Luteinizing Hormone Peak Research Articles

Thyroid function in girls with central precocious puberty.

PurposeObesity is a well-known risk factor for central precocious puberty (CPP). Recently, elevated thyroid stimulating hormone (TSH) was reported in obese youth. However, few data regarding the relationship between CPP and TSH are available. The aim of this study was to evaluate thyroid function in girls with CPP and the relationship between CPP and serum TSH concentration.MethodsThis was a retrospective cross-sectional study. A total of 1,247 girls aged between 6.0 and 8.9 years who had undergone a gonadotropin-releasing hormone (GnRH) stimulation test to determine the presence of puberty were studied. Subjects were classified into CPP (n=554) and non-CPP (n=693) groups according to the results of the GnRH stimulation test. Characteristics and laboratory data of the CPP and non-CPP groups were compared and correlations between those characteristics and laboratory data and TSH concentration were evaluated. Serum TSH concentration in the CPP group was higher than that of the non-CPP group (3.19±1.55 mIU/L vs. 2.58±1.34 mIU/L, P<0.001).ResultsSerum free thyroxine (fT4) concentration in the CPP group was notably lower than that of the non-CPP group (1.38±0.14 ng/dL vs. 1.44±0.18 ng/dL, P<0.001). Across all subjects, 149 girls (11.9%) had hyperthyrotropinemia. The prevalence of hyperthyrotropinemia was higher in the CPP group compared to the non-CPP group (15.7% vs. 8.9%, P<0.001). TSH concentrations were positively correlated with age, height, weight, BMI, bone age, bone age advance, insulin-like growth factor 1 (IGF-1), IGF-1 standard deviation score, basal luteinizing hormone (LH), peak LH and basal follicle-stimulation hormone. TSH concentrations were negatively correlated with fT4. Multiple linear regression analysis showed that age (β=0.548, P<0.001) and peak LH (β=0.019, P=0.008) were independently associated with serum TSH concentration.ConclusionsHyperthyrotropinemia in girls with CPP tends to be associated with pubertal LH elevation. In conclusion, pubertal onset may be associated with thyroid function.

Ovarian response in oocyte donation cycles under LH suppression with GnRH antagonist or desogestrel progestin: retrospective and comparative study

Here are investigated the serum hormones in ovarian stimulation cycles of oocyte donors (OD), under endogenous luteinizing hormone (LH) suppression with GnRH antagonist (antGnRH) vs. desogestrel (DSG) (progesterone-primed [PP]). OD underwent ovarian stimulation with gonadotropins at a private, university-based, infertility center between January 2017 and March 2018. Endogenous LH peak was controlled with either daily injections of antGnRH or with daily oral 75 mcg DSG (PP) until triggering. LH and progesterone were measured at trigger and the following day. A total of 404 OD cycles were included. There were no differences in age (26.7 ± 4.9 vs. 27.1 ± 4.8 years), AMH (3.7 ± 2.1 vs. 4.1 ± 2.7 ng/ml), and body mass index (BMI) (22.4 ± 2.8 vs. 22.1 ± 3.0 kg/m2) between PP and antGnRH groups, respectively. On the day of trigger, progesterone was lower in PP compared to antGnRH (0.9 ± 0.7, vs. 1.5 ± 1.2 ng/ml, p < .001), whereas no significant differences existed in estradiol or LH. On the day after trigger, lower progesterone in PP vs. antGnRH (10.8 ± 6.0 vs. 13.4 ± 7.9 ng/ml, p=.002) was observed. No differences were observed in the number of retrieved oocytes or the clinical pregnancies among recipients. Our study shows that endocrine response to DSG differs significantly as compared to antGnRH use for the control of endogenous LH without apparent impact on number of retrieved oocytes or the clinical pregnancies among recipients.

Validation of an Accurate and Noninvasive Tool to Exclude Female Precocious Puberty: Pelvic Ultrasound With Uterine Artery Pulsatility Index.

