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Depression is one of the most common affective disorders in people's life. Women are susceptibility to depression during puberty, peripartum and menopause transition, when they are suffering from sex hormone fluctuation. A lot of studies have demonstrated the neuroprotective effect of estrogen on depression in women, however, the effect of FSH on depression is unclear. In this study, we investigated the role of FSH on depression in mice. Our study demonstrated that FSH induced depression-like behaviors in mice in a dose-dependent manner. This induction was associated with elevated levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF- α in both serum and hippocampal tissues. Additionally, FSH treatment resulted in impaired synaptic plasticity and a reduction in the expression of key synaptic proteins. It is noteworthy that the depression-like behaviors, inflammatory cytokines expression and synaptic plasticity impairment induced by FSH could be alleviated by knocking down the expression of FSH receptor (FSHR) in the hippocampus of the mice. Therefore, our findings reveal that FSH may play an important role in the pathogenesis of depression and targeting FSH may be a potential therapeutic strategy for depression during hormone fluctuation in women. [ABSTRACT FROM AUTHOR]

Purpose: To examine the ability of testicular histopathology in Non-obstructive azoospermia (NOA) in predicting sperm retrieval rate (SR), sperm quality and assisted reproductive technology success. Methods: A retrospective study recruited clinically diagnosed NOA patients between 2007 and 2015. Testicular biopsy and conventional sperm extraction (TESE) were done concomitantly. Correlation between pathological categories, SR rate, sperm quality and success of intracytoplasmic sperm injection (ICSI) was studied. FSH was measured as a predictor of fertility. Results: One hundred eighteen patients were recruited. Histopathological classification was hypospermatogenesis (HS) 45 (38%), maturation arrest (MA) 22(19%), Sertoli cell only syndrome (SCOS) 34 (29%) and normal spermatogenesis (NS) 17 (14%). FSH value was above normal level in 34 (76%) of HS, 19 (86%) of MA, 32 (94%) of SCOS and 5 (29%) of NS. Positive SR was obtained in 108 (92%) patients. The highest SR rate was seen in NS group 100% and the lowest was in SCOS 26 (77%). The worst sperm quality was found in SCOS as type C represents 46%, followed by MA 40% and HS 24%. Patients had ICSI following TESE had variable success rate as success of ICSI was seen (9/15) for HS, (0/7) for MA, (5/15) for SCOS and (8/9) for NS. FSH is strongly correlated to SR, quality of sperm and success of ICSI as positive SR in normal FSH patients was obtained in 28 (100%) of normal FSH, 70 (97%) of high FSH and 10 (56%) of double high FSH (p value < 001). The success of ICSI significantly correlates with FSH value as normal FSH has 77% success ICSI rate, high FSH (52%) and double high FSH (0%) (p value < 0.001). Conclusions: Testicular biopsy and histopathology findings in NOA are strongly correlated SR rate, quality of sperms, and success of ICSI. FSH is a strong noninvasive predictor of fertility in NOA patients. [ABSTRACT FROM AUTHOR]

Purpose: There is several albeit not univocal evidence suggesting that ovarian reserve is not related to the chance of natural pregnancy, provided that the remnant follicular pool is sufficient to ensure regular menstrual cycles. Nevertheless, available studies have some methodological limitations, and the issue cannot be considered definitively ascertained. Methods: To further address this issue, we retrospectively selected infertile women whose infertility diagnostic work-up was unremarkable (unexplained infertility-cases) and matched them by age and study period to a group of infertile women who were diagnosed with severe male infertility (controls). If ovarian reserve impacts on natural fertility, one had to expect lower ovarian reserve among women with unexplained infertility. Tested biomarkers included AMH, AFC and day 2–3 serum FSH. The primary aim was the frequency of women with serum AMH < 0.7 ng/ml. Results: Two-hundred fifty-two women with unexplained infertility and 252 women with male infertility were included. All biomarkers of ovarian reserve did not differ between the study groups. AMH levels < 0.7 ng/mL were observed in 26 (10%) women with unexplained infertility and 35 (14%) women with male infertility (p = 0.28). The adjusted OR was 0.76 (95% CI: 0.44–1.33). Significant differences did not also emerge when repeating this dichotomous analysis using other biomarkers and other thresholds for the definition of low-ovarian reserve. Conclusion: This study confirms that ovarian reserve is unremarkable to natural conception. Physicians and patients should be aware of this concept to avoid inappropriate counseling and undue clinical decisions. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovarian syndrome (PCOS) is a metabolic disorder, and its pathogenesis is still unclear, but the changes in the hypothalamicpituitary-gonadal (HPG) axis are considered one of the main causes in the development of PCOS. Kisspeptin is a peptide encoded by the KISS gene that regulates the hypothalamus-pituitary-gonadal (HPG), which may be concerned with the pathogenesis of PCO. Aim: To identify the relation between serum Kisspeptin and sex hormones and metabolic parameters among normal and PCO women. Methods: A prospective case-control study was conducted among 64 subjects (32 with PCO and 32 with the control group). The serum Kisspeptin level was measured using enzyme-linked immunosorbent assay (ELISA) and correlated with other hormones such as LH, FSH, DHEA, testosterone, and prolactin. Results: Serum kisspeptin level was significantly higher in the PCOS group when compared to the control group. There was a statistically significant positive correlation between kisspeptin and each of HOMA IR, LH, FSH, DHEA, testosterone, and prolactin. Conclusions: The increase in kisspeptin level may play a role in pathogenesis of PCOS, and may represent a novel link between metabolic and hormonal disturbance in PCOS females since this peptide was correlated with HOMA-IR, LH, FSH, DHEA, testosterone and prolactin. [ABSTRACT FROM AUTHOR]

Objective: To study the effect of switching to a follicle-stimulating hormone (FSH) preparation other than that to which infertile male patients have not had an effective response. Patients and methods: Seventy-four normogonadotropinemic, non-obstructive, oligozoospermic patients who were poor responders to the administration of highly purified FSH (hpFSH) (Group 1 (n = 22) and Group 3 (n = 15)) or to recombinant human FSH (rhFSH) (Group 2 (n = 22) and Group 4 (n = 15)) were selected for this prospective study. After 3 months of washout from treatment with the first FSH preparation of choice, rhFSH was administered to patients in Groups 1 and 4 and hpFSH to those in Groups 2 and 3. Serum luteinizing hormone, FSH, total testosterone levels, conventional sperm parameters, testicular volume, and the number of pregnancies were evaluated at study entry and after the first and second treatment cycles. Results: Comparing treatment groups, the greatest improvement in sperm parameters was recorded in the groups of patients prescribed the switch in FSH preparation. Group 1 had the greatest benefit from therapy, with the highest pregnancy rate after the second treatment cycle. Indeed, eight couples achieved pregnancy (36.4%), compared to Groups 2 (n = 4; 18.2%), 3 (n = 1; 6.7%), and 4 (n = 2; 13.3%) (p = 0.04). Conclusions: The results of this study suggest that a therapeutic scheme involving the "switching" of the FSH preparation yields better results than a protocol using the same FSH preparation for six months. These findings, if confirmed by further studies, will help us better design a treatment strategy with FSH for infertile patients with oligozoospermia. [ABSTRACT FROM AUTHOR]

Metformin treatment decreases elevated concentrations of anterior pituitary hormones. The aim of this prospective, cohort study was to investigate whether hyperthyroidism modulates the impact of metformin on gonadotroph secretory function. The study population included 48 postmenopausal women with untreated type 2 diabetes or prediabetes, 24 of whom had coexisting grade 1 subclinical hyperthyroidism. Both groups were matched for age, insulin sensitivity, and gonadotropin levels. Over the entire study period, all participants were treated with metformin (2.55–3 g daily). Plasma glucose, insulin, thyroid‐stimulating hormone (TSH), total and free thyroid hormones, follicle‐stimulating hormone (FSH), luteinizing hormone (LH), estradiol, prolactin, adrenocorticotropic hormone (ACTH), and insulin‐like growth factor‐1 (IGF‐1) were assayed at entry and 6 months later. At baseline, the study groups differed in levels of TSH and thyroid hormones but not in body mass index, blood pressure, glucose homeostasis markers (fasting glucose, homeostatic model assessment 1 of insulin resistance ratio [HOMA1‐IR], and glycated hemoglobin [HbA1c]), and the remaining hormones. There were no differences between both groups in the degree of reduction in plasma glucose and HbA1c in response to metformin treatment. Although metformin decreased HOMA1‐IR in both groups, this effect was stronger in women with hyperthyroidism than with normal thyroid function (−50 ± 20% vs −30 ± 15%). Similar relationships were observed for FSH (−43 ± 21% vs −21 ± 12%). Only in hyperthyroid women did the drug reduce LH concentration (by 35 ± 17%). Metformin did not affect circulating levels of TSH, total and free thyroxine, total and free triiodothyronine, estradiol, prolactin, ACTH, and IGF‐1. The obtained results indicate that hyperthyroidism enhances the gonadotropin‐lowering effects of metformin, as well as the fact that this agent has a neutral effect on the hypothalamic–pituitary–thyroid axis in case of its overactivity. [ABSTRACT FROM AUTHOR]

