Basal Serum Luteinizing Hormone Research Articles

Evaluation of the diagnostic value of different serum biomarkers in girls with central precocious puberty

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

The influence of body composition on the response to dynamic stimulation of the endocrine pituitary-testis axis.

Testosterone treatment is generally not recommended in men with obesity induced low serum testosterone. However, distinguishing this condition from overt testosterone deficiency in men with obesity where treatment should be initiated is a diagnostic challenge and tools to differentiate these conditions are scarce but could be of important clinical relevance. To investigate the association between body composition and dynamic responses of the pituitary-testis axis in men. Single-center cross-sectional study including 112 healthy men. Participants went through a full biochemical assessment of the pituitary-testis axis, and dynamic stimulatory tests of luteinizing hormone (LH) secretion (gonadotropin-releasing hormone (GnRH)-test) and testosterone secretion (choriogonadotropin (hCG)-test). A subset (N = 78) further had a DXA-scan performed. A higher body mass index (BMI) was associated with lower basal serum LH (BU = -0.44, 95% CI: -0.88--0.01, p = 0.04). The GnRH-stimulated LH increase was not significantly associated with BMI (BU = -0.10, 95% CI: -0.72-0.51, p = 0.74). Furthermore, a high BMI was associated with low basal testosterone (BU -0.02, 95% CI: -0.03--0.02, p < 0.001), and free testosterone (BU -15.0, 95% CI: -19.9--10.0, p < 0.001) and men with overweight and obesity had significantly lower testosterone (9%, p = 0.003 and 24%, p < 0.001) and free testosterone (25%, p = 0.006 and 50%, p < 0.001) concentrations compared to men with normal weight. The HCG-stimulated testosterone increase was significantly less dependent on BMI compared to the influence of BMI on basal testosterone concentrations (p = 0.04 for the interaction). Dynamic sex hormone responses following pituitary-testis axis stimulation were less dependent on BMI, compared to the influence of BMI on basal hormone concentrations and could potentially assist clinical decision making in patients with obesity suspected of testosterone deficiency.

Novel MKRN3 Missense Mutations Associated With Central Precocious Puberty Reveal Distinct Effects on Ubiquitination.

Loss-of-function mutations in the maternally imprinted genes, MKRN3 and DLK1, are associated with central precocious puberty (CPP). Mutations in MKRN3 are the most common known genetic etiology of CPP. This work aimed to screen patients with CPP for MKRN3 and DLK1 mutations and analyze the effects of identified mutations on protein function in vitro. Participants included 84 unrelated children with CPP (79 girls, 5 boys) and, when available, their first-degree relatives. Five academic medical institutions participated. Sanger sequencing of MKRN3 and DLK1 5' upstream flanking and coding regions was performed on DNA extracted from peripheral blood leukocytes. Western blot analysis was performed to assess protein ubiquitination profiles. Eight heterozygous MKRN3 mutations were identified in 9 unrelated girls with CPP. Five are novel missense mutations, 2 were previously identified in patients with CPP, and 1 is a frameshift variant not previously associated with CPP. No pathogenic variants were identified in DLK1. Girls with MKRN3 mutations had an earlier age of initial pubertal signs and higher basal serum luteinizing hormone and follicle-stimulating hormone compared to girls with CPP without MRKN3 mutations. Western blot analysis revealed that compared to wild-type MKRN3, mutations within the RING finger domain reduced ubiquitination whereas the mutations outside this domain increased ubiquitination. MKRN3 mutations were present in 10.7% of our CPP cohort, consistent with previous studies. The novel identified mutations in different domains of MKRN3 revealed different patterns of ubiquitination, suggesting distinct molecular mechanisms by which the loss of MRKN3 results in early pubertal onset.

P-607 Basal serum luteinizing hormone and total testosterone levels do not impact the outcomes of in-vitro fertilization in women with polycystic ovarian syndrome (PCOS)