OBJECTIVE. The purpose of this study is to validate the accuracy of pelvic ultrasound (US) with the evaluation of uterine artery pulsatility index (PI) to exclude female precocious puberty. MATERIALS AND METHODS. Tanner breast development score, luteinizing hormone (LH) peak after gonadotropin-releasing hormone (GnRH) stimulation, and uterine and ovarian volumes and diameters were assessed with pelvic US in 495 girls at a single institution. The study population was divided as follows: prepubertal (n = 207), pubertal with physiologic activation of the hypothalamic-pituitary-ovarian axis (n = 176), and central precocious puberty (CPP; n = 112). PI was measured with spectral Doppler US at the ascending branches of the right uterine artery (50-Hz filter; time gain compensation, 73; pulse repetition frequency, 6.6). ROC analyses and t tests were performed. RESULTS. The mean (± SD) PI values in the prepubertal, pubertal, and CPP groups were 6.3 ± 1.4, 3.4 ± 1.1, and 4.1 ± 1.5, respectively (p < 0.001). The best PI cutoff value to distinguish pubertal from prepubertal girls was 4.6 (sensitivity, 83%; specificity, 94%; positive predictive value, 95%; negative predictive value, 80%; accuracy, 87%). ROC AUC values for LH peak (cutoff value, 5 mU/mL) and for spectral Doppler US PI plus longitudinal uterine diameter (i.e., the combination of a PI of 4.6 with a longitudinal uterine diameter of 35 mm) were 0.9272 and 0.9439, respectively (p = 0.7925). The negative predictive values for LH peak and for PI plus longitudinal uterine diameter were 89% and 88%, respectively. CONCLUSION. A PI greater than 4.6 at spectral Doppler US combined with a longitudinal uterine diameter less than 35 mm allows noninvasive exclusion of female precocious puberty with comparable accuracy and lower costs compared to examination of LH peak after GnRH stimulation. Therefore, PI plus longitudinal uterine diameter might be used as a noninvasive first-line test to exclude precocious puberty and thereby avoid further investigations.

Nppc/Npr2/cGMP signaling cascade maintains oocyte developmental capacity

The follicle must fulfill the following criteria if it is to survive the period between early embryonic life and the luteinizing hormone (LH) peak. It should (i) be surrounded by pregranulosa cells; (ii) complete the first meiotic division and become dormant; and (iii) continue metabolism during the dormant stage. Interaction between the natriuretic peptide precursor type C (Nppc) and its receptor, natriuretic peptide receptor 2 (Npr2), affects female fertility through the production of oocytes with developmental capacity and maintain oocyte meiotic arrest. While Nppc is expressed in mural cells, cumulus cells express Npr2. Nppc/Npr2 system exerts its biological function on developing follicles by increasing the production of intracellular cyclic guanosine monophosphate (cGMP). This pathway not only contributes to the development of ovary and the uterus, but aids the formation of healthy eggs in terms of their morphological and genetic aspects. A defect in this pathway leads to asmall ovarian size, string-like uterine horns, and thin endometrium and myometrium. Disorganized chromosomes, abnormal cumulus expansion and early meiotic resumption occur in animals with defective Nppc/Npr2 signaling. The types and number of oocytes also decrease when there is incompetent Nppc/Npr2 signaling. This paper extends on most recent and relevant experimental evidence regarding Nppc/Npr2/cGMP signaling with regard to its crucial role in maintaining oocyte meiotic arrest and the production of oocytes with developmental capacity. We further discuss whether the agonist or antagonist forms of the members of this exciting pathway can be usedfor triggering final oocyte maturation.

Analysis of the cut point of peak level of luteinizing hormone in gonadotropin-releasing hormone agonist test in obese girls with precocious puberty

Objective To explore the significance of the cut point of peak level of luteinizing hormone(LH) in gonadotropin-releasing hormone (GnRH) agonist test in the diagnosis of precocious puberty in obese girls. Methods According to the diagnostic criteria of children′s central precocious puberty diagnosis consensus (2015), 796 cases of precocious puberty (peak level of LH ≥3.3 IU/L) in Children′s Hospital of Zhejiang University School of Medicine from January 2014 to December 2015 were divided into normal weight group (573 cases), overweight group (170 cases) and obesity group (53 cases). The 3 groups were compared in terms of basic level of LH, basic level of follicle stimulating hormone (FSH), peak level of LH and FSH, ratio of LH(peak)/FSH(peak), sex hormone binding protein (SHBG), and children with 3.3 IU/L ≤peak level of LH <5.0 IU/L were followed up.The accuracy of the diagnosis of central precocious puberty using peak level of LH was analyzed by using receiver operating characteristic (ROC) curve. Results The median of LH (peak) in the obese group was 6.92 IU/L, the median of SHBG was 46.52 nmol/L, the median of LH (peak) in normal weight group was 8.92 IU/L, and the median of SHBG was 87.28 nmol/L.There were significant differences between the 2 groups (P<0.05, 0.001). A total of 89 cases in normal weight group and 65 cases of obesity/overweight group (3.3 IU/L ≤peak level of LH <5.0 IU/L) were followed up for 1 year, and 18 cases in normal weight group and 33 cases in obesity/overweight group developed to central precocious puberty, while the number of cases in the 2 groups was significantly different (P<0.001). The ROC curve analysis showed that the cut point of peak level of LH was 4.16 IU/L, the sensitivity was 0.606, the specificity was 0.656, and the Jordan index was the largest (0.344). Conclusions The peak level of LH in GnRH agonist test is important for the diagnosis of central precocious puberty in girls, but the effect of body mass index on its cut point needs to be considered. Key words: Body mass index; Precocious puberty; Gonadotropin-releasing hormone agonist test; Receiver operating characteristic curve

