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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]

Assisted reproduction is a key aspect of modern animal breeding, providing valuable assistance in improving breeding programs. In this field, the administration of exogenous hormones, such as follicle-stimulating hormone (FSH), plays a crucial role in the induction of multiple ovulations. However, commercial FSH used in veterinary practice has been derived primarily from pituitary glands, obtained mostly from pigs for nearly four decades. Although these hormones have contributed significantly to the advancement of assisted reproductive techniques, they have certain limitations that warrant further improvements. These limitations include contamination with luteinizing hormone (LH), the potential risk of pathogen contamination, the potential to trigger an immune response in non-pig species, and the short half-life in circulation, requiring the implementation of complex 8-dose superovulation schedules. Our research team has developed and characterized a new variant of bovine follicle-stimulating hormone (bscrFSH) to address these limitations. The new hormone is produced recombinantly in CHO cell cultures, with a specific productivity of about 30 pg/cell/day. The bscrFSH can be purified to a high purity of 97 % using a single step of immobilized metal affinity chromatography (IMAC). N-glycan analysis of bscrFSH showed that approximately 74 % of the glycans corresponded to charged structures, including mono-, di-, tri-, and tetra-sialylated glycans. Superovulation trials conducted in cattle revealed that bscrFSH, administered at a total dose of about 0.5 μg per kg of body weight, using a decrescent schedule of 4 doses with 24-h intervals, resulted in an average yield of 8–12 transferable embryos per animal. Further research is required; however, the preliminary findings indicate that bscrFSH, currently packaged under the provisional brand name of Cebitropin B, holds potential as a commercial product for assisted reproduction in ruminants. • The bovine FSH variant (brscFSH) designed by the team is functional in inducing superovulation in cattle. • brscFSH can be produced at 30 pg/cell/day and purified to >95% purity using immobilized-metal affinity chromatography (IMAC). • brscFSH yields 8–12 transferable embryos on average at 0.5 μg/kg in a four-dose schedule over 12 hours. • Further studies are needed to assess brscFSH in two/single-dose schedules and in other species like sheep, goats, camelids, and mares. • brscFSH is now available for research use only on the Centro de Biotecnología y Biomedicina SpA website. [ABSTRACT FROM AUTHOR]

Purpose: Diet-related factors are of great significance in the regulation of hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-gonad (HPG) axes. In this study, we aimed to investigate the effects of chronic exposure to a high fat diet (HFD), fructose or sucralose on the endocrine functions. Methods: Male, Sprague-Dawley rats received a normal chow diet, HFD, 10% fructose or 0.02% sucralose for 10 weeks. Behavioral changes were assessed by open field (OFT) and elevated plus-maze (EPM) tests at week 8. H&E staining was used to observe pathological changes in adrenal cortex, testis and perirenal adipose tissue. Serum hormone concentrations were quantified via enzyme-linked immunosorbent assay (ELISA). The mRNA expression levels of genes along the HPA and HPG axes were determined using real-time PCR. Results: All types of dietary interventions increased body weight and disturbed metabolic homeostasis, with anxiogenic phenotype in behavioral tests and damage to cell morphology of adrenal cortex and testis being observed. Along the HPA axis, significantly increased corticotropin releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone (CORT) concentrations were observed in the HFD or 0.02% sucralose group. For HPG axis, gonadotropin-releasing hormone (GnRH) and estradiol (E2) concentrations were significantly increased in all dietary intervention groups, while decreased concentrations of follicle-stimulating hormone (FSH) and testosterone (T) were also detected. Moreover, transcriptional profiles of genes involved in the synthesis of hormones and corresponding hormone receptors were significantly altered. Conclusion: Long-term consumption of HFD, fructose or sucralose manifested deleterious effects on endocrine system and resulted in the dysregulation of HPA and HPG axes. [ABSTRACT FROM AUTHOR]

Objective: Our aim was to show that anti-Mullerian hormone (AMH) may be used as a quantitative marker of ovarian reserve in Turkish girls aged 18 years and younger and establish the reference values for AMH in Turkish girls. Material and Methods: This retrospective study included girls between 8-18 years old, without premature ovarian failure or without genetic factors resulting in ovarian dysgenesis. Blood specimens were collected after overnight fasting early in the morning during the early follicular phase. Measurement of serum levels of gonadotropins and AMH was done. Mean serum AMH levels of different age groups and best fitting curve representing AMH percentiles (10th, 25th, 50th, 75th, 90th) were calculated. Results: In total 785 girls with a mean age of 16.16±1.90 years were included, divided into seven age groups. The mean serum AMH level for the total cohort was 5.20±4.19 ng/mL. There was a significant difference between the mean values of AMH in age groups as follows: ≤12 and 17-≤18 (p=0.011). The best fitting curves for AMH percentiles were 4th order polynomial functions. There was a significant correlation between AMH and age and follicle stimulating hormone levels (r=0.148, p<0.001 and r=-0.092, p=0.010). Conclusion: Our results reflect the real-life data for serum AMH values in Turkish girls. Our nomogram may be useful for counseling adolescents about their ovarian reserve and diagnosing other gynecological diseases. A longitudinal study is necessary for improving the predictive value of AMH values in girls aged 18 and younger. [ABSTRACT FROM AUTHOR]

The inhibin alpha (INHA) serves as a marker for the number of fully developed ovarian follicles and plays a crucial role in regulating the secretion of pituitary FSH (follicle-stimulating hormone) and the frequency of ovulation. This study aims to examine the effect of INHA gene polymorphisms on the litter size of thin-tailed sheep. Detection of single nucleotide polymorphisms (SNPs) in the INHA gene was performed using PCR and DNA sequencing techniques. A total of 45 ewes were included in the study. Three SNPs were identified: g.236311141G>C, g.236311367G>A, and g.236311368G>A. Further investigation of the g.236311367G > A variant revealed that individuals with the GA genotype had a significantly higher litter size than those with the AA or GG genotype (p<0.05). SNPs at positions g.236311141G/C and g.236311368G/A were non-synonymous mutations resulting in amino acid changes p.A225P and V301I, respectively. Our results suggest that g.236311367G>A loci may serve as a potential molecular marker for improving the litter size trait in thin-tailed sheep. [ABSTRACT FROM AUTHOR]

Background & Objective: There is disagreement about the correlation between serum 25-OH vitamin D (25OH-D) concentrations and ovarian reserve. The aim of this study was to evaluate the correlation between serum levels of 25OH-D and ovarian reserve parameters, including Anti-mullerian hormone (AMH), Follicle stimulating hormone (FSH), and Antral follicular count (AFC) in the tropical zone. Materials & Methods: In this cross-sectional study, 148 infertile women were enrolled. On the third day of their cycles, vitamin D3, FSH, and AMH were measured. An ultrasound scan was done for the measurement of the ovaries AFC. Participants were divided into women with normal ovarian reserve (NOR) and women with diminished ovarian reserve (DOR). Then two groups were compared based on the levels of vitamin D. Results: Our findings showed that there were significant differences in vitamin D levels between the DOR and NOR groups (11.52±12.24 and 22.74±12.7, respectively), (P value <0.001). The partial Spearman correlation test depicted an inverse relationship between vitamin D and FSH (rho=-0.21, P =0.009). Also, there was a positive relationship between vitamin D and AMH and AFC, (rho=0.27, P=0.001) and (rho=0.39, P< 0.001) respectively. Conclusion: This study demonstrated that there was an inverse relationship between levels of vitamin D and FSH and a positive relationship with AMH and AFC. It appears that the level of vitamin D is important in DOR. [ABSTRACT FROM AUTHOR]

Background & Objective: A competent embryo, receptive endometrium and a series of highly coordinated molecular events between them are all essential for successful implantation. Evaluation of certain molecules which may be used as biomarkers may help to predict pregnancy outcome and detect subtle implantation defect. The present study was conducted with aim to assess the relationship between serum concentrations of adrenomedullin (ADM) and pentraxin3 (PTX3) measured at the day of embryo transfer and successful implantation in assisted reproductive technique cycles. Materials & Methods: This prospective cohort study included 88 frozen embryo transfer (FET) cycles. All patients received sequential oestrogen & progesterone medications. Embryo transfer (with a minimum of one top quality embryo) was scheduled after 4 days (D3 embryo), 6 days (D5 embryo) of progesterone administration. The serum ADM and PTX3 levels were analyzed 1 hour before the embryo transfer (ET) using ELISA kits. A possible association between these two markers levels and embryo implantation was evaluated. Results: Overall, biochemical pregnancy rate was 25% (22/88). Data were then categorized into pregnant (22/88) & non-pregnant (66/88). No significant difference were found between the two groups regarding female age, endometrial thickness, number of oocyte collected, oestradiol level (E2), FSH level, grade and number of embryo transferred (P>0.05). The ADM levels were higher on the day of ET, although was not significant in pregnant group (254.60 pg/ml vs 248.18pg/ml). PXT3 levels (pg/ml) were lower in pregnant compared to non-pregnant group (25.396±11.78 vs 28.431±16.51, P=0.428). Conclusion: Higher ADM and lower PTX3 levels at the day of embro transfer may be associated with successful implantation. [ABSTRACT FROM AUTHOR]