Oogenesis involves two phases: initial volumetric growth driven by nutrient accumulation and subsequent nuclear maturation. While melatonin (MLT) has been employed as a supplement to enhance the quality of fully grown oocytes during nuclear maturation phase, its impact on oocyte growth remains poorly studied. Here, we provide in vivo evidence demonstrating that follicle‐stimulating hormone increases MLT content in ovary. Administration of MLT improves oocyte growth and quality in mice and goats by enhancing nutrient reserves and mitochondrial function. Conversely, MLT‐deficient mice have smaller oocytes and dysfunctional mitochondria. Exploring the clinical implications of MLT in promoting oocyte growth, we observe that a brief 2‐day MLT treatment enhances oocyte quality and reproductive performance in older mice. These findings highlight the role of MLT in regulating oocyte growth and provide a specific treatment window for optimizing oocyte quality and reproductive performance in female animals. [ABSTRACT FROM AUTHOR]

This study explored the alteration in kisspeptin and reproductive hormones during different superovulation protocols (SOP) in dromedary camel. The kisspeptin and reproductive hormonal profile, ovarian response, and the quality and quantity of embryos in dromedary camel donors were evaluated. A total of thirty donor camels were divided into two groups: the 5dSOP group, which received diluent containing 400 mg pFSH dissolved in 20 ml and administered two times daily for 5 days at decreasing doses (2.5, 2, 1.5, and 1 ml); and the 3dSOP group, which received diluent containing 400 mg pFSH dissolved in 12 ml and administered two times daily for 3 days at decreasing doses (3 ml, 2 ml, and 1 ml). Ultrasonography was used to monitor the ovarian environment, recording daily follicle count and dimensions and the time taken for follicles to mature. On the sixth day after mating, a corpus luteum (CL) count was conducted. On the 8th day after mating, records of the quantity and quality of embryos collected were kept. Blood samples from the jugular vein were collected at the commencement of the superovulation protocol and at 8:00 a.m. for the following 48 h to measure the concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), kisspeptin (KP), and progesterone (P4). The findings indicated that the 3dSOP yielded superior results compared to the 5dSOP in terms of follicle quantity and size, as well as the quantity of CL and embryos. This improvement was attributed to significantly higher concentrations of reproductive hormones, including FSH, LH, E2, kisspeptin, and P4 (P ≤ 0.05), in the 3dSOP than in the 5dSOP. In conclusion, reducing the duration of superovulation protocols contributed to the proliferation of follicles with improved dimensions and counts, ultimately resulting in a greater quantity of embryos of superior quality. The levels of FSH, LH, E2, KP, and P4 were affected significantly by SOP and time of evaluation. • This is the first experiment to study the alteration in kisspeptin, FSH, LH, E2, and P4 during superovulation protocols in camel. • This study recommended reducing the doses of pFSH to three days instead of five days. • There were significantly higher concentrations of FSH, LH, E2, kisspeptin, and P4 in the 3dSOP than in the 5dSOP. [ABSTRACT FROM AUTHOR]

Background: Polycystic Ovary Syndrome (PCOS) is a hormonal disorder characterized by irregular periods, excess androgen levels, and polycystic ovaries, affecting many women of reproductive age. Methods and Results: This study employed statistical and molecular analyses to compare hormone and metabolic markers between PCOS patients and controls. Sanger sequencing identified two INSR gene variants linked to high insulin and pre-diabetic conditions. Statistically, no significant age differences were detected (p = 0.492) between the overall PCOS patient pool and controls. However, a substantial variation in Vitamin D levels was observed within PCOS patients compared to controls (p = 0.0006), suggesting an association with PCOS. Correlations between Vitamin D and insulin, as well as HbA1c levels (R2 = 0.141 and 0.143, respectively), suggest Vitamin D’s potential impact on glycemic control. Significant differences were found in HbA1c (p < 0.0001), insulin (p < 0.0001), and LDL (p = 0.0004) levels between PCOS patients and controls, highlighting marked disparities in these metabolic markers. LH levels also showed a significant contrast (p < 0.0001), while progesterone levels displayed a notable difference (p = 0.007) between the two groups. Correlation analyses within PCOS patients demonstrated associations among LDL, HbA1c, and insulin, with no such correlations observed in control cases. Additionally, Sanger sequencing identified two INSR gene variants, c.3614C > T (p.Pro1205Leu) and c.3355C > T (p.Arg1119Trp), associated with high insulin, LH, and pre-diabetic conditions. These amino acid changes may trigger metabolic imbalances and hormonal irregularities, potentially contributing to the development of PCOS. Conclusions: The findings highlight the multifaceted nature of PCOS, revealing significant metabolic, hormonal, and genetic differences compared to controls. These insights may inform tailored interventions and management strategies for the complex associations characteristic of PCOS. [ABSTRACT FROM AUTHOR]

The Tianzhu white yak, a globally rare species, holds immense value as a source for yak materials. While the Fas/FasL pathway is pivotal in granulosa cells apoptosis, its precise molecular workings remain enigmatic. This study endeavours to decipher the role of follicle‐stimulating hormone (FSH) in suppressing ovarian granulosa cells (GC) apoptosis in the Tianzhu white yak. Utilizing advanced cell culture techniques, we employed the MTT method, flow cytometry, fluorescence labelling and RT‐PCR to investigate the apoptotic effects of FSH on yak GCs. Our results reveal that FSH's inhibitory effect on GC apoptosis follows a normal distribution pattern, peaking at an FSH concentration of 100 ng/mL with an apoptosis inhibition rate of 89.31%. When serum was withdrawn, an FSH concentration of 2 × 106 ng/mL reduced apoptosis by 72.84%. Annexin V‐FITC staining revealed membrane invaginations, bubble and protrusion formation on the cell surface, and alterations in membrane structure and cell morphology. Flow cytometry analysis further demonstrated that FSH administration prior to early granulosa cell apoptosis had a more profound effect than during gradual apoptosis, both showing a suppressive effect on early follicular granulosa cell apoptosis. A transcription‐level analysis conducted 3 h prior to serum withdrawal, with the addition of 100 ng/mL FSH, revealed intricate regulations in the expression of Fas/FasL. Notably, we observed a gradual increase in FasL expression over time, yet the presence of FSH effectively down‐regulated FasL expression to baseline levels, without notable changes in Fas expression. Immunocytochemical analysis further confirmed the presence of both Fas and FasL on the cell membrane, nucleus and cytoplasm, with varying intensities depending on the duration of FSH treatment. Our findings suggest that FSH may suppress the apoptotic pathway in follicular primarily by down‐regulating FasL expression, indicating that Fas‐regulated mitochondrial pathways play a more prominent role compared to death receptor pathways. This study offers a fresh perspective on the mechanism underlying follicular atresia in Tianzhu white yaks and lays a solid theoretical foundation for the expansion of this endangered species' population. [ABSTRACT FROM AUTHOR]

The study was conducted on 70 blood samples, which were divided into two parts: • Patient group: 35 samples were from patients with polycystic ovary syndrome. • Control group (healthy women): 35 samples were from healthy women (as a control group). The ages of both groups ranged between (18-45) years for the period from 4/1/2024 - 6/1/2024. From Samarra General Hospital in Salah al-Din Governorate, blood was then collected from patients and healthy people and separated using a centrifuge. Then biochemical variables were measured, which included (glucose, LH, FSH, iron, magnesium, and vitamin D). The results of the current research showed a significant increase in each of the levels (glucose, LH, iron, and magnesium). In the blood serum of patients with polycystic ovary syndrome compared with the control group, there was a significant decrease in the level of (Vit D, FSH) in both groups at its level, probability P ≤ 0.001. [ABSTRACT FROM AUTHOR]

Abstract Background Neural stem and progenitor cells (NSPCs) from extra-neural origin represent a valuable tool for autologous cell therapy and research in neurogenesis. Identification of proneurogenic biomolecules on NSPCs would improve the success of cell therapies for neurodegenerative diseases. Preliminary data suggested that follicle-stimulating hormone (FSH) might act in this fashion. This study was aimed to elucidate whether FSH promotes development, self-renewal, and is proneurogenic on neurospheres (NS) derived from sheep ovarian cortical cells (OCCs). Two culture strategies were carried out: (a) long-term, 21-days NS culture (control vs. FSH group) with NS morphometric evaluation, gene expression analyses of stemness and lineage markers, and immunolocalization of NSPCs antigens; (b) NS assay to demonstrate FSH actions on self-renewal and differentiation capacity of NS cultured with one of three defined media: M1: positive control with EGF/FGF2; M2: control; and M3: M2 supplemented with FSH. Results In long-term cultures, FSH increased NS diameters with respect to control group (302.90 ± 25.20 μm vs. 183.20 ± 7.63 on day 9, respectively), upregulated nestin (days 15/21), Sox2 (day 21) and Pax6 (days 15/21) and increased the percentages of cells immunolocalizing these proteins. During NS assays, FSH stimulated NSCPs proliferation, and self-renewal, increasing NS diameters during the two expansion periods and the expression of the neuron precursor transcript DCX during the second one. In the FSH-group there were more frequent cell-bridges among neighbouring NS. Conclusions FSH is a proneurogenic hormone that promotes OCC-NSPCs self-renewal and NS development. Future studies will be necessary to support the proneurogenic actions of FSH and its potential use in basic and applied research related to cell therapy.