Efficiency of CIDR-Based Protocols Including GnRH Instead of eCG for Estrus Synchronization in Sheep.

Simple SummaryThis study examines the preovulatory and ovulatory events (in terms of the timing of onset of estrus behavior, preovulatory LH surge, and ovulation) and the yields obtained (in terms of ovulation rate, progesterone secretion, and fertility) after insertion of controlled internal drug release (CIDR) devices for 5 days and treatment with equine chorionic gonadotrophin (eCG) or gonadotrophin-releasing hormone (GnRH).The present study examined, for meat sheep (Segureña breed; 2–5-years old, mean body score of 3.5 ± 0.5), the timings of onset of estrus behavior, preovulatory luteinizing hormone (LH) surge and ovulation, and the ovulation rate and fertility obtained after insertion of controlled internal drug release (CIDR) devices for 5 days plus treatment with equine chorionic gonadotrophin (eCG; single dose at CIDR removal, n = 19 ewes) or gonadotrophin-releasing hormone (GnRH, either in a single dose at 56 h after CIDR removal, group CIDR-GnRH, n = 19 ewes; or in one dose at CIDR insertion and another dose 56 h after CIDR removal, group GnRH-CIDR-GnRH, n = 19 ewes). In all the ewes, the appearance of estrus behavior ranged between 84% and 90% and all females showing estrus signs had subsequent preovulatory LH peaks and ovulations. Onset of these events was earlier in the CIDR-eCG group than in the CIDR-GnRH and GnRH-CIDR-GnRH groups (p < 0.05). These differences were mainly determined by the onset of estrus behavior, since timing and intervals of LH peak and ovulation were similar among treatments. In fact, the range of ovulations was narrower in the GnRH-CIDR-GnRH group, which suggests better synchronization of follicular growth (p < 0.05). In conclusion, protocols with two doses of GnRH offer similar yields to eCG protocols.

"Hormone of darkness" and human reproductive process: direct regulatory role of melatonin in human corpus luteum.

To investigate the possible role of melatonin on human luteal cell function. Corpora lutea were obtained from normally menstruating women (25-38years old) in the midluteal phase (days 5-6 from ovulation) at the time of surgery for non-endocrine gynecologic diseases. The protocol was approved by the institutional review board of Università Cattolica del Sacro Cuore in Rome and all patients provided written informed consent. The corpora lutea were dated on the basis of the presumptive day of ovulation (day 0) , determined by urinary luteinizing hormone (LH) peak, ultrasound detection of corpus luteum or disappearance of the dominant follicle, and a rise in the plasma P concentration. ELISA or EIA kit and immunohistochemistry were performed. Melatonin was able to increase progesterone release and to influence the balance between luteotrophic and luteolityc factors. In addition, melatonin expression and MT2 receptor were detected, confirming the direct action of this indoleamine on CL. Melatonin may play an intriguing role in direct regulation of CL function and in establishing and maintaining of initial pregnancy. In conclusion, melatonin could become a relevant medication for improving ovarian and luteal function and in the early stages of pregnancy, opening new opportunities for the management of several ovarian-luteal and pregnancy diseases.

