Pregnancy co-treated with oral gonadotropin-releasing hormone antagonist in a woman with premature ovarian insufficiency: a case report.

To the best of our knowledge, this is the first case of pregnancy with a healthy baby after treatment with an oral gonadotropin-releasing hormone (GnRH) antagonist in women with premature ovarian insufficiency. A 36-year-old female presented at our hospital after being diagnosed with premature ovarian insufficiency by a previous doctor. We administered clomiphene, human menopausal gonadotropin (hMG), and GnRH antagonist (injection) together with estrogen replacement for 11 cycles (27 months), but no follicular development was observed. When the oral GnRH antagonist (relugolix), which has recently become available, was used in the 12th cycle, follicular growth of 13 mm was confirmed on the 14th day of stimulation. After stimulation, the use of hMG and GnRH antagonist (injection) was continued, and a maturation trigger, human chorionic gonadotropin 10000 IU, was administered. Oocyte retrieval was performed successfully, intracytoplasmic sperm injection and frozen embryo transfer were performed, and fetal heartbeat was confirmed. The patient was admitted to the perinatal management facility. She delivered a healthy baby of 3,732 g via cesarean section at 41 weeks +2. This case shows the possibility of using an oral GnRH antagonist as an option for infertility treatment.

Gonadotropin-Releasing Hormone (GnRH) Agonist Protocol Improves Pregnancy Outcomes During In Vitro Fertilization (IVF) and Intracytoplasmic Sperm Injection (ICSI) Treatment in Young Infertile Women: A Retrospective Study.

Objective The objective of this study was to determine if gonadotropin-releasing hormone agonist (GnRH-a) or gonadotropin-releasing hormone antagonist (GnRH-ant) protocols during in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) treatment in young infertile women improve their pregnancy outcomes. Methodology We retrospectively reviewed the records of 876 young infertile women aged 20-35 years who underwent fresh embryo transfer in IVF/ICSI cycles. The data were collected from their initial visits to the reproductive medicine center of the Second Affiliated Hospital of Zhengzhou University between January 2019 and December 2022. We divided them into two groups according to the controlled ovarian hyperstimulation (COH) protocols: GnRH-a (n = 580) and GnRH-ant (n = 296). The primary outcome assessed in this study was the live birth rate. The secondary observation indicators included the total dose and duration of gonadotropin (Gn), total embryo transfer, day three (D3) embryo transfer, total two pro-nuclei (2PN) cleavage count, number of fertilizations, and implantation rate. Results The live birth rate had no clinical significance (P > 0.05). The total dose and duration of Gn stimulation in the GnRH-ant group were lower than in the GnRH-a group (P  < 0.05). The total embryo transfer, D3 embryo transfer, total cleavage count, total 2PN cleavage count, number of fertilizations, transfer, and mature oocytes in metaphase II (MII) of D3 embryos in the GnRH-a group were higher than those in the GnRH-ant group (P  < 0.05). The clinical pregnancy rate and implantation rate of the GnRH-a group were higher than those of the control group. Conclusions The total embryo transfer, D3 embryo transfer, total cleavage count, total 2PN cleavage count, number of fertilizations, transfer and MII of D3 embryos, clinical pregnancy, and implantation rates were significantly higher in the GnRH-a protocol group. The total dosage of Gn and duration of Gn stimulation were lower in the GnRH-ant group than in the GnRH-a group. These findings provide the basis for the selection of the COH protocol in normal Chinese ovarian response patients undergoing IVF/ICSI.

Efficacy of GnRH Pulses in Hypogonadism Secondary to Primary Empty Sella: Case Report.

This study aims to assess the effectiveness of pulsed gonadotropin-releasing hormone (GnRH) micropump replacement therapy in the treatment of hypogonadotropic hypogonadism (HH) caused by primary empty sella (PES).The efficacy of pulsed GnRH replacement therapy using the micropump was evaluated in a middle-aged male patient with HH who had experienced the loss of his only child. Relevant literature was also consulted to compare the differences between pulse GnRH treatment and conventional treatment in terms of the development of secondary sexual characteristics, sex hormone levels, sperm production rate, and sperm activity rate in male patient with HH.In this report, a 45-year-old male diagnosed with HH and PES presented with fatigue and decreased libido. The main characteristics included decreased follicle stimulating hormone (FSH) levels of 0.03 mIU/mL, luteinizing hormone (LH) levels of 0.02 mIU/mL, and testosterone (T) levels of 0.72 nmol/L. Magnetic resonance imaging (MRI) revealed an empty sella. Semen analysis showed a small number of normal sperm with reduced motility. During treatment with the micropump pulse GnRH, the patient experienced no side effects and showed improvements in fatigue, reduced libido, sexual urge, anxiety, and feelings of inferiority. LH, FSH, and T levels returned to normal, while sperm activity rate increased to 79.9%. Ultimately, the patient's spouse achieved a natural pregnancy.Pulsed gonadotropin delivery using the micropump demonstrates good efficacy and tolerability, and aligns more closely with the physiological rhythm of GnRH secretion in the human body.