Background: Neural stem and progenitor cells (NSPCs) from extra-neural origin represent a valuable tool for autologous cell therapy and research in neurogenesis. Identification of proneurogenic biomolecules on NSPCs would improve the success of cell therapies for neurodegenerative diseases. Preliminary data suggested that follicle-stimulating hormone (FSH) might act in this fashion. This study was aimed to elucidate whether FSH promotes development, self-renewal, and is proneurogenic on neurospheres (NS) derived from sheep ovarian cortical cells (OCCs). Two culture strategies were carried out: (a) long-term, 21-days NS culture (control vs. FSH group) with NS morphometric evaluation, gene expression analyses of stemness and lineage markers, and immunolocalization of NSPCs antigens; (b) NS assay to demonstrate FSH actions on self-renewal and differentiation capacity of NS cultured with one of three defined media: M1: positive control with EGF/FGF2; M2: control; and M3: M2 supplemented with FSH. Results: In long-term cultures, FSH increased NS diameters with respect to control group (302.90 ± 25.20 μm vs. 183.20 ± 7.63 on day 9, respectively), upregulated nestin (days 15/21), Sox2 (day 21) and Pax6 (days 15/21) and increased the percentages of cells immunolocalizing these proteins. During NS assays, FSH stimulated NSCPs proliferation, and self-renewal, increasing NS diameters during the two expansion periods and the expression of the neuron precursor transcript DCX during the second one. In the FSH-group there were more frequent cell-bridges among neighbouring NS. Conclusions: FSH is a proneurogenic hormone that promotes OCC-NSPCs self-renewal and NS development. Future studies will be necessary to support the proneurogenic actions of FSH and its potential use in basic and applied research related to cell therapy. [ABSTRACT FROM AUTHOR]

Follicle-stimulating hormone (FSH) administration is applied in the management of subjects affected by hypogonadotropic hypogonadism. Whilst this application is widely recognized and established alone or in combination with human chorionic gonadotropin (hCG), a similar strategy is empirically advocated in idiopathic male factor infertility (MFI). In this setting, FSH therapy has been used to increase sperm quantity, quality, and pregnancy rate when FSH plasma concentrations are below 8 IU/L and when the seminal tract is not obstructed. In the literature, several studies suggested that giving FSH to patients with idiopathic MFI increases sperm count and motility, raising the overall pregnancy rate. However, this efficacy seems to be limited, and about 10–18 men should be treated to achieve one pregnancy. Thus, several papers suggest the need to move from a replacement approach to an overstimulating approach in the management of FSH therapy in idiopathic MFI. To this aim, it is imperative to determine some pharmacologic markers of FSH efficacy. Furthermore, it should be useful in clinical practice to distinguish, before starting the treatment, among patients who might respond or not to FSH treatment. Indeed, previous studies suggest that infertile men who have normal levels of gonadotropins in plasma might not respond to FSH treatment and about 50% of patients might be defined as "non-responders". For these reasons, identifying predictive markers of FSH action in spermatogenesis and clinical markers of response to FSH treatment is a fascinating area of study that might lead to new developments with the aim of achieving personalization of the treatment of male infertility. From this perspective, seminal parameters (i.e., spermatid count), testicular cytology, genetic assessment, and miRNA or protein markers in the future might be used to create a tailored FSH therapy plan. The personalization of FSH treatment is mandatory to minimize side effects, to avoid lost time with ineffective treatments, and to improve the efficacy, predicting the most efficient dose and the duration of the treatment. This narrative review's objective is to discuss the role of the different putative factors which have been proposed to predict the response to FSH treatment in idiopathic infertile men. [ABSTRACT FROM AUTHOR]

This study aims to explore whether glycerol monolaurate (GML) can improve reproductive performance of female zebrafish (Danio rerio) and the survival percentage of their offspring. Three kinds of isonitrogenous and isolipid diets, including basal diet (control) and basal diet containing 0.75 g/kg GML (L_GML) and 1.5 g/kg GML (H_GML), were prepared for 4 weeks feeding trial. The results show that GML increased the GSI of female zebrafish. GML also enhanced reproductive performance of female zebrafish. Specifically, GML increased spawning number and hatching rate of female zebrafish. Moreover, GML significantly increased the levels of triglycerides (TG), lauric acid, and estradiol (E2) in the ovary (P < 0.05). Follicle-stimulating hormone (FSH) levels in the ovary and brain also significantly increased in the L_GML group (P < 0.05). Besides, dietary GML regulated the hypothalamus-pituitary-gonad (HPG) axis evidenced by the changed expression levels of HPG axis-related genes in the brain and ovary of the L_GML and H_GML groups compared with the control group. Furthermore, compared with the control group, the expression levels of HPG axis-related genes (kiss2, kiss1r, kiss2r, gnrh3, gnrhr1, gnrhr3, lhβ, and esr2b) in the brain of the L_GML group were significantly increased (P < 0.05), and the expression levels of HPG axis-related genes (kiss1, kiss2, kiss2r, gnrh2, gnrh3, gnrhr4, fshβ, lhβ, esr1, esr2a, and esr2b) in the brain of the H_GML group were significantly increased (P < 0.05). These results suggest that GML may stimulate the expression of gnrh2 and gnrh3 by increasing the expression level of kiss1 and kiss2 genes in the hypothalamus, thus promoting the synthesis of FSH and E2. The expression levels of genes associated with gonadotropin receptors (fshr and lhr) and gonadal steroid hormone synthesis (cyp11a1, cyp17, and cyp19a) in the ovary were also significantly upregulated by dietary GML (P < 0.05). The increasing expression level of cyp19a also may promote the FSH synthesis. Particularly, GML enhanced the richness and diversity and regulated the species composition of intestinal microbiota in female zebrafish. Changes in certain intestinal microorganisms may be related to the expression of certain genes involved in the HPG axis. In addition, L_GML and H_GML both significantly decreased larvae mortality at 96 h post fertilization and their mortality during the first-feeding period (P < 0.05), revealing the enhanced the starvation tolerance of zebrafish larvae. In summary, dietary GML regulated genes related to HPG axis to promote the synthesis of E2 and FSH and altered gut microbiota in female zebrafish, and improved the survival percentage of their offspring. [ABSTRACT FROM AUTHOR]

Somatostatin (SST) plays diverse physiological roles in vertebrates, particularly in regulating growth hormone secretion from the pituitary. While the function of SST as a neuromodulator has been studied extensively, its role in fish and mammalian reproduction remains poorly understood. To address this gap, we investigated the involvement of the somatostatin system in the regulation of growth and reproductive hormones in tilapia. RNA sequencing of mature tilapia brain tissue revealed the presence of three SST peptides: SST6, SST3, and low levels of SST1. Four different isoforms of the somatostatin receptor (SSTR) subfamily were also identified in the tilapia genome. Phylogenetic and synteny analysis identified tiSSTR2-like as the root of the tree, forming two mega clades, with SSTR1 and SSTR4 in one and SSTR2a, SSTR3a, and SSTR5b in the other. Interestingly, the tiSSTR-5 isoforms 5x1, 5x2, and 5x3 were encoded in the sstr3b gene and were an artifact of misperception in the nomenclature in the database. RNA-seq of separated pituitary cell populations showed that SSTRs were expressed in gonadotrophs, with sstr3a enriched in luteinizing hormone (LH) cells and sstr3b significantly enriched in follicle-stimulating hormone (FSH) cells. Notably, cyclosomatostatin, an SSTR antagonist, induced cAMP activity in all SSTRs, with SSTR3a displaying the highest response, whereas octreotide, an SSTR agonist, showed a binding profile like that observed in human receptors. Binding site analysis of tiSSTRs from tilapia pituitary cells revealed the presence of canonical binding sites characteristic of peptide-binding class A G-protein-coupled receptors. Based on these findings, we explored the effect of somatostatin on gonadotropin release from the pituitary in vivo. Whereas cyclosomatostatin increased LH and FSH plasma levels at 2 h post-injection, octreotide decreased FSH levels after 2 h, but the LH levels remained unaffected. Overall, our findings provide important insights into the somatostatin system and its mechanisms of action, indicating a potential role in regulating growth and reproductive hormones. Further studies of the complex interplay between SST, its receptors, and reproductive hormones may advance reproductive control and management in cultured populations. [ABSTRACT FROM AUTHOR]

Background/Aim: Endometrial cancer is one of the most prevalent gynaecologic cancers in advanced nations and act as the largest proportion of tumours occurring in the uterine corpus. The aim of the study was to identify potential diagnostic biomarkers for endometrial cancer among the evaluated hormones and tumour markers to enhance early detection and improve patient outcomes. Methods: A comparison was made between two groups of women: 30 individuals who were healthy and 30 individuals who had endometrial cancer. The participants in both groups were carefully selected to ensure that they were similar in terms of age and body mass index (BMI). Luteinising hormone (LH), follicle-stimulating hormone (FSH), oestradiol (E2), cancer antigen 125 (CA-125) and carcinoembryonic antigen (CEA) were analysed. Results: As compared to healthy individuals, females diagnosed with endometrial tumour and cancer exhibited notably elevated levels of LH, FSH, E2, CA-125 and CEA. Conversely, they demonstrated significantly reduced levels of prolactin in their serum. Conclusions: Endometrial cancer patients had significantly raised concentrations of LH, E2, FSH, PRL, CEA and CA-125 in their serum, indicating hormonal dysregulation in the development of endometrial cancer. It is not advisable to rely solely on LH, E2, FSH, PRL, CA-125 or CEA as screening markers for endometrial cancer. Instead, they should be considered as part of a comprehensive screening panel that needs to be developed in the future. [ABSTRACT FROM AUTHOR]