Copyright of Turkish Journal of Obstetrics & Gynecology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Turkish Journal of Obstetrics & Gynecology is the property of Galenos Yayinevi Tic. LTD. STI and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Polycystic ovary syndrome (PCOS) is one of the most prevalent endocrinopathies among young women. Ultrasound evidence of polycystic ovaries is one of its crucial diagnostic criteria. Objectives: Our main objective is to study the contribution of ultrasound data in diagnosing PCOS. In addition, we aim to establish a new cutoff point for the use of ultrasound and to determine its sensitivity as well as its specificity. Design: It was a prospective study, including all patients presenting with clinical hyperandrogenism. Methods: The ultrasound examination of these patients was performed using a novel ultrasound machine (18 MHz) compared to an older ultrasound machine (2 Hz–8 MHz). Inclusion criteria encompassed adult female patients over 18 years presenting symptoms suggestive of PCOS, particularly hyperandrogenism and oligo-anovulation, meeting Rotterdam's diagnostic criteria. Prior to inclusion, assessments were conducted to eliminate other potential causes explaining hyperandrogenism or menstrual disorders in both groups. Results: We examined 92 patients diagnosed with PCOS. Menstrual disorders were the main symptoms, with amenorrhea being more frequent in the PCOS group (G1) (48.9% vs the control group (G2): 11.1%). The follicle number was significantly lower in the control group, as assessed by both ultrasound machines (p < 10−3). The accuracy of the new ultrasound device was evaluated compared to the old one using the receiver operating characteristic (ROC) curve, revealing a cutoff of 18 follicles (sensitivity of 68.1%, specificity of 100%) and an area under the curve of 0.955. We found a significant difference between the median values of the number of follicles (NF) by both ultrasound machines (18 vs 12). It was positively correlated with an index of r = 0.916. For the volume, it was distinctively higher in G1 (p < 10−3). ROC curve analysis revealed an ovarian volume cutoff of 9.25 ml with a sensitivity of 48.9% and a specificity of 100%. Both ultrasound machines were positively correlated with an index of r = 0.979 (p < 10−3). Conclusion: In conclusion, we were able to establish significant correlations between the new and the old ultrasound devices for both the NF and ovarian volume. Our study is distinctive as it represents the first on the African continent to re-evaluate the ultrasound criterion for PCOS. Plain language summary: Validating ultrasound criteria for PCOS in North African patients In this study, we explored patients using ultrasound to better diagnose Polycystic Ovary Syndrome (PCOS) in North African women. Ovarian follicles are small sacs in a woman's ovaries that not only release eggs but also produce important hormones like estrogen and progesterone. These hormones regulate the menstrual cycle, prepare the body for pregnancy, and influence many aspects of a woman's health and well-being. We set new standards for measuring follicles and ovaries to improve diagnosis accuracy. Background: Polycystic Ovary Syndrome (PCOS) is often diagnosed using ultrasound in North African women. Current ultrasound standards may not be accurate enough for this group. This study aimed to improve PCOS diagnosis by setting new standards for measuring ovarian sizes and follicle numbers. Methods: We reviewed a new ultrasound method. We then established new measurement thresholds specific to North African women. These new standards were tested for accuracy in diagnosing PCOS. Results: Our new measurement thresholds were more accurate in diagnosing PCOS. The improved standards led to better identification of PCOS in North African women. This suggests that current ultrasound methods might need adjustments based on population-specific data. Conclusions: Using ultrasound with new measurement standards can improve PCOS diagnosis in North African women. Adjusting diagnostic criteria to specific populations may enhance overall healthcare outcomes. [ABSTRACT FROM AUTHOR]

Introduction: Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disturbance that affects many women worldwide and is characterized by chronic anovulation, hyperandrogenism, and ovarian dysfunction. Placenta-derived mesenchymal stem cells (PDMSCs) are derived from the placenta and have advantages over other sources of MSCs in terms of availability, safety, and immunomodulation. Materials and methods: In this experimental study, twenty female Wistar rats were assigned to four groups (n = 5) including control, sham, PCOS, and PCOS+PDMSCs groups. Then, PCOS was induced in the rats through administering letrozole for 21 days. PDMSCs (1 × 106 cells) were injected through the tail vein. Fourteen days after the cell infusion, evaluation was performed on the number of healthy follicles, corpus luteum, and cystic follicles as well as the levels of testosterone, follicle-stimulating hormone (FSH), luteinizing hormone (LH), fasting blood glucose, fasting insulin, and insulin resistance. Moreover, the serum levels of cholesterol, triglyceride (TG), high-density lipoprotein (HDL), and low-density lipoprotein (LDL) were measured. Liver function was also determined by the evaluation of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels. Results: The number of corpus luteum and primordial, primary, secondary, and antral follicles was significantly elevated in the PCOS+PDMSCs group compared to the PCOS group. However, the number of cystic follicles significantly decreased in the PCOS+PDMSCs group. The LH and testosterone levels also decreased significantly, while FSH levels increased significantly in the PCOS+PDMSCs group. The levels of fasting blood glucose, fasting insulin, and insulin resistance notably decreased in the PCOS+PDMSCs group. Moreover, the lipid profile improved in the PCOS+PDMSCs group along with a significant decrease of cholesterol, LDL, and TG and an increase in HDL. The PCOS+PDMSCs group exhibited marked decreases in the AST and ALT levels as well. Conclusion: The results of this study suggest that PDMSCs are a potential treatment option for PCOS because they can effectively restore folliculogenesis and correct hormonal imbalances, lipid profiles and liver dysfunction in a rat model of PCOS. However, further research is needed to establish the safety and effectiveness of PDMSCs for treating PCOS. [ABSTRACT FROM AUTHOR]

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]

Introduction: Nirogacestat is a targeted gamma secretase inhibitor approved in the United States for adults with progressing desmoid tumors. In the phase 3 DeFi study (NCT03785964) of nirogacestat, ovarian toxicity (OT) was identified as a safety signal among females of reproductive potential (FORP). This analysis further describes the incidence, presentation, and resolution of OT. Methods: Patients were randomized to twice‐daily oral nirogacestat (150 mg) or placebo, taken in continuous 28‐day cycles. Investigator‐identified OT in FORP was based on abnormal reproductive hormone values or perimenopausal symptoms (or both). Adverse event follow‐up was conducted to assess OT resolution. Post hoc analyses included return of menstruation and return of follicle‐stimulating hormone (FSH) to within normal limits (WNL) (≤20.4 mIU/mL). Results: Of 92 randomized females, 73 in the safety population were FORP (n = 36 nirogacestat, n = 37 placebo). OT was identified in 75% (27 of 36) receiving nirogacestat and 0% (0 of 37) receiving placebo. As of October 24, 2022, investigators reported OT resolution in 78% (21 of 27) of patients, with median OT duration of 19.1 weeks. Off‐treatment resolution was reported in all 11 patients (100%) who stopped nirogacestat treatment; of these, all nine with available menstruation information experienced return of menstruation and eight had FSH WNL at last reported assessment. Resolution was reported in 10 of 14 (71%) while on nirogacestat; of these, all 10 experienced return of menstruation and seven had FSH WNL. Two patients were lost to follow‐up. Conclusion: Most FORP treated with nirogacestat experienced OT, with the majority resolving, including all who stopped treatment, suggesting that OT is transient. In the phase 3 DeFi study of nirogacestat, a targeted gamma secretase inhibitor approved in the United States for adults with progressing desmoid tumors, ovarian toxicity was identified as a safety signal in most females of reproductive potential. The majority (78%) of ovarian toxicity events resolved, including in 100% of patients who stopped nirogacestat for any reason, suggesting that ovarian toxicity with nirogacestat is transient. [ABSTRACT FROM AUTHOR]

Purpose: The study aimed to investigate the correlation between the change of sex hormone levels and ocular surface parameters in girls with idiopathic central precocious puberty(ICPP). Methods: Eighteen girls with ICPP and 18 age-matched normal girls participated in this study, all of the participants had undergone physical measurements, laboratory tests, imaging examination and ocular surface assessments. Results: The Objective Scatter Index (OSI) in the ICPP group was significantly higher than in the control group (P = 0.031), girls with ICPP showed slightly lower MNITBUT compared to the normal control group, although this difference was not statistically significant. Bivariate analysis revealed a positive association between estradiol and OSI (r=0.383, P=0.021), Additionally, in the study population, both Luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) were negatively correlated with Mean noninvasive tear breakup time (MNITBUT) (r=-0.359, P=0.031)(r=-0.357, P=0.032). Conclusion: In comparison with the normal control group, alterations in the OSI were observed in girls with ICPP. This alteration may be associated with an elevation in estrogen levels. Although there was a slight non-significant decrease in NITBUT in ICPP girls, the negative correlation between LH and FSH with MNITBUT suggests new perspective for further investigation. [ABSTRACT FROM AUTHOR]