Effect of body mass index on progesterone level on trigger day in gonadotropin-releasing hormone antagonist cycles.

OBJECTIVE: To investigate the effect of body mass index (BMI) on progesterone (P) level on trigger day in gonadotropin-releasing hormone antagonist (GnRH-ant) cycles. METHODS: This study was a retrospective cohort study. From October 2017 to April 2022, 412 in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) patients who were treated with GnRH-ant protocol for controlled ovarian hyperstimulation (COH) in the reproductive center of our hospital were selected as the research objects. Patients were divided into three groups according to BMI level: normal weight group (n = 230):18.5 kg/m2≤BMI < 24 kg/m2; overweight group (n = 122): 24 kg/m2≤BMI < 28 kg/m2; Obesity group (n = 60): BMI ≥ 28 kg/m2. Variables with p < .10 in univariate analysis (BMI, basal FSH, basal P, FSH days, Gn starting dose and E2 level on trigger day) and variables that may affect P level on trigger day (infertility factors, basal LH, total FSH, HMG days and total HMG) were included in the multivariate logistic regression model to analyze the effect of BMI on P level on trigger day of GnRH-ant protocol. RESULTS: After adjustment for confounding factors, compared with that in normal weight patients, the risk of serum P elevation on trigger day was significantly lower in overweight and obese patients (OR = 0.434 and 0.199, respectively, p < .05). CONCLUSION: The risk of P elevation on trigger day in GnRH-ant cycles decreased with the increase of BMI, and BMI could be used as one of the predictors of P level on trigger day in GnRH-ant cycles.

Insulin sensitivity, body composition and bone mineral density after testosterone treatment in transgender youth with and without prior GnRH agonist therapy.

Background: 1.8% of youth identify as transgender; a growing proportion are transgender male (female sex, male gender identity). Many receive gonadotropin releasing hormone agonist (GnRHa) therapy to suppress endogenous puberty and/or will start testosterone to induce secondary sex characteristics that align with gender identity. Objectives: To determine the effects of 12 months of testosterone on cardiometabolic health among transgender youth, including insulin sensitivity, body composition, and bone mineral density and whether changes in outcomes differ based on prior GnRHa treatment. Methods: Participants (n = 19, baseline age 15.0 ± 1.0 years) were examined prior to and 12 months after testosterone therapy in a longitudinal observational study. Fasted morning blood draw, a 2-hour 75-gram oral glucose tolerance test, body composition and bone mineral density (dual-energy X-ray absorptiometry) were assessed at baseline and 12 months. Insulin sensitivity was estimated by HOMA-IR and Matsuda index. Changes were compared with mixed linear regression models evaluating time (baseline, 12 months), group (GnRHa treatment yes/no), and their interaction. Results: In the entire cohort, fasted insulin decreased (median [25,75 %ile]: -3 [-5, 0] mIU/L, p = 0.044) and 2-hour glucose increased (mean ± standard deviation): +18.5 ± 28.9 mg/dL, p = 0.013 from baseline after 12 months of testosterone therapy. There were no significant changes in HOMA-IR (p = 0.062) or Matsuda index (p = 0.096), nor by GnRHa status. Absolute (+6.2 [4.7, 7.5] kg, p = 0.016) and percent fat-free mass increased (+7.3 [5.4, 9.1] %, p = 0.003) and percent fat mass declined (-7.4 [-9.3, 5.3]%, p = 0.005) for the entire cohort. There were time*group interactions for absolute (p = 0.0007) and percent fat-free mass (p = 0.033). There were time*group interactions for bone mineral content (p = 0.006). Conclusions: Twelve months of testosterone in transgender adolescents resulted in changes in body composition and bone mineral density, with baseline differences between the +/-GnRHa group and convergence after 12 months. There were no changes in insulin sensitivity over time or between groups.

[Comparative Study of the Embryo Development and Clinical Outcomes of 3 Ovarian Stimulation Protocols in Different Age Groups]. / 不同年龄段人群三种促排卵方案胚胎发育及临床结局比较.

