Basal Luteinizing Hormone Research Articles

SUN-483 High-Fat Diet Suppresses Basal Lh Pulsatile Levels in Female Mice at Estrus

Pubertal timing and reproductive maturation in females are known to be susceptible to obesogenic diets. Metabolic energy balance and reproduction are homeostatic processes that are tightly regulated, in part, by hypothalamic neurons in the arcuate nucleus (ARC) and high-fat diet is reported to steadily increase estradiol levels in rodents compared to standard chow. Estradiol regulates the hypothalamic-pituitary-gonadal axis via negative feedback mechanisms in estrogen-sensitive ARC neurons by modulating the pulsatile release of the gonadotropin luteinizing hormone (LH). However, it is unclear how exactly the circulating estradiol milieu of adult females interacts with a state of high caloric fat intake to alter the parameters of LH release, such as pulse frequency, pulse amplitude, and basal set points of pulsatile release. The objective of this study was to use a non-invasive method of measuring pulsatile LH release patterns at different stages of the estrous cycle in mice fed a high-fat diet, using an ultrasensitive mouse LH assay (1). Starting at weaning age (21 days old), female C57BL/6J mice were fed ad libitum with either regular chow diet (RD) or 60% kcal high-fat diet (HFD), and free access to water. After 12 weeks on either RD or HFD, estrous cyclicity was determined via examination of vaginal cytological smears. Blood samples were collected when mice were at diestrus, followed by one full estrous cycle, and then collected again at estrus. To examine LH pulsatile release during both estrous cycle stages, mice had tail tips snipped and whole blood samples were collected and immediately frozen in assay buffer at 10-second intervals for 3 hours (between 0900 and 1200 hours). Pulsatile LH release was analyzed for pulse frequency, basal mean LH levels, and pulse amplitude using the DynPeak algorithm program. Compared to RD controls, mice fed a HFD displayed significantly lower basal LH levels during estrus, but not diestrus. However, there were no differences in pulse amplitude between HFD and RD fed mice. Mice on HFD (at both diestrus and estrus) also showed a trend towards increased pulse frequency. These results suggest that endogenous circulating estradiol influences the impact that HFD has on regular pulsatile release of LH by changing the set point for basal LH levels, thereby modulating when obesogenic diet-induced changes may be most detrimental. This has implications on how diet may put women at risk of failing reproductive health when ovarian estradiol levels drastically change, for example during menopause or with hormone replacement therapy. 1) Steyn FJ et al. Development of a methodology for and assessment of pulsatile luteinizing hormone secretion in juvenile and adult male mice. Endocrinology 2013;154(12):4939-4945. doi:10.1210/en.2013-1502.

SAT-177 GLUT1-Mediated Glucose Metabolism Is Necessary for GnRH-Induced Gonadotrope Secretion of LH and Is Increased by Androgen

Women with polycystic ovary syndrome (PCOS) have a high prevalence of metabolic comorbidities including dyslipidemia, metabolic syndrome, and type 2 diabetes mellitus. However, the impact of systemic metabolic dysregulation on reproduction is not completely understood. In particular, women with PCOS have elevated androgen as well as elevated blood glucose, insulin, and free fatty acids. These circulating factors can directly interact with gonadotrope cells within the highly vascular pituitary. We therefore postulate that gonadotropes “sense” nutrient availability in their microenvironment and respond to changes by adapting hormone production accordingly. Deciphering how androgens and “nutrient sensing” interact at the level of the gonadotrope may be central to understanding PCOS and improving reproductive outcomes. To understand the impact of metabolic state and nutrient availability on gonadotrope function, we must first determine the cellular metabolic program that supports gonadotrope secretion of luteinizing hormone (LH). Due to the high energy demand of rapid protein synthesis required for LH production, we hypothesized that gonadotropes engage anaerobic glycolysis in response to GnRH stimulation. To test this hypothesis, we measured the cellular energetics of the gonadotrope cell line LβT2 in response to GnRH via extracellular flux analysis. We found that GnRH increases the extracellular acidification rate, a proxy for anaerobic glycolysis. Using microscopy and flow cytometry, we determined that glucose transporter 1 (GLUT1) protein is exclusively expressed in primary gonadotropes in the pituitary and is the most highly expressed GLUT transporter mRNA in both primary gonadotropes and LβT2 cells. Additionally, GLUT1 mediates the GnRH-stimulated increase in glucose uptake. Knockdown of GLUT1 in LβT2 cells diminished GnRH-induced glucose uptake and LH secretion; while overexpression of GLUT1 in LβT2 increased basal LH secretion. Moreover, GnRH-induced LH secretion was proportional to glucose availability. Lastly, an 8-hour treatment with 10nM DHT increased GLUT1 protein expression in LβT2 cells and primary female gonadotropes and increased GnRH-induction of GLUT1 translocation to the cell surface as observed by microscopy. These results implicate glucose uptake through GLUT1 as necessary for gonadotrope secretion of LH and therefore reproductive function. We conclude that GLUT1 expression and translocation may be an important point of regulation by androgen in the HPG-axis and in PCOS. Sources of Research Support: NIH Grant P50 HD012303 awarded to ML and PM; DN is a recipient of the UCSD IRACDA Fellowship (K12 GM068524) and the University of California’s Presidents Postdoctoral Fellowship.