The classic way to produce single-chain (sc) glycoprotein hormones is to fuse their two subunits through the carboxy-terminal peptide (CTP) from human Choriogonadotropin (hCG). The CTP confers a longer half-life to single-chain hormones thanks to its four O-glycosyl side chains. However, unlike syncytiotrophoblastic cells, most cells used for recombinant protein production do not transfer O-glycosyl chains efficiently. We thus choose to fuse the hFSH subunits with a linker comprising two N -glycosyl side chains (sc-hFSH LNN) or none (sc-hFSH L0N), that were generated using two expression systems, HEK293 and CHO K1 cells. Their production levels and biological activities were tested and compared. Both expression systems successfully produced biologically active sc-hFSH, but, in our hands, CHO K1 cells yielded about 30-fold higher amounts of recombinant protein than HEK293 cells. Moreover, sc-hFSH L0N was considerably less expressed than sc-hFSH LNN in both cell types. Our data show that sc-hFSH L0N and sc-hFSH LNN produced from both cell lines stimulate cAMP and progesterone production in mLTC cells expressing hFSH receptors and exhibit similar B/I (in vitro Bioactivity/Immuno activity) ratios. Finally, the ratio of in vivo / in vitro bioactivities for sc-hFSH LNN relative to natural pituitary heterodimeric hFSH increased 8-fold, most likely because of a longer half-life in the blood. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the feasibility of different gonadotropin assays for determining total and intact luteinizing hormone (LH), and follicle‐stimulating hormone (FSH) immunoreactivity in urine (U‐LH‐ir and U‐FSH‐ir, respectively) during early infancy. Design, Patients and Measurements: Morning urine samples were obtained from 31 infants, aged between 0 and 6 months, to study the age‐related course of urinary gonadotropins. Additionally, we investigated bi‐hourly urine samples of a 5‐day‐old male neonate for 24 h to observe the course of urinary gonadotropins during a daily cycle. We employed different immunofluorometric assays for measuring total and intact U‐LH‐ir, and U‐FSH‐ir. Results: In neonates up to 21 days of age, the U‐LH‐ir levels measured by the regular LH assay (also detecting hCG) were significantly higher than those determined by the total (specific) LH assays (p =.004). U‐FSH‐ir was higher in girls than boys during both the first and the next 5 months (p =.02 and p <.001, respectively), whereas total U‐LH‐ir was higher in boys until 6 months of age (p <.001). Total U‐LH‐ir/U‐FSH‐ir ratio was significantly higher in boys than girls across the first half‐year (p <.001). Conclusions: The assessment of total U‐LH‐ir and U‐FSH‐ir, and their respective ratio constitutes a noninvasive, practical and scalable tool to investigate sex‐specific changes during early infancy, with the ratio being significantly higher in boys than girls. Only highly specific LH assays detecting beta‐subunit and its core fragment in addition to intact LH should be used for determining U‐LH‐ir in the neonatal period to avoid potential cross‐reactivity with hCG of placental origin. [ABSTRACT FROM AUTHOR]

AbstractObjectiveMethodsResultsConclusionsTo investigate the comprehensive effects of daily chronic asprosin administration on various pubertal and reproductive parameters in female rats. This study aims to elucidate the role of asprosin in regulating the onset of puberty and its influence on hormonal profiles and ovarian histology.Asprosin was administered intraperitoneally (i.p.) at a dose of 500 ng/kg daily for eight weeks. Hormonal assays and histological analyses were performed to evaluate the effects of asprosin on the onset of puberty and reproductive function.Daily chronic administration of asprosin accelerated the onset of the first oestrus. Hormonal assays revealed significant elevations in serum levels of Follicle-Stimulating Hormone (FSH) and Oestradiol (E2), while Inhibin B levels decreased. Histological evaluations demonstrated an increased number of primary and secondary follicles in ovarian tissue, without affecting primordial follicle counts or reproductive organ weights.Role of adipokines in regulating puberty and reproductive function has increasingly gained recognition. This study aimed to provide the first comprehensive examination of the effects of daily chronic asprosin administration on pubertal and reproductive parameters in female rats. Utilising hormonal assays and histological analyses, asprosin was administered intraperitoneally (i.p.) at a dose of 500 ng/kg, daily, for eight weeks. Our findings revealed that daily chronic administration of asprosin accelerated the onset of the first oestrus. Hormonal assays showed significant elevations in serum levels of Follicle-Stimulating Hormone (FSH) and Oestradiol (E2), while Inhibin B levels decreased. Histological evaluations demonstrated an increased number of primary and secondary follicles in ovarian tissue, without affecting primordial follicle counts or reproductive organ weights. These results provide new insights into asprosin’s role in advancing the age of first oestrus and modulating hormonal profiles, thereby offering potential benefits to the female reproductive system. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the role of basal and follicle-stimulating hormone (FSH)-stimulated inhibin B in differentiating premature thelarche from gonadotropin-dependent precocious puberty (GDPP). Method: This was a prospective interventional study. Basal and FSH-stimulated inhibin B levels were estimated in girls presenting with thelarche < 8 years age (n = 10), healthy girls with normal pubertal development (pubertal control) (n = 8) and healthy prepubertal girls (prepubertal control) (n = 7). Girls with early puberty were classified as premature thelarche or GDPP based on GnRH agonist stimulation test. Results: Median (IQR) basal inhibin B levels (pg/mL) in premature thelarche was 5.42 (2.91, 30.58) and FSH-stimulated inhibin B was 236.72 (111.53, 4431.73) (P = 0.043). Median (IQR) basal inhibin B in GDPP was 64.11 (24.96, 792.45) pg/mL and FSH-stimulated inhibin B was 833.66 (500.11–1266.18) pg/mL (P = 0.043). Basal inhibin B was discriminatory between GDPP and premature thelarche (P = 0.032). Median (IQR) basal inhibin B in prepubertal and pubertal controls was 20.36 (9.61, 29.12) and 75.48 (58.55, 165.55) pg/mL, respectively. Conclusion: Basal inhibin B is useful in differentiation of premature thelarche from GDPP while the role of FSH-stimulated inhibin B needs to be further explored in large sample size. [ABSTRACT FROM AUTHOR]

Context The co-occurrence of hormonal changes during menopause and the risk of cardio-metabolic disorders has been well studied. Objective We explored the association of circulating levels of follicle-stimulating hormone (FSH) with diabetes (DM) among postmenopausal women. Method In this systematic review and meta-analysis, the search was performed in PubMed, Scopus, Web of Sciences, Epistemonikos, and Cochrane Library up to September 2023. Risk of bias was assessed by Newcastle-Ottawa Quality Assessment Scale. Pooled estimates of mean differences in FSH levels were compared between postmenopausal women with and without DM. Correlations between FSH and fasting blood glucose (FBG)/insulin/homeostatic model assessment for insulin resistance (HOMA-IR) as well as pooled effect sizes with their 95% CIs for risk of DM were calculated. Results In this study, 14 articles, including 7878 postmenopausal women, met eligibility criteria. Most of the included studies had a low/moderate risk of bias. Women with DM had significantly lower FSH levels than those without DM (standardized mean difference [SMD] −0.751 [95% CI, −1.129 to −.372], I2 = 82.46%, n = 1416). The pooled effect size for diabetes was 0.861 (95% CI, 0.740-1.001; I2 = 80.11%). The pooled risk estimate for DM based on the categorical FSH levels (high vs low) was (HR = 0.550; 95% CI, 0.356-0.850, I2 = 0). The significant inverse correlation was found between FSH levels and glycemic parameters: FBG (r = −0.285 [95% CI −0.441 to −0.113]; n = 1229), HOMA-IR (r = −0.241[−0.378 to −0.0924]; n = 1229) and insulin (r = −0.337 [−0.434 to −0.232]; n = 959)]. There were no statistically significant differences between estradiol levels among diabetic and nondiabetic groups; however, the SMD for luteinizing hormone was similar to that reported for FSH. Conclusion The available data indicated an indirect association between FSH levels and glucose disturbances among postmenopausal women, notwithstanding heterogeneity among included studies, and the complexity of various influential factors needs to be considered. Further efforts should be made to clarify the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Dioxins are endocrine disruptors that may disturb male sexual and reproductive function. Studies on human populations are limited, and their results are controversial. This study evaluated the impact of dioxin exposure on reproductive and thyroid hormone levels and sexual function in men. A total of 140 men working in four military airbases (three bases were formerly contaminated with dioxin by the herbicide spraying campaign in the Vietnam War) were recruited to measure the serum dioxin levels. Four reproductive hormones (testosterone, follicle-stimulating hormone, luteinizing hormone (LH), and prolactin) and three thyroid hormones (free triiodothyronine (FT3), free thyroxin (FT4), and thyroid stimulating hormone) were measured. Male sexual function endpoints including sexual drive, erection, ejaculation, problems, and overall satisfaction were assessed by the Brief Male Sexual Function Inventory. The percentage of subjects with low testosterone and LH levels was 19.6% and 16.7%, respectively. Dioxins, especially 2,3,7,8-tetrachlorodibenzo-P-dioxin and toxic equivalent concentrations of polychlorinated dibenzo-p-dioxins/polychlorinated dibenzofurans, were inversely associated with testosterone and prolactin levels, but positively associated with FT3 and FT4, and showed adverse relationships with sexual function, such as sexual drive, problems, and overall satisfaction. Our results suggested that exposure to dioxin disrupts the homeostasis of reproductive and thyroid hormones leading to adverse effects on male sexual function. [ABSTRACT FROM AUTHOR]

Female fertility depends on the ovarian reserve of follicles, which is determined at birth. Primordial follicle development and oocyte maturation are regulated by multiple factors and pathways and classified into gonadotropin-independent and gonadotropin-dependent phases, according to the response to gonadotropins. Folliculogenesis has always been considered to be gonadotropin-dependent only from the antral stage, but evidence from the literature highlights the role of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) during early folliculogenesis with a potential role in the progression of the pool of primordial follicles. Hormonal and molecular pathway alterations during the very earliest stages of folliculogenesis may be the root cause of anovulation in polycystic ovary syndrome (PCOS) and in PCOS-like phenotypes related to antiepileptic treatment. Excessive induction of primordial follicle activation can also lead to premature ovarian insufficiency (POI), a condition characterized by menopause in women before 40 years of age. Future treatments aiming to suppress initial recruitment or prevent the growth of resting follicles could help in prolonging female fertility, especially in women with PCOS or POI. This review will briefly introduce the impact of gonadotropins on early folliculogenesis. We will discuss the influence of LH on ovarian reserve and its potential role in PCOS and POI infertility. [ABSTRACT FROM AUTHOR]

