Basal Serum LH Research Articles

P-325 Endometriosis has no negative effect on embryo quality and morphokinetics. A retrospective case control study

Abstract Study question Does endometriosis affect embryo quality assessed by a time-lapse morphokinetic model analysis? Summary answer Endometriosis does not seem to have a negative effect on embryo morphokinetics and embryo quality assessed by a time-lapse in-house model. What is known already Endometriosis is strongly associated with infertility. Clinical studies suggest lower implantation and pregnancy rates in women with endometriosis. Embryos of women with endometriosis exhibit a higher incidence of developmental delay and arrested development than those derived from women without the disease. Poor oocyte and embryo quality have been suggested as a possible cause. It has been found that time-lapse systems which capture images of embryos at frequent time intervals allow continuous assessment of their quality. Developing an in-house model for embryo selection based on embryos with known implantation data (KID) enables detecting the highest quality embryos selected for transfer. Study design, size, duration A retrospective case control study between July 2013 and December 2020 which evaluated embryos from 58 ICSI cycles of women with endometriosis and 487 ICIS cycles of healthy women treated for male factor infertility. Morphokinetic parameters and rate of high-quality embryos were compared. High-quality was considered as: time to pronucleus fading (tPNf)<24.08, T2<26.6, S2<0.9, and t8<56 hours following insemination for cleavage embryos, and t2<26.6, S2<0.9, t8<56 and time to start blastulation (tSB)<96.6 hours for blastocysts. Participants/materials, setting, methods At a single infertility unit, women with endometriosis were compared to healthy women with male factor infertility as the control group. The main outcome was embryo kinetics which included: time to polar body extrusion (tPB2), time to pronucleus fading (tPNf), cleavage timings (t2-t8), synchrony of the second and third cycles (S2 and S3), duration of the second cycle (CC2) time to start blastulation (tSB). These parameters were set based on an in-house morphokinetic model. Main results and the role of chance We compared 154 embryos derived from 58 ICSI cycles of women with endometriosis to 1,387 embryos derived from 487 ICSI control cycles of couples with male factor as a single cause of infertility.There was a wider use of agonist protocol (48.3% vs 15.7%,p<0.001) and a higher rate of nuliparity (81% vs 61.5%, p = 0.003) in women with endometriosis compared to the control group. Demographic and treatment parameters were comparable including: maternal age, BMI, Gravidity, number of cycles, gonadotropins dosage, basal serum FSH, basal serum LH, estradiol and progesterone level at the day of ovum pick-up, number of oocytes aspirated, number of mature oocytes. There was no difference in tPB2, tPNf, t2-t8, S2 and S3, CC2, tSB between the groups. The rate of top quality embryos was comparable for both groups; for day 3 p = 0.25 and for day 5 p = 0.72. Pregnancy rate for the study and control group was 38.8% and 45%, respectively, p = 0.36. Limitations, reasons for caution One limitation is the retrospective methodology. Endometriosis severity was not taken into account which might be a confounding factor. The strengths are a single center study with embryos cultured under the same standardized laboratory conditions. However, a larger scale study might be needed. Wider implications of the findings Time lapse in-house model is an additive informative tool for embryo quality. Opposed to what was thought so far, the use of our time-lapsed system demonstrated that embryos of women with endometriosis had similar quality to healthy women. This can be used to reassure women with endometriosis before IVF treatment. Trial registration number not applicable

Insulin Growth Factor 1 Predicts Central Precocious Puberty in Girls 6 to 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 LH ≥ 0.3 IU/L or luteinizing hormone-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: To assess the utility of serum IGF-1 and IGFBP-3 in identifying CPP in girls aged 6 to 8 years old. Methods: The study was a single-center retrospective study. Girls with confirmed CPP (n=44) and isolated premature adrenarche/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-old when baseline clinical and laboratory diagnostic criteria are inconclusive, possibly avoiding more invasive procedures.