Morning basal luteinizing hormone, a good screening tool for diagnosing central precocious puberty.

PurposeThe standard method used to diagnose central precocious puberty (CPP) is the gonadotropin releasing hormone stimulation test (GnRHST). However, this test is inconvenient for children because it is time-consuming and requires multiple samples. This study aimed to determine the reliability of morning unstimulated luteinizing hormone (mLH) level when screening for CPP, with an emphasis on the influence of diurnal variation.MethodsThis study included 160 girls with signs of early puberty (SMR 2) under 8 years of age. They were classified as CPP or non-CPP based on their standard GnRHST. The auxological, biochemical, and hormonal characteristics of subjects were retrospectively evaluated. The prognostic value of single morning unstimulated gonadotropin level was examined for use in CPP screening.ResultsOf 160 patients, 121 (75.6%) presented with CPP, and 39 (24.4%) were determined to be prepubertal. The mLH/mFSH (morning unstimulated follicular stimulating hormone) ratio showed significant differences between the 2 groups (P<0.001). The mLH was correlated with GnRHST variables (r=0.532, P<0.001). The mLH cutoff point when screening for CPP was 0.22 IU/L, which had sensitivity and specificity of 69.4% and 82.1%, respectively. In regression analysis, bone age (BA) (odds ratio [OR], 1.018; 95% confidence interval [CI], 0.967–1.071; P=0.506) and body mass index (BMI) (OR, 0.874; 95% CI, 0.583–1.310; P=0.515) were not significant predictors. The mLH≥0.22 IU/L group (OR, 9.596; 95% CI, 3.853–23.900; P<0.001) was highly suggestive of CPP.ConclusionsIn this study, single morning unstimulated luteinizing hormone had clinical efficacy for CPP screening, but BA advanced over chronological age and BMI was not useful for CPP screening.

Luteinising hormone profiles in conception and non-conception natural cycles

Objective: The aim of this study was to assess whether luteinising hormone (LH) surge characteristics influenced the likelihood of conceiving naturally. Methods: This was a single-cycle, home-based, observational, case-controlled study. Volunteers collected daily urine samples for one menstrual cycle. LH was measured and the basal levels, surge day, peak day, peak concentration and magnitude of LH surges were examined. Predictive models using sociodemographic data, LH surge characteristics, and sociodemographic data combined with LH profile properties, were evaluated. Results: The surge profile did not differ between cycles with early or late ovulation and was not affected by age or body mass index (BMI). The mean LH surge day was day 16 for both groups. Mean LH surge and concentrations did not differ between groups (surge concentration 54.8 IU/l vs. 58.2 IU/l and peak concentration 82.0 IU/l vs. 81.6 IU/l for pregnant vs. non-pregnant volunteers, respectively). Non-pregnant volunteers were more likely, however, to have a raised or a reduced basal LH on day 6 or have an atypical LH profile. Sociodemographic characteristics were significant predictors of pregnancy, and sociodemographic variable-based models had the greatest predictive ability for conception, providing up to 65% predictive accuracy. Conclusions: Sociodemographic variables can be used to predict the likelihood of a woman conceiving naturally. Provided an LH surge is present, its profile does not relate to the likelihood of spontaneous pregnancy. The conception rate was significantly lower, however, in women with elevated or reduced basal levels of LH, suggesting that follicular maturation needs an optimal basal level of LH in natural conception cycles. Trial registration: ClinicalTrials.gov identifier: NCT01577147.

Modulation of anterior pituitary cell luteinizing hormone secretory activity by neuropeptide Y in early pregnant pigs.