The pituitary gland orchestrates multiple endocrine organs by secreting tropic hormones, and therefore plays a significant role in a myriad of physiological processes, including skeletal modeling and remodeling, fat and glucose metabolism, and cognition. Expression of receptors for each pituitary hormone and the hormone itself in the skeleton, fat, immune cells, and the brain suggest that their role is much broader than the traditionally attributed functions. FSH, believed solely to regulate gonadal function is also involved in fat and bone metabolism, as well as in cognition. Our emerging understanding of nonreproductive functions of FSH, thus, opens potential therapeutic opportunities to address detrimental health consequences during and after menopause, namely, osteoporosis, obesity, and dementia. In this review, we outline current understanding of the cross-talk between the pituitary, bone, adipose tissue, and brain through FSH. Preclinical evidence from genetic and pharmacologic interventions in rodent models, and human data from population-based observations, genetic studies, and a small number of interventional studies provide compelling evidence for independent functions of FSH in bone loss, fat gain, and congnitive impairment. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The aim of this study is to evaluate the relationship between semen parameters, complete blood count, and hormone levels on the day of spermiogram. METHODS: Semen parameters of 230 patients who were examined for full blood count test and hormone levels on the day of spermiogram were included in the study. Patients were grouped according to the total motile sperm count (TMSC), semen parameters, hemogram, and hormone levels were compared between groups. RESULTS: No statistically significant difference was found between groups in neutrophil ratios, neutrophil, lymphocyte, platelet counts, neutrophile-to-lymphocyte ratio (N/L), and platelet-to-lymphocyte ratio (P/L). However, white blood cell (WBC) and lymphocyte counts were weakly positively correlated with sperm concentration (p=0.021, p=0.026), and a weakly significant positive correlation was found with WBC and neutrophil count for motility (p=0.038, p=0.004). FSH level was found to be lower in cases with TMSC >20 m than those with TMSC <5 m and 5-10 m (p=0.004, p=0.022). LH was found to be lower in cases with TMSC >20 m than those with TMSC <5 m (p=0.048). A negative correlation was found for both FSH and LH levels with sperm concentration, motility, and TMSC (p<0.001, p=0.014). CONCLUSION: In this study, a significant negative correlation was demonstrated between FSH, LH levels and sperm concentration, motility, TMSC. N/L and P/L cannot be used as predictive markers of sperm quality. The results of a significant positive correlation between WBC, neutrophil counts, and sperm parameters encourage researchers to conduct prospective randomized controlled trials with larger sample sizes and different inflammatory and hormonal markers. [ABSTRACT FROM AUTHOR]

Introduction and aim. Recently, infertility has become a global problem and the frequency of the "male" factor in family infertility has reached 40-50%. The aim of the research is to investigate the role of some biochemical indicators (endocrine factors and fructose) in determining male infertility. Material and methods. In the study, the spermogram of 101 men aged 20-46 with idiopathic male infertility, the concentration of follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin and testosterone hormones in their blood, and the concentration of fructose in their sperm samples were analyzed, and their correlations were determined. Results. The concentration of FSH in the blood serum of men with asthenozoospermia and oligozoospermia increased statistically significantly by 57.7% and 2.4 times, respectively, compared to the control. More serious endocrinological disorders were recorded in men with azoospermia. In men with non-obstructive azoospermia, the concentration of FSH is 8.8 times, that of LH is 2.9 times; while prolactin increased by 89.0% compared to the control, testosterone concentration decreased by 22.9%. The fructose concentration in the oligozoospermia group compared to the control group increased by 60.8% (pH1<0.001), and in the non-obstructive azoospermia group by 2.0 times (pH1=0.001). A positive correlation between FSH and LH and a negative correlation between fructose concentration and forward motility of spermatozoa were determined in both asthenospermic and oligozoospermic patients (1=0.544; p=0.002). In case of non-obstructive azoospermia, FSH and prolactin, in azoospermia, LH and testosterone were directly proportional. Conclusion. During male infertility, there is a serious relationship between sperm indicators and endocrine disorders. An increase in the concentration of fructose is the main indicator of a decrease in the number and motility of spermatozoa. A high concentration of FSH and LH in men with azoospermia can be considered one of the important indicators in the diagnosis of non-obstructive azoospermia. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is the leading cause of anovulatory infertility. Inadequate understanding of the ovulation drivers hinders PCOS intervention. Herein, we report that follicle stimulating hormone (FSH) controls follicular fluid (FF) glutamine levels to determine ovulation. Murine ovulation starts from FF-exposing granulosa cell (GC) apoptosis. FF glutamine, which decreases in pre-ovulation porcine FF, elevates in PCOS patients FF. High-glutamine chow to elevate FF glutamine inhibits mouse GC apoptosis and induces hormonal, metabolic, and morphologic PCOS traits. Mechanistically, follicle-development-driving FSH promotes GC glutamine synthesis to elevate FF glutamine, which maintain follicle wall integrity by inhibiting GC apoptosis through inactivating ASK1-JNK apoptotic pathway. FSH and glutamine inhibit the rapture of cultured murine follicles. Glutamine removal or ASK1-JNK pathway activation with metformin or AT-101 reversed PCOS traits in PCOS models that are induced with either glutamine or EsR1 -KO. These suggest that glutamine, FSH, and ASK1-JNK pathway are targetable to alleviate PCOS. [ABSTRACT FROM AUTHOR]

One of the most common and difficult questions that a forensic practitioner faces is the estimation of time since death. The goal of this study is to investigate the post-mortem interval in relation to degenerative histological alterations and biochemical hormonal analysis of follicular stimulating hormone (FSH), dihydrotestosterone (DHT), testosterone (T) and dehydroepiandrosterone (DHEA) in pituitary, testicular and adrenal glands respectively. One hundred adult male albino rats were divided into five groups (0, 1, 5, 10 and 15 days post-mortem groups). The glands showed normal histological structure at time of death. Autolysis started in the glands within 1 day post-mortem (PM) and became marked with increase post-mortem interval. FSH level in pituitary gland, T hormone and DHT levels in testicular gland and DHEA level in adrenal gland revealed statistically significant reductions by ELISA (enzyme-linked immunosorbent assay) with increased post-mortem interval. Glandular hormones proved to be a useful parameter consistent with the histopathological changes for the estimation of post-mortem interval from the pituitary, adrenal and testicular glands. New equations for estimation of the post-mortem interval (PMI) were performed and appeared to be useful in estimating the post-mortem interval. [ABSTRACT FROM AUTHOR]

A local commodity, Yellow rasbora Rasbora lateristriata (Bleeker, 1854), can potentially be used as food by the Kulon Progo community. Added to that, aquaculture is known to optimize this potential and will also prevent illegal fishing where yellow rasbora are listed as a vulnerable species in the IUCN Red list. This study induced male yellow rasbora using the hormone OODEV® injection, which comprises Pregnant Mare Serum Gonadotropin (PMSG) and anti-dopamine. Yellow rasbora was nurtured to the age of six months and treated with four different treatments (dose) for a month, namely 0 mL/Kg, 0.25 mL/Kg, 0.5 mL/Kg, and 0.75 mL/Kg. Observed parameters included motility (movement and duration) as well as sperm count, sperm viability, sperm morphology, sperm morphometry, gonad somatic index (GSI), and survival rate (SR). Data obtained were analyzed using SPSS with the One-way ANOVA test and continued with Duncan's test if the results were significant. The obtained results had no significant effect on the IGS value. In addition, administration of OODEV® also improved sperm quality with the best results at 0.75 mL/Kg in terms of motility with the highest progressive movement compared to other doses but not significant compared to the control and significantly longer movement duration compared to other doses. In terms of morphometry and tail width, it was not significant compared to other doses, longest tail length but not significant with other doses except with 0.25 mL/Kg, and significantly had the longest sperm total length. Every dose showed a 100% percentage of survival rate. [ABSTRACT FROM AUTHOR]

Depression is one of the most common affective disorders in people’s life. Women are susceptibility to depression during puberty, peripartum and menopause transition, when they are suffering from sex hormone fluctuation. A lot of studies have demonstrated the neuroprotective effect of estrogen on depression in women, however, the effect of FSH on depression is unclear. In this study, we investigated the role of FSH on depression in mice. Our study demonstrated that FSH induced depression-like behaviors in mice in a dose-dependent manner. This induction was associated with elevated levels of pro-inflammatory cytokines, including IL-1β, IL-6, and TNF-α in both serum and hippocampal tissues. Additionally, FSH treatment resulted in impaired synaptic plasticity and a reduction in the expression of key synaptic proteins. It is noteworthy that the depression-like behaviors, inflammatory cytokines expression and synaptic plasticity impairment induced by FSH could be alleviated by knocking down the expression of FSH receptor (FSHR) in the hippocampus of the mice. Therefore, our findings reveal that FSH may play an important role in the pathogenesis of depression and targeting FSH may be a potential therapeutic strategy for depression during hormone fluctuation in women.

Abstract Background Infertility is an important health problem, affecting couples worldwide. Non-obstructive azoospermia is the most severe form of azoospermia, which is mostly idiopathic or caused by different causes such as chemotherapy and genetic disorders. Testicular fine needle aspiration (or testicular sperm aspiration (TESA)) is simple, cost-effective and less invasive than testicular sperm extraction. Materials and methods Three hundred twenty Middle Eastern patients with NOA were recruited in this study. The patients underwent routine infertility assessment including medical, surgical, and reproductive history, physical examination, semen analysis, and hormonal profile including FSH, Testosterone, and inhibin B in addition to Genetic assessment including karyotype and Y-chromosome micro-deletion. Results Testicular sperm aspiration was positive in 70 patients (22.18%). Serum FSH levels were clearly elevated in the patients with negative sperm retrieval (mean = 21.39 U/L), while they were reduced in the patients with positive sperm retrieval (mean = 14.61 U/L). Testosterone value did not clearly correlate with the results of testicular sperm aspiration in the two groups of patients, and testicular volume was normal for most of the patients in the two groups. Patients with Y-chromosome micro-deletion were 11.22% of the total patients studied and they had negative TESA results, while 13.12% of patients had Klinefelter Syndrome and their TESA results were negative. Conclusion We confirmed that there are many factors that negatively affect Testicular sperm aspiration results: high FSH and low inhibin B levels, smoking, and genetic disorders. Despite the absence of sperm in the semen, some NOA patients have a chance to have children by using this technique.