Objective: The main purpose of this study is to compare the embryo development and clinical outcomes of women in different age groups undergoing in vitro fertilization (IVF) processes using gonadotrophin-releasing hormone (GnRH) antagonist protocol, GnRH agonist long protocol, and early follicular phase protocol. We aim to provide reliable reference for future clinical treatments. Methods: We conducted a detailed analysis of patients who underwent treatment between January 2021 and February 2023. 1) In the overall patient population, we comprehensively compared the basic characteristics, the embryo development, and the clinical outcomes of patients treated with three different ovarian stimulation protocols, including the GnRH antagonist protocol group (n=4173), the agonist long protocol group (n=2410), and the early follicular phase long protocol group (n=341). 2) We divided the overall population into three age groups, one group for patients under 30 years old (n=2576), one for patients aged 30-35 (n=3249), and one for patients older than 35 years old (n=1099). Then, we compared the three stimulation protocols based on the group division. We separately compared the embryo development and clinical outcomes of patients using the three stimulation protocols in the under 30 years old, the 30-35 years old, and the over 35 years old age groups. With this analysis, we aimed to explore the response of different age groups to different stimulation protocols and their impact on the success rate of IVF. Results: 1) In the overall population, we found that the average number of oocytes retrieved in the GnRH agonist long protocol group was significantly higher than that in the GnRH antagonist protocol group ([13.85±7.162] vs. [13.36±7.862], P=0.0224), as well as the early follicular phase long protocol group ([13.85±7.162] vs. [11.86±6.802], P<0.0001). Patients in the GnRH antagonist protocol group not only had a significantly lower starting dose of gonadotrophin (Gn) compared to the other two groups (P<0.05) but also had a significantly lower number of days of Gn use (P<0.05). The blastocyst formation rate in the GnRH antagonist protocol group was the highest among the three groups, significantly higher compared to the GnRH agonist long protocol group (64.91% vs. 62.35%, P<0.0001) and the early follicular phase long protocol group (64.91% vs. 61.18%, P=0.0001). However, there were no significant differences in the clinical pregnancy rates or the live birth rates among the three groups treated with different ovarian stimulation protocols (P>0.05). 2) In the <30 age group, the blastocyst formation rate in the GnRH antagonist protocol group was the highest among the three groups, significantly higher compared to the GnRH agonist long protocol group (66.12% vs. 63.33%, P<0.0001) and the early follicular phase long protocol group (66.12% vs. 62.13%, P=0.0094). In the 30-35 age group, the blastocyst formation rate in the GnRH antagonist protocol group was the highest among the three groups, significantly higher compared to the GnRH agonist long protocol group (64.88% vs. 62.93%, P=0.000 9) and the early follicular phase long protocol group (64.88% vs. 60.39%, P=0.0011). In the >35 age group, the blastocyst formation rate in the GnRH antagonist protocol group was significantly higher than that in the GnRH agonist long protocol group (59.83% vs. 56.51%, P=0.0093), while there was no significant difference compared to that of the early follicular phase long protocol group (P>0.05). In the three age groups, we found that there were no significant differences in clinical pregnancy rate, live birth rate, and neonatal outcome indicators (fetal weight and Apgar score) among the three stimulation protocols (antagonist protocol, GnRH agonist long protocol, and early follicular phase long protocol) (P>0.05). The findings showed no significant differences between clinical and neonatal outcomes in patients of all ages, regardless of the ovarian stimulation protocol, suggesting that the three ovarian stimulation protocols have similar therapeutic effects in patients of different ages. The results of this study have important implications for the selection of an appropriate ovarian stimulation protocol and the prediction of treatment outcomes. Conclusion: In the younger than 30 and 30-35 age groups, the GnRH antagonist protocol showed a more significant advantage over the GnRH agonist long protocol and the early follicular phase long protocol. This suggests that for younger and middle-aged patients, the antagonist protocol may lead to better outcomes during ovarian stimulation. In the older than 35 age group, while the antagonist protocol still outperformed the GnRH agonist long protocol, there was no significant difference compared to the early follicular phase long protocol. This may imply that with increasing age, the early follicular phase long protocol may have effects similar to the antagonist protocol to some extent. The advantages of the antagonist protocol lie in its ability to reduce stimulation duration and the dosage of GnRH, while enhancing patient compliance with treatment. This means that patients may find it easier to accept and adhere to this treatment protocol, thereby improving treatment success rates. Particularly for older patients, the use of the antagonist protocol may significantly increase the blastocyst formation rate, which is crucial for improving the success rates. Although there were no significant differences in the clinical outcomes of patients treated with the three protocols in each age group, further research is still needed to validate these findings. Future multicenter studies and increased sample sizes may help comprehensively assess the efficacy of different stimulation protocols. Additionally, prospective studies are needed to further validate these findings and determine the optimal treatment strategies.