Numerous reports indicate that neuropeptide Y (NPY) is implicated in the regulation of anterior pituitary (AP) gonadotropin secretion in prepuberal and cyclic females. This study was performed to explain whether NPY directly affects basal and gonadotropin-releasing hormone- (GnRH-) induced luteinizing hormone (LH) secretion and intracellular accumulation by AP cells and whether NPY and its receptor (Y1 and Y2) mRNAs are expressed in the AP gland in pregnant pigs (days 14 - 16). Additionally, the expression of genes encoding β subunit of luteinizing hormone (β-LH) and GnRH receptor (GnRH-R) was determined in porcine AP gland. Anterior pituitaries were dispersed with trypsin and the obtained pituitary cells (2 x 105 cells/ml) were pre-incubated (72 h) and then experimentally treated for 3.5 h with GnRH (100 ng/ml), NPY (10-8, 10-7 and 10-6 M) alone, or in chosen combinations with GnRH. The LH contents in culture media and cellular homogenates were measured by radioimmunoassay. The expression of NPY, Y1 and Y2 NPY receptors, GnRH-R and β-LH mRNAs in the AP gland was determined by the real-time PCR method. NPY (10-8, 10-7 and 10-6 M) had no effect on basal LH secretion or basal and GnRH-induced LH accumulation in AP cells. The lowest dose of NPY (10-8 M) decreased, while higher doses of NPY only showed a tendency to inhibit GnRH-induced release of LH from AP cells. The presence of mRNAs for NPY and its receptor Y2, as well as β-LH and GnRHR was confirmed in the porcine AP gland. These results indicate that NPY and one of its receptors (Y2) are expressed in the porcine anterior pituitary and this neuropeptide might be involved in the modulation of LH secretion by AP cells in pregnant pigs.

Adequacy of basal luteinizing hormone levels in the diagnosis of central precocious puberty.

Aim:To determine the clinical, anthropometric, and laboratory parameters that could be used for differentiating central precocious puberty from premature thelarche in girls who had breast development between the ages of 3 and 8 years.Material and Methods:The study included 344 girls (196 girls with idiopathic central precocious puberty, 148 girls with premature thelarche) who underwent gonadotropin- releasing hormone stimulation tests for breast development. Age at diagnosis, bone age, anthropometric measurements, basal/stimulated hormone levels were recorded. Univariate regression analysis was performed to determine the parameters that could be used for differentiating precocious puberty from premature thelarche. Significant parameters in univariate analyses were grouped according to the thresholds determined using receiver operating characteristic curves and reevaluated through multivariate analysis.Results:The bone age, height-standard deviation score, body mass index-standard deviation score, and growth velocity-standard deviation score at diagnosis were found to be higher; pubertal stages were found to be more advanced; uterus and ovary volumes were found to be larger; and the basal/peak luteinizing hormone, follicle-stimulating hormone, luteinizing hormone/follicle-stimulating hormone levels were found to be higher in the subjects with precocious puberty. There was no difference between estradiol levels between the two groups. The best thresholds to differentiate the two groups were found as 0.65 IU/L (78% sensitivity, 100% specificity), 1.9 IU/L (100% sensitivity, 72% specificity), 0.25 (67% sensitivity, 100% specificity) and 1.1 (69% sensitivity, 71% specificity), respectively, for basal luteinizing hormone, follicle-stimulating hormone, luteinizing hormone/follicle-stimulating hormone ratio, and the growth velocity-standard deviation score.Conclusion:In girls presenting with early breast development, a basal luteinizing hormone level of ≥0.65 IU/L and a luteinizing hormone/follicle-stimulating hormone ratio of ≥0.25 are sensitive ways to demonstrate activation of the hypothalamo-pituitary-gonadal axis. Among these, the variable that gives the best sensitivity and specificity is the measurement of basal luteinizing hormone levels (≥0.65 IU/L), which can be used as a screening test in the diagnosis of central precocious puberty.

Comparative Study of the Therapeutic Effects of Two Corpus Luteum Support Regimens on Patients with Frozen Embryo Transfer

Aim: To investigate the efficacy of two corpus luteum support programs in patients with frozen embryo transfer (FET). Methods: A retrospective analysis of the complete clinical data of 340 patients undergoing in vitro fertilization embryo transfer in the Department of Reproductive Medicine, Jingzhou Central Hospital from September 2016 to July 2018. These patients were divided into group A and B according to the luteal support program. We compared the clinical outcomes of the two corpus luteum preparations by comparing the laboratory parameters of the two groups of patients with clinical pregnancy indicators. Results: We found there was no significant difference in the results of general conditions in the two groups of patients, such as infertility age and duration, body mass index (BMI), basal follicle stimulating hormone (FSH), basal luteinizing hormone (LH), basal estrogen (E2) levels, the endometrial thickness, the number of transplanted high-quality embryos on the day of transplantation and so on (P > 0.05). We found that the implantation rate (32.55%), biochemical pregnancy rate (53.57%), and clinical pregnancy rate (51.78%) in group B were significantly higher than those in group A (25.26%, 35.11%, and 34.66%, respectively) (P 0.05). Conclusion: We conclude that patients who are scheduled for frozen embryo transfer use progesterone vaginal sustained release capsules combined with luteal progesterone luteal support, have improved clinical pregnancy rates.