Time of copulation during estrus period on estrus duration and LH response in Boer goats

The objectives of this investigation were to determine the effect of the time of copulation during the estrus period on estrus duration and luteinizing hormone (LH) response in goats. A controlled randomized study with two replicates (first = n = 12; second = n = 24), in which Boer does were divided at each replicate into three groups, was performed. Copulations at the beginning of estrus (two copulas within the first 4 h after estrus; COP-1; n = 12), copulations around the middle of estrus (two copulas around 16 h after estrus; COP-2; n = 12), and noncopulations (only mounts) throughout the estrus period (control group; CON; n = 12) were performed. Estrus duration for CON group was 41.3 ± 8.2 h; for COP-1, it was 34.0 ± 5.3 h, and for COP-2, it was 39.7 ± 6.9 h (P = 0.04). Differences were detected between COP-1 and CON groups (P = 0.01) and between COP-1 and COP-2 groups (P = 0.05) but not between CON and COP-2 groups (P = 0.56). The LH peak time for the CON group was 20.0 ± 8.0 h; for the COP-1 group, it was 13.0 ± 3.6 h, and for the COP-2 group, it was 20.5 ± 5.8 h (P = 0.04). The COP-1 group was different than the COP-2 (P = 0.02) and CON groups (P = 0.03), and no differences were detected between these last two groups (P = 0.87). It was concluded that copulation reduced estrus duration and hastened the LH peak time only when performed during the beginning of estrus.

The effect of overweight on the luteinizing hormone level after gonadorelin stimulation test in girls with idiopathic central precocious puberty.

PurposeWe investigated the effect of overweight on luteinizing hormone (LH) levels after a gonadorelin stimulation test in Korean girls with idiopathic central precocious puberty (CPP).MethodsMedical records of 234 girls diagnosed with idiopathic CPP were reviewed retrospectively. CPP was diagnosed when the peak LH levels after gonadorelin stimulation was >5.0 U/L. The enrolled girls had a peak LH level >5.0 U/L after a gonadorelin stimulation test. Selected girls were classified as normoweight (body mass index [BMI] below the 85th percentile with respect to age) and overweight (BMI greater than the 85th percentile with respect to age).ResultsThe peak LH (8.95±2.85 U/L vs. 11.97±8.42 U/L, P<0.01) and peak follicle-stimulating hormone (9.60±2.91 U/L vs. 11.17±7.77 U/L, P=0.04) after gonadorelin stimulation were lower in overweight girls with idiopathic CPP than in normoweight girls with idiopathic CPP. Being overweight was negatively associated with peak LH levels after gonadorelin stimulation test (odds ratio, 0.89; 95 % confidence interval, 0.81–0.98, P=0.02).ConclusionsIn girls with idiopathic CPP, being overweight led to a lower LH peak after gonadorelin stimulation. Further research is needed to better understand the role of overweight on gonadotropin secretion in precocious puberty.

Profile of LH release in response to intramuscular treatment with kisspeptin in Bos indicus and Bos taurus prepubertal heifers

The main objective of this study was to evaluate the effect of intramuscular (I.M.) administration of different doses of kisspeptin (Kp) on the pattern of luteinizing hormone (LH) release in Bos taurus and Bos indicus prepubertal heifers. Holstein heifers weighing 215.1 ± 38.6 kg (n = 24; aged 5–8 mo) and Gyr heifers weighing 215.4 ± 31.4 kg (n = 24; aged 6–10 mo) were enrolled in this study. The animals were confirmed as non-cyclical by absence of a corpus luteum (CL) as determined by ultrasound scanning of the ovaries and low circulating P4 concentrations (<1.0 ng/mL) evaluated at a 10-day interval (on day −10 and day 0). For each genetic group, heifers were randomly assigned to one of four treatments: Kp at 2.5 μg/kg body weight (Kp2.5), Kp at 5.0 μg/kg (Kp5), Kp at 10 μg/kg (Kp10), or gonadotropin-releasing hormone (GnRH) agonist (0.01 mg of buserelin acetate per heifer), all administered by I.M. injection. All animals responded to the treatments with an LH surge (P < 0.01). There was an effect of breed (P < 0.01) on induced LH release, with Holstein heifers having a greater area under the curve for LH (AUC; P < 0.01) and greater LH peak amplitude (P < 0.01) than Gyr heifers. Nevertheless, greater AUC for LH occurred in Kp10 heifers for both breeds. There was no effect of breed on LH AUC or LH peak amplitude after GnRH agonist treatment. For both breeds, heifers treated with Kp displayed an earlier (P < 0.01) LH peak with a reduced amplitude of the LH peak (P < 0.01) and reduced LH AUC (P < 0.01) compared to heifers treated with GnRH agonist. Thus, both zebu and taurus immature heifers treated with I.M. Kp injection responded with a rapid and dose-dependent LH surge, although even large doses of the native Kp-10 did not mimic the magnitude or duration of the LH surge produced by the GnRH agonist. The early onset of the LH surge after Kp treatment and the short duration suggest that the effects of Kp were likely due to pituitary rather than hypothalamic action. Finally, there seems to be a greater responsiveness to Kp in Bos taurus than in Bos indicus prepubertal heifers, although LH release after GnRH agonist treatment was similar for the two breeds.