Abstract Background Elevated FSH often occurs in women of advanced maternal age (AMA, age ≥ 35) and in infertility patients undergoing controlled ovarian stimulation (COS). There is controversy on whether high endogenous FSH contributes to infertility and whether high exogenous FSH adversely impacts patient pregnancy rates. Methods The senescence-accelerated mouse-prone-8 (SAMP8) model of female reproductive aging was employed to assess the separate impacts of age and high FSH activity on the percentages (%) of viable and mature ovulated oocytes recovered after gonadotropin treatment. Young and midlife mice were treated with the FSH analog equine chorionic gonadotropin (eCG) to model both endogenous FSH elevation and exogenous FSH elevation. Previously we showed the activin inhibitor ActRIIB:Fc increases oocyte quality by preventing chromosome and spindle misalignments. Therefore, ActRIIB:Fc treatment was performed in an effort to increase % oocyte viability and % oocyte maturation. Results The high FSH activity of eCG is ootoxic to ovulatory oocytes, with greater decreases in % viable oocytes in midlife than young mice. High FSH activity of eCG potently inhibits oocyte maturation, decreasing the % of mature oocytes to similar degrees in young and midlife mice. ActRIIB:Fc treatment does not prevent eCG ootoxicity, but it restores most oocyte maturation impeded by eCG. Conclusions FSH ootoxicity to ovulatory oocytes and FSH maturation inhibition pose a paradox given the well-known pro-growth and pro-maturation activities of FSH in the earlier stages of oocyte growth. We propose the FOOT Hypothesis (“FSH OoToxicity Hypothesis), that FSH ootoxicity to ovulatory oocytes comprises a new driver of infertility and low pregnancy success rates in DOR women attempting spontaneous pregnancy and in COS/IUI patients, especially AMA women. We speculate that endogenous FSH elevation also contributes to reduced fecundity in these DOR and COS/IUI patients. Restoration of oocyte maturation by ActRIB:Fc suggests that activin suppresses oocyte maturation in vivo. This contrasts with prior studies showing activin A promotes oocyte maturation in vitro. Improved oocyte maturation with agents that decrease endogenous activin activity with high specificity may have therapeutic benefit for COS/IVF patients, COS/IUI patients, and DOR patients attempting spontaneous pregnancies.

Abstract Experimental evidence indicates that follicle-stimulating hormone (FSH), an essential hormone for reproduction, can act directly on endothelial cells inducing atherosclerosis activation and development. However, it remains unknown whether the FSH-receptor (FSHR) is expressed in human atherosclerosis plaques. To demonstrate the FSHR presence, we used immunohistochemical and immunoelectron microscopy involving a specific monoclonal antibody FSHR1A02 that recognizes an epitope present in the FSHR-ectodomain. In all 55 patients with atherosclerotic plaques located in carotid, coronary, femoral arteries, and iliac aneurysm, FSHR was selectively expressed in arterial endothelium covering atherosclerotic plaques and endothelia lining intraplaque neovessels. Lymphatic neovessels were negative for FSHR. M1-macrophages, foam cells, and giant multinucleated cells were also FSHR-positive. FSHR was not detected in normal internal thoracic artery. Immunoelectron microscopy performed in ApoEKO/hFSHRKI mice with atherosclerotic plaques, after injection in vivo with mouse anti-hFSHR monoclonal antibody FSHR1A02 coupled to colloidal gold, showed FSHR presence on the luminal surface of arterial endothelial cells covering atherosclerotic plaques. Therefore, FSHR can bind, internalize, and deliver into the plaque circulating ligands to FSHR-positive cells. In conclusion, we report FSHR expression in endothelial cells, M1-macrophages, M1-derived foam cells, giant multinucleated macrophages, and osteoclasts associated with human atherosclerotic plaques.

Abstract Background Resveratrol is a natural polyphenolic compound present in plants and red wine with many potential health benefits. This compound has various anti-inflammatory and anti-tumor properties and can improve cellular mitochondrial activity. This trial was designed to evaluate the effect on the outcome of IVF of Resveratrol supplementation in women > 35 years with good ovarian reserve (AMH > 1.2 ng/ml). Women were randomized to receive or placebo or Resveratrol (150 mg per day) for three months preceding the ovarian stimulation (OS). All patients were stimulated with a starting dose of recombinant FSH ranging between 150 and 300 IU according to age and ovarian reserve. GnRH antagonist flexible protocol was adopted for pituitary suppression. Triggering was performed with urinary hCG (10.000 IU). Results The study was conducted between January 2019 and December 2022 with aa total of 37 cases and 33 controls were recruited. No statistically significant differences in the number of oocytes retrieved, biochemical pregnancy, clinical pregnancy and live birth rates were observed between women treated with resveratrol and control group. A statistically significant increase in the follicle output rate (FORT) and follicle-to oocyte index (FOI) was observed in women treated with resveratrol-based nutraceutical (0.92 versus 0.77 [p = 0.02], and 0.77 versus 0.64 [p = 0.006], respectively). Conclusions Preliminary results from this study indicate that pre-treatment with resveratrol may improve ovarian sensitivity to exogenous FSH, which in turn may decrease the risk of hypo-response to OS in advanced reproductive age women.

Background Letrozole, an aromatase inhibitor, inhibits the final stage of conversion of androgens into estrogens, affecting organs and tissues such as the ovaries, breasts, adipose tissue, and bone. This mechanism greatly reduces the effects of estrogen. Estrogens are important for controlling the metabolism of fats and lipoproteins, influencing total protein, total antioxidants, and total cholesterol. FSH stimulation can benefit patients with pituitary dysfunction and is used to promote ovulation in women who have not become pregnant. It also provides controlled stimulation of ovarian hyperstimulation, which increases the number of follicles in in vitro fertilization. The Aim To assess the difference in the level (total cholesterol, Triglyc- erides, High density lipoprotein and total antioxidants) of infertility treat- ment among the three study groups, the group that injected by FSH, the group that took Letrozole, and the control group. Material and Method A study was conducted between October 2022 and May 2023. It involved one hundred and twenty patients, divided into three groups: those who took Letrozole continuously for more than one month, those who were injected by FSH continuously for more than one month, and the control group who did not take any drugs to induce ovu- lation. Results The results of this study showed an increase in the total an- tioxidant levels and total protein capacity levels in FSH compared to the other LET groups and the control group. Our study showed a significant difference (p value < 0.0001) in cholesterol concentrations, and total an- tioxidant capacity, compared to all studied groups, and an increase in total cholesterol levels was observed, as there was a significant difference (p value = 0.0012) in comparison to all studied groups.

INTRODUCTION: Mutations in the Fragile X Messenger Ribonucleoprotein 1 (FMR1) gene cause Fragile X Syndrome, the most common monogenic cause of intellectual disability. Mutations of FMR1 are also associated with reproductive disorders, such as early cessation of reproductive function in females. While progress has been made in understanding the mechanisms of mental impairment, the causes of reproductive disorders are not clear. FMR1-associated reproductive disorders were studied exclusively from the endocrine perspective, while the FMR1 role in neurons that control reproduction was not addressed. RESULTS: Here, we demonstrate that similar to women with FMR1 mutations, female Fmr1 null mice stop reproducing early. However, young null females display larger litters, more corpora lutea in the ovaries, increased inhibin, progesterone, testosterone, and gonadotropin hormones in the circulation. Ovariectomy reveals both hypothalamic and ovarian contribution to elevated gonadotropins. Altered mRNA and protein levels of several synaptic molecules in the hypothalamus are identified, indicating reasons for hypothalamic dysregulation. Increased vascularization of corpora lutea, higher sympathetic innervation of growing follicles in the ovaries of Fmr1 nulls, and higher numbers of synaptic GABAA receptors in GnRH neurons, which are excitatory for GnRH neurons, contribute to increased FSH and LH, respectively. Unmodified and ovariectomized Fmr1 nulls have increased LH pulse frequency, suggesting that Fmr1 nulls exhibit hyperactive GnRH neurons, regardless of the ovarian feedback. CONCLUSION: These results reveal Fmr1 function in the regulation of GnRH neuron secretion, and point to the role of GnRH neurons, in addition to the ovarian innervation, in the etiology of Fmr1-mediated reproductive disorders.