Fertility Preservation and Ovarian Hyperstimulation Syndrome Management in Cancer Care: A Pathophysiological Perspective on Gonadotropin-Releasing Hormone Agonists and Antagonists.

This narrative review delves into the evolving landscape of fertility preservation techniques, with a particular focus on their use in patients undergoing oncology treatment that carries a risk of ovarian insufficiency. Advances in established methods such as cryopreservation of oocytes and embryos are highlighted, and the increasing use of gonadotropin-releasing hormone (GnRH) agonists is discussed. The review also addresses the complexities and controversies associated with these approaches, such as the 'flare-up' effect associated with GnRH agonists and the potential of GnRH antagonists to reduce the risk of ovarian hyperstimulation syndrome. Despite advances in fertility preservation, the report highlights the challenges we face, including the need for personalized treatment protocols and the management of associated risks. It calls for continued research and collaboration between healthcare professionals to refine these techniques and ultimately improve reproductive outcomes for patients facing the prospect of fertility-impairing treatment.

Acupuncture combined with gonadotropin-releasing hormone agonists improves endometrial receptivity and pregnancy outcome in patients with recurrent implantation failure of in vitro fertilization-embryo transfer.

OBJECTIVE: Gonadotropin-releasing hormone agonists (GnRHa), combined with other auxiliary treatments, can improve pregnancy outcomes in in vitro fertilization-embryo transfer (IVF-ET). This research investigated the effect of acupuncture combined with GnRHa in patients with recurrent implantation failure (RIF) of IVF-ET. METHODS: A total of 164 patients who intended to undergo frozen-thawed embryo transfer after RIF of IVF-ET were selected for experiments and then divided into the control (received conventional hormone replacement therapy (HRT) for endometrial preparation) and study groups (received a combination of acupuncture, GnRHa, and HRT for endometrial preparation) (n = 82). Endometrial thickness (EMT), endometrial morphological classification, submucosal uterine blood flow classification, clinical pregnancy rate, embryo implantation rate, and early abortion rate for each transfer cycle were compared between the two groups. RESULTS: EMT of the study group was higher than that of the control group 1 day before transfer. There were more patients with linear endometrium (A + B type) in the study group on the day of endometrial transformation than in the control group. The number of patients with type I submucosal uterine blood flow in the study group was decreased and the number of patients with type III was increased compared with the control group on the day of endometrial transformation. The clinical pregnancy rate and embryo implantation rate of the study group were higher than those of the control group. CONCLUSION: Acupuncture combined with GnRHa improves the endometrial receptivity of patients with RIF of IVF-ET, thereby increasing clinical pregnancy rates and improving pregnancy outcomes.

Effect of GnRH agonist down-regulation combined with hormone replacement treatment on reproductive outcomes of frozen blastocyst transfer cycles in women of different ages.

Objective: To investigate the effect of GnRH agonist (GnRH-a) down-regulation prior to hormone replacement treatment (HRT) to prepare the endometrium in frozen embryo transfer (FET) cycles in women of different ages. Methods: This was a retrospective study, and after excluding patients with adenomyosis, endometriosis, severe endometrial adhesions, polycystic ovary syndrome (PCOS), and repeated embryo implantation failures, a total of 4,091 HRT cycles were collected. Patients were divided into group A (<35 years old) and group B (≥35 years old), and each group was further divided into HRT and GnRHa-HRT groups. The clinical outcomes were compared between groups. Results: There was no statistically significant difference in clinical outcomes between the HRT and GnRHa-HRT groups among women aged <35 years. In women of advanced age, higher rates of clinical pregnancy and live birth were seen in the GnRHa-HRT group. Logistic regression analysis showed that female age and number of embryos transferred influenced the live birth rate in FET cycles, and in women aged ≥ 35 years, the use of GnRH-a down-regulation prior to HRT improved pregnancy outcomes. Conclusions: In elderly woman without adenomyosis, endometriosis, PCOS, severe uterine adhesions, and RIF, hormone replacement treatment with GnRH agonist for pituitary suppression can improve the live birth rate of FET cycles.

Development of a Novel Patient-Reported Outcome Measure to Assess Symptoms and Impacts of Androgen Deprivation Therapy for Advanced Prostate Cancer.

