of 20 g) were randomly divided into three groups: corn-based diet (Corn), fresh brown rice-based diet (BR1) and stored brown rice-based diet (BR6), with 8 replicates of 10 birds per pen, in a 42-day feeding trial. The results showed that lipid oxidation indexes increased and fatty acid composition changed significantly in BR6 (p < 0.05). The dietary replacement of corn with brown rice showed no effects on growth performance of broilers (p > 0.05). However, palmitic acid and oleic acid increased, and stearic acid, linoleic acid and docosadienoic acid decreased in the broiler breast muscle of the BR1 and BR6 groups (p < 0.05). Ileum antioxidant enzyme activities increased in the BR1 and BR6 groups compared to the Corn group (p < 0.05), and the activities of α-amylase, trypsin, chymotrypsin and lipase decreased in the BR6 group compared to the BR1 and Corn groups (p < 0.05). Also, compared to the BR1 group, the overall expression of metabolites involved in drug metabolism—cytochrome P450, GnRH secretion and the estrogen signaling pathway in broiler ileum were down-regulated in the BR6 group (p < 0.05). In conclusion, the lipid oxidation of stored brown rice decreased digestive enzyme activities and changed metabolic characteristics in the ileum of broilers. While replacing corn with brown rice did not affect broiler growth performance, it reduced the contents of unsaturated and essential fatty acids in breast muscle and enhanced the ileal antioxidant functions of broilers. Full article