Effectiveness of basal LH in monitoring central precocious puberty treatment in girls.

Treatment of central precocious puberty (CPP) is based on administration of GnRH agonists in order to suppress hypothalamic-pituitary-gonadal axis and thus induce the stabilization or regression of pubertal development. Our aim was to determine whether the single basal serum LH and/or FSH concentration could be an effective tool to assess the efficacy of treatment to suppress activation of hypothalamic-pituitary axis. Serum LH and FSH were measured before and after the GnRH injection, as well as E2 basal levels in 60 girls with documented idiopathic CPP at diagnosis and 18 and 30 months after the beginning of therapy. At diagnosis, peaks of >5IU/L of LH and of FSH were observed in 100 and 91.6% of girls, respectively, with basal LH values of <1IU/L in 70% and basal FSH levels of <1IU/L in 10%. E2 were <20pg/mL in 36.6%. After 18 months, a suppressed peak (i.e. <3IU/L) was recorded in 85% of girls (p<0.01) for LH and in 98.3% for FSH (p<0.01). Basal LH <1IU/L was detected in 85% (p<0.01) and basal FSH ≤1IU/L in 40% (p<0.01). Serum E2 ≤20pg/mL was recorded in 61.6% (p<0.01). After 30 months, all patients showed LH suppressed peak (p<0.01) and 98.3% suppressed FSH peak (p<0.01). 100% showed basal LH concentrations <1IU/L (p<0.01) and 38.3% FSH basal values <1UI/mL (p<0.01). E2 ≤20pg/mL was observed in 32.72% (p=NS). Basal LH values are a reliable indicator of the efficacy of GnRHa therapy after 30 months of GnRHa therapy.

SUN-097 Gonadotropins Levels Measurement in First Morning Voided Urine as a Diagnostic Tool for Central Precocious Puberty

Background: GnRH stimulation test is the gold standard for the diagnosis of central precocious puberty (CPP). However, it is invasive and costly. Previous studies showed that increased urinary gonadotropins (Gn) level in first morning voided (FMV) urine reflected the integration of elevated nocturnal Gn secretions. Therefore, it could be used to diagnose CPP. Nevertheless, its cutoff value for diagnosis of CPP is limited. Objective: To determine the association of Gn levels in FMV urine and serum during pubertal development and establish cutoff value of FMV urinary Gn as an alternative noninvasive method for diagnosis of CPP in girls. Methods: Sixty-one girls who had breast development before 8 years of age with sign of rapid pubertal progression (advanced bone age and/or increased height velocity) underwent subcutaneous GnRH agonist test. FMV urinary Gn were also collected on the same day. Both serum and urinary Gn levels were measured using electrochemiluminescence immunoassay (ECLIA) technique. The definite diagnosis of CPP is based on stimulated serum LH > 5 IU/L. FMV urinary Gn were compared between CPP and premature thelarche (PT) groups. The correlation between serum and urinary Gn were assessed and the cutoff value of urinary Gn to diagnose CPP was established. FMV urinary Gn of 480 Thai school girls (control) were also collected to determine the reference values according to their breast Tanner (BT) stages. Results: FMV ULH level in girls with CPP was significantly higher than that of PT (2.46 VS 0.8 IU/L; median, P <0.001). However, the level of ULH in PT group was not different from control group with BT1. FMV ULH and ULH: UFSH were well correlated with basal serum LH (r=0.63 and 0.73, respectively, Ps<0.001) and peak serum LH (r=0.44 and 0.54, respectively, Ps<0.001). Base on receiver operating characteristics analysis, basal serum LH was the best parameter to differentiate CPP from PT (area under the curve 0.797–0.926). ULH levels at ≥ 1.13 IU/L and ≥ 1.52 provide optimal sensitivity (72.3 and 68.1 %, respectively) and specificity (85.7 and 100 %, respectively). Combined ULH level ≥ 1.13 IU/L with ULH: UFSH ≥ 0.17 increased specificity from 85.7 to 92.9 % for predicting a positive GnRH agonist test. (peak LH ≥ 5 IU/L) Conclusions: First morning voided urinary Gn levels measurement is a highly potential method for the diagnosis of CPP in girls due to its good correlation with GnRH agonist test. Further study in a larger number of patients with close monitoring of clinical outcome is required before recommending as a standard investigation in CPP.