Abstract Study question Do basal serum luteinizing hormone (LH) and total testosterone (TT) levels affect the outcomes of patients with PCOS undergoing in vitro fertilization? Summary answer LH and TT does not impact number of mature oocytes, fertilization rates, and high-quality blastocysts frozen, in PCOS with GnRH-antagonist protocol IVF with hyper-responses. What is known already The impact of basal serum LH and TT levels on IVF outcomes is debatable. Worldwide, there are many clinics that will postpone ovarian stimulation until a lower basal LH or TT is obtained in women with PCOS based on the assumption that outcomes will subsequently be more successful. However, hormones are released in a pulsatile fashion and single levels are unlikely to reflect patient status. There is a paucity of research addressing this concern. Study design, size, duration We completed a single university-centre retrospective cohort study comparing the outcomes of PCOS patients undergoing freeze-all GnRH antagonist IVF cycles divided into 50% groupings for basal serum LH and TT levels between the dates of January, 2013 and December, 2019. There were 76 women identified and confirmed on chart review to have a diagnosis of PCOS per the 2003 Rotterdam criteria. Participants/materials, setting, methods Patients were divided into the 50% with the lowest LH levels(1.0-7.0 IU/L) and highest LH(7.1-29.0 IU/L). The same was done for TT(0.30-1.50 vs. 1.6-5.6 nmol/L). These two groups were compared using chi-square test and t-test as indicated. Demographics included: serum estradiol, follicle stimulating hormone, thyroid stimulating hormone, prolactin, TT, free testosterone, gravida, parity, female age, male age, semen analysis parameters, antral follicle count, and duration of infertility. IRB approval was obtained(2020-5971). Data is X±SD. Main results and the role of chance When assessing based on LH, there were no differences in demographics(P &amp;gt; 0.05 in all cases) except for TT(1.4±1.0 vs. 1.9±0.9 nmol/L-p=0.02) and free-testosterone(0.6±0.5 vs. 0.9±0.5 nmol/L-p=0.03). The number of oocytes collected(26.8±7.4 vs. 27.3±9.6-p=0.82), mature oocytes(19.9± 6.8 vs. 20.2±7.8-p=0.88), and frozen high-quality blastocysts(7.0±4.4 vs. 8.2±5.1-p=0.25) were similar. The percent of MII that fertilized(75%±16 vs. 74%±19-p=0.78), the percent of 2PN that grew to blastocysts(47%±23 vs. 55%±27-p=0.18) and the percent of MII that grew to blastocyst(35%±18 vs. 40%±19-p=0.25) were similar. Among subjects who underwent embryo transfer, clinical pregnancy rates(33% vs. 45%-p=0.36) and live birth rates(22% vs 32%-p=0.39) were similar when comparing lowest vs. highest percentile, respectively. When comparing demographics by TT grouping, differences were previous pregnancies(0.9±1.2 vs. 0.3±0.7-p=0.02), serum TSH(1.66±0.96 vs. 2.43±1.90 nmol/L-p=0.04), and duration of infertility(2.3±2.0 vs 3.7±2.7years-p=0.04). The number of oocytes collected(27.5±7.5 vs. 28.3±9.7-p=0.73), MII oocytes(20.5±6.9 vs. 20.4±8.3-p=0.98), and frozen high-quality blastocysts(6.9±4.0 vs. 8.1±5.7-p=0.32) were similar. The percent of MII that fertilized(73%±19 vs. 74%±17-p=0.96), the percent of 2PN that grew into blastocysts(48%±23 vs. 53%±28-p=0.50) and the percent of MII that grew to blastocyst(34%±17 vs. 38%±19-p=0.36) were similar. Among subjects undergoing embryo transfer, clinical pregnancy rates(46% vs. 44%-p=0.90) and live birth rates(38% vs 26%-p=0.33) were similar when comparing lowest vs. highest percentile respectively. Limitations, reasons for caution Our study was limited to GnRH-antagonist cycles with freeze all embryos. Thus, findings may not be applicable to IVF cycles with fresh embryo transfer. It is a retrospective study and therefore is at risk for inherent biases. Wider implications of the findings Our findings provide reassurance that elevated basal serum LH and TT levels do not impact IVF outcomes in hyper-responding patients and therefore should not result in cycle cancellation or delay in those with PCOS undergoing GnRH-antagonist cycles with anticipated hyper-responses. Trial registration number N/A

The Effects of City Lockdown Policy on Frozen Embryo Transfer Outcome during COVID-19 Epidemic in Hubei Province, China.