INTRODUCTION: This qualitative research study was conducted to develop a novel, comprehensive, patient-reported outcome measure (PRO), the "Symptoms and Impacts of Androgen Deprivation Therapy (ADT) for Prostate Cancer" (SIADT-PC), assessing hormonal therapy-related symptoms and their impacts on men with advanced prostate cancer. METHODS: Concept elicitation (CE) interviews were conducted among adult men with prostate cancer to evaluate their experiences with ADT. Based on key symptom and impact concepts mentioned, an initial PRO measure was developed. The draft measure was further assessed in cognitive debriefing (CD) interviews with men with prostate cancer, in which participants reviewed items, response options, and recall periods. Initial item-based psychometric analyses were conducted using interview data. The draft questionnaire was revised on the basis of participant feedback, quantitative psychometric results, and consultation with clinical experts. RESULTS: A total of 21 participants were interviewed (CE concept elicitation, n = 12; CD cognitive debriefing, n = 17; n = 8 completed both). Mean participant age (SD) was 59.7 (8.7) years and 76.2% were white. The de novo SIADT-PC measure consists of 27 items: 11 symptoms (e.g., fatigue, hot flashes, and erectile dysfunction), 2 long-term symptoms (e.g., weight gain), 10 impacts (e.g., impacts on physical activities and relationships), and 4 related to mode of administration (i.e., injection-site reactions). Items were assessed with a 5-point verbal rating scale, with answer choices that capture frequency or severity. CONCLUSIONS: Once fully validated, this de novo measure may be used in clinical studies and clinical practice to assess hormone therapy-related symptoms and impacts, enabling physicians to identify timely and appropriate interventions.

Active immunization with recombinant GnRH6-CRM197 inhibits reproductive function of male rats.

Gonadotropin-releasing hormone (GnRH) vaccines have been successfully used for the inhibition of gonadal development and function, but current GnRH-based vaccines often present variability in the response. Cross-reactive material 197 (CRM197) has been used as carrier molecules to enhance an immune response to associated antigens. So, the synthetic mammalian tandem-repeated GnRH hexamer (GnRH6) gene was integrated into the expression plasmid pET-21a. Recombinant GnRH6-CRM197 protein was subsequently overexpressed in Escherichia coli strain BL21 and purified through Nickel column affinity chromatography and the antigenicity and biological effects of GnRH6-CRM197 were evaluated in rats. Sixteen 4-month-old adult male rats were randomly divided into two groups: the GnRH6-CRM197 group (n = 8) and the control group (n = 8). The GnRH6-CRM197 group rats were subcutaneously immunized with 100 µg of GnRH6-CRM197, administered thrice at 2-week intervals with GnRH6-CRM197.The control group received only a white oil adjuvant. Following the initial immunization, the weights of animals were recorded, and blood samples were collected from the orbital sinus at 4, 4.5, 5, 5.5, 6, 6.5, and 7 months. Serum antibody titers and testosterone concentrations were quantified using ELISA and CLIA, respectively. Additionally, testicular tissues were collected for morphological examination. The results revealed a significant increase in serum GnRH antibody titers (p < 0.05), but a significant decrease in serum testosterone concentrations (p < 0.05), and the weight, length, width, and girth of the testis, and the number of spermatogonia cells, spermatocytes, and sperm cells in the immunized rats. Furthermore, seminiferous tubules revealed significant atrophy and no sperm were observed in the immunized animals. Thus, GnRH6-CRM197 may be an effective antigen and a potential immunocastration vaccine.

Retrospective evaluation of patients diagnosed with central precocious puberty who reached the final height.

OBJECTIVES: Central precocious puberty (CPP) is the onset of puberty before the age of 8 in girls and 9 in boys. The primary goal of CPP treatment is control and arrest of puberty development. In this study, it was aimed to determine the factors associated with final height in patients who received gonadotropin-releasing hormone analogs (GnRHa) treatment and reached their final height. METHODS: From the medical records of the patients, age on admission, bone age (BA), weight-standard deviation score (SDS), height-SDS, BMI-SDS, target height-SDS, basal LH, FSH, E2, age at menarche, and pelvic USG findings were obtained. RESULTS: The mean age on admission of the 67 female patients was 7.5 ± 0.60 years. On admission, 4.5 % of the patients were obese and 19.4 % were overweight. There was no difference between BMI-SDS at admission and after treatment. The mean age at menarche was 11.57 ± 0.78 years. About 58.2 % of the patients reached the target height, 35.8 % exceeded the target height, and 6 % were below the target height. The mean height-SDS and predicted adult height (PAH) on admission were better in patients who exceeded the target height. It was determined that target height-SDS had a positive effect on delta height-SDS, while BA/CA ratio had a negative effect. CONCLUSIONS: It was found that GnRHa treatment did not have a negative effect on BMI-SDS. It was shown that 94 % of the patients who received GnRHa treatment reached the target height, and in fact, 35.8 % exceeded the target height. A greater final height may be associated with good height-SDS and PAH values on admission.