Impact of Body Mass Index on Implantation Rate in ICSI Cycles

Background: obesity and overweight are recognized as a growing global health problem Worldwide, prevalence of overweight or obesity, defined as an adult body mass index (BMI) of 25 kg m² or greater. Patterns of overweight and obesity differ between countries, regions and by country income, with overweight or obesity more prevalent among men in developed countries and among women in developing countries. Aim of the Work: This study aimed to evaluate the impact of female increased body mass index (BMI) on implantation rate and clinical pregnancy in women undergoing ICSI cycle. Patients and Methods: this is a retrospective study conducted on a total of 400 cycles of assisted reproduction treatment has been evaluated from Orabi IVF Centre and Mit_Ghamr IVF Centre. Data recruited from patient files from January 2016 to July 2018 who did ICSI trial during this period. Patients who included in our study were sub divided into 2 groups according to BMI: 1 st group: normal weight with BMI between 18 and 24.9 kg/m2. (200 case), 2 nd group: overweight and obese women ≥ 25 kg/m2 (200 case). Results: we showed that overweight and obese infertile women had a higher basal serum FSH, LH and estradiol levels than normal weight women. In our study group the duration of infertility was progressively higher as BMI increased. The two groups were comparable regarding female age were not statistically different in both groups. The duration of infertility showed no significant difference between the two groups. As in group (1) it ranges from 10-17 years with median duration of 6 years, while in group (2) it ranges from 0.5-23 with a median duration of 5 years this result a significant difference with p-value (0.057).Conclusion: female overweight and obesity appeared to have deleterious effects on ovarian response to stimulation in women undergoing IVF and implantation rate. Moreover, female obesity compromised IVF outcome.

Impact of Body Mass Index on Implantation Rate in ICSI Cycles

Background: obesity and overweight are recognized as a growing global health problem Worldwide, prevalence of overweight or obesity, defined as an adult body mass index (BMI) of 25 kg m² or greater. Patterns of overweight and obesity differ between countries, regions and by country income, with overweight or obesity more prevalent among men in developed countries and among women in developing countries. Aim of the Work: This study aimed to evaluate the impact of female increased body mass index (BMI) on implantation rate and clinical pregnancy in women undergoing ICSI cycle. Patients and Methods: this is a retrospective study conducted on a total of 400 cycles of assisted reproduction treatment has been evaluated from Orabi IVF Centre and Mit_Ghamr IVF Centre. Data recruited from patient files from January 2016 to July 2018 who did ICSI trial during this period. Patients who included in our study were sub divided into 2 groups according to BMI: 1 st group: normal weight with BMI between 18 and 24.9 kg/m2. (200 case), 2 nd group: overweight and obese women ≥ 25 kg/m2 (200 case). Results: we showed that overweight and obese infertile women had a higher basal serum FSH, LH and estradiol levels than normal weight women. In our study group the duration of infertility was progressively higher as BMI increased. The two groups were comparable regarding female age were not statistically different in both groups. The duration of infertility showed no significant difference between the two groups. As in group (1) it ranges from 10-17 years with median duration of 6 years, while in group (2) it ranges from 0.5-23 with a median duration of 5 years this result a significant difference with p-value (0.057).Conclusion: female overweight and obesity appeared to have deleterious effects on ovarian response to stimulation in women undergoing IVF and implantation rate. Moreover, female obesity compromised IVF outcome.