Objective To evaluate whether there is a difference in clinical pregnancy rate and live birth rate between the corresponding period in 2019 and COVID-19 city lockdown period in 2020 in frozen embryo transfer (FET). Methods In one single in vitro fertilization (IVF) center (Shiyan, Hubei province, China), a retrospective cohort analysis was conducted, with a sample size of 59 patients in the lockdown period (2020.1.23-2020.2.23, 2020 group) and 34 patients in the corresponding 2019 period (2019.1.23-2019.2.23, 2019 group). Implantation, biochemical and clinical pregnancy, miscarriage, and live birth rates were all measured. Results Age, basal serum follicle-stimulating hormone (FSH), basal serum luteinizing hormone (LH), basal serum E2, and serum total T were all comparable between the two groups. On the day of progesterone administration, endometrial thickness was similar (8.5 ± 1.3 vs. 8.2 ± 1.4, P = 0.356). The number of transferred blastocysts was not significantly different. The two groups had similar clinical pregnancy rate (61.8% vs. 61.0%, P > 0.05) and live birth rate (47.1% vs. 49.2%, P > 0.05), which did not significantly differ. Nonetheless, there was a significant difference in the cancelled cycle rate between the two groups (0% vs. 28.0%, P = 0.043). Conclusions Lockdown period FET versus corresponding period FET outcome did not show any significant difference in terms of pregnancy rate and live birth rate between two groups of patients. Although there was no significant difference, in the 2020 group, the live birth rate was higher compared with that in the 2019 group. There was a significant difference in the rate of cancelled cycles due to the seal off control. In summary, artificial endometrial preparation is an appropriate protocol for special periods.

Clinical Outcomes of In Vitro Maturation After Oocyte Retrieval With Gynecological Surgery for Refractory Polycystic Ovary Syndrome: A Retrospective Cohort Study.

ObjectiveTo explore the clinical outcomes of unstimulated in vitro maturation (IVM) after oocyte retrieval with gynecological surgery (IVM-surgery) for refractory polycystic ovary syndrome (PCOS) and analyze the influencing factors.MethodsPatients with refractory PCOS who underwent unstimulated IVM-surgery from June 2014 to September 2018 were included in this retrospective cohort study. Matured IVM oocytes were freshly fertilized and subsequently frozen at the blastocyst stage. Frozen-thawed embryo transfer was then conducted according to the desire of patients. Oocytes and embryological outcomes, reproductive outcomes were evaluated. Influencing factors of oocytes and embryological outcomes were analyzed by univariate analysis and multivariate analysis. Receiver operating characteristic curves were used to evaluate the predict value of serum hormone levels for oocytes and embryological outcomes.ResultsA total of 93 patients with refractory PCOS who underwent unstimulated IVM-surgery were included in this study.13 patients (13/85, 15.3%) had spontaneous pregnancy and live birth after surgery. 34 patients (34/93, 36.6%) obtained blastocysts and received embryo transfer, of which 13 patients (13/34, 38.2%) eventually achieved live birth by IVM. Higher anti-Mullerian hormone, antral follicle count and basal serum luteinizing hormone (LH) levels were strongly correlated with higher number of oocytes retrieved (P = 0.004, 0.004, 0.040, respectively). Higher basal serum follicle-stimulating hormone (FSH) and LH were significantly associated with higher oocyte maturation rate (P = 0.001 and P = 0.004, respectively) and blastocyst formation (P = 0.036 and P = 0.003, respectively). There was a significant linear correlation between basal serum FSH and LH (r = 0.500, P <0.001). What is more, basal serum FSH and LH had predictive value for oocytes and embryological outcomes.ConclusionUnstimulated IVM-surgery provided the opportunity for both spontaneous pregnancy and assisted reproductive technology. Basal FSH and LH were significantly associated with oocyte maturation rate and blastocyst formation of unstimulated IVM-surgery.

Prediction, assessment, and management of suboptimal GnRH agonist trigger: a systematic review.

This systematic review aimed to identify baseline patient demographic and controlled ovarian stimulation characteristics associated with a suboptimal response to GnRHa triggering, and available options for prevention and management of suboptimal response. PubMed, Google Scholar, Medline, and the Cochrane Library were searched for keywords related to GnRHa triggering, and peer-reviewed articles from January 2000 to September 2021 included. Thirty-seven studies were included in the review. A suboptimal response to GnRHa triggering was more likely following long-term or recent oral contraceptive use and with a low or high body mass index. Low basal serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and estradiol serum levels were correlated with suboptimal oocyte yield, as was a low serum LH level on the day of triggering. A prolonged stimulation period and increased gonadotropin requirements were correlated with suboptimal response to triggering. Post-trigger LH < 15 IU/L best correlated with an increased risk for empty follicle syndrome and a lower oocyte retrieval rate. Retriggering with hCG may be considered in patients with suboptimal response according to post-trigger LH, as in cases of failed aspiration. Pre-treatment assessment of patient characteristics, with pre- and post-triggering assessment of clinical and endocrine cycle characteristics, may identify cases at risk for suboptimal response to GnRHa triggering and optimize its utilization.