In females, the pathophysiological mechanism of poor ovarian response (POR) is not fully understood. Considering the expression level of p62 was significantly reduced in the granulosa cells (GCs) of POR patients, this study focused on identifying the role of the selective autophagy receptor p62 in conducting the effect of follicle-stimulating hormone (FSH) on antral follicles (AFs) formation in female mice. The results showed that p62 in GCs was FSH responsive and that its level increased to a peak and then decreased time-dependently either in ovaries or in GCs after gonadotropin induction in vivo. GC-specific deletion of p62 resulted in subfertility, a significantly reduced number of AFs and irregular estrous cycles, which were same as pathophysiological symptom of POR. By conducting mass spectrum analysis, we found the ubiquitination of proteins was decreased, and autophagic flux was blocked in GCs. Specifically, the level of nonubiquitinated Wilms tumor 1 homolog (WT1), a transcription factor and negative controller of GC differentiation, increased steadily. Co-IP results showed that p62 deletion increased the level of ubiquitin-specific peptidase 5 (USP5), which blocked the ubiquitination of WT1. Furthermore, a joint analysis of RNA-seq and the spatial transcriptome sequencing data showed the expression of steroid metabolic genes and FSH receptors pivotal for GCs differentiation decreased unanimously. Accordingly, the accumulation of WT1 in GCs deficient of p62 decreased steroid hormone levels and reduced FSH responsiveness, while the availability of p62 in GCs simultaneously ensured the degradation of WT1 through the ubiquitin‒proteasome system and autophagolysosomal system. Therefore, p62 in GCs participates in GC differentiation and AF formation in FSH induction by dynamically controlling the degradation of WT1. The findings of the study contributes to further study the pathology of POR. [ABSTRACT FROM AUTHOR]

Adiponectin is an important adipokine involved in glucose and lipid metabolism, but its secretion and potential role in regulating glucose utilization during ovarian development remains unclear. This study aims to investigate the mechanism and effects of follicle-stimulating hormones (FSHs) on adiponectin secretion and its following impact on glucose transport in the granulosa cells of rat ovaries. A range of experimental techniques were utilized to test our research, including immunoblotting, immunohistochemistry, immunofluorescence, ELISA, histological staining, real-time quantitative PCR, and transcriptome analysis. The immunohistochemistry results indicated that adiponectin was primarily located in the granulosa cells of rat ovaries. In primary granulosa cells cultured in vitro, both Western blot and immunofluorescence assays demonstrated that FSH significantly induced adiponectin secretion within 2 h of incubation, primarily via the PKA signaling pathway rather than the PI3K/AKT pathway. Concurrently, the addition of the AdipoR1/AdipoR2 dual agonist AdipoRon to the culture medium significantly stimulated the protein expression of GLUT1 in rat granulosa cells, resulting in enhanced glucose absorption. Consistent with these in vitro findings, rats injected with eCG (which shares structural and functional similarities with FSH) exhibited significantly increased adiponectin levels in both the ovaries and blood. Moreover, there was a notable elevation in mRNA and protein levels of AdipoRs and GLUTs following eCG administration. Transcriptomic analysis further revealed a positive correlation between the expression of the intraovarian adiponectin system and glucose transporter. The present study represents a novel investigation, demonstrating that FSH stimulates adiponectin secretion in ovarian granulosa cells through the PKA signaling pathway. This mechanism potentially influences glucose transport (GLUT1) and utilization within the ovaries. [ABSTRACT FROM AUTHOR]

Background: Prokineticin 2 (PROK2), an important neuropeptide that plays a key role in the neuronal migration of gonadotropin-releasing hormone (GnRH) in the hypothalamus, is known to have regulatory effects on the gonads. In the present study, the impact of intracerebroventricular (icv) PROK2 infusion on hypothalamic-pituitary–gonadal axis (HPG) hormones, testicular tissues, and sperm concentration was investigated. Methods and results: Rats were randomly divided into four groups: control, sham, PROK2 1.5 and PROK2 4.5. Rats in the PROK2 1.5 and PROK2 4.5 groups were administered 1.5 nmol and 4.5 nmol PROK2 intracerebroventricularly for 7 days via an osmotic mini pump (1 µl/h), respectively. Rat blood serum follicle stimulating hormone (FSH), luteinizing hormone (LH) and testosterone hormone levels were determined with the ELISA method in the blood samples after 7 days of infusion. GnRH mRNA expression was determined with the RT-PCR in hypothalamus tissues. analyze Sperm concentration was determined, and testicular tissue was examined histologically with the hematoxylin–eosin staining method. It was observed that GnRH mRNA expression increased in both PROK2 infusion groups. Serum FSH, LH and testosterone hormone levels also increased in these groups. Although sperm concentration increased in PROK2 infusion groups when compared to the control and sham, the differences were not statistically significant. Testicular tissue seminiferous epithelial thickness was higher in the PROK2 groups when compared to the control and sham groups. Conclusion: The present study findings demonstrated that icv PROK2 infusion induced the HPG axis. It could be suggested that PROK2 could be a potential agent in the treatment of male infertility induced by endocrinological defects. [ABSTRACT FROM AUTHOR]

Background: Infertility is an important health problem, affecting couples worldwide. Non-obstructive azoospermia is the most severe form of azoospermia, which is mostly idiopathic or caused by different causes such as chemotherapy and genetic disorders. Testicular fine needle aspiration (or testicular sperm aspiration (TESA)) is simple, cost-effective and less invasive than testicular sperm extraction. Materials and methods: Three hundred twenty Middle Eastern patients with NOA were recruited in this study. The patients underwent routine infertility assessment including medical, surgical, and reproductive history, physical examination, semen analysis, and hormonal profile including FSH, Testosterone, and inhibin B in addition to Genetic assessment including karyotype and Y-chromosome micro-deletion. Results: Testicular sperm aspiration was positive in 70 patients (22.18%). Serum FSH levels were clearly elevated in the patients with negative sperm retrieval (mean = 21.39 U/L), while they were reduced in the patients with positive sperm retrieval (mean = 14.61 U/L). Testosterone value did not clearly correlate with the results of testicular sperm aspiration in the two groups of patients, and testicular volume was normal for most of the patients in the two groups. Patients with Y-chromosome micro-deletion were 11.22% of the total patients studied and they had negative TESA results, while 13.12% of patients had Klinefelter Syndrome and their TESA results were negative. Conclusion: We confirmed that there are many factors that negatively affect Testicular sperm aspiration results: high FSH and low inhibin B levels, smoking, and genetic disorders. Despite the absence of sperm in the semen, some NOA patients have a chance to have children by using this technique. [ABSTRACT FROM AUTHOR]

Background: Elevated FSH often occurs in women of advanced maternal age (AMA, age ≥ 35) and in infertility patients undergoing controlled ovarian stimulation (COS). There is controversy on whether high endogenous FSH contributes to infertility and whether high exogenous FSH adversely impacts patient pregnancy rates. Methods: The senescence-accelerated mouse-prone-8 (SAMP8) model of female reproductive aging was employed to assess the separate impacts of age and high FSH activity on the percentages (%) of viable and mature ovulated oocytes recovered after gonadotropin treatment. Young and midlife mice were treated with the FSH analog equine chorionic gonadotropin (eCG) to model both endogenous FSH elevation and exogenous FSH elevation. Previously we showed the activin inhibitor ActRIIB:Fc increases oocyte quality by preventing chromosome and spindle misalignments. Therefore, ActRIIB:Fc treatment was performed in an effort to increase % oocyte viability and % oocyte maturation. Results: The high FSH activity of eCG is ootoxic to ovulatory oocytes, with greater decreases in % viable oocytes in midlife than young mice. High FSH activity of eCG potently inhibits oocyte maturation, decreasing the % of mature oocytes to similar degrees in young and midlife mice. ActRIIB:Fc treatment does not prevent eCG ootoxicity, but it restores most oocyte maturation impeded by eCG. Conclusions: FSH ootoxicity to ovulatory oocytes and FSH maturation inhibition pose a paradox given the well-known pro-growth and pro-maturation activities of FSH in the earlier stages of oocyte growth. We propose the FOOT Hypothesis ("FSH OoToxicity Hypothesis), that FSH ootoxicity to ovulatory oocytes comprises a new driver of infertility and low pregnancy success rates in DOR women attempting spontaneous pregnancy and in COS/IUI patients, especially AMA women. We speculate that endogenous FSH elevation also contributes to reduced fecundity in these DOR and COS/IUI patients. Restoration of oocyte maturation by ActRIB:Fc suggests that activin suppresses oocyte maturation in vivo. This contrasts with prior studies showing activin A promotes oocyte maturation in vitro. Improved oocyte maturation with agents that decrease endogenous activin activity with high specificity may have therapeutic benefit for COS/IVF patients, COS/IUI patients, and DOR patients attempting spontaneous pregnancies. [ABSTRACT FROM AUTHOR]

Background: The effects of novel non‐cytotoxic and immunotherapy drugs for cancer treatment on human testicular function have not been studied systematically. Objectives: The present study aimed to characterize effects of non‐cytotoxic and immunotherapy drugs in patients with cancers who had not been previously treated with gonadotoxic chemo‐ or radiotherapy. Materials and methods: This study involved 34 men, not previously treated with gonadotoxic regimens, in a mixed longitudinal (Cohort 1: 19 men about to start and approximately 1 year on non‐cytotoxic and immunotherapy treatment) and cross‐sectional (Cohort 2: 15 men already on non‐cytotoxic and immunotherapy treatment) study using data modeling to estimate within‐person time‐course changes in testicular exocrine and endocrine functions. Cohort 1 provided 45 paired semen and blood samples (34 prior to and nine during treatment) and Cohort 2 provided 45 sets of samples (15 pre‐treatment, 30 on treatment), including six men in Cohort 2 who had pre‐treatment spermatozoa cryostorage prior to the study. Men on non‐cytotoxic and immunotherapy treatment had undergone a median of 33.5 months long‐term treatment. Results: Spermatozoa output and concentration were reduced by about 50%, with corresponding increases in serum follicle‐stimulating hormone and decreases in serum inhibin B. Serum testosterone, luteinizing hormone, and sex hormone‐binding globulin were unaffected by non‐cytotoxic and immunotherapy treatment. Conclusion: Within limits of the present study of sample size and duration of on‐non‐cytotoxic and immunotherapy treatment, non‐cytotoxic and immunotherapy drugs have a modest effects on testicular exocrine function (sperm production) or its hormonal correlates (follicle‐stimulating hormone, inhibin B), with minimal impact on testicular endocrine (testosterone, luteinizing hormone) function. [ABSTRACT FROM AUTHOR]