Plane of nutrition before and after 6 months of age in Holstein-Friesian bulls: II. Effects on metabolic and reproductive endocrinology and identification of physiological markers of puberty and sexual maturation

The aim of this study was (1) to examine the effect of plane of nutrition during the first and second 6 mo of life on systemic concentrations of reproductive hormones and metabolites in Holstein-Friesian dairy bulls, and (2) to establish relationships with age at puberty and postpubertal semen production potential. Holstein-Friesian bull calves (n = 83) with a mean (standard deviation) age and body weight of 17 (4.4) d and 52 (6.2) kg, respectively, were assigned to a high or low plane of nutrition for the first 6 mo of life. At 24 wk of age, bulls were reassigned, within treatment, either to remain on the same diet or to switch to the opposite diet until puberty, resulting in 4 treatment groups: high-high, high-low, low-low, and low-high. Monthly blood samples were analyzed for metabolites (albumin, urea, total protein, β-hydroxybutyrate, glucose, nonesterified fatty acid, triglycerides and creatinine), insulin, insulin-like growth factor-1, leptin, adiponectin, FSH, and testosterone. A GnRH challenge was carried out at 16 and 32 wk of age (n = 9 bulls per treatment). Blood was collected at 15-min intervals for 165 min, with GnRH administered (0.05 mg/kg of body weight, i.v.) immediately after the third blood sample. Blood samples were subsequently analyzed for LH, FSH, and testosterone. Stepwise regression was used to detect growth and blood measurements to identify putative predictors of age at puberty and subsequent semen quality traits. Metabolic hormones and metabolites, in general, reflected metabolic status of bulls. Although FSH was unaffected by diet, it decreased with age both in monthly samples and following GnRH administration. Testosterone was greater in bulls on the high diet before and after 6 mo of age. Testosterone concentrations increased dramatically after 6 mo of age. Luteinizing hormone was unaffected by diet following GnRH administration but basal serum LH was greater in bulls on a high diet before 6 mo of age. In conclusion, the plane of nutrition offered before 6 mo of age influenced metabolic profiles, which are important for promoting GnRH pulsatility, in young bulls.

Early prenatal androgen exposure reduces testes size and sperm concentration in sheep without altering neuroendocrine differentiation and masculine sexual behavior

Prenatal androgens are largely responsible for growth and differentiation of the genital tract and testis and for organization of the control mechanisms regulating male reproductive physiology and behavior. The aim of the present study was to evaluate the impact of inappropriate exposure to excess testosterone (T) during the first trimester of fetal development on the reproductive function, sexual behavior, and fertility potential of rams. We found that biweekly maternal T propionate (100 mg) treatment administered from Day 30–58 of gestation significantly decreased (P < 0.05) postpubertal scrotal circumference and sperm concentration. Prenatal T exposure did not alter ejaculate volume, sperm motility and morphology or testis morphology. There was, however, a trend for more T-exposed rams than controls to be classified as unsatisfactory potential breeders during breeding soundness examinations. Postnatal serum T concentrations were not affected by prenatal T exposure, nor was the expression of key testicular genes essential for spermatogenesis and steroidogenesis. Basal serum LH did not differ between treatment groups, nor did pituitary responsiveness to GnRH. T-exposed rams, like control males, exhibited vigorous libido and were sexually attracted to estrous females. In summary, these results suggest that exposure to exogenous T during the first trimester of gestation can negatively impact spermatogenesis and compromise the reproductive fitness of rams.