Effect of Maternal Body Mass Index in Relation to Embryo Quality and Clinical Outcomes in Couples underlying ICSI.

Background: The rising incidence of obesity coupled with its detrimental effects on fertility led to greater numbers of overweight and obese women utilizing assisted reproduction technologies (ART), such as in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI). Aim of the Work: To evaluate the impact of body mass index on embryo quality and clinical outcomes in couples underlying ICSI. Patients and methods: a retrospective observational comparative study was conducted on 400 Women at ART Unit, International Islamic Centre for Population Studies and Research (IICPSR), Al-Azhar University. Data were recruited from the patient`s files who did ICSI trial in IICPSR from December 2015 to December 2017, after exclusion of cycles in which the body mass index (BMI) was not recorded. After approval of the local ethics committee, all pregnant women were briefed about the nature of the study and informed consent was obtained from them before inclusion in the study. Results: The duration of infertility was progressively higher as BMI increased. Basal luteinizing hormone, follicle-stimulating hormone, and estradiol levels were higher in group 2 than in group 1. Higher total doses of gonadotropin were required in group 2 to obtain equivalent ovarian response than in group 1. No significant difference was observed on ovarian response and embryonic parameters. Serum estradiol level on ovulation triggering day was significantly higher in group 2. Ovarian hyperstimulation and cycle outcome were not significantly different between both groups. Conclusion: Overweight and obesity appear to have independent adverse effects on ovarian response to stimulation and outcomes in women undergoing ICSI.

Elevated basal luteinizing hormone does not impair the outcome of human menopausal gonadotropin and medroxyprogesterone acetate treatment cycles

The potential effects of high basal luteinizing hormone (LH) levels on human reproduction were controversial. To demonstrate the effects of elevated basal LH levels on the outcome of patients undergoing in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles, we performed a retrospective data analysis of 1011 polycystic ovarian syndrome (PCOS) patients treated with human menopausal gonadotropin and medroxyprogesterone acetate (hMG + MPA) protocol at our center between Nov. 2013 and Jun. 2017. PCOS patients with elevated basal LH levels had significantly higher LH exposure during the stimulation period. The group with LH ≥ 10 mIU/mL showed a lower mean total hMG dose used but higher numbers of oocytes retrieved, metaphase II oocytes, embryos and top-quality embryos developed than the groups with lower basal LH levels. Moreover, partial correlation analysis showed that the basal LH level was negatively correlated with the total hMG dose but positively correlated with the numbers of oocytes retrieved, metaphase II oocytes, embryos, and top-quality embryos. There were no significant differences in the rates of oocyte retrieval, fertilization, implantation, clinical pregnancy and miscarriage between the groups based on frozen embryo transfer (FET). We concluded that elevated basal LH level does not impair the final outcome of hMG + MPA-treated IVF/ICSI cycles in PCOS women.

Subnormal Growth Velocity and Related Factors During GnRH Analog Therapy for Idiopathic Central Precocious Puberty

Objective:Data concerning subnormal growth velocity (GV) and factors that influence this during gonadotropin-releasing hormone analog (GnRHa) therapy for idiopathic central precocious puberty (ICPP) are scarce. We investigated the incidence of subnormal GV and associated factors in patients receiving GnRHa therapy for ICPP.Methods:In this retrospective cohort study, the records of 50 girls who had been diagnosed with ICPP and started on GnRHa treatment before the age of eight years were investigated. Subnormal GV frequency, related factors during GnRHa therapy and the effect on final height were examined.Results:During the treatment, a significant decrease in the annual GV and GV standard deviation score (SDS) of the patients was observed. In 16 (32%) patients GV never declined below -1 SDS, while a decline was noted once and twice in 19 (38%) and 15 (30%) patients respectively. The median age of detection of subnormal GV was 9.9 (4.9-10.9) years. Patients with pubic hair at diagnosis were found to have an increased risk of subnormal GV (p=0.016). There was a significant negative correlation between diagnostic basal luteinizing hormone (LH) level and the first and second year GV SDS (p=0.012 and 0.017 respectively). A significant negative correlation between bone age at diagnosis and 3rd year GV SDS, and 4th year GV SDS (p=0.002 and p=0.038) was also observed. LH suppression significantly increased during treatment (p=0.001).Conclusion:In girls with ICPP the risk of subnormal GV appears highest at the 3rd year of GnRHa treatment, particularly in those patients with, at the time of diagnosis, pubic hair in conjunction with high baseline and peak LH and advanced BA and excessive LH suppression on follow-up.