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.

Seasonal ovarian development in relation to the gonadotropins, steroids, aromatase and steroidogenic factor 1 (SF-1) in the banded gourami, Trichogaster fasciata

The endocrine regulation of gonadal development and annual variation of key sex steroids is the basic knowledge to understand the reproductive cycle of teleost fish. Present study was aimed to investigate the levels of gonadotropins in relation to the follicular development and plasma steroids during the reproductive cycle of female Trichogaster fasciata. Female fish were sampled and ovarian development is described histologically throughout the year in relation to the seasonal variations of gonadosomatic index (GSI); follicle stimulating hormone (FSH) and luteinizing hormone (LH); three key steroids for folliculogenesis and maturation i.e. testosterone (T), 17β-estradiol (E2) and 17α20βdihydroxy4pregnen3one (17,20β-P). Relatively higher level of FSH was observed till the ovary reaches in late vitellogenic stage confirms that FSH regulates the early folliculogenesis of the ovary, whereas LH peak was observed in the postvitellogenic stage, which indicates that maturation and ovulation were controlled by LH. Seasonal steroid profiles show that both T and E2 reach its maximum level prior to the 17,20β-P which attain its peak value in the month of August. Thus, single peak values of LH and 17,20β-P coinciding with GSI peak, clearly indicates that T. fasciata breeds only once in a year. Furthermore, to elucidate the molecular basis of the reproductive cycle, this study analyzes the other key factors of ovarian function such as cyp19a1a gene expression, aromatase activity and SF-1 localization throughout the year. cyp19a1a gene expression and the aromatase activity were highest in vitellogenic stages indicate that relatively higher E2 production in this stage is regulated by FSH. Immunohistochemical localizations of aromatase and SF-1 in the cellular layer of oocytes demonstrated that aromatase is FSH-dependent and SF-1 could be regulated by both FSH and LH as relatively higher amount of aromatase was localized in the vitellogenic stage oocytes than the postvitellogenic and post germinal vesicle breakdown (post-GVBD) stages; whereas, high amount of SF-1 was observed in vitellogenic, postvitellogenic and post-GVBD stages. These data regarding the reproductive endocrinology of T. fasciata may be useful to understand the interaction between gonadotropins, steroids, aromatase and SF-1 in teleost fishes and may contribute to restoration of the ecologically important fish through artificial reproduction.

Association between Body Mass Index and Serum Dehydroepiandrosterone Sulfate Level in 8-Year-Old Girls.

BackgroundAdiposity may play a role as a potential trigger for adrenarche. The purpose of this study was to evaluate the association between body mass index (BMI) and serum dehydroepiandrosterone sulfate (DHEAS) level.MethodsThe medical records of 8-year-old girls who presented to our clinic between 2014 and 2016 with concerns regarding pubertal changes were retrospectively reviewed. The 192 girls were divided into two groups depending on activation of the hypothalamic-pituitary-gonadal (HPG) axis. Group I included 77 subjects with a breast Tanner stage 1 with unknown HPG axis or thelarche without activated HPG axis. Group II included 115 subjects with activated HPG axis. Serum DHEAS level ≥1.1 μmol/L was regarded as biochemical adrenarche.ResultsBased on correlation analyses, BMI standard deviation score (SDS) was positively correlated with height SDS, bone age divided by chronological age (BA/CA), and DHEAS level in all subjects (r=0.269, r=0.270, r=0.298; all P<0.001, respectively). BMI SDS was negatively correlated with peak luteinizing hormone level in group II (r=−0.236, P=0.011). Based on multiple linear regression analyses, BMI SDS was associated with serum DHEAS level in all subjects (β=0.280, P<0.001), group I (β=0.415, P=0.001), and group II (β=0.206, P=0.030). DHEAS level was also associated with BA/CA in all subjects (β=0.402, P<0.001), group I (β=0.494, P<0.001), and group II (β=0.347, P<0.001).ConclusionBMI SDS was associated with DHEAS level, which was associated with BA/CA. Childhood obesity may influence the development of adrenarche, which may contribute to advanced skeletal maturation.