A multi-center clinical study of early predictors and follow-up parameters for girls with rapidly progressive central precocious puberty

Objective To study the early diagnostic predictors and key follow-up parameters for girls with rapidly progressive central precocious puberty(RP-CPP). Methods A total of 260 girls with CPP participated in a prospective, nonrandomized, multi-center, nested case control study. After follow-up six months without any therapy, 114 girls were divided into RP-CPP(n=70)and slowly progressive CPP(SP-CPP)(n=44)groups. Results The basal serum LH and insulin-like growth factor Ⅰstandard deviation score(IGF-ⅠSDS)were the important risk factors of RP-CPP(OR 4.04, 1.578), especially the former. The receiver operating characteristic(ROC)curve revealed that the areas under the ROC curve of basal LH and IGF-ⅠSDS were 0.83 and 0.807, respectively. The levels of basal LH and IGF-ⅠSDS were at 0.52 mIU/ml and 0.35 respectively for the accuracy diagnosis of RP-CPP with the maximum Youden indexs. After follow-up for six months, the change levels of height, breast stages, bone age/chronological age ratio, serum LH, uterine and ovarian volume in RP-CPP group were significantly higher than those in SP-CPP group(all P<0.05). Conclusions The level of basal serum LH and IGF-ⅠSDS may be used as the risk predictors for early diagnosis for girls with RP-CPP. The change levels of basal LH, progress rates of gonad and sex character, height, and impaired growth potential seem to be the key follow-up parameters for CPP progress. (Chin J Endocrinol Metab, 2017, 33: 312-316) Key words: Central precocious puberty; Predictors; Follow-up parameters

First Morning Voided Urinary Gonadotropin Measurements as an Alternative to the GnRH Test

Aims: We studied whether first morning voided (FMV) urinary gonadotropin measurements could be used as a noninvasive alternative to the GnRH test in the assessment of the hypothalamic-pituitary-gonadal function in children. Methods: In a single-center study, we compared FMV urinary gonadotropin concentrations with basal and GnRH-stimulated serum gonadotropin levels in 274 children and adolescents (78 girls, 196 boys) aged 5-17 years referred for growth and pubertal disorders. The concordance between FMV urinary gonadotropin concentrations and GnRH test results was assessed. Results: FMV urinary LH (U-LH), urinary FSH (U-FSH) and their ratios correlated well with the corresponding basal and GnRH-stimulated serum parameters (r ≥ 0.66, p < 0.001). Receiver operating characteristic curve analyses using urinary and serum LH and FSH concentrations showed that FMV U-LH and U-LH/U-FSH performed equally well as the GnRH test in the differentiation of early puberty (Tanner stage 2) from prepuberty (Tanner stage 1) (area under the curve 0.768-0.890 vs. 0.712-0.858). FMV U-LH and U-LH/U-FSH performed equally well as basal serum LH in predicting a pubertal GnRH test result (area under the curve 0.90-0.93). Conclusion: FMV U-LH determination can be used for the evaluation of pubertal development and its disorders, reducing the need for invasive GnRH stimulation tests.

Olfactomedin 1 Deficiency Leads to Defective Olfaction and Impaired Female Fertility.

Olfactomedin 1 (OLFM1) is a glycoprotein highly expressed in the brain. Olfm1(-/-) female mice were previously reported to have reduced fertility. Previous microarray analysis revealed Olfm1 among the most highly upregulated genes in the uterine luminal epithelium upon embryo implantation, which was confirmed by in situ hybridization. We hypothesized that Olfm1 deficiency led to defective embryo implantation and thus impaired fertility. Indeed, Olfm1(-/-) females had defective embryo implantation. However, Olfm1(-/-) females rarely mated and those that mated rarely became pregnant. Ovarian histology indicated the absence of corpora lutea in Olfm1(-/-) females, indicating defective ovulation. Superovulation using equine chorionic gonadotropin-human chorionic gonadotropin rescued mating, ovulation, and pregnancy, and equine chorionic gonadotropin alone rescued ovulation in Olfm1(-/-) females. Olfm1(-/-) females had a 13% reduction of hypothalamic GnRH neurons but comparable basal serum LH levels and GnRH-induced LH levels compared with wild-type controls. These results indicated no obvious local defects in the female reproductive system and a functional hypothalamic-pituitary-gonadal axis. Olfm1(-/-) females were unresponsive to the effects of male bedding stimulation on pubertal development and estrous cycle. There were 41% fewer cFos-positive cells in the mitral cell layer of accessory olfactory bulb upon male urine stimulation for 90 minutes. OLFM1 was expressed in the main and accessory olfactory systems including main olfactory epithelium, vomeronasal organ, main olfactory bulb, and accessory olfactory bulb, with the highest expression detected in the axon bundles of olfactory sensory neurons. These data demonstrate that defective fertility in Olfm1(-/-) females is most likely a secondary effect of defective olfaction.