Predictors of bone maturation, growth rate and adult height in children with central precocious puberty treated with depot leuprolide acetate.

Children with central precocious puberty (CPP) are treated with gonadotropin-releasing hormone agonists (GnRHa) to suppress puberty. Optimizing treatment outcomes continues to be studied. The relationships between growth, rate of bone maturation (bone age/chronological age [ΔBA/ΔCA]), luteinizing hormone (LH), predicted adult stature (PAS), as well as variables influencing these outcomes, were studied in children treated with depot leuprolide (LA Depot) Methods: Subjects (64 girls, seven boys) with CPP received LA Depot every 3 months for up to 42 months. Multivariate regression analyses were conducted to examine the predictors affecting ΔBA/ΔCA, PAS and growth rate. Ninety percent of subjects (18 of 20) were suppressed (LH levels <4 IU/L) at 42 months. Over 42 months, the mean growth rate declined 2 cm/year, the mean BA/CA ratio decreased 0.21 and PAS increased 8.90 cm for girls (n=64). PAS improved to mid-parental height (MPH) in 46.2% of children by 30 months of treatment. Regression analysis showed that only the Body Mass Index Standardized Score (BMI SDS) was significantly associated (β+0.378 and +0.367, p≤0.05) with growth rate. For PAS, significant correlations were with MPH (β+0.808 and +0.791, p<0.001) and ΔBA/ΔCA (β+0.808 and +0.791, p<0.001). For ΔBA/ΔCA, a significant association was found only with BA at onset of treatment (β-0.098 and -0.103, p≤0.05). Peak-stimulated or basal LH showed no significant influence on growth rate, ΔBA/ΔCA or PAS. Growth rate and bone maturation rate normalized on treatment with LA Depot. LH levels were not significantly correlated with growth rate, ΔBA/ΔCA or PAS, suggesting that suppression was adequate and variations in gonadotropin levels were below the threshold affecting outcomes.

Evaluation of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal axis.

This study aimed to identify the predictive value of basal sex hormone levels for activation of the hypothalamic-pituitary-gonadal (HPG) axis in girls. Gonadotropin-releasing hormone (GnRH) stimulation tests were performed and evaluated in a total of 1750 girls with development of secondary sex characteristics. Correlation analyses were conducted between basal sex hormones and peak luteinizing hormone (LH) levels ≥5 IU/L during the GnRH stimulation test. Receiver operating characteristic (ROC) curves for basal levels of LH, follicle-stimulating hormone (FSH), LH/FSH, and estradiol (E2) before the GnRH stimulation test were plotted. The area under the curve (AUC) and 95% confidence intervals (CIs) were measured for each curve. The maximum AUC value was observed for basal LH levels (0.77, 95% CI: 0.74-0.79), followed by basal FSH levels (0.73, 95% CI: 0.70-0.75), the basal LH/FSH ratio (0.68, 95% CI: 0.65-0.71), and basal E2 levels (0.61, 95% CI: 0.59-0.64). The appropriate cutoff value of basal LH levels associated with a positive response of the GnRH stimulation test was 0.35 IU/L, with a sensitivity of 63.96% and specificity of 76.3% from the ROC curves when Youden's index showed the maximum value. When 100% of patients had peak LH levels ≥5 IU/L, basal LH values were >2.72 IU/L, but the specificity was only 5.45%. Increased basal LH levels are a significant predictor of a positive response during the GnRH stimulation test for assessing activation of the HPG axis in most girls with early pubertal signs.

Infertility treatment strategy involving combined freeze-all embryos and single vitrified-warmed embryo transfer during hormonal replacement cycle for in vitro fertilization of women with hypogonadotropic hypogonadism.

Hypogonadotropic hypogonadism (HH) is a condition caused by the deficient secretion of pituitary gonadotropins, leading to diminished ovarian function. Several studies of in vitro fertilization (IVF) in women with HH revealed acceptable clinical pregnancy outcomes but high multiple pregnancy rates after multiple fresh embryo transfer (ET). The purpose of this study was to analyze the outcomes of combined freeze-all embryos and single vitrified-warmed ET in women with HH. Of 91 infertile women with HH (basal luteinizing hormone and follicle-stimulating hormone levels <2.0 mIU/mL), we excluded patients aged ≥40 years (n = 2) and women who preferred fresh ET (n = 10). Seventy-nine women underwent 117 oocyte retrieval cycles and 135 vitrified-warmed ET during hormone replacement (HR) cycles from 2008 to 2014 at the Kato Ladies Clinic and Juntendo University Hospital. In 26 single cleavage ET cycles, the rates of clinical pregnancy and live birth were 34.6% (9/26 ET) and 26.9% (7/26 ET), respectively. Regarding the outcomes after single vitrified-warmed blastocyst transfer, clinical pregnancy and live birth rates were 65.1% (71/109 ET) and 50.5% (55/109 ET), respectively. Multiple conceptions and ovarian hyperstimulation syndrome did not occur in any of the women with HH. Our results demonstrated that IVF followed by single vitrified-warmed ET in adjusted endocrine milieu during the HR cycle is an effective fertility treatment for women with HH and decreases the incidence of complications, including multiple conceptions.