Insulin-like Growth Factor 1, but Not Insulin-Like Growth Factor-Binding Protein 3, Predicts Central Precocious Puberty in Girls 6–8 Years Old: A Retrospective Study

Background: Central precocious puberty (CPP) in females is characterized by thelarche before 8 years of age. Evidence of reproductive axis activation confirms the diagnosis (basal serum luteinizing hormone (LH) ≥0.3 IU/L or LH-releasing hormone (LHRH)-stimulated LH ≥5 IU/L). Stimulation testing is the diagnostic gold standard but is time-consuming and costly. Serum levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor-binding protein 3 (IGFBP-3) are increased in girls with CPP. Objective: The aim of the study was to assess the utility of serum IGF-1 and IGFBP-3 in identifying CPP in girls aged 6–8 years. Methods: The study was a single-center retrospective study. Girls with confirmed CPP (n = 44) and isolated premature precocious adrenarche/ precocious thelarche (PA/PT, n = 16) had baseline biochemical profiling and LHRH stimulation testing. Serum IGF-1 and IGFBP-3 results were converted to standard deviation scores (SDS). Correlations were calculated and receiver operating characteristic curves were plotted. Results: Girls with CPP had higher basal and peak LH, IGF-1 SDS, and growth velocity (p < 0.05). IGF-1 SDS correlated positively with basal and peak LH (p < 0.05). IGF-1 SDS (1.75–2.15) differentiated CPP and PA/PT with 89% sensitivity and 56% specificity (basal LH) and 94% specificity and 55% sensitivity (peak LH). IGFBP-3 SDS did not differ between groups or by CPP parameters. Conclusions: In clinical practice, IGF-1 SDS may be an additional tool for identifying CPP in girls aged 6 to 8 years when baseline clinical and laboratory diagnostic criteria are inconclusive, possibly avoiding more time-consuming and costly procedures.

Impact of body mass index on intracytoplasmic sperm injection in women with polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a condition that affects fertility. There are two types of PCOS; the normal/lean type and overweight/obese type. The aim of this study was to assess baseline characteristics, ovarian response, quality of oocytes, embryos, pregnancy, implantation and live birth rates in normal/lean and overweight/obese patients with PCOS undergoing ICSI compared with patients without PCOS. This retrospective case-control analytical study included 38 normal/lean and 17 overweight/obese patients with PCOS, and 98 normal/lean and 17 overweight/obese patients without PCOS. Parameters were observed based on baseline characteristics, ovarian response to dosage and duration of gonadotropin administered, number of oocytes, matured oocytes, fertilization rate, embryo quality and development, pregnancy, implantation and live birth rates. Basal serum luteinizing hormone in normal/lean PCOS was significantly higher compared with non-PCOS groups. Total dosage of gonadotropin used was significantly lower in normal/lean PCOS compared with other groups. End estradiol levels in normal/lean PCOS was significantly higher compared with the non-PCOS groups. Number of follicles, retrieved oocytes and matured oocytes were significantly higher in PCOS groups compared with the non-PCOS groups. However, there were no differences in fertilized oocytes, cleavage, number of top-quality embryos, pregnancy, implantation, and live birth rates among groups. This present study suggests that normal/lean PCOS requires lower gonadotropin dosages and that patients with PCOS have more follicles and oocytes compared with patients without PCOS, however the number of fertilized oocytes and embryos from patients with PCOS were the same as those from patients without PCOS and suggested that the quality of retrieved oocytes in PCOS might be compromised.

Diagnostic evaluation of central precocious puberty in girls

The gonadotropin-releasing hormone (GnRH) stimulation test is the gold standard for confirming the activation of the hypothalamic-pituitary-gonadal axis in central precocious puberty (CPP). However, it is time-consuming and costly. Our aim was to search for a simpler diagnostic modality for CPP by 1) evaluating the performance of basal serum luteinizing hormone (LH), 2) constructing a practical scoring system, and 3) determining the optimal single sampling time for serum LH in the GnRH stimulation test. Data of girls aged between 3 and 9yearsat the time of the GnRH stimulation test, who attended our endocrine clinic at the MacKay Children's Hospital for signs of puberty between July 2014 and June 2019, were analyzed retrospectively. We recorded patients' age, height, weight, breast Tanner stage (BS), bone age, serum LH, and follicle-stimulating hormone (FSH). Receiver operating characteristic (ROC) curves and the Youden index were used to obtain the optimal basal serum LH level. Binary logistic regression was employed to construct a practical scoring system. Cross-sectional, cumulative frequency, and ROC curves were used to simplify the GnRH stimulation test. Overall, 381 sets of GnRH stimulation tests were performed in 313 patients. Basal serum LH≥0.2 IU/L demonstrated 70% sensitivity and 70% specificity for predicting positive GnRH stimulation test results. The practical scoring system (3×BS+3×LH+4×FSH) showed 76% sensitivity and 72% specificity. The serum LH level at 30min after intravenous gonadorelin exhibited 99% sensitivity and 100% specificity. Single sampling of serum LH at 30th minute post-injection of GnRH demonstrated a diagnostic performance equivalent to the traditional GnRH stimulation test in diagnosing CPP. Therefore, this approach could become the simplest diagnostic modality.