Background: Alarming trends show an increase in referrals of girls with suspected early puberty. However, variations in defining precocious puberty exist. GnRH stimulation test is the gold standard diagnostic test, which is expensive and challenging to interpret. Moreover, intravenous GnRH might not be available. Therefore, we sought to evaluate the diagnostic performance of basal serum Luteinizing Hormone and Anti-Mullerian hormone in girls with central precocious puberty, as an easier alternative to GnRH stimulation test. The study was conducted on 26 Egyptian girls presenting with early puberty at age < 8 years. Several evaluations including Tanner staging and GnRH stimulation test were performed. Basal serum luteinizing hormone, follicle stimulating hormone, and anti-Mullerian hormone were analyzed, and ROC curve was performed. Results: The mean age of the patients at diagnosis was 5 ± 2.8 years. Most patients had breast Tanner 3 (76.9%). Bone age was advanced in 65.4% of patients. Basal luteinizing hormone level significantly differed between central precocious puberty and controls (p < 0.001), with an area under the curve of 0.840. A cut-off of 0.29 IU/L provided 84.62% sensitivity and 76.92% specificity. Conclusions: Basal luteinizing hormone out-performs follicle-stimulating hormone and anti-Mullerian hormone as a screening tool and valuable indicator of central precocious puberty, potentially reducing the necessity of GnRH stimulation test. [ABSTRACT FROM AUTHOR]

Objectives: The present study aimed to investigate the relationship between male hormones and metabolic dysfunction-associated fatty liver disease (MAFLD) in males. Methods: Data from the Fangchenggang Area Male Health and Examination Survey (FAMHES) were used to analyze the male hormone levels between MAFLD patients and controls. Univariate and multivariate logistic regression analyses were performed to identify risk factors for MAFLD. Receiver operating characteristic curve analysis was used to assess the diagnostic performance of male hormones for MAFLD. Result: A total of 1578 individuals were included, with 482 individuals (30.54%) of MAFLD, including 293 (18.57%) with mild disease and 189 (11.98%) with moderate-to-severe disease. The MAFLD patients were significantly older than those without MAFLD. The LH, FSH, and SHBG levels in the MAFLD patients were significantly greater than those in the control group. Age, FSH, LH, SHBG, and estradiol were all risk factors for MAFLD. Age, FSH, and LH were risk factors for moderate-to-severe MAFLD. FSH was an independent risk factor for MAFLD and moderate-to-severe MAFLD. FSH showed an excellent diagnostic value, with an AUC of 0.992 alone and 0.996 after adjusting age. Conclusions: Our findings indicate that FSH may be a potential diagnostic and predictive biomarker for MAFLD. [ABSTRACT FROM AUTHOR]

Hyperandrogenemia is associated with polycystic ovarian syndrome (PCOS) and imbalances in the pituitary hormones, luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) levels. Apelin and its receptor, APJ (class A, rhodopsin‐like G‐ protein‐coupled receptor), belongs to adipokines, and its expression has been shown in the pituitary. It is also well known that, hyperandrogenism and PCOS have deregulation of different adipokines. Whether hyperandrogenism also deregulates the apelin system in the pituitary has yet to be investigated. Thus, we have investigated the expression and localization of apelin and its receptor, APJ, in the letrozole‐induced hyperandrogenised pituitary of female mice. Our results showed that the apelin, APJ and androgen receptor (AR) expression were upregulated in the anterior pituitary. Furthermore, the immunostaining of LH exhibited increased abundance than FSH. The circulating LH was also found to be elevated compared to FSH levels. The increased LH synthesis and secretion coincides with elevated apelin system in the pituitary of hyperandrogenised mice. Recently, a direct role of apelin has also been reported in the female pituitary, where apelin inhibits LH secretion. Thus, apelin could be one of the factors for deregulated gonadotropin secretion in hyperandrogenised conditions. However, more research is needed to fully understand the complex interactions between apelin and androgen regarding gonadotropin secretion in hyperandrogenised conditions. [ABSTRACT FROM AUTHOR]

The objective of this study was to investigate the effects of salmon gonadotropin releasing hormone analog (S-GnRH-A) and human chorionic gonadotropin (HCG) on the serum levels of gonadotropins (GtHs) and sex steroid hormones in Manchurian trout during sexual maturity. Females in the treatment group were injected with 20 µg/kg S-GnRH-A and 400 IU/kg HCG, whilst males were injected with half the amount. Blood samples were collected at 0, 5, 10, and 20 days post injection (dpi). The results showed an increase in female follicle-stimulating hormone (FSH) levels in the treatment group at 5 dpi, and from 5 dpi onwards, a difference was observed between the groups, with higher FSH levels in the treatment group compared to the control group. In males, FSH levels showed group differences at only 5 dpi (p < 0.05) and were higher in the treatment group. In females, luteinizing hormone (LH) peaked at 10 dpi in the treatment group, and there were differences between the two groups at 10 dpi and 20 dpi. In males, LH was significantly higher in the treatment group than in the control group at 5 dpi and 10 dpi (p < 0.05). In females, estradiol (E2) was significantly higher in the treatment group than in the control group at 5 dpi and 10 dpi (p < 0.05), whereas in males, the difference between the two groups was only observed at 5 dpi (p < 0.05). The female testosterone (T) level in the treatment group was significantly higher than that of the control group at 5 dpi and 10 dpi (p < 0.05), while T levels were significantly higher in the male treatment group than in the control group at 5 dpi (p < 0.05). The level of 17α–hydroxyprogesterone (17α-OHP) in the females of the treatment group was significantly higher than that of the control group at 5 dpi and 10 dpi (p < 0.05), and 17α-OHP levels were significantly higher in the male treatment group than in the control group at 10 and 20 dpi (p < 0.05). The fish were successfully spawned after S-GnRH-A and HCG injections, and brood amount, fertilization rate, and hatching rate were significantly increased (p < 0.05). This study provides a framework for a better understanding of the mechanisms of exogenous hormone-mediated control of reproduction in Manchurian trout. [ABSTRACT FROM AUTHOR]

Objective: To reveal the overall sperm retrieval rate (SRR) and range in patients with azoospermia factor c (AZFc) microdeletion azoospermia by microdissection testicular sperm extraction (mTESE) and discuss the differences of preoperative patient factors among studies with various SRRs. Patients and Methods: We searched PubMed, Web of Science and Embase until February 2023. All studies reporting SRRs by mTESE and required parameters of patients with AZFc microdeletions were included. The primary outcome was the SRR and, if available, the pregnancy rate (PR) and live‐birth rate (LBR) after intracytoplasmic sperm injection were also investigated as secondary outcomes. Results: Eventually 11 cohort studies were included in this review. A total number of 441 patients underwent mTESE and in 275 of them sperm was obtained, reaching an overall SRR of 62.4%. The SRRs among studies had a wide range from 25.0% to 85.7%. The studies reporting higher SRRs generally had older mean ages, and higher follicle‐stimulating hormone and testosterone levels. Only four studies provided practical data on pregnancies and live‐born children of patients with AZFc microdeletions, so the overall PR and LBR were unavailable. Conclusions: The overall SRR of patients with AZFc microdeletion azoospermia was 62.4%. The effect of patient factors in SR needs further evidence in future work. [ABSTRACT FROM AUTHOR]

Tao-Hong-Si-Wu-Tang (THSWT), a traditional Chinese herbal remedy, is commonly utilized for the treatment of female perimenopausal depression through regulating menstruation, but the mechanism remains unknown. In this study, ICR mice were randomly divided into six groups: low, medium, and high dose of THSWT (0.5, 1.5, and 4.5 g/kg), soy isoflavone (250 mg/kg), ovariectomy group, and control group. All mice, except the control group, had ovaries removed and were exposed to hypoxic stimulation for 28 days to establish a perimenopausal depression mice model. The mice, having unrestricted access to food and water, were administered THSWT treatment for a duration of 14 days. The Western blotting and Enzyme linked immunosorbent assay kits were used to determine protein and hormone levels, respectively. Experimental results showed that THSWT reduced the immobility time of mice from 150.8 s to 104.9 s in the tail suspension test, and it decreased the immobility time of mice from 165.7 s to 119.0 s in the forced swimming test, outperforming the results obtained with soy isoflavones. In addition, THSWT upregulated the protein expression of follicle-stimulating hormone receptor and downregulated the protein expression of corticotropin-releasing hormone-receptor 1 in the hippocampus. Compared with the oophorectomized group, treatment with THSWT decreased the levels of corticosterone and adrenocorticotropic hormone in serum by 173.7 and 23.4 ng/mL, respectively. These findings showed that THSWT could stimulate the perimenopausal nerve tissue and regulate the level of serum hormones in mice. THSWT exhibited promising potential as a viable alternative drug for hormone treatment of perimenopause in clinical use. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to investigate the protective effects of gallic acid (GA) against ovarian damage induced by bisphenol A (BPA) exposure in female rats. We evaluated whether GA can mitigate the adverse effects of BPA on ovarian structure, inflammatory markers, oxidative stress, apoptosis, and reproductive hormone levels. Methods: Thirty-two female rats were categorized into four groups: control, GA, BPA, and GA+BPA. Histopathological evaluations of ovarian tissue were performed using hematoxylin-eosin staining. The immunohistochemical analysis was conducted for inflammatory, oxidative DNA damage, and apoptotic markers (Tumor necrosis factor alpha [TNFα], cyclooxygenase-2 [COX2], interleukin-1 beta [IL-1β], 8-hydroxydeoxyguanosine [8-OHdG], and caspase 3). Oxidative stress was assessed by measuring malondialdehyde and superoxide dismutase levels. Furthermore, follicle-stimulating hormone (FSH), luteinizing hormone (LH), estrogen, and progesterone levels were quantified using enzyme-linked immunosorbent assay. Results: Histopathological outcomes revealed that BPA significantly induced follicular degeneration, which was effectively mitigated by GA treatment (P < 0.05). Immunohistochemical analysis highlighted the exacerbation of inflammatory responses and oxidative DNA damage and apoptosis (TNFα, COX-2, IL-1β, 8-OHdG, and caspase 3) in BPA-exposed tissues, which were reduced in the presence of GA (P < 0.05). The assessment of oxidative stress demonstrated that GA could significantly decrease lipid peroxidation and partially restore antioxidant defense mechanisms disrupted by BPA (P < 0.05). Hormonal profiling indicated that BPA exposure altered the levels of FSH, LH, estrogen, and progesterone, with GA treatment showing a capacity to modulate these changes, especially in progesterone levels (P < 0.05). Conclusions: The findings suggest that GA exhibits protective properties against BPA-induced ovarian damage through its antioxidative and anti-inflammatory activities, alongside its ability to modulate hormonal imbalances. This research underscores the therapeutic potential of GA in safeguarding reproductive health against environmental toxicants. [ABSTRACT FROM AUTHOR]