Concentraciones de LH en periodos de transición reproductiva en cabras criollas x Nubia con diferente condición nutricional

Se determinó el efecto de las reservas corporales de energía (IMC) y el consumo diario de alimento (CA), sobre la LH sérica durante las transiciones hacia época anovulatoria (TA) y reproductiva (TR). Doce cabras Criollas/Nubia, ovariectomizadas con implantes s.c. de 17-b estradiol, se dividieron en dos grupos (n=6), uno de IMC alto (IMCA) y otro bajo (IMCB). Dentro de grupo de IMC se establecieron dos subgrupos (n=3); con restricción de alimento (CRCA) y sin restricción temporal (SRCA). Se determinó la frecuencia de pulsos (FPLH), concentración media (CMLH) y basal de LH (CBLH). Durante TA se observó disminución gradual de FPLH, CMLH y CBLH (2.08, 1.41, 0.41 pulsos/6 h; 2.1, 1.21, 0.51 ng/ml; 1.3, 0.8, 0.4 ng/ml; P&lt;0.01). En TR aumentaron CMLH y CBLH (1.01, 1.58, 1.87 ng/ml; 0.57, 0.98, 1.04 ng/ml; P&lt;0.01). Cabras con IMCA presentaron mayor FPLH que las de IMCB durante TA (2.05 vs 0.55 pulsos/6 h; P&lt;0.05) y TR (3.2 vs 0.9 pulsos/6 h; P&lt;0.01) y mayor CMLH durante TR (2.1 vs 0.87 ng/ml; P&lt;0.01). Durante TA, la restricción en CA provocó disminución más temprana de CMLH y CBLH en cabras con IMCA (P&lt;0.05), haciéndolas similares a cabras con IMCB. Independientemente del IMC, durante TR la restricción en CA disminuyó FPLH y CBLH (P&lt;0.05). En cabras criollas cruzadas, la secreción de LH es modulada por el IMC y el CA durante los periodos de transición reproductiva. A su vez durante TA, la restricción temporal en CA puede disminuir la secreción de LH aún en cabras con IMC alto.

Prognostic models for high and low ovarian responses in controlled ovarian stimulation using a GnRH antagonist protocol.