Basal serum luteinizing hormone value as the screening biomarker in female central precocious puberty.

PurposePrecocious puberty refers to the development of secondary sex characteristics before ages 8 and 9 years in girls and boys, respectively. Central precocious puberty (CPP) is caused by premature activation of the hypothalamus-pituitary-gonadal (HPG) axis and causes thelarche in girls before the age of 8. A gonadotropin-releasing hormone (GnRH) stimulation test is the standard diagnostic modality for diagnosing CPP. However, the test cannot always be used for screening because it is expensive and time-consuming. This study aimed to find alternative reliable screening parameters to identify HPG axis activation in girls <8 years old (CPP) and for girls 8–9 years old (early puberty, EP).MethodsFrom January 2013 to June 2015, medical records from 196 girls younger than 9 years old with onset of breast development were reviewed, including 126 girls who had a bone age (BA) 1 year above their chronological age. All patients underwent a GnRH stimulation test, and 117 underwent pelvic sonography. The girls were divided into 4 groups based on age and whether the GnRH stimulation test showed evidence of central puberty. Subanalyses were also conducted within each group based on peak luteinizing hormone (LH) level quartiles.ResultsBasal serum LH level was the most sensitive marker for screening CPP and EP. The cutoff values were 0.245 IU/L for CPP under 8 years old (P=0.049, area under the curve [AUC]=0.764, 88% sensitivity, 48% specificity) and 0.275 IU/L for EP between 8–9 years old (P=0.005, AUC=0.813, 79% sensitivity, 77% specificity). Peak LH level decreased as BMI z-score among subgroups increased when there was no difference in BA; however, higher BA eliminated this effect.ConclusionsBasal serum LH level is a useful screening parameter for diagnosing CPP and EP in girls. Peak LH levels were lower with increasing BMI z-score, although older BA eliminated this effect.

Development of Prediction Models Using Machine Learning Algorithms for Girls with Suspected Central Precocious Puberty: Retrospective Study.

BackgroundCentral precocious puberty (CPP) in girls seriously affects their physical and mental development in childhood. The method of diagnosis—gonadotropin-releasing hormone (GnRH)–stimulation test or GnRH analogue (GnRHa)–stimulation test—is expensive and makes patients uncomfortable due to the need for repeated blood sampling.ObjectiveWe aimed to combine multiple CPP–related features and construct machine learning models to predict response to the GnRHa-stimulation test.MethodsIn this retrospective study, we analyzed clinical and laboratory data of 1757 girls who underwent a GnRHa test in order to develop XGBoost and random forest classifiers for prediction of response to the GnRHa test. The local interpretable model-agnostic explanations (LIME) algorithm was used with the black-box classifiers to increase their interpretability. We measured sensitivity, specificity, and area under receiver operating characteristic (AUC) of the models.ResultsBoth the XGBoost and random forest models achieved good performance in distinguishing between positive and negative responses, with the AUC ranging from 0.88 to 0.90, sensitivity ranging from 77.91% to 77.94%, and specificity ranging from 84.32% to 87.66%. Basal serum luteinizing hormone, follicle-stimulating hormone, and insulin-like growth factor-I levels were found to be the three most important factors. In the interpretable models of LIME, the abovementioned variables made high contributions to the prediction probability.ConclusionsThe prediction models we developed can help diagnose CPP and may be used as a prescreening tool before the GnRHa-stimulation test.