Short Adult Height After Rapid-tempo Puberty: When is it too Late to Treat?

A rarely reported phenomenon of rapid-tempo puberty in which the physical changes of puberty and testosterone levels increase very rapidly has not been reported outside apart from in two reviews. The resulting rapid advancement of skeletal age causes early completion of growth with shorter adult stature than expected. This appears to be genetic given its occurrence in the present report in two families, one with three brothers, one with two. We also describe potential treatments and found for the youngest that early initiation of standard therapy preserved or reclaimed adult height (AH) potential. The foreshortened AH in this situation involves rapidly advancing puberty resulting from high circulating testosterone levels leading to rapid advance in skeletal age. This was recognized earlier among younger brothers and treatment with gonadotropin-releasing analogues, growth hormone (GH) and/or aromatase inhibitor therapy (AIT) was tried. Two brothers in family A and family B were treated. Case 5 started treatment early enough so his AH was within target height (mid-parental height) range. Cases 2, 3, 4 were tried on GH and/or AIT with outcomes suggesting benefit. The prevalence and mechanism of rapid-tempo puberty requires further study. Furthermore, as illustrated by two of the current cases, this phenomenon may have a heightened prevalence, or at least may occur, in children previously diagnosed with constitutional delay of growth, underscoring the need to be cautious in assurance of a normal AH outcomes in this population, based on data from a single assessment.

Exercise-induced muscle hormone "irisin" controls luteinizing hormone and follicle-stimulating hormone secretion by bovine gonadotrophs.

Irisin is a hormone secreted by muscle in response to exercise. The irisin receptor (IrisinR) is a heterodimer of integrin alpha V (ITGAV) and integrin beta 5 (ITGB5) subunits. Since irisin may mediate some beneficial effects of exercise on animal reproduction, we tested the hypothesis that bovine gonadotrophs express IrisinR and irisin stimulates luteinizing hormone (LH) and follicle stimulating hormone (FSH) secretion by gonadotrophs. Reverse transcription polymerase chain reaction was used to detect the mRNA expression of both ITGAV and ITGB5 in the anterior pituitary glands (APs) of post pubertal heifers and mouse gonadotroph cell line "LßT2." Western blotting was used to detect protein expression in bovine APs. Immunofluorescence microscopy, utilizing the same antibody, visualized IrisinR on the plasma membrane of majority of gonadotrophs. We prepared AP cells from healthy postpubertal heifers, cultured them for 3.5 d, and treated them with increasing concentrations (0, 0.01, 0.1, 1, or 10 nM) of irisin for 5 min before either no treatment or gonadotropin-releasing hormone (GnRH) stimulation. After 2 h, media were harvested for LH and FSH assays. Irisin (0.1-10 nM) stimulated basal LH and FSH secretion, and these stimulatory effects were inhibited by the extracellular signal-regulated kinase or SMAD pathway inhibitors. In the presence of GnRH, irisin at 0.01-1 nM stimulated LH and FSH secretion. A higher dose of irisin (10 nM), however, suppressed the GnRH-induced LH and FSH levels. In conclusion, bovine gonadotrophs expressed IrisinR, and irisin controlled LH and FSH secretion from bovine gonadotrophs.

[Value of single-phase gonadotropin-releasing hormone stimulation test in diagnosis of central precocious puberty in girls with different levels of body mass index]. / 单时相GnRHæ¿€å‘è¯•éªŒå¯¹ä¸åŒä½“é‡æŒ‡æ•°å¥³ç«¥ä¸­æž¢æ€§æ€§æ—©ç†Ÿè¯Šæ–­ä»·å€¼çš„ç ”ç©¶.

OBJECTIVES: To investigate the value of single-phase gonadotropin releasing hormone (GnRH) stimulation test in the diagnosis of central precocious puberty (CPP) in girls with different levels of body mass index (BMI). METHODS: A retrospective analysis was performed for the data of 760 girls with breast development before 7.5 years of age who attended the Third Affiliated Hospital of Zhengzhou University from January 2017 to August 2023. According to the results of GnRH stimulation test and clinical manifestations, they were divided into a CPP group (297 girls) and a non-CPP group (463 girls). According to the values of BMI, the girls were divided into a normal weight group (540 girls), an overweight group (116 girls), and an obese group (104 girls). The receiver operating characteristic (ROC) curve was used to investigate the value of single-phase GnRH stimulation test in the diagnosis of CPP in girls with different levels of BMI. RESULTS: Luteinizing hormone (LH)/follicle-stimulating hormone at 30 minutes after GnRH stimulation had an area under the curve (AUC) of 0.985 in the diagnosis of CPP, which was higher than the AUC at 0, 60, and 90 minutes (P<0.05). LH at 30 minutes had a similar diagnostic value to LH at 60 minutes (P>0.05). LH at 30 minutes was negatively correlated with BMI and BMI-Z value (P<0.05).The AUC for diagnosing CPP in normal weight, overweight, and obese girls at 30 minutes LH was 0.952, 0.965, and 0.954, respectively (P<0.05). CONCLUSIONS: The 30-minute GnRH stimulation test has a good value in the diagnosis of CPP in girls with different levels of BMI and is expected to replace the traditional GnRH stimulation test, but the influence of BMI on LH level should be taken seriously.