Comparison of Serum Progesterone levels and Incidence of Pregnancy with Urinary and Recombinant HCG in Women Undergoing ICSI

Objective: Luteinizing hormone (LH) surge is important in the final maturation of the oocyte and in oocyte retrieval. The structural similarity of human chorionic gonadotropin (HCG) and LH allow its binding to HCG/LH receptor. So, we aimed to compare the efficacy of urinary HCG (uHCG) and recombinant HCG (rHCG) for induction of oocyte maturation, triggering ovulation and incidence of pregnancy through assessing the serum levels of estrogen, progesterone, and βHCG in infertile women undergoing intracytoplasmic sperm injection (ICSI) cycles. Subjects and Methods: Eighty-one Egyptian females were recruited in this study including 71 infertile females undergoing ICSI and 10 apparently healthy females as a control group. The infertile female patients were classified based on the treatment used for triggering of mature follicles into 35 infertile females received 1000 IU uHCG and 36 infertile females received 500 µg rHCG. Serum levels of basal follicle stimulating hormone (FSH) and LH, estrogen (E2), progesterone (P) and βHCG were measured at different times of menstrual cycle by ELISA methods. Results: serum FSH and LH were similar in all the studied groups. Serum P level at day 5 embryo transfer and number of retrieved and mature oocytes were comparable in the rHCG and uHCG groups. While Serum P level at day oocyte pick up was significantly higher in rHCG group than in uHCG group. The successful pregnancy was higher in uHCG group than in rHCG group. Conclusion: the uHCG more effective biochemical pregnancy rate more than rHCG. However, rHCG showed equivalent efficacy to uHCG in terms of serum P level at day 5 embryo transfer, the number of retrieved oocytes and mature oocytes in female patients undergoing ICSI. While rHCG increases the serum P level at day oocyte pick up to abnormal high level which may reduce the incidence of pregnancy in females received rHCG.

Neurokinin B Regulates Gonadotropin Secretion, Ovarian Follicle Growth, and the Timing of Ovulation in Healthy Women.

Context:Neurokinin B (NKB) is obligate for human puberty, but its role in adult female gonadotropin secretion and ovarian follicle growth is unknown.Objective:To investigate antagonism of NKB on pulsatile gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion and ovarian follicle development in healthy women.Design:Open investigation of the effects of a neurokinin-3 receptor (NK3R) antagonist (NK3Ra) vs a no-treatment control cycle.Setting:Clinical research facility.Patients or other participants:Healthy women with regular menses (n = 13).Intervention(s):NK3Ra MLE4901 40 mg taken orally twice daily from cycle day 5 to 6 for 7 days.Main outcome measure(s):LH secretion, ovarian follicle growth, and timing of ovulation.Results:NK3Ra administration reduced basal LH secretion without a change in pulse frequency and delayed the LH surge by 7 days, the duration of treatment [mean cycle day ± standard error of the mean (SEM), 22 ± 1 days vs 15 ± 1 days in control cycles; P = 0.0006]. Follicle growth (mean diameter at the end of administration of NK3Ra administration ± SEM, 9.3 ± 0.4 mm vs 15.1 ± 0.9 mm in control cycles; P < 0.0001) and rising estradiol concentrations (mean ± SEM, 166 ± 29 pmol/L vs 446 ± 86 pmol/L in control cycles; P < 0.0001) were prevented. After treatment, follicle development resumed and normal preovulatory follicle diameter and estradiol concentrations were demonstrated. Postovulatory progesterone rise was similarly delayed (peak cycle day, 30 ± 2 vs 22 ± 1; P = 0.002) and cycle length was prolonged (35 ± 1 days vs 29 ± 1 days in control cycles; P = 0.0003) but luteal progesterone excretion was unaffected by the NK3Ra (LH surge day +7 mean urinary progesterone levels ± SEM, 58 ± 10 pmol/mol vs 48±7 pmol/mol creatinine in control cycles; nonsignificant).Conclusion:These data demonstrate the involvement of NKB-NK3R signaling in the physiological regulation of GnRH/LH secretion, determining normal follicle development in women.