Prediction Models for Girls with Suspected Central Precocious Puberty Using Machine Learning Algorithms

Central precocious puberty (CPP) in girls is a common pediatric endocrine disease, which seriously affects the physical and mental development in childhood, and significantly increases the risk of cervical or breast cancer in adulthood. Since children of false puberty often present with similar clinical symptoms as those of CPP, it is important to differentiate CPP from false puberty at diagnosis. Gonadotropin releasing hormone (GnRH) or GnRH analogue (GnRHa) stimulation test is used to diagnose CPP. However, they are expensive and make patients uncomfortable with repeated blood sampling. Although previous studies have made great efforts to solve this problem, it is still open. Our study aims to combine multiple CPP-related features and construct machine learning models to replace the GnRHa stimulation test. We leveraged clinical and laboratory data of 1,757 girls performed with GnRHa test, to develop XGBoost and Random Forest classifiers for prediction of response to GnRHa test. Meanwhile, the local interpretable model-agnostic explanations (LIME) algorithm was used to the black-box classifiers to increase their interpretability. The XGBoost classifier with 19 variables achieved the optimal performance with a specificity of 85.39%, a sensitivity of 77.94% and an AUC of 0.89. Basal serum luteinizing hormone, follicle-stimulating hormone, insulin-like growth factor-I, prolactin, growth hormone, height, uterine and ovarian volumes are factors with high feature importance. In the interpretable models of LIME, above variables are demonstrated to have high contributions to the prediction probability. The prediction models we developed can help diagnose CPP in a certain extent. Funding: This work was supported by Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center (Grant NO. KCP-2016-002). Conflict of Interest: The authors have declared that no competing interests exist. Ethical Approval Statement: The study design was approved by the appropriate ethics review boards.

Melatonin concentration in follicular fluid is correlated with antral follicle count (AFC) and in vitro fertilization (IVF) outcomes in women undergoing assisted reproductive technology (ART) procedures

The aim of the present study was to evaluate the possible relationship between melatonin levels in the follicular fluid (FF) and in vitro fertilization (IVF) outcomes in women undergoing assisted reproductive treatment. Sixty-three females (20 to 40 years old) scheduled for IVF were divided into three groups based on their antral follicle count (AFC). We determined FF melatonin concentrations in group A (AFC≦6, n = 21), group B (7≦AFC≦14, n = 22), group C (AFC≧15, n = 20) on oocyte retrieval day. Patients in group C had significantly higher melatonin levels as compared to patients in groups A and B (p < .001). Melatonin levels of the patients were significantly positively correlated with antral follicle count (AFC, p < .001), serum anti-Müllerian hormone(AMH) levels (p =.001), serum estradiol (E2) levels on human chorionic gonadotropin (HCG) administration day (p = .001), total follicle-stimulating hormone (FSH) dose (p = .002), starting FSH dose (p = .035), number of retrieved oocytes (p < .001), total fertilized oocytes (p < .001), normally fertilized oocytes (p < .001), cleaved oocytes (p < .001), number of high-quality day 3 embryos (p = .004), blastocysts obtained (p = .007) and total embryos obtained (day3 embryos + day5/6 blastocysts) (p = .005). The levels were significantly negatively correlated with age (p < .001), basal serum FSH levels (p = .003), serum FSH (p = .001) and serum luteinizing hormone (LH) levels (p = .003) on HCG administration day. This is the first demonstration of a significant positive correlation of melatonin concentrations with AFC in patients undergoing IVF. We propose that FF melatonin levels may influence the IVF outcomes.

Temporal changes in serum luteinizing hormone following ovariohysterectomy and gonadotropin-releasing hormone vaccination in domestic cats.

Measurement of circulating luteinizing hormone (LH) concentrations in cats and temporal changes following ovariohysterectomy (OHE) or possibly GnRH vaccination may be informative for assessing their fertility, contraception or sterilization status. In this study, serum LH concentrations were measured in domestic cats (n=6) immediately prior to and up to 120days post-OHE. Basal LH concentrations of females previously subjected to OHE (n=4; ~1.5years post-OHE) were compared pre- and post-vaccination with a GnRH immunocontraceptive, and to LH concentrations in intact females. Basal serum LH concentrations (2.67±0.43ng/ml; mean±SEM) in intact females increased (p<.01) by 30days post-OHE (5.65±0.87ng/ml) but then declined (p<.05) to pre-OHE levels (mean range, 3.26-3.62ng/ml) at days 60-120 post-OHE. Serum LH (3.84±0.51ng/ml) in four females ~1.5years after OHE tended to be higher (p=.10) than those of intact females prior to OHE. Three months following first or second GnRH immunocontraceptive vaccine treatment, serum LH values in females previously subjected to OHE decreased (p<.05) to concentrations similar to those observed in intact females. Our preliminary results suggest that OHE of domestic cats causes a marked increase in basal LH levels within the first few weeks after ovariohysterectomy followed by a return to pre-OHE basal values over the next several months. Reduced LH concentrations after GnRH vaccine may indicate the effectiveness of the immunocontraceptive in reducing the circulating levels of GnRH, thereby reducing secretion of LH.