Effectiveness of the triptorelin stimulation test compared with the classic gonadotropin-releasing hormone stimulation test in diagnosing central precocious puberty in girls.

PURPOSE: The gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for diagnosing central precocious puberty (CPP). Gonadorelin (Relefact) is used for the test but is not always readily available; triptorelin is used as an alternative. The purpose of this study was to evaluate the diagnostic validity of the triptorelin test compared with the GnRH test in the diagnosis of CPP in girls. METHODS: This retrospective study included 100 girls with premature thelarche (PT) who underwent a hypothalamic-pituitary-gonadal axis evaluation. In the overall group, 50 girls were tested with intravenous gonadorelin (Relefact) and 50 girls were tested with subcutaneous triptorelin acetate (Decapeptyl). Luteinizing hormone (LH) and follicle-stimulating hormone levels were measured at baseline and 30, 45, 60, and 90 minutes after gonadorelin injection or 30, 60, 90, and 120 minutes after triptorelin injection. RESULTS: Clinical characteristics of age, height, weight, body mass index, and bone age were similar between the 2 groups. The highest LH level was reached 60 minutes after stimulation in both groups. Approximately 20% of the gonadorelin group and 24% of the triptorelin group were diagnosed with CPP (P=0.52). Among those diagnosed with CPP, the mean peak LH concentrations were 8.15 mIU/mL and 9.73 mIU/mL in the gonadorelin and triptorelin groups, respectively. CONCLUSION: The triptorelin test showed similar trends of LH elevation and diagnostic rate compared with the traditional GnRH test for diagnosing CPP. This suggests that the triptorelin test may be a valid alternative to the GnRH test for differentiating CPP from self-limiting PT. Our study also demonstrated that a triptorelin stimulation test for up to 120 minutes was sufficient to diagnose CPP.

Revolutionizing Infertility Management through Novel Peptide-based Targets.

Around 48 million couples and 186 million people worldwide have infertility; of these, approximately 85% have an identifiable cause, the most common being ovulatory dysfunctions, male infertility, polycystic ovary syndrome, and tubule disease. The remaining 15% have infertility for unknown reasons, including lifestyle and environmental factors. The regulation of the hypothalamic- pituitary-adrenal axis (HPA) is crucial for the secretion of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), which are essential for female reproductive functions. GnRH is the primary reproductive axis regulator. The pattern of GnRH, FSH, and LH release is determined by its pulsatile secretion, which in turn controls endocrine function and gamete maturation in the gonads. Peptides called Kisspeptin (KP), Neurokinin-B (NKB), and Orexin influence both positive and negative feedback modulation of GnRH, FSH, and LH secretion in reproduction. This review article mainly focuses on the historical perspective, isoform, and signaling pathways of KP, NKB, and Orexin novel peptide-based targets including clinical and preclinical studies and having a promising effect in the management of infertility.

Diagnostic Value of Single LH and LH/FSH Ratio at 60-minute after GnRHa Stimulation Test for Central Precocious Puberty.

OBJECTIVES: To evaluate the diagnostic value of luteinizing hormone (LH) and LH/follicle stimulating hormone (FSH) ratio at 60 min after gonadotropin-releasing hormone analogs (GnRHa) stimulation test for central precocious puberty (CPP) in girls. METHODS: Two hundred and fifty-seven girls, aged 3 to 7.5 y, suspected of precocious puberty at authors' hospital from April 2020 through November 2023 were enrolled in the study. The blood was taken at 0, 30, 60 min after GnRHa stimulation test, and LH and LH/FSH were detected by chemiluminescence assay. The diagnostic efficacy was analysed by Mann-Whitney U test, spearman's correlation analysis and receiver operating characteristic (ROC) analysis. The proportion of obesity was analysed by Chi-square test. RESULTS: LH and LH/FSH at different times were statistically significantly different (P <0.05) between the CPP and non-CPP groups. Spearman's correlation analysis showed that the level of LH and LH/FSH at 60 min had the strongest consistency with the peak of LH (r = 0.9988, P <0.001) and LH/FSH (r = 0.9981, P <0.001). ROC curve analysis showed that the area under the ROC curves at 60 min of LH and LH/FSH were 0.975 and 0.997 with a cut-off value of 5.70 IU/L and 0.609, respectively. CONCLUSIONS: The peak of LH and LH/FSH in the diagnosis of CPP can be determined by LH and LH/FSH at 60 min after the triptorelin acetate is injected. This will reduce the number of blood draws required compared with the traditional stimulation test, which is more effective and acceptable for children.