Characterization of the LH peak after short and long fixed‐time artificial insemination protocols in sheep raised in the tropics

The aim of this study was to evaluate the peak in luteinizing hormone (LH) and the pregnancy rate of sheep (Texel×Santa Inês) in the tropics using short- (6days) and long-term (12days) progesterone protocols followed by artificial insemination (AI) both in and out of the breeding season. Experiment 1 was conducted within (IN) the breeding season (autumn, n=36), and experiment 2 was conducted outside (OUT) of the breeding season (spring, n=43). In each experiment, the sheep were divided into two groups (6 or 12days) according to the duration of treatment with a single-use progesterone release vaginal device (CIDR® , Pfizer, São Paulo, SP, Brazil), and blood samples were collected from 10 animals per group every 4hr to measure the LH and progesterone concentrations. In the spring, the characteristics of the LH peak did not differ between groups; but in the autumn, there were differences between groups at the beginning (G-6 IN: 36.44±5.46hr; G-12 IN: 26.57±4.99hr) and end of the LH peak (G-6 IN: 46.22±7.51hr; G-12 IN: 34.86±8.86hr). The results showed alterations in the LH peak during the breeding season only in the sheep undergoing the short-term protocol.

LHCGR Gene Analysis in Girls with Non-Classic Central Precocious Puberty.

Luteinizing hormone (LH) is a useful parameter in diagnosing precocious puberty. The pubertal response of serum LH to a GnRH stimulation test is varied, and clinical symptoms of precocious puberty are sometimes disproportionate with serum LH concentrations. Many patients present in a state of precocious puberty that advances rapidly, but the post-GnRH peak LH remains prepubertal. LH receptor mutations are suspected of involvement in the non-classic type of central precocious puberty (CPP). To examine the association between LHCGR polymorphism and non-classic CPP in subjects exhibiting a peak LH<5 IU/L on a GnRH stimulation test. In total, 102 girls with non-classic CPP and 100 normal adult women were enrolled. All subjects underwent LHCGR gene analysis by the Sanger method, and patients and controls were compared. Auxological data and gonadotropin concentrations were analyzed in the 102 patients. Of these patients, 75 completed GnRH agonist treatment, and the treatment outcomes were analyzed. A total of seven variants were identified, including two missense mutations (g.48698754 G/A and g.48688613 G/A) that were found in the patient group (no patients contained both mutations). In silico analysis of these missense mutations suggested the possibility of damaging the LHCGR. However, no significant association was found between the identified LHCGR variants and non-classic CPP. GnRH agonist treatment decreased bone age advancement and increased predicted adult height. LHCGR gene polymorphisms do not appear to be a major causative factor for the relatively low concentration of LH in patients with non-classic CPP. GnRH agonist treatment improved clinical parameters in these patients.

Результати контрольованої стимуляції овуляції у програмах донації ооцитів

The objective: of the study was to study the effectiveness of controlled ovarian stimulation in oocyte donors depending on the stimulation protocol. Materials and methods. To achieve this goal, the medical documentation of 120 oocyte donors was analyzed, which was stimulated in the Medical Center «Mother and Child» in 2012–2015. All medical cards were divided into two groups: the first group included women in which was used a gonadotropin-releasing hormone agonist (n=70) in the stimulation cycle to prevent premature luteinizing hormone peaks (n=70), and the second group used an antagonist (n=50). Results. The average duration of stimulation in case of usage of gonadotropin-releasing hormone agonists was on average 2 days longer. The total amount of recombinant follicle-stimulating hormone was also significantly (on average 500 IU) more, and the resulting follicle and oocytes – less. Сonclusion. Thus, the study showed that optimal protocol for obtaining donor oocytes is a protocol with usage daily doses of a gonadotropin-releasing hormone antagonist to prevent premature luteinizing hormone peaks. Further search for the purpose of optimizing the schemes of stimulation of superovulation in donors is to be carried out within the framework of this particular protocol. Key words: in vitro fertilization, stimulation of superovulation, donation of oocytes.

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.

Serum Osteocalcin Levels in Girls with Central Precocious Puberty: Relation to the Onset of Puberty.