STUDY QUESTIONCan predictors of low and high ovarian responses be identified in patients undergoing controlled ovarian stimulation (COS) in a GnRH antagonist protocol?SUMMARY ANSWERCommon prognostic factors for high and low ovarian responses were female age, antral follicle count (AFC) and basal serum FSH and LH.WHAT IS KNOWN ALREADYPredictors of ovarian response have been identified in GnRH agonist protocols. With the introduction of GnRH antagonists to prevent premature LH rises during COS, and the gradual shift in use of long GnRH agonist to short GnRH antagonist protocols, there is a need for data on the predictability of ovarian response in GnRH antagonist cycles.STUDY DESIGN, SIZE, DURATIONA retrospective analysis of data from the Engage trial and validation with the Xpect trial. Prognostic models were constructed for high (>18 oocytes retrieved) and low (<6 oocytes retrieved) ovarian response. Model building was based on the recombinant FSH (rFSH) arm (n = 747) of the Engage trial. Multivariable logistic regression models were constructed in a stepwise fashion (P < 0.15 for entry). Validation based on calibration was performed in patients with equivalent treatment (n = 199) in the Xpect trial.PARTICIPANTS/MATERIALS, SETTING, METHODSInfertile women with an indication for COS prior to IVF. The Engage and Xpect trials included patients of similar ethnic origins from North America and Europe who had regular menstrual cycles. The main causes of infertility were male factor, tubal factor and endometriosis.MAIN RESULTS AND THE ROLE OF CHANCEIn the Engage trial, 18.3% of patients had a high and 12.7% had a low ovarian response. Age, AFC, serum FSH and serum LH at stimulation Day 1 were prognostic for both high and low ovarian responses. Higher AFC and LH were associated with an increased chance of high ovarian response. Older age and higher FSH correlated with an increased chance of low ovarian response. Region (North America/Europe) and BMI were prognostic for high ovarian response, and serum estradiol at stimulation Day 1 was associated with low ovarian response. The area under the receiver operating characteristic (ROC) curve (AUC) for the model for a high ovarian response was 0.82. Sensitivity and specificity were 0.82 and 0.73; positive and negative predictive values were 0.40 and 0.95, respectively. The AUC for the model for a low ovarian response was 0.80. Sensitivity and specificity were 0.77 and 0.73, respectively; positive and negative predictive values were 0.29 and 0.96, respectively. In Xpect, 19.1% of patients were high ovarian responders and 16.1% were low ovarian responders. The slope of the calibration line was 0.81 and 1.35 for high and low ovarian responses, respectively, both not statistically different from 1.0. In summary, common prognostic factors for high and low ovarian responses were female age, AFC and basal serum FSH and LH. Simple multivariable models are presented that are able to predict both a too low or too high ovarian response in patients treated with a GnRH antagonist protocol and daily rFSH.LIMITATIONS, REASONS FOR CAUTIONAnti-Müllerian hormone was not included in the prediction modelling.WIDER IMPLICATIONS OF THE FINDINGSThe findings will help with the identification of patients at risk of a too high or too low ovarian response and individualization of COS treatment.STUDY FUNDING/COMPETING INTERESTSFinancial support for this study and the editorial work was provided by Merck, Sharp & Dohme Corp. (MSD), a subsidiary of Merck & Co. Inc., Whitehouse Station, NJ, USA. F.J.B. received a grant from CVZ to his institution; P.J.M.V. and H.W. are employees of MSD, and B.M.J.L.M. was an employee of MSD at the time of development of this manuscript.TRIAL REGISTRATION NUMBERSNCT 00696800 and NCT00778999.

A Modified Technique of Laparoscopic Ovarian Drilling for Polycystic Ovary Syndrome Using Harmonic Scalpel

Objective: To review our experience with a modified technique of laparoscopic ovarian drilling (LOD) using harmonic scalpel as a new energy modality and to compare its effect with electrocautery in managing Clomiphene resistant polycystic ovary syndrome as regard to ovulation rate, pregnancy rate, hormonal profile and ultrasonographic changes that reflect ovarian reserve and reproductive outcome. Patients and methods: Sixty patients presented by infertility due to PCOS were randomly allocated into two equal groups. Group I was subjected to laparoscopic ovarian drilling using electrocautery and Group II were subjected to laparoscopic ovarian drilling using harmonic scalpel. All patients were assessed twice (before the induction procedure and three months later, if pregnancy did not occur). Patients were assessed clinically (to determine menstrual regularity and body mass index), sonographically (to measure ovarian volume and antral follicle count at time of ovarian quiescence) and laboratory (to measure basal serum LH, FSH, LH/FSH ratio, total testosterone and estradiol). Also a 2nd look laparoscopy was performed in those patients who failed to conceive within six months of the initial laparoscopic procedure to assess the presence of adhesion and its type. Results: Laparoscopic ovarian drilling using harmonic scalpel improved menstrual pattern, ovulation rate, pregnancy rate, hormonal profile similar to electrocautery without a significant difference. However it was associated significantly with a minimal effect on ovarian volume, antral follicle count and post operative adhesion. Conclusions: We consider our LOD technique using harmonic scalpel as a new energy modality in managing Clomiphene resistant polycystic ovary syndrome practicable with less extensive destruction of the ovarian capsule and thereby of the ovarian reserve and with minimal incidence of post operative adhesion.