Letrozole is a non‐steroidal, third‐generation aromatase inhibitor used in humans. Although letrozole is not approved for use in animals, it is used off‐label in cases of synchronization and infertility. The aim of this study was to determine the pharmacokinetics of letrozole after a single intravenous administration at three different doses in ewes during the breeding season and its effect on gonadotropins (luteinizing hormone (LH) and follicle‐stimulating hormone (FSH)) at the beginning of proestrus. The study was carried out on 24 healthy Merino ewes. Ewes were randomly divided into four groups (n = 6) as control, 0.5, 1, and 2 mg/kg. Plasma concentrations of letrozole were measured using HPLC‐UV and were analyzed by non‐compartmental analysis. LH and FSH concentrations were measured with a commercial ELISA kit. The terminal elimination half–life (t1/2ʎz) was significantly prolonged from 11.82 to 18.44 h in parallel with the dose increase. The dose‐normalized area under the concentration–time curve (AUC) increased, and total body clearance (ClT) decreased at the 1 and 2 mg/kg doses (0.05 L/h/kg) compared with the 0.5 mg/kg dose (0.08 L/h/kg). There were no differences in the volume of distribution at steady‐state and initial (C0.083h) plasma concentration values between dose groups. The decreased ClT, prolonged t1/2ʎz, and increased AUC at increasing doses showed the nonlinear kinetic behavior of letrozole. Letrozole significantly reduced LH concentration without affecting FSH concentration at all doses. As a result, letrozole has the potential to be used in synchronization methods and manipulation of the follicular waves due to its effect on LH secretion. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate total testosterone distribution in male idiopathic infertility. Methods: A retrospective, real-world case-control clinical study was conducted. Cases consisted of men evaluated for couple infertility, specifically those with alterations in semen parameters and normal gonadotropin levels, and after excluding all known causes of male infertility. Controls were male subjects who underwent semen analysis for screening purposes, without any abnormality detected. The total testosterone distribution was evaluated in cases and controls. Further analyses were performed subgrouping cases according to total testosterone reference threshold suggested by scientific societies (i.e., 3.5 ng/mL). Results: Cases included 214 idiopathic infertile men (mean age 38.2 ± 6.2 years) and controls 224 subjects with normozoospermia (mean age 33.7 ± 7.5 years). Total testosterone was not-normally distributed in both cases and controls, with positive asymmetric distribution slightly shifted on the left in cases. The rate of subjects with testosterone lower than 3.5 ng/mL was higher in cases (23.8%) than controls (4.5%) (p < 0.001). In cases with testosterone lower than 3.5 ng/mL, a significant direct correlation between testosterone and the percentage of normal morphology sperms was highlighted, also applying multivariate stepwise linear regression analysis (R = 0.430, standard error = 0.3, p = 0.020). Conclusion: Although idiopathic infertile men show by definition altered semen analysis and gonadotropins within reference ranges, testosterone serum levels are widely variable in this population. Approximately a quarter of these patients present some sort of functional hypogonadism. Our data support the need to better classify idiopathic male infertility and total testosterone serum levels could be a supportive parameter in tracing the patient's therapeutic profile. [ABSTRACT FROM AUTHOR]

Polycystic ovarian syndrome (PCOS), marked by oxidative stress and hormonal imbalances, causes infertility, insulin resistance, and diverse health problems. It not only affects physical health but also can strain marriages and lead to divorce, posing a notable societal issue. The levels of hormones (Estradiol (E2), Dihydroepiandrosterone sulfate (DHEA), luteinizing hormone (LH), folliclestimulating hormone (FSH), progesterone (PROG) Testosterone (TEST)), total antioxidant capacity (TAC) and Malondialdehyde (MDA) in PCOS Women attending the gynecology Clinic at Nnewi were investigated. This cross-sectional study had 45 participants with PCOS as a test group and 45 participants without PCOS as the control group between the ages of 18-50 recruited. All the biochemical parameters were determined by enzyme-linked immunoassay technique. Data was expressed as Mean ± standard deviation. The differences in parameters studied between the PCOS group (test) and the control group were evaluated using an independent t-test. Statistical significance was set at p-value < 0.05. Result showed significant higher differences in the mean serum levels of DHEA (87.40±65.90), LH (34.7±36.1), FSH (19.61±14.73) and Testosterone (3.04±1.36) in women with PCOS compared with the control (1.035±0.54),( 20.76±18.1), (13.2±10.19), and (3.04±1.36)(p< 0.05) respectively. A higher significant difference exists in the mean serum MDA values of the test group (women with PCOS compared with the control group(p<0.05). This study concluded that oxidative stress and hormone imbalance occurred among participants with PCOS attending the gynecology clinic of Nnamdi Azikiwe University Teaching Hospital in Nnewi. [ABSTRACT FROM AUTHOR]

Background: Resveratrol is a natural polyphenolic compound present in plants and red wine with many potential health benefits. This compound has various anti-inflammatory and anti-tumor properties and can improve cellular mitochondrial activity. This trial was designed to evaluate the effect on the outcome of IVF of Resveratrol supplementation in women > 35 years with good ovarian reserve (AMH > 1.2 ng/ml). Women were randomized to receive or placebo or Resveratrol (150 mg per day) for three months preceding the ovarian stimulation (OS). All patients were stimulated with a starting dose of recombinant FSH ranging between 150 and 300 IU according to age and ovarian reserve. GnRH antagonist flexible protocol was adopted for pituitary suppression. Triggering was performed with urinary hCG (10.000 IU). Results: The study was conducted between January 2019 and December 2022 with aa total of 37 cases and 33 controls were recruited. No statistically significant differences in the number of oocytes retrieved, biochemical pregnancy, clinical pregnancy and live birth rates were observed between women treated with resveratrol and control group. A statistically significant increase in the follicle output rate (FORT) and follicle-to oocyte index (FOI) was observed in women treated with resveratrol-based nutraceutical (0.92 versus 0.77 [p = 0.02], and 0.77 versus 0.64 [p = 0.006], respectively). Conclusions: Preliminary results from this study indicate that pre-treatment with resveratrol may improve ovarian sensitivity to exogenous FSH, which in turn may decrease the risk of hypo-response to OS in advanced reproductive age women. [ABSTRACT FROM AUTHOR]

Simple Summary: The development of ovarian follicles is mainly regulated by the follicle-stimulating hormone (FSH) released by the pituitary gland. FSH acts on the granulosa cell receptor FSHR to regulate oocyte development, follicular maturation, and ovulation. In this study, the optimal dose of FSH for promoting granulosa cells was explored by combining massively parallel sheep genome CRISPR-Cas9 knockout screening and transcriptome analysis. The CRISPR-Cas9 knockout libraries were designed on Chr 2, 3 and X and the sheep granulosa cell libraries were knocked out. This may be the first time that two methods have been combined to identify new FSH-responsive genes and pathways not foreseen in previous studies. Follicle-stimulating hormone (FSH) regulates ovarian follicle development through specific gene expression programs. Granulosa cells (GCs) are somatic cells surrounding the oocytes, secreting gonadotropins to regulate ovulation and promote follicular development. By analyzing the effects of different doses of FSH on the proliferation of GCs, we found that adding 10 ng/mL of FSH, as the optimal concentration, could promote the growth of GCs. Furthermore, we have successfully constructed the first CRISPR-Cas9 knockout library targeting the genes on chromosomes 2 and 3 and the X chromosomes of the sheep massively parallel coding gene, as well as an ovarian GCs knockout cell library. For the first time, we have exposed the knockout cell library to a concentration of 10 ng/mL FSH to explore the underlying mechanisms. Through this screening, we have identified 836 positive–negative screening genes that are responsive to FSH, thereby revealing the regulatory mechanisms and screening the functionality of candidate genes. Next, RNA-Seq of control (0 ng/mL), low (10 ng/mL), and high (100 ng/mL) doses of FSH revealed 1708 differentially expressed genes, and combined with 836 genes, we obtained 129 FSH dose-dependent genes with extremely significant differences. This enables us to delve deeper into investigating and identifying the mechanisms by which FSH regulates GCs. More generally, we have discovered new regulatory factors and identified reproductivity-associated major effectors. These findings provide novel research directions for further studies on sheep reproduction. [ABSTRACT FROM AUTHOR]

Background: Some medical conditions, including polycystic ovarian syndrome (PCOs), may lead to infertility. In PCOs, hormonal imbalance is significant. Antioxidants such as natural antioxidants have many health benefits, including positive effects on hormone production. Objective: Since herbal medicines are more acceptable to people, the present study was designed to evaluate the effect of an aqueous extract of orchid (SA), with antioxidative effects, on the structure of the ovary and the hypothalamic-pituitarygonadal axis hormones and free testosterone in PCOs rats. Materials and Methods: In this experimental study, 64 healthy female Wistar rats (180-200 gr) were randomly divided into 60 and 89 day control groups, PCOs, and 4 PCOs + SA groups that received 40, 80, 160, and 320 mg/kg of SA. Serum levels of gonadotropin-releasing hormone, estrogen, progesterone, testosterone, follicle-stimulating hormone, and luteinizing hormone were measured. In addition, the ovaries were extracted and examined histologically. Results: The amount of primordial, primary, secondary, and Graafian follicles and serum levels of follicle-stimulating hormone and progesterone hormones decreased in PCOs groups, while atretic follicles and the serum levels of gonadotropin-releasing hormone, luteinizing hormone, estrogen, and free testosterone were increased. SA at different doses regulated hormonal and histological imbalances caused by PCOs, and 320 mg/kg was the most effective. Conclusion: The aqueous extract of orchids root can have a positive effect on the improvement of polycystic ovary syndrome. This effect can be achieved by regulating the level of sex hormones and correcting follicular abnormalities in the ovarian tissue. [ABSTRACT FROM AUTHOR]