Objective: Betatrophin is a hepatokine that modulates hepatic glucose and lipid metabolism and contributes to non-alcoholic fatty liver disease (NAFLD) pathogenesis. Therefore, this study aimed to investigate the relationship between NAFLD and betatrophin levels in hypogonadal males. Methods: The study included 56 newly diagnosed hypogonadal males aged 18-60 and 60 eugonadal males of similar age and body mass index. All participants were assessed for anthropometric and metabolic parameters, liver function tests, and betatrophin levels. Transient elastography was used to evaluate liver steatosis [controlled attenuation parameter (CAP)] and fibrosis [liver stiffness measurement (LSM)]. Accordingly, hypogonadal and control groups were divided into NAFLD (n = 64) and non-NAFLD (n = 52). Results: Controlled attenuation parameter, LSM, waist circumference (WC), triglycerides (TG), IR index homeostasis model assessment (HOMA-IR), and betatrophin were significantly higher in the hypogonadal group than controls. Hepatic steatosis and fibrosis (67.9%-43.3%) were higher in hypogonadal males. Triglycerides, HOMA-IR, and betatrophin were higher, and total testosterone was significantly lower in the NAFLD group. Serum betatrophin was also significantly higher in patients with fibrosis than without. There was a significant positive correlation between WC, TG, HOMA-IR, betatrophin, and LSM and CAP. The predictive factors were TG (ß = 0.329, P < .001), betatrophin (ß = 0.221, P = .029), HOMA-IR (ß = 0.213, P = .019) for CAP, and betatrophin for LSM (ß = 0.466, P < .001). Conclusion: Non-alcoholic fatty liver disease is more common in hypogonadal males than in eugonadal males. Betatrophin is an independent risk factor for developing and progressing NAFLD. However, more research is needed to explain the causal relationship between betatrophin and NAFLD. [ABSTRACT FROM AUTHOR]

Purpose: To investigate whether the ovarian stimulation with follitropin delta in an individualized algorithm-based manner is inferior to recombinant human-follicle stimulating's follitropin alfa or follitropin beta conventional dosing regarding a series of established primary endpoints. Methods: We conducted a registered systematic review (CRD42024512792) on PubMed-MEDLINE, Web of Science™, Cochrane Database of Systematic Reviews, and Scopus. Our search was designed to cover all relevant literature, particularly randomized controlled trials. We critically and comparatively analyzed the outcomes for each primary endpoint based on the intervention, reflected by the positive βhCG test, clinical pregnancy, vital pregnancy, ongoing pregnancy, live birth, live birth at 4 weeks, and multiple pregnancies. Results: Six randomized controlled trials were included in the quality assessment as priority manuscripts, revealing an 83.3% low risk of bias. Follitropin delta led to non-significant differences in each parameter of interest from positive βhCG test (691; 53.44% vs. 602; 46.55%), ongoing pregnancies (603; 53.79% vs. 518; 46.20%), clinical and vital pregnancies (1,073; 52.80% vs. 959; 47.19%), to live birth and at 4 weeks (595; 54.14% vs. 504; 45.85%) with only 2 losses, and even multiple pregnancies (8; 66.66% vs. 4; 33.33%). However, follitropin delta was well-tolerated among hypo- and hyper-responders without significant risk of ovarian hyperstimulation syndrome and/or preventive interventions in contrast with follitropin alfa or follitropin beta. Conclusion: The personalized individualized-based algorithm dosing with follitropin delta is non-inferior to conventional follitropin alfa or follitropin beta. It is as effective in promoting a similar response in women without significant comparable adverse effects. [ABSTRACT FROM AUTHOR]

Endocrine therapy plays a crucial role in hormone receptor-positive breast cancer and is closely related to the patient’s menopausal status. This manuscript aimed to explore two key questions in assessing menopausal status of breast cancer patients. Firstly, for premenopausal patients receiving ovarian function suppression (OFS) therapy, persistently elevated estradiol (E2) levels post-treatment may be attributed to either “true” or “pseudo” elevation, with caution needed due to potential interference from endocrine therapy drugs such as fulvestrant, abemaciclib, exemestane and tamoxifen. Secondly, when determining whether patients under OFS therapy have reached physiological menopause, factors such as the impact of chemotherapy on menopausal status and the complexity of hormone levels around menopause need to be considered. It is recommended to consider switching treatments based on the patient’s age and original endocrine therapy, and to regularly monitor levels of estradiol and follicle-stimulating hormone (FSH). In challenging cases, a comprehensive evaluation can be conducted by incorporating markers such as anti-Mullerian hormone (AMH), inhibin B (INHB) and androgen. [ABSTRACT FROM AUTHOR]

Background: Dysovulatory infertility is a major cause of infertility. It is treated with ovulation induction complemented with an assisted reproductive technique such as intrauterine insemination (IUI) and timed intercourse (TI). The data to compare the efficacy of IUI vs TI in superovulated cycles is limited. Aim: Comparison of pregnancy rates following IUI vs TI in letrozole and follicle-stimulating hormone (FSH) cycles in dysovulatory infertility. Method: Following the history and examination of subjects enrolled, baseline hormonal levels were done on day 2, transvaginal ultrasonography (TVS) for number and size of follicles and endometrial thickness was done on days 8, 10, and 12, and ultrasonography (USG) to confirm ovulation was done on day 14, if confirmed, it was followed by IUI or TI. Urine pregnancy test (UPT) at 2 weeks established successful conception. Those not conceiving received another cycle, to a maximum of 3 cycles. Result: A total of 120 subjects received 320 cycles. Intrauterine insemination shows better conception rates than TI (p-value < 0.05). The clinical pregnancy rate for the IUI group is 18.5% (28 in 154 cycles) and 10% (16 in 166) in the TI group. The success rate is positively correlated with younger age of patients, better educational status, and higher socioeconomic status. Conclusion: Intrauterine insemination combined with letrozole and FSH-stimulated dysovulatory infertility is an effective method to improve pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Background: Central nervous system damage in multiple sclerosis (MS) leads to severe physical disability and neurological defects. Sexual dysfunction and infertility in patients with MS have often been neglected in previous studies. Aerobic exercise is suggested to improve circulating testosterone levels and sexual function. Therefore, the purpose of this study was to investigate the effect of aerobic exercise on sex hormone levels in a cuprizone rat model of MS. Materials and Methods: In this experimental study, 30 male rats (aged 70 days, 154.55 ± 18.1 g) were randomly divided into five groups: MS, exercise-MS (EX-MS), MS-EX, EX-MS-EX, and normal control (control). MS was induced by feeding cuprizone pellets (0.2%) to the rats for six weeks. The exercise groups performed an aerobic exercise protocol on a treadmill five days/week for six weeks before and during the induction of the MS model. Serum testosterone, follicle stimulating hormone (FSH), and luteinising hormone (LH) levels were measured using the ELISA method with standard kits (ZellBio Germany). Luxol fast blue staining (LFB) of the corpora collosa were performed. Results: The results showed a significant decrease in the serum levels of testosterone, FSH, and LH in the MS groups compared to the control group (P<0.05). There was a significant increase in the serum levels of testosterone, FSH, and LH in the EX-MS-EX, and EX-MS groups compared to the MS group (P<0.05). Conclusion: Aerobic exercise could improve the level of sex hormones in the cuprizone rat model of MS and may be used to attenuate sexual dysfunction in patients with MS. [ABSTRACT FROM AUTHOR]

An artificial ovary based on the alginate (ALG) hydrogel has been widely implemented to preserve prepubertal female fertility. However, this platform is not fully capable of successful an ovary microenvironment simulation for follicle development, holding great potential for its improvement. Therefore, this experimental study aimed to evaluate the effect of an amniotic membrane extract (AME) -loaded hydrogel on the mouse preantral follicles in vitro development. In order to have better follicle development, first, the impact of different concentrations of follicle-stimulating hormone (FSH) was evaluated on the mouse preantral follicles encapsulated in ALG. Later, the appropriate dose was adjusted for the follicles encapsulated in the ALG-AME hydrogel. Results demonstrated that 100 mIU/ml FSH showed a significant follicle survival rate compared with 10 mIU/ml FSH (P=0.005). According to MTT assay finding, the rate of weight loss, and rheology evaluations, ALG containing 1 mg/ml AME was identified as an optimal sample of follicle culture instead of other AME concentrations. Follicle diameter significantly increased in the ALG-AME 1 hydrogel compared with the ALG control group without AME (P=0.027). The storage modulus of ALG-AME 1 was 773 Pa and retained the follicle morphology for 13 days. No statistically substantial difference was seen in survival, antrum cavity formation, and competent oocyte in terms of the normal chromosomal arrangement and meiotic spindle rate in comparison with the control group. It can be concluded that ALG-AME 1 could not significantly impact the mouse preantral follicle [ABSTRACT FROM AUTHOR]