Osteocalcin is the non-collagenous protein produced by osteoblasts in bone. When it is released into systemic circulation in its uncarboxylated form, it regulates fat and glucose metabolism. Recent studies have shown that osteocalcin is also involved in male fertility. Because the onset of puberty is determined by ethnic, genetic, environmental, and metabolic factors, we focused on determining the role of osteocalcin in the onset of puberty. Central precocious puberty (CPP) is defined as the activation of the hypothalamic-pituitary-gonadal axis before the age of 8 in girls and 9 in boys. CPP is diagnosed when peak luteinizing hormone (LH) reaches ≥ 5.0 IU/l after stimulation with gonadotropin-releasing hormone (GnRH). This retrospective study included 206 girls who showed breast budding before the age of 8 and whose bone age was more advanced than their chronological age. The CPP group included 100 girls who were diagnosed with CPP, and 106 girls were the non-CPP group whose peak LH did not reach ≥ 5.0 IU/l after GnRH stimulation test. Serum osteocalcin levels were measured to investigate the relationship between osteocalcin and the onset of puberty. Our data showed that serum osteocalcin levels were significantly higher in the CPP group (87.7 ± 24.4 ng/ml vs. 68.3 ± 19.5 ng/ml, P < 0.001). The multivariate analysis revealed that an increase in bone age and peak LH was significantly associated with the serum osteocalcin level. The results of this study suggest that serum osteocalcin is associated with the onset of puberty in girls.

Overexpression of Endometrial Estrogen Receptor-Alpha in The Window of Implantation in Women with Unexplained Infertility.

BackgroundFailure in the endometrial receptivity may account for a significant number of infertility cases including unexplained infertility in women. Reduction in the endometrial estrogen receptor-alpha (ER-α) expression during implantation may be a critical event that coincides with the expression of specific genes and the formation of a receptive endometrium. The aim of the present study was to assess the expression of ER-α in the mid-secretory phase in the endometrium of women with unexplained infertility.Materials and MethodsThis case-control study was carried out on randomly selected fertile (n=10) and infertile (n=16) women whose source of infertility remained unexplained. We evaluated the expression of ER-α and glycode-lin-A (GdA) through mRNA level measurement with real-time polymerase chain reaction (PCR) in the endometrium of fertile women and patients suffering from unexplained infertility and fertile women. Endometrial biopsies of each subject were collected during a single menstrual cycle 7 days after the peak of luteinizing hormone (LH+7).ResultsEndometrial expression level of ER-α was significantly (P<0.05) higher in the patients with unexplained infertility compared to the control. Significantly (P<0.05) lower levels of GdA expression were seen in women with unexplained infertility. A statistically non-significant negative correlation was observed between ER-α and GdA mRNA expression.ConclusionOur findings demonstrate that reduction in the endometrial GdA expression is associated with elevated expression of ER-α in mid-luteal phase. Disruption in the endometrial ER-α expression, which leads to defects in uterine receptivity, may contribute to unexplained infertility.

Induction of the LH Surge in Premenarchal Girls Confirms Early Maturation of the Hypothalamic-Pituitary-Ovarian Axis.

To determine whether premenarchal girls exhibit positive estradiol feedback similar to regularly cycling adult women when given exogenous estradiol. This was a prospective clinical cohort study at 2 institutions. Nine girls and 6 women received a 7-day course of transdermal estradiol designed to produce physiologic, mid-cycle circulating estradiol levels. Participants collected daily morning urine for luteinizing hormone (LH), estradiol metabolites (E1c), and progesterone metabolites (Pdg), corrected for creatinine. Main outcomes were percentage increase in LH from nadir to peak and the absolute value of peak LH between the 2 groups, using t testing and linear mixed-effects modeling. All participants exhibited a positive feedback response to estradiol. Adult women had a 532.8% (95% confidence interval [CI]: 253.7-1119) increase in LH after estradiol exposure; premenarchal girls had a 497.9% increase (95% CI: 274.5-903.2; P = .86). The absolute value of the LH surge in women was 9.50 mLU/mgCr (95% CI: 2.59- 43 34.90) and in premenarchal girls was 2.57 mLU/mgCr (95% CI: 0.53-12.49; P = .15). Premenarchal girls can mount an LH surge proportionally similar to regularly cycling adults. This occurs earlier in puberty than previously believed, in contrast to current dogma that maturation of the hypothalamic-pituitary-ovarian axis occurs after menarche and is the rate-limiting step for the establishment of regular, ovulatory cycles. Failure to achieve regular cycles may instead be due to nutritional or ovarian factors. Young girls who fail to ovulate shortly after menarche may warrant further evaluation for endocrinopathies.