Relationships between Serum Luteinizing Hormone Level, Endometrial Thickness and Body Mass Index in Polycystic Ovary Syndrome Patients with and without Endometrial Hyperplasia.

The endometrial hyperplasia measured by ultrasound in polycystic ovary syndrome (PCOS) women is strongly related to pathologic endometrial thickness, but there is no consensus on the relation between serum luteinizing hormone (LH) and either of these factors: pathologic endometrial hyperplasia and body mass index (BMI). In this observational cross-sectional study, three hundred fifty infertile PCOS women were involved in this research. An endometrial biopsy was taken by using a pipelle instrument, regardless of menstrual cycle's day and all samples were reported by the same pathologist. Basal serum LH level was compared between two subgroups (hyperplasia and non-hyperplasia). The intended population was divided into three groups according to BMI and basal serum LH, later on the comparison was made in three groups. Chi-square test was applied to compare nominal variables between groups. Mann-Whitney U, and one way ANOVA tests were used to compare means on the basis of the result of normality test. The frequency of endometrial hyperplasia was 2.6%. Endometrial thickness in the patients with endometrial hyperplasia was significantly higher than that of a normal endometrium (10.78 ± 3.70 vs. 7.90 ± 2.86 respectively, P=0.020). There was no relation between endometrial hyperplasia and serum LH (P=0.600). The ANOVA test showed serum LH levels were not the same among three BMI groups (P=0.007). Post hoc test was also performed. It showed that the LH level in normal BMI group was significantly higher than those of other groups (P=0.005 and P=0.004), but there was no statistical difference between overweight and obese groups (P=0.8). We found no relationship between BMI and endometrial thickness in PCOS patients (P=0.6). Sonographic endometrial stripe thickness is predictive for endometrial hyperplasia in PCOS women. We could not find out any relationship between serum LH level and BMI with endometrial thickness in PCOS patients. However, our study confirmed a diverse relationship between serum LH level and BMI in PCOS patients.

Acquired Hypogonadotropic Hypogonadism (AHH) in Thalassaemia Major Patients: An Underdiagnosed Condition?

IntroductionIn males, acquired hypogonadotropic hypogonadism (AHH) includes all disorders that damage or alter the function of gonadotropin-releasing hormone (GnRH) neurons and/or pituitary gonadotroph cells. The clinical characteristics of AHH are androgen deficiency and lack, delay or halt of pubertal sexual maturation. AHH lead to decreased libido, impaired erectile function, and strength, a worsened sense of well-being and degraded quality of life (QOL).Patients and methodsWe studied 11 adult men with thalassemia major (TM) aged between 26 to 54 years (mean ± SD: 34.3 ± 8.8 years) with AHH. Twelve age- and sex-matched TM patients with normal pubertal development were used as a control group. All patients were on regular transfusions and iron chelation therapy. Fasting venous blood samples were collected two weeks after transfusion to measure serum concentrations of IGF-1, free thyroxine (FT4), thyrotropin (TSH), cortisol, luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone (TT), prolactin and estradiol (E2), glucose, urea, creatinine and electrolytes (including calcium and phosphate). Liver functions and screening for hepatitis C virus seropositivity (HCVab and HCV-RNA) were performed. Iron status was assessed by measuring serum ferritin levels, and evaluation of iron concentrations in the liver (LIC) and heart using MRI- T2*. Bone mineral density was measured at the lumbar spine (L1–L4) for all patients with AHH by dual energy X-ray absorptiometry (DXA) using Hologic QDR 4000 machine.ResultsThe mean basal serum LH and FSH concentrations in AHH patients were 2.4 ± 2.2 IU/L and 1.2 ± 0.9 IU/L respectively; these, values were significantly lower compared to the control group. Semen analysis in 5 patients with AHH showed azoospermia in 3 and oligoasthenozoospermia in 2. The percentage of patients with serum ferritin level >2000 ng/ml (severe iron load) was significantly higher in AHH patients compared to controls, 5/11 (45.4 %) versus1/12 (8.3%), p=0.043. Heart iron concentrations (T2* values) were significantly lower in AHH patients compared to controls (p=0.004). Magnetic resonance imaging in the 3 azoospermic patients revealed volume loss and reduction of pituitary signal intensity. Heart T2* values were significantly reduced in the AHH group vs. the controls (p=0.004). On the other hand, liver iron concentration (mg/g dry weight) was not different between the two groups of TM patients. Using DXA, 63.6 % (7/11) of patients with AHH were osteoporotic, and 36.3 % (4/11) were osteopenic.ConclusionsIn this cohort of thalassemic patients iron overload and chronic liver disease appear to play a role in the development of AHH. Treatment of AHH in TM patients is a vital and dynamic field for improving their health and QOL. Early identification and management of AHH are very crucial to avoid long-term morbidity, including sexual dysfunction and infertility. Therapy aims to restore serum testosterone levels to the mid–normal range. Many exciting opportunities remain for further research and therapeutic development.