This study aimed to produce single-chain recombinant Anguillid eel follicle-stimulating hormone (rec-eel FSH) analogs with high activity in Cricetulus griseus ovary DG44 (CHO DG44) cells. We recently reported that an O-linked glycosylated carboxyl-terminal peptide (CTP) of the equine chorionic gonadotropin (eCG) β-subunit contributes to high activity and time-dependent secretion in mammalian cells. We constructed a mutant (FSH-M), in which a linker including the eCG β-subunit CTP region (amino acids 115–149) was inserted between the β-subunit and α-subunit of wild-type single-chain eel FSH (FSH-wt). Plasmids containing eel FSH-wt and eel FSH-M were transfected into CHO DG44 cells, and single cells expressing each protein were isolated from 10 and 7 clones. Secretion increased gradually during the cultivation period and peaked at 4000–5000 ng/mL on day 9. The molecular weight of eel FSH-wt was 34–40 kDa, whereas that of eel FSH-M increased substantially, with two bands at 39–46 kDa. Treatment with PNGase F to remove the N glycosylation sites decreased the molecular weight remarkably to approximately 8 kDa. The EC50 value and maximal responsiveness of eel FSH-M were approximately 1.23- and 1.06-fold higher than those of eel FSH-wt, indicating that the mutant showed slightly higher biological activity. Phosphorylated extracellular-regulated kinase (pERK1/2) activation exhibited a sharp peak at 5 min, followed by a rapid decline. These findings indicate that the new rec-eel FSH molecule with the eCG β-subunit CTP linker shows potent activity and could be produced in massive quantities using the stable CHO DG44 cell system. [ABSTRACT FROM AUTHOR]

STUDY QUESTION How does a gonadotrophin-releasing hormone (GnRH) agonist versus a GnRH antagonist protocol affect ovarian response when using an individualized fixed daily dose of follitropin delta for ovarian stimulation? SUMMARY ANSWER The BEYOND trial data demonstrate thatindividualized fixed-dose follitropin delta is effective when used in a GnRH agonist protocol, compared with a GnRH antagonist protocol, in women with anti-Müllerian hormone (AMH) ≤35 pmol/l and no increased risk of ovarian hyperstimulation syndrome (OHSS). WHAT IS KNOWN ALREADY The efficacy and safety of an individualized fixed daily dose of follitropin delta (based on body weight and AMH) have been established in randomized controlled trials (RCTs) using a GnRH antagonist protocol. Preliminary study data indicate that individualized follitropin delta is also efficacious in a GnRH agonist protocol (RAINBOW trial, NCT03564509). There are no prospective comparative data using individualized follitropin delta for ovarian stimulation in a GnRH agonist versus a GnRH antagonist protocol. STUDY DESIGN, SIZE, DURATION This is the first randomized, controlled, open-label, multi-centre trial exploring efficacy and safety of individualized follitropin delta dosing in a GnRH agonist versus a GnRH antagonist protocol in participants undergoing their first ovarian stimulation cycle for IVF/ICSI. A total of 437 participants were randomized centrally and stratified by centre and age. The primary endpoint was the number of oocytes retrieved. Secondary endpoints included ongoing pregnancy rates, adverse drug reactions (including OHSS), live births, and neonatal outcomes. PARTICIPANTS/MATERIALS, SETTING, METHODS Participants (18–40 years; AMH ≤35 pmol/l) were enrolled at specialist reproductive health clinics in Austria, Denmark, Israel, Italy, the Netherlands, Norway, and Switzerland. The mean number of oocytes retrieved was compared between the GnRH agonist and antagonist protocols using a negative binomial regression model with age and AMH at screening as factors. Analyses were based on all randomized subjects, using a multiple imputation method for randomized subjects withdrawing before the start of stimulation. MAIN RESULTS AND THE ROLE OF CHANCE Of the 437 randomized subjects, 221 were randomized to the GnRH agonist, and 216 were randomized to the GnRH antagonist protocol. The participants had a mean age of 32.3 ± 4.3 years and a mean serum AMH of 16.6 ± 7.8 pmol/l. A total of 202 and 204 participants started ovarian stimulation with follitropin delta in the GnRH agonist and antagonist groups, respectively. The mean number of oocytes retrieved was statistically significantly higher in the agonist group (11.1 ± 5.9) versus the antagonist group (9.6 ± 5.5), with an estimated mean difference of 1.31 oocytes (95% CI: 0.22; 2.40, P  =   0.0185). The difference in number of oocytes retrieved was influenced by the patients' age and ovarian reserve, with a greater difference observed in patients aged <35 years and in patients with high ovarian reserve (AMH >15 pmol/l). Both the GnRH agonist and antagonist groups had a similar proportion of cycle cancellations (2.0% [4/202] versus 3.4% [7/204]) and fresh blastocyst transfer cancellations (13.4% [27/202] versus 14.7% [30/204]). The estimated ongoing pregnancy rate per started cycle was numerically higher in the GnRH agonist group (36.9% versus 29.1%; difference: 7.74% [95% CI: −1.49; 16.97, P  =   0.1002]). The most commonly reported adverse events (≥1% in either group; headache, OHSS, nausea, pelvic pain, or discomfort and abdominal pain) were similar in both groups. The incidence of early moderate/severe OHSS was low (1.5% for the agonist group versus 2.5% for antagonist groups). Estimated live birth rates per started cycle were 35.8% and 28.7% in the GnRH agonist and antagonist groups, respectively (treatment difference 7.15%; 95% CI: −2.02; 16.31; P  =   0.1265). The two treatment groups were comparable with respect to neonatal health data for singletons and twins and for incidence of congenital malformations (2.7% and 3.3% for the GnRH agonist versus antagonist groups, respectively). LIMITATIONS, REASONS FOR CAUTION All participants had AMH ≤35 pmol/l and were ≤40 years old. Clinicians should remain cautious when using a GnRH agonist protocol in patients with AMH >35 pmol/l (i.e. those with an increased OHSS risk). The incidence of OHSS in the GnRH antagonist group may have been lower if a GnRH agonist trigger had been allowed. Outcomes of transfers with cryopreserved blastocysts were not followed up, therefore the cumulative live birth rates and neonatal outcomes after cryotransfer are unknown. WIDER IMPLICATIONS OF THE FINDINGS In women with AMH ≤35 pmol/l, an individualized fixed daily dose of follitropin delta resulted in a significantly higher number of oocytes retrieved when used in a GnRH agonist protocol compared with a GnRH antagonist protocol, with no additional safety signals observed and no additional risk of OHSS. Live birth rates following ovarian stimulation with individualized follitropin delta were not statistically different between the GnRH protocols; however, the trial was not powered to assess this endpoint. There were no safety concerns with respect to neonatal health after ovarian stimulation with follitropin delta in either protocol. STUDY FUNDING/COMPETING INTEREST(S) The trial was funded by Ferring Pharmaceuticals. EE, EP, and MS have no competing interests. AP has received research support from Ferring, and Gedeon Richter, and honoraria or consultation fees from Preglem, Novo Nordisk, Ferring, Gedeon Richter, Cryos, Merck A/S. BC has received consulting fees from Ferring and Merck, and his department received fees from Ferring to cover the costs of patient enrolment. MBS has received support to attend meetings and/or travel from Ferring, and was a board member for FertiPROTEKT e.V. until 2023. JS has received honoraria or consultation fees from Ferring and Merck, and support for attending meetings and/or travel from Ferring, Merck, and GoodLife. TS has received support/travel expenses from Ferring for attending a congress meeting, and participated in an advisory board for Merck. YS has received grants/research support from Ferring and support to attend a professional society congress meeting from Merck. RL and PP are employees of Ferring Pharmaceuticals. PP is a BOD member of PharmaBiome and owns stocks of Takeda Pharmaceuticals. TRIAL REGISTRATION NUMBER ClinicalTrials.gov identifier NCT03809429; EudraCT Number 2017-002783-40. TRIAL REGISTRATION DATE 7 April 2019. DATE OF FIRST PATIENT'S ENROLMENT 2 May 2019. [ABSTRACT FROM AUTHOR]

This review addresses the current understanding of In Vitro Maturation (IVM) treatment, including indications and effective treatment protocols influencing oocyte developmental competence. A comprehensive literature search was performed to gather relevant studies, clinical trials, and reviews related to IVM. Databases such as PubMed, MEDLINE, and pertinent medical journals were searched. The selected literature was analyzed and synthesized to offer a comprehensive overview. IVM has emerged as a promising technique for inducing maturation in immature oocytes across various developmental stages. Its applications extend to areas utilizing In Vitro Fertilization (IVF), gaining traction as a treatment option for Polycystic Ovary Syndrome (PCOS) and fertility preservation in cancer patients. Recent advancements have led to improved global pregnancy rates, resulting in successful births. IVM also holds potential in reducing risks associated with conventional IVF, including ovarian hyperstimulation syndrome and multiple pregnancies. Despite these advantages, IVM adoption in clinical practice remains limited. Ongoing research aims to refine therapeutic protocols and expand clinical indications. IVM holds promise in assisted reproductive technology, spanning applications from cancer patient fertility preservation to addressing PCOS. Enhanced pregnancy rates highlight efficacy, while risk reduction compared to IVF underscores its importance. Further research is needed for optimal use across patient groups, emphasizing protocol refinement and expanded applications. [ABSTRACT FROM AUTHOR]