Outcomes of vaginal repair and vaginal repair combined with GnRHa administration in the treatment of cesarean section scar defects: A randomized clinical trial.

STUDY OBJECTIVE: To prospectively investigate whether the application of vaginal repair (VR) of cesarean section scar defect (CSD) combined with a gonadotropin-releasing hormone agonist (GnRHa) achieve better clinical outcomes than VR alone. DESIGN: A randomized clinical trial. SETTING: University hospital. PATIENTS: A total of 124 women with CSD were undergoing expectant management from December 2016 to September 2021. 61 were randomised to VR+ GnRHa and 63 to VR alone. INTERVENTION: Vaginal repair combined with GnRHa and vaginal repair alone. MEASURES AND MAIN RESULTS: The primary outcome was the duration of menstruation and thickness of the remaining muscular layer (TRM) at 6 months after surgery. Secondary outcomes included the length, width and depth of the CSD; operation time; estimated blood loss; hospitalization time; and operative complications. Women were treated with either VR (n = 63) or VR + GnRHa (n = 61). Menstruation and TRM in patients pre. vs. post comparisons either with VR or VR + GnRHa are significant improved (P < .05). Significant differences in menstruation duration and TRM occurred in patients treated with VR + GnRHa compared with those treated with VR (P < .05). Moreover, the rate of CSD after surgery in the VR group was significantly higher than that in the VR + GnRHa group (P = .033), and CSD patients in the VR + GnRHa group achieved better therapeutic effects than those in the VR group (P = .017). Patients who received VR + GnRHa had a shorter menstruation duration and a greater increment of TRM postoperatively than did patients treated with VR alone (P = .021; P = .002, respectively). CONCLUSION: VR + GnRHa therapy has a greater potential to improve scar healing and reduce the number of menstruation days than VR alone for symptomatic women with CSD. PRéCIS: Vaginal Repair Combined with GnRHa Creates Better Therapeutic Effects of CSD. TRIAL REGISTRATION: Date of registration: October 13, 2016, Date of initial participant enrollment: December 20, 2016, Clinical trial identification number: NCT02932761, URL of the registration site: ClinicalTrials.gov, Figshare DOI: 10.6084/m9.figshare.24117114 LINK TO THE CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov/study/NCT02932761.

Effectiveness of gonadotropin-releasing hormone agonists for ovarian function suppression in premenopausal patients with hormone receptor-positive breast cancer: a retrospective single-center real-world study.

PURPOSE: This study evaluated the effectiveness of ovarian function suppression (OFS) of various gonadotropin-releasing hormone agonists (GnRHa) combined with aromatase inhibitors (AI) in premenopausal patients with hormone receptor-positive (HR-positive) breast cancer. Potential risk factors associated with insufficient OFS were analyzed. PATIENTS AND METHODS: Premenopausal HR-positive breast cancer patients who had received AI with GnRHa were studied retrospectively. Patients were divided into different groups according to monthly or trimonthly GnRHa schedules they received, and the effectiveness of OFS was compared between groups. Insufficient OFS was defined as at least one instance of estradiol ≥ 30 pg/ml. Patient data was gathered from medical records for this comparison. RESULTS: Of the 264 patients enrolled in this study, 117 were administered 3.6 mg of goserelin monthly (goserelin 1 M group), 63 received 3.75 mg of leuprorelin monthly (leuprorelin 1 M group) and 84 were given 11.25 mg of leuprorelin every three months (leuprorelin 3 M group). Overall, 7.20% experienced insufficient OFS. The incidence rates in the three GnRHa depot groups were 7.69%, 6.35%, and 7.14%, respectively, without a significant statistical difference (P = 0.900). Notably, younger patients exhibited a higher likelihood of insufficient OFS [OR = 0.900, 95%CI (0.824-0.982), P = 0.018]. CONCLUSION: Insufficient OFS remains a concern during GnRHa and AI treatment. The effectiveness of the three GnRHa depots commonly used in China seems comparable. Younger patients face a heightened risk of insufficient OFS.