Genetic causes account for 10–15% of male factor infertility, making the genetic investigation an essential and useful tool, mainly in azoospermic and severely oligozoospermic men. In these patients, the most frequent findings are chromosomal abnormalities and Y chromosome long arm microdeletions, which cause a primary severe spermatogenic impairment with classically increased levels of FSH. On the other hand, polymorphisms in the FSH receptor (FSHR) and FSH beta chain (FSHB) genes have been associated with different FSH plasma levels, due to variations in the receptor sensitivity (FSHR) or in the production of FSH from the pituitary gland (FSHB). Here, we describe an unusual patient with a combined genetic alteration (classic AZFc deletion of the Y chromosome and TT homozygosity for the -211G>T polymorphism in the FSHB gene (rs10835638)), presenting with cryptozoospermia, severe hypospermatogenesis, and normal LH and testosterone plasma concentrations, but low FSH levels. The patient partially benefitted from treatment with FSH (150 IU three times/week for 6 months) which allowed him to cryopreserve enough motile spermatozoa to be used for intracytoplasmic sperm injection. According to our knowledge, this is the first report of an infertile man with AZFc microdeletion with low FSH plasma concentrations related to homozygosity for the -211G>T polymorphism in the FSHB gene. [ABSTRACT FROM AUTHOR]

The current study was aimed to investigate the impact of white light of various intensity of illumination on some reproductive and hematological parameters of female quail (Coturnix coturnix), Where 80 one-day-old birds were used, separated into four groups distributed as follows: The 1st represented as control was exposed to natural lighting, while 2ed,3rd,4th was subjected to different intensity of light represented by 0.6, 25 and 45 lux, respectively, for 5 h/day, each group was divided into 4 replicates. The study continued for 8 weeks. The results indicates a notable raise in the level of FSH and LH hormone with an increase in ovarian weight, an elevate in the number of outgrowth and grown-up follicles for groups exposed to 25 and 45 lux light intensity compared to control and 0.6 lux. It was observed for the same groups an increases in the weight of the edible organs (heart, liver and gizzard). In addition, there was a clear increase in the number of RBC, WBC, lymphocytes, hemoglobin and PCV levels, while the 25 and 45 lux groups showed a decline in the level of MCV with a raise in MCH and MCHC compared with the control and 0.6 lux. It conclude that the intensity of different lighting had positive effects in improving some reproductive and blood characteristics of female quail. [ABSTRACT FROM AUTHOR]

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17α-methyltestosterone (MT), as a synthetic androgen, has been widely used in medicine and aquaculture industry. However, the related molecular regulating mechanism of MT effects on hypothalamic-pituitary-gonadal axis has not been well addressed. This study first evaluated the effects of MT treatment on pituitary of mandarin fish (Siniperca chuatsi). Transcriptome analysis revealed a lot of differentially expressed genes were found in pituitary after MT treatment in early stage (10 and 20 dat), with a relatively few genes found in late stage (30 and 40 dat). Among them, several reproduction related genes were significantly upregulated after MT treatment, while only the expression of follicle-stimulating hormone beta submit (fshb) was significantly inhibited in all stages. Moreover, in vitro experiment also revealed MT significantly inhibited the expression of fshb and promoted the expression of androgen receptors in pituitary. However, dual-luciferase assay revealed that MT activated the promotor activity of fshb via androgen receptors. Finally, we also demonstrated FSH could directly activate the promotor of cyp19a1a by several ways. In all, we first demonstrated exogenous MT could inhibit the expression of fshb in pituitary and further decrease the production of estrogen in gonad by FSH signaling pathway in mandarin fish.

Somatostatin (SST) plays diverse physiological roles in vertebrates, particularly in regulating growth hormone secretion from the pituitary. While the function of SST as a neuromodulator has been studied extensively, its role in fish and mammalian reproduction remains poorly understood. To address this gap, we investigated the involvement of the somatostatin system in the regulation of growth and reproductive hormones in tilapia. RNA sequencing of mature tilapia brain tissue revealed the presence of three SST peptides: SST6, SST3, and low levels of SST1. Four different isoforms of the somatostatin receptor (SSTR) subfamily were also identified in the tilapia genome. Phylogenetic and synteny analysis identified tiSSTR2-like as the root of the tree, forming two mega clades, with SSTR1 and SSTR4 in one and SSTR2a, SSTR3a, and SSTR5b in the other. Interestingly, the tiSSTR-5 isoforms 5x1, 5x2, and 5x3 were encoded in the sstr3b gene and were an artifact of misperception in the nomenclature in the database. RNA-seq of separated pituitary cell populations showed that SSTRs were expressed in gonadotrophs, with sstr3a enriched in luteinizing hormone (LH) cells and sstr3b significantly enriched in follicle-stimulating hormone (FSH) cells. Notably, cyclosomatostatin, an SSTR antagonist, induced cAMP activity in all SSTRs, with SSTR3a displaying the highest response, whereas octreotide, an SSTR agonist, showed a binding profile like that observed in human receptors. Binding site analysis of tiSSTRs from tilapia pituitary cells revealed the presence of canonical binding sites characteristic of peptide-binding class A G-protein-coupled receptors. Based on these findings, we explored the effect of somatostatin on gonadotropin release from the pituitary in vivo. Whereas cyclosomatostatin increased LH and FSH plasma levels at 2 h post-injection, octreotide decreased FSH levels after 2 h, but the LH levels remained unaffected. Overall, our findings provide important insights into the somatostatin system and its mechanisms of action, indicating a potential role in regulating growth and reproductive hormones. Further studies of the complex interplay between SST, its receptors, and reproductive hormones may advance reproductive control and management in cultured populations.

Background: Chronic physical stress has many effects on the nervous system and can cause structural changes in different parts of the brain and hemomodulatory, including hormonal. Current pharmacotherapeutic treatments have limited efficacy and are associated with many deleterious side effects Aim: The aim of this research is to determine how apis dorsata forest honey administration affects FSH and LH levels in rats who are subjected to forced swim tests as a model of chronic physical stress placed in a container filled with water from which it cannot escape. Methods: This was an experimental laboratory study with 32 rats divided into four treatment groups: control (C), Treatment 1 (T1) with a forced swim test + honey (2 g/rat/day), Treatment 2 (T2) with a forced swim test + honey (4 g/rat/day), and Treatment 3 (T3) with a forced swim test + honey (6 g/rat/day). All treatments were administered for 14 days. Then blood was taken for FSH and LH serum tests, and a one-way ANOVA and Duncan test were used to statistically test the data analysis. Results: The results of this study indicate that the administration of forest honey had no significant effect (p > 0.05) on the FSH parameter, but there was a significant decrease in LH levels in the T2 and T3 groups (p [Open Vet J 2024; 14(2.000): 738-742]

Introduction. Approaches to treatment of infertility have been progressively updated because the field of assisted reproductive technologies (ART) is a science-based symbiosis of the latest knowledge and advances in medicine, biology, and genetics. Today, a real-world clinical practice of a reproductive specialist needs to be assessed in the Russian Federation (RF) both in terms of a retrospectively analyzed development of RF in vitro fertilization (IVF) technologies and identifying promising approaches for infertility treatment in the future.Aim: analysis of current therapeutic tendencies and promising trends in real clinical practice of infertility in the Russian Federation.Materials and Methods. In 2022–2023 under the auspices of the Institute for Preventive and Social Medicine and the National Alliance for Public Health Advancement, a survey of reproductive doctors practicing at commercial and government ART centers was carried out. The questionnaire contained questions regarding describing a RF female patient’s portrait with an expected ovarian reserve and response to ovarian stimulation to propose a choice of ovarian stimulation protocol as well as basic and concomitant pharmacotherapy.Results. The opinion of 425 fertility doctors from 156 ART centers in 42 cities of the Russian Federation was assessed. A portrait of a female patient with infertility in the Russian Federation was determined in accordance with the ovarian reserve, expected response to gonadotropin-based stimulation (normal response – 40 %, hyporesponse – 40 %, hyperresponse – 20 % of patients). The basic pharmacotherapy in the stimulation protocol in the IVF program based on agonists and antagonists of gonadotropinreleasing hormone (GnRH), various gonadotropin-containing drugs in female patients with expected normal, hypo- and hyperresponse to ovarian stimulation was assessed. The dominant protocol consists of using GnRH antagonist most often observed in patients with hyper- (95 % of cases), normal (75 % of cases) and hypo-response (45.5 %). Preferences in the basic and concomitant pharmacotherapy in IVF programs were identified as well as current trends in embryo transfer in fresh and cryoprotocols (a tendency to freeze all obtained embryos - “freeze-all” strategy), preimplantation genetic testing methods (used in 30 % of protocols in normal responders, 60 % in hyporesponders and 10 % in hyperresponders) were described.Conclusion. Our study provides the most large-scale analysis of the real-world clinical practice of RF reproductive specialists. A portrait of a RF female patient with infertility, expected ovarian reserve and response to ovarian stimulation was described. Contemporary approaches to select stimulation protocol, basic and concomitant pharmacotherapy in real-world clinical practice were identified. The data obtained represent an important significant cross-section for current practical approaches in real-world practice of RF fertility doctors and can serve as the basis for assessing developing ART methods in the Russian Federation as well as be used to create an evidence base for analyzing future clinical and economic effectiveness of IVF programs in the Russian Federation.