Infants born with severe central disorders of the hypothalamic‐pituitary‐gonadal axis leading to gonadotropin deficiency not only lack pubertal development in adolescence, but also lack infantile mini‐puberty. This period of mini‐puberty, where infants have gonadotropin and sex steroid concentrations up into the adult range, is vital for future reproductive capacity, particularly in boys. At present, there is no consensus on the diagnosis or management of infants with gonadotropin deficiency due to congenital hypogonadotropic hypogonadism or multiple pituitary hormone deficiency. Case series suggest that gonadotropin treatment in male infants with absent mini‐puberty is effective in promoting both testicular descent in those with undescended testes and also facilitating increased penile size. Moreover, replacement with follicle‐stimulating hormone increases the testicular Sertoli cell population, measurable as an increase in testicular volume and inhibin B, thus hypothetically increasing the capacity for spermatogenesis in adult life for these patients. However, long‐term follow‐up data is limited for both outcomes pertaining to fertility and nonreproductive sequelae, including neurodevelopment and psychological well‐being. The use of international registries for patients with gonadotropin deficiency is a key element in the collection of high‐quality, geographically widespread data to inform best‐practice management from birth to adulthood. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate the efficacy of peri-trigger female reproductive hormones (FRHs) in the prediction of oocyte maturation in normal ovarian reserve patients during the in vitro fertilization-embryo transfer (IVF-ET) procedure. Materials and Methods: A hospital database was used to extract data on IVF-ET cases from January 2020 to September 2021. The levels of female reproductive hormones, including estradiol (E2), luteinizing hormone (LH), progesterone (P), and follicle-stimulating hormone (FSH), were initially evaluated at baseline, the day of the trigger, the day after the trigger, and the day of oocyte retrieval. The relative change in E2, LH, P, FSH between time point 1 (the day of trigger and baseline) and time point 2 (the day after the trigger and day on the trigger) was defined as E2_RoV1/2, LH_RoV1/2, P_RoV1/2, and FSH_RoV1/2, respectively. Univariable and multivariable regression were performed to screen the peri-trigger FRHs for the prediction of oocyte maturation. Results: A total of 118 patients were enrolled in our study. Univariable analysis revealed significant associations between E2_RoV1 and the rate of MII oocytes in the GnRH-agonist protocol group (p < 0.05), but not in the GnRH-antagonist protocol group. Conversely, P_RoV2 emerged as a potential predictor for the rate of MII oocytes in both protocol groups (p < 0.05). Multivariable analysis confirmed the significance of P_RoV2 in predicting oocyte maturation rate in both groups (p < 0.05), while the association of E2_RoV1 was not significant in either group. However, within the subgroup of high P_RoV2 in the GnRH-agonist protocol group, association was not observed to be significant. The C-index was 0.83 (95% CI [0.73–0.92]) for the GnRH-agonist protocol group and 0.77 (95% CI [0.63–0.90]) for the GnRH-antagonist protocol group. The ROC curve analysis further supported the satisfactory performance of the models, with area under the curve (AUC) values of 0.79 for the GnRH-agonist protocol group and 0.81 for the GnRH-antagonist protocol group. Conclusions: P_RoV2 showed significant predictive value for oocyte maturation in both GnRH-agonist and GnRH-antagonist protocol groups, which enhances the understanding of evaluating oocyte maturation and inform individualized treatment protocols in controlled ovarian hyperstimulation during IVF-ET for normal ovarian reserve patients. [ABSTRACT FROM AUTHOR]

Background & Objective: Consecutive miscarriages are considered recurrent pregnancy loss (RPL), which affects 1-2% of women and may be unpleasant for couples attempting to conceive. Patients and healthcare professionals confront a difficult situation in this regard. The present study was conducted with aim to investigate the potential role of anti-mullerian hormone (AMH) in predicting the rate of live birth in women with RPL who are trying to conceive naturally. Materials & Methods: This cross-sectional study involved 60 pregnant women from Baghdad and Al-Najaf infertility centers (June 2022 - June 2023), recording age, gestational age, miscarriage frequency, fetal outcomes, parity, and number of live births. AMH levels were measured using Minividas Biomeriux 2020 (France), followed by assessments of FSH and Estradiol. Low AMH prompted further tests for autoimmune and genetic disorders. Inclusion criteria were all pregnant women with spontaneous or induced pregnancies and a history of recurrent miscarriage. Exclusions were those with unexplained pregnancy loss and male factor infertility. Results: The mean age of participants was 32.8 years, with 46.7% aged 21-30 years. AMH levels were higher in females aged 21-30 years, those with two abortions, and those with two parities. A significant correlation was observed between age over 40 years and a history of four abortions. Conclusion: AMH emerges as a crucial biomarker that intertwines with various aspects of female reproductive health, including miscarriage history, age, and parity. Future research is needed to deeply investigate the mechanisms behind these associations and offer more comprehensive insights into female fertility dynamics. [ABSTRACT FROM AUTHOR]

Follicle-stimulating hormone (FSH) binds to its membrane receptor (FSHR) in granulosa cells to activate various signal transduction pathways and drive the gonadotropin-dependent phase of folliculogenesis. Both FSH insufficiency (due to genetic or nongenetic factors) and FSH excess (as encountered with ovarian stimulation in assisted reproductive technology [ART]) can cause poor female reproductive outcomes, but the underlying molecular mechanisms remain elusive. Herein, we conducted single-follicle and single-oocyte RNA sequencing analysis along with other approaches in an ex vivo mouse folliculogenesis and oogenesis system to investigate the effects of different concentrations of FSH on key follicular events. Our study revealed that a minimum FSH threshold is required for follicle maturation into the high estradiol-secreting preovulatory stage, and such threshold is moderately variable among individual follicles between 5 and 10 mIU/mL. FSH at 5, 10, 20, and 30 mIU/mL induced distinct expression patterns of follicle maturation–related genes, follicular transcriptomics, and follicular cAMP levels. RNA sequencing analysis identified FSH-stimulated activation of G proteins and downstream canonical and novel signaling pathways that may critically regulate follicle maturation, including the cAMP/PKA/CREB, PI3K/AKT/FOXO1, and glycolysis pathways. High FSH at 20 and 30 mIU/mL resulted in noncanonical FSH responses, including premature luteinization, high production of androgen and proinflammatory factors, and reduced expression of energy metabolism-related genes in oocytes. Together, this study improves our understanding of gonadotropin-dependent folliculogenesis and provides crucial insights into how high doses of FSH used in ART may impact follicular health, oocyte quality, pregnancy outcome, and systemic health. [ABSTRACT FROM AUTHOR]

Background: This study aimed to assess the correlation between serum levels of anti-Mullerian hormone (AMH), basal folliclestimulating hormone (FSH), basal luteinizing hormone (LH), and basal estradiol with pregnancy outcomes. Methods: Conducted at Shariati Hospital in Tehran from 2020 to 2021, this prospective cohort study included women under 38 years old with idiopathic recurrent miscarriage (IRM). Individuals with AMH levels below 1 ng/mL were classified as the poor responder group. All participants with IRM received a daily combination of 20 mg prednisolone and 200 mg progesterone vaginal suppositories from the beginning of pregnancy until 12 weeks, along with aspirin and folic acid. Pregnancy was monitored until 36 weeks, and outcomes were evaluated over two years using univariate and multiple logistic regression, with P-values < 0.05 considered significant. Results: The study comprised 128 individuals with a mean age of 36.4 ± 3.9 years. Of these, 80 became pregnant, while 48 did not. Among the pregnant individuals, 34 had terminations before 26 weeks (13 ongoing and 21 clinical), while 46 had pregnancies lasting 26 weeks or longer. Maternal age (RR = 1.23, 95% CI: 1.10 - 1.90, P = 0.001), history of abortion (RR = 1.262, 95% CI: 1.052 - 1.327, P = 0.008), and low serum AMH level (RR = 0.752, 95% CI: 0.227 - 0.934, P = 0.035) were significantly associated with the probability of subsequent pregnancies. Maternal age (RR = 1.108, 95% CI: 1.05 - 1.350, P = 0.025) and history of abortion (RR = 1.097, 95% CI: 1.02 - 1.161, P = 0.042) were the only factors associated with the risk of non-pregnancy. Conclusions: The study findings suggest that AMH levels in women with IRM significantly influence pregnancy outcomes, including abortion and live births at 26 weeks or more. The univariate analysis revealed significant correlations between age, serum AMH levels, previous history of abortion, and the risk of abortion. Additionally, AMH levels were found to relate to follicle storage rather than egg quality, indicating that AMH does not predict live birth after IVF. Overall, this prospective study underscores the importance of maternal age, AMH level, and previous abortion history in predicting pregnancy outcomes. [ABSTRACT FROM AUTHOR]

Background and objective: No clear-cut markers for predicting positive sperm retrieval (+SR) at microdissection testicular sperm extraction (mTESE) have been identified thus far. Our aim was to conduct a systematic review and meta-analysis to evaluate the ability of follicle-stimulating hormone (FSH), inhibin B (InhB), and anti-Müllerian hormone (AMH) to predict +SR in men with nonobstructive azoospermia (NOA) undergoing mTESE. Methods: We performed a search in the PubMed, EMBASE, Web of Science, and Scopus databases according to the Preferred Reporting Items for Systematic Review and Meta-analysis statement. Thirty-four publications were selected for inclusion in the analysis. Key findings and limitations: Overall, the mean +SR rate was 45%. Pooled standardized mean difference (SMD) values revealed significant hormonal differences between the +SR and −SR groups, with lower FSH (SMD −0.30), higher InhB (SMD 0.54), and lower AMH (SMD −0.56) levels in the +SR group. Pooled odds ratios (Ors) revealed no significant prediction of +SR by either FSH (OR 1.03, 95% confidence interval [CI] 1.00–1.06) or InhB (OR 1.01, 95% CI 1.00–1.02), despite variations in baseline levels and study heterogeneity. Conversely, AMH had significant predictive value (OR 0.82, 95% CI 0.73–0.92), with lower baseline levels in the +SR group. InhB and FSH levels were higher in the +SR group, while InhB exhibited the opposite trend. Conclusions and clinical implications: Despite study heterogeneity, our meta-analysis findings support the ability of AMH to predict +SR for men with NOA undergoing mTESE. Patient summary: We conducted a review and analysis of results from previous studies. Our findings show that for men with an infertility condition called nonobstructive azoospermia, blood levels of anti-Müllerian hormone can predict successful extraction of sperm using a microsurgical technique. Levels of two other hormones did not predict successful sperm extraction.