Adrenocortical production is associated with higher levels of luteinizing hormone in nonobese women with polycystic ovary syndrome.

Objective. Insulin resistance (IR) and ovarian and adrenal hyperandrogenism are a common finding in women with polycystic ovary syndrome (PCOS). The aim of the present study was to access possible differences in insulin resistance, gonadotropins, and androgens production in obese and nonobese PCOS women. Study Design. We studied 37 PCOS women (16 nonobese and 21 obese) and 18 nonobese controls. Fasting glucose, insulin, androgens, and gonadotropins levels were determined. Salivary cortisol was measured basal and in the morning after dexamethasone (DEX) 0.25 mg. Results. Nonobese PCOS women showed higher basal salivary cortisol and serum dehydroepiandrosterone sulfate and luteinizing hormone (LH) levels than controls and obese PCOS. These hormones levels did not differ between the obese and control groups. After DEX administration no differences were found between the three groups. In PCOS women, salivary cortisol levels showed negative correlation with BMI (r = −0.52; P = 0.001) and insulin (r = −0.47; P = 0.003) and positive correlation with LH (r = 0.40; P = 0.016). Conclusion. Our results show an increased adrenocortical production in nonobese PCOS women, not related to IR and associated with a normal hypothalamic-pituitary-adrenal suppression. Higher LH levels might be involved in this event.

The Utility of Basal Serum Luteinizing Hormone Levels for Screening Central Precocious Puberty in Girls

1 the pubertal response group of patients who had 5 IU/L peak LH levels in the GnRH stimulation test, and the prepubertal response group of patients who had LH levels <5 IU/L. Chronological and bone ages, height, weight, body mass index, gonadotropin response to GnRH stimulation, and basal levels of LH, fol- licle-stimulating hormone, and estradiol were studied in both groups. The relationship between basal LH and peak-stimulated LH was evaluated using Spearman's correlation. To determine the optimal cut-off val- ues of basal LH levels for differentiating between two groups, the receiver operating characteristic (ROC) curves were analyzed. Results: When the correlation between basal LH levels and peak LH after GnRH stimulation was analyzed in all subjects (N=90), basal LH levels had a statistically significant positive correlation with peak stimulated LH levels (rs=0.493, p<0.001). The cut-off level of optimal basal LH was 0.1 IU/L, according to the ROC curves. Its sensitivity was 73.3%, and its specificity was 77.8%. Conclusion: The study results showed that serum basal LH levels are useful for screening CPP in girls.

Factors that predict a positive response on gonadotropin-releasing hormone stimulation test for diagnosing central precocious puberty in girls.

PurposeThe rapid increase in the incidence of precocious puberty in Korea has clinical and social significance. Gonadotropin-releasing hormone (GnRH) stimulation test is required to diagnose central precocious puberty (CPP), however this test is expensive and time-consuming. This study aimed to identify factors that can predict a positive response to the GnRH stimulation test.MethodsClinical and laboratory parameters, including basal serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), and estradiol (E2), were measured in 540 girls with clinical signs of CPP.ResultsTwo hundred twenty-nine of 540 girls with suspected CPP had a peak serum LH level higher than 5 IU/L (the CPP group). The CPP group had advanced bone age (P<0.001), accelerated yearly growth rate (P<0.001), increased basal levels of LH (P=0.02), FSH (P<0.001), E2 (P=0.001), and insulin-like growth factor-I levels (P<0.001) compared to the non-CPP group. In contrast, body weight (P<0.001) and body mass index (P<0.001) were lower in the CPP group. Although basal LH was significantly elevated in the CPP group compared to the non-CPP group, there was considerable overlap between the 2 groups. Cutoff values of basal LH (0.22 IU/L) detected CPP with 87.8% sensitivity and 20.9% specificity.ConclusionNo single parameter can predict a positive response on the GnRH stimulation test with both high sensitivity and specificity. Therefore, multiple factors should be considered in evaluation of sexual precocity when deciding the timing of the GnRH stimulation test.