Diurnal variation of gonadotropin levels in girls with early stages of puberty.

Purpose Pubertal gonadotropin secretion shows circadian pattern and the luteinizing hormone (LH) levels tend to rise in later stages of puberty in girls. We studied the usefulness of basal LH in the evaluation of central precocious puberty with emphasis on the influence of sampling time.Methods Medical records of 334 girls that underwent gonadotropin-releasing hormone stimulation test (GnRHST) were reviewed. Auxological and laboratory data were compared between those with early morning (EM, before 10 AM) and late morning/afternoon (LM/A, after 10 AM) basal samples.Results Among those in sexual maturity rating (SMR) 2, EM samples showed higher basal LH (P=0.004) compare to LM/A samples, whereas those in SMR 3 showed no difference in LH levels between EM and LM/A samples. Among girls with pubertal response, EM group showed higher basal LH (P=0.031) and follicular stimulating hormone (P=0.008) than LM/A group. The EM basal LH was more closely related with the peak stimulated LH than the LM/A basal LH did (rs=0.871 vs. rs=0.524). The optimal basal LH cutoffs to predict a pubertal response to GnRHST were 0.11 IU/L with a sensitivity of 66.7% and a specificity of 78.7% in EM group, and 0.07 IU/L with a sensitivity of 60.0% and a specificity of 78.9% in LM/A group, respectively.Conclusions In girls with early stages of puberty, EM basal LH is a more sensitive screening tool than the LM/A basal LH. Diurnal variation should be considered in evaluating children with precocious puberty.

Independent relationship between body mass index and LH peak value of GnRH stimulation test in ICPP girls: A cross-sectional study.

The effect of obesity on idiopathic central precocious puberty (ICPP) girls is still under discussion. The relationship between body mass index (BMI) and sexual hormone levels of gonadotropin-releasing hormone (GnRH) stimulation test in ICPP girls is controversial and the underlying mechanism is unclear. This study aims to further explore the independent effect of excess adiposity on peak luteinizing hormone (LH) level of stimulation test in ICPP girls and the role of other related factors. A retrospective cross-sectional study was performed on 618 girls diagnosed as having ICPP, including 355 cases of normal weight, 99 cases of overweight and 164 cases of obese. The results showed that obese group had more progressed Tanner stage and no significant difference (P=0.28) in LH peak was found as basal LH value was used as a covariate. The obese group had higher total testosterone (TT), adrenocorticotrophic hormone (ACTH), 17-α hydroxyprogesterone (17-αOHP) and androstendione (AN), with significantly increased fasting insulin (FIN) and homeostasis model of assessment for insulin resistance index (HOMA-IR). Stratified analysis showed inconsistency of the relationship between BMI-standard deviation score (BMI-SDS) and LH peak in different Tanner stages (P for interaction=0.017). Further smoothing plot showed linear and non-linear relationship between BMI-SDS and LH peak in three Tanner stages. Then linear regression model was used to analyze the relationship between BMI-SDS and LH peak in different Tanner stages, with and without different confounding factors being adjusted. In B2 stage, BMI-SDS was negatively associated with LH peak. In B3 stage, when BMI-SDS <1.5, as BMI-SDS increased, the level of LH peak decreased (model I: β=-1.8, 95% CI=-4.7 to 1.1, P=0.214). When BMI-SDS ≥1.5, BMI-SDS was significantly positively associated with LH peak (model I: β=4.5, 95% CI=1.7 to 7.4, P=0.002). In B4 stage, when BMI-SDS <1.5, BMI-SDS was negatively associated with LH peak (model I: β=-11.6, 95% CI=-22.7 to-0.5, P=0.049). When BMI-SDS ≥1.5, BMI-SDS was positively associated with LH peak (model I: β=-4.2, 95% CI=-3.3 to 11.7, P=0.28). It is concluded that there is an independent correlation between BMI-SDS and LH peak of stimulation test in ICPP girls, their relationships are different in different Tanner stages, and the effect of BMI-SDS can be affected by adrenal androgens, estradiol and glucose metabolism parameters.

Acute Psychosocial Stress Inhibits LH Pulsatility and Kiss1 Neuronal Activation in Female Mice.