AbstractChinese herbs contain substances that regulate female hormones. Our study confirmed that Zingiberis rhizoma carbonisata contains Zingiberis rhizoma-based carbon dots (ZR-CDs), which exert regulatory effects on serum oestradiol and FSH in mice and show impacts on endometrial growth and follicular development that potentially affect the ability of female fertility. ZR-CDs were characterized to clarify the microstructure, optical features, and functional group characteristics. It shows that ZR-CDs are spherical carbon nanostructures ranging from 0.97 to 2.3 nm in diameter, with fluorescent properties and a surface rich in functional groups. We further investigated the impact of ZR-CDs on oestradiol and FSH in serum, growth, and the development of ovarian and uterine using normal female mice and exogenous oestradiol intervention model. It was observed that ZR-CDs accelerated oestrogen metabolism and attenuated oestradiol-induced endometrial hyperplasia. Simultaneously, ZR-CDs triggered an increase in FSH, even in the presence of high-serum oestradiol that inhibits FSH secretion. Our findings suggest that ZR-CDs could be a potential therapeutic treatment for anovulatory menstruation.

Background and Aim: Producing and transferring embryos in vitro are profitable for enhancing premium beef genetics. Reducing costs and enhancing the effectiveness of hormone protocols before ovum pick-up (OPU) yield advantages. This study aimed to confirm that estradiol benzoate (EB) treatment resulted in more medium- and large-sized follicles before OPU and of higher oocyte quality after OPU than non-hormonal treatments, comparable to those undergoing gonadotropin-releasing hormone (GnRH) with follicle-stimulating hormone (FSH) plus prostaglandin F2α (PGF2α) and progesterone-releasing controlled internal drug release (CIDR) or EB with progesterone-releasing CIDR hormonal treatments. Materials and Methods: 30 crossbred Japanese black cows were divided into five equal groups, which were either untreated or treated with different hormone protocols before OPU. Group 1 (cows in estrus) and group 2 (cows in diestrus) were the untreated controls. Cows in group 3 were treated with GnRH + FSH + CIDR + PGF2α. Cows in group 4 received EB, and those in group 5 received EB + CIDR + PGF2α. After administering the protocols, all cow follicles were examined through ultrasonography and categorized by size. Subsequently, all cows underwent OPU, and the oocytes were collected and graded from A to D according to standard criteria. Results: Group 3 presented the highest large follicle numbers, and groups 3–5 had more medium follicle numbers, not different among groups but they had this parameter more than those of control groups 1 and 2. Moreover, groups 3–5 did not differ in combined grades A + B oocytes (good-quality oocytes). Groups 3 and 4 had more A + B oocytes than control groups 1 and 2, whereas group 5 was not different in this parameter from group 1. Conclusion: Among the three hormone protocols, EB treatment proved the most cost-effective and efficient, yielding more high-quality oocytes compared to the non-treatment protocols. To reduce the limitations of EB use in the future, this study suggests researching natural EB phytoestrogens as alternative treatments for improving ovarian function before OPU in other cattle breeds.

Abstract Background We aimed to examine sex-specific associations between sex- and thyroid-related hormones and the risk of metabolic dysfunction-associated fatty liver disease (MAFLD) in patients with type 2 diabetes mellitus (T2DM). Methods Cross-sectional analyses of baseline information from an ongoing cohort of 432 T2DM patients (185 women and 247 men) in Xiamen, China were conducted. Plasma sex-related hormones, including estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), progesterone, and total testosterone (TT), and thyroid-related hormones, including free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), and parathyroid hormone (PTH), were measured using chemiluminescent immunoassays. MAFLD was defined as the presence of hepatic steatosis (diagnosed by either hepatic ultrasonography scanning or fatty liver index (FLI) score > 60) since all subjects had T2DM in the present study. Results Prevalence of MAFLD was 65.6% in men and 61.1% in women with T2DM (P = 0.335). For men, those with MAFLD showed significantly decreased levels of FSH (median (interquartile range (IQR)):7.2 (4.9–11.1) vs. 9.8 (7.1–12.4) mIU/ml) and TT (13.2 (10.4–16.5) vs. 16.7 (12.8–21.6) nmol/L) as well as increased level of FT3 (mean ± standard deviation (SD):4.63 ± 0.68 vs. 4.39 ± 0.85 pmol/L) than those without MAFLD (all p-values

Background: Polycystic ovary syndrome (PCOS) is a multifaceted endocrine disorder affecting many women during their reproductive years. It is characterized by oligo/amenorrhea, anovulatory cycles, polycystic ovaries, and insulin resistance. This review explores the hormonal and metabolic alterations associated with PCOS, comparing them to functional hypothalamic amenorrhea (FHA). Key aspects include the abnormally high LH pulse frequency in PCOS, indicating hyperactive gonadotropin-releasing hormone (GnRH), and the role of hyperandrogenemia in exacerbating the condition by increasing LH pulse secretion from the pituitary gland. Additionally, the review examines the neuroendocrine basis for PCOS. Methods: The methodology involved analyzing neuroendocrine pathways and physical manifestations through PubMed, ScienceDirect, and Scopus databases. Findings indicate that PCOS is primarily characterized by androgen excess, ovulatory dysfunction, and disruption of the hypothalamic-pituitary-ovarian (HPO) axis. Hormonal dysregulation includes disturbances in GnRH, insulin, LH/FSH ratio, and androgens. GnRH stimulates LH and FSH release from the pituitary, regulating ovarian function, while Anti-Müllerian hormone (AMH) inhibits follicular development in PCOS. Conclusion: The review concludes by highlighting the hormonal alterations, including decreased frequency and amplitude of LH pulses, disruptions in GnRH, LH, and FSH. Genetic predispositions and disturbances in the LH/FSH ratio can lead to impaired follicle growth and polycystic ovaries. This comprehensive exploration underscores the importance of understanding the hormonal and neuroendocrine mechanisms underlying PCOS, contributing to better diagnosis and treatment strategies

Abstract In mammals reproduction is regulated by many factors, among others by the peptides belonging to the RFamide peptide family. However, the knowledge concerning on the impact of recently identified member of this family (QRFP43) on the modulation of the gonadotrophic axis activity is still not fully understood and current research results are ambiguous. In the present study we tested the in vivo effect of QRFP43 on the secretory activity of the gonadotrophic axis at the hypothalamic-pituitary level in Polish Merino sheep. The animals (n = 48) were randomly divided into three experimental groups: controls receiving an icv infusion of Ringer-Locke solution, group receiving icv infusion of QRFP43 at 10 μg per day and 50 μg per day. All sheep received four 50 min icv infusions at 30 min intervals, on each of three consecutive days. Hypothalamic and pituitaries were collected and secured for further immunohistochemical and molecular biological analysis. In addition, during the experiment a blood samples have been collected for subsequent RIA determinations. QRFP43 was found to downregulate Kiss mRNA expression in the MBH and reduce the level of IR material in ME. This resulted in a reduction of GnRH IR material in the ME. QRFP43 increased plasma FSH levels while decreasing LH levels. Our findings indicate that QRFP43 inhibits the activity of the gonadotropic axis in the ovine at the level of the hypothalamus and may represent another neuromodulator of reproductive processes in animals.

In vertebrates, folliculogenesis and ovulation are regulated by two distinct pituitary gonadotropins: follicle-stimulating hormone (FSH) and luteinizing hormone (LH). Currently, there is an intriguing consensus that a single hypothalamic neurohormone, gonadotropin-releasing hormone (GnRH), regulates the secretion of both FSH and LH, although the required timing and functions of FSH and LH are different. However, recent studies in many non-mammalian vertebrates indicated that GnRH is dispensable for FSH function. Here, by using medaka as a model teleost, we successfully identify cholecystokinin as the other gonadotropin regulator, FSH-releasing hormone (FSH-RH). Our histological and in vitro analyses demonstrate that hypothalamic cholecystokinin-expressing neurons directly affect FSH cells through the cholecystokinin receptor, Cck2rb, thereby increasing the expression and release of FSH. Remarkably, the knockout of this pathway minimizes FSH expression and results in a failure of folliculogenesis. Here, we propose the existence of the "dual GnRH model" in vertebrates that utilize both FSH-RH and LH-RH. Folliculogenesis and ovulation are regulated by separate hormones (FSH and LH), though the release of both has been thought to be regulated by the same upstream hormone, GnRH. Here they show that in fish, FSH release is regulated by a distinct hormone, FSH-RH, thereby revisiting our current understanding of gonadotropin release. [ABSTRACT FROM AUTHOR]