Psychosocial stress, such as isolation and restraint, disrupts reproductive neuroendocrine activity. Here we investigate the impact of psychosocial stress on luteinizing hormone (LH) pulses and gene expression and neuronal activation within Rfrp and Kiss1 cells in female mice. Mice were ovariectomized (OVX) and handled daily to habituate to the tail-tip blood collection procedure. Blood was collected every 5 minutes for 180 minutes for measurement of LH. After 90 minutes, stress animals were placed into restraint devices and isolated to new cages. No-stress control animals remained in their home cages. LH pulses occurred at regular intervals during the entire 180-minute sampling period in controls. In contrast, stress induced a rapid and robust suppression of pulsatile LH secretion. Stress reduced the frequency of pulses by 60% and diminished basal LH levels by 40%; pulse amplitude was unaffected. In a separate cohort of OVX females, brains were collected after 45, 90, or 180 minutes of stress or in no-stress controls. At all time points, stress induced a potent decrease in arcuate Kiss1 neuronal activation, using cfos induction as a marker, with a 50% to 60% suppression vs control levels, whereas Rfrp and cfos coexpression in the dorsal-medial nucleus was elevated after 45 minutes of stress. Although arcuate Kiss1 gene expression remained stable, Rfrp expression was elevated 20% after 180 minutes of stress. These findings demonstrate rapid suppression of LH pulsatile secretion by psychosocial stress, associated with reduced cfos induction in Kiss1 neurons and time-dependent increases in Rfrp neuronal activation and messenger RNA.

Relationship of gonadotropin hormone levels with testicular dysfunction in patients suffered from varicocele before and after stimulation by gonadotropin releasing hormone

Introduction: Since the early diagnosis and treatment of varicocele during adolescence can help in reducing the risk of future infertility, finding an appropriate indication is very important in order to avoid unnecessary treatment as well as avoid future infertility. Currently, surgery indications for varicocele in adolescents are including high-grade varicocele and testicular volume loss which there is no relation between these cases and semen parameters. Objectives: In the current study, the relationship of gonadotropin hormone levels was compared to testicular dysfunction in varicocele patients before and after stimulation by gonadotropin releasing hormone (GnRH). Patients and Methods: Around 60 patients between 18-30 years old were divided into two groups; patients with normal semen analysis (A) and patients with abnormal semen analysis (B). Hormonal analysis including the measurement of basal luteinizing hormone (LH) and Follicle-stimulating hormone (FSH) (bLH and bFSH) and also measurements of LH and FSH after GnRH stimulation test (sLH and sFSH) were carried out. Data were analyzed using t test by SPSS statistical software. Results: Of 60 patients, 30 patients had normal semen (group A) and 30 patients had abnormal semen parameters (group B). The bLH in group A was lower than group B and bFSH in group A were more than group B, but there was not a significant difference between them. sLH levels were significantly higher in group A than those of group B and sFSH levels in group B were greater than group A. However the difference was not significant. Conclusion: Testicular volume loss is not suitable criteria for prediction of testicular dysfunction; GnRH stimulation test has a potential for identifying patients with varicocele that are requiring prophylaxis surgery. Increasing serum levels of LH after stimulation by GnRH can also be applied as a suitable index for prophylaxis surgery in varicocele patients to prevent infertility in future.

Hyperandrogenism in adolescent girls: relationship with the somatotrophic axis.

During puberty there is a physiologic increase in adrenal and ovarian androgens. It has been suggested that the somatotrophic axis may be related to the development of hyperandrogenism and anovulation in non-obese adult women with polycystic ovarian syndrome (PCOS). The objective of the study was to investigate whether ovarian androgen secretion in young postmenarchal girls is related to the function of their somatotropic axis. This was a cross-sectional study of adolescent girls. We studied non-obese adolescent girls with hyperandrogenism (HA; n = 21) matched with control girls (C; n = 25) for chronological age, age at menarche and body mass index. We obtained a fasting blood sample for measurement of serum glucose, insulin, 17-hydroxyprogesterone (17OH-Prog), dehydroepiandrosterone-sulfate (DHEA-S), androstenedione, sex hormone-binding globulin (SHBG), total testosterone, IGF-I, IGF-II, IGFBP-1, IGFBP-3, ghrelin, leptin, AMH (antiMüllerian hormone), luteinizing hormone (LH) and follicle stimulating hormone (FSH) during the follicular phase of the menstrual period. We performed an oral glucose tolerance test to determine blood glucose, insulin and ghrelin levels and urine samples to measure urinary GH (growth hormone) levels. As expected, the hyperandrogenic girls had significantly higher Ferriman scores, basal total testosterone, free androgen index (FAI), androstenedione, AMH, and basal LH levels compared with the girls in controls. Serum IGF-I, IGF-II, IGFBP-3 and urinary GH did not differ between HA and C. There was a correlation between urinary GH and FAI in all girls (r 0.29, p < 0.05). In addition, in HA girls FAI correlated with insulin, homeostasis model assessment (HOMA) and ghrelin. We observed a correlation between urinary GH and FAI in the hyperandrogenic and control girls, suggesting that the function of the somatotrophic axis may influence the secretion of androgens in adolescent girls.