The utility of basal serum LH in prediction of central precocious puberty in girls

The mainstay of distinction between prepubertal girls and girls who are suspected of having central precocious puberty (CPP) is based on gonadotropin measurements after a GnRH stimulation test to evaluate hypothalamic-pituitary-gonadal axis maturity. The objective of this study was to determine whether a single basal gonadotropin measurement carries a useful predictive value in verifying or refuting the diagnosis of CPP. Basal serum LH and FSH were measured by a chemiluminescent immunometric assay in a cohort of girls who had been evaluated for CPP before and after GnRH stimulation test. Peak LH levels higher than 5 IU/l were considered a pubertal response. Eighty girls with suspected breast development before 8 years of age were enrolled to the study, out of whom 42 had CPP. Low basal serum LH (≤0.1 IU/l) was sufficient to rule out the diagnosis of CPP in 94.7% of the 38 prepubertal girls; the sensitivity of basal LH levels for this purpose was only 64%. The basal FSH and the basal LH to FSH ratio achieved less efficient predictive value with 76 and 71% sensitivity and 73 and 86% specificity respectively. A single basal LH measurement may be adequate to confirm but not to refute the presence of CPP in most of the girls who are evaluated for early pubertal signs.

Effects of serotonin antagonists in sexually impotent men.

Thirty-one men affected with sexual impotence were studied. Since sexual function in the male seems to be controlled by both dopaminergic stimulatory and serotoninergic inhibitory mechanisms, the patients were treated with serotonin antagonists. In basal conditions mean serum LH, FSH, PRL and testosterone did not significantly differ from those found in normal subjects; no significant variations, except for PRL reduction, were observed after treatment. Both methysergide, in association with bromocriptine or mesterolone, and metergoline, either alone or in association with mesterolone, were ineffective in significantly improving sexual activity.

Endocrine profile of 45 patients with Sertoli cell only syndrome.

The basal serum levels of FSH, LH, prolactin and testosterone were determined in 45 patients with Sertoli cell only syndrome and were compared with the same in patients with Klinefelter's syndrome, oligozoospermic men and normal, fertile men. The serum FSH and LH levels in patients with Sertoli cell only syndrome were significantly higher than in normal males. The elevation of gonadotropins in patients with this syndrome was not so high, and the testosterone not lowered, as those in patients with Klinefelter's syndrome. The finding that the basal serum LH levels were elevated and serum testosterone levels were in normal range, demonstrated that there was compensated dysfunction of the Leydig cells in patients with Sertoli cell only syndrome.

Obesity and the Emergence of Sleep-Wake Gonadotropin Secretion in Girls during Early Pubertal Development

It has been clearly established that obesity is associated with reduced gonadotropin secretion in men and women. In normal women, early studies involving relatively few subjects had shown that serum LH levels were significantly reduced in obese individuals compared with levels of normal-weight controls (1, 2). Subsequent larger studies that examined the relationship of LH secretory dynamics to body weight included women with polycystic ovary syndrome (PCOS) as well as normal women (3, 4). In particular, LH secretion in both groups of obese women was characterized by reduced basal levels and decreased pulse amplitude, whereas LH frequency appeared unaffected. Recently, it was demonstrated that morbidly obese women with normal menstrual function exhibited a similar pattern of LH suppression compared with that of normal women (5). In adolescent girls, there are essentially no data concerning the influence of obesity on the rate and amplitude of LH secretion. However, during puberty the progressive maturation of gonadotropin secretion in normal girls through various stages of development has been well documented (6). Given the observed impact of obesity on LH secretion in adults, it seems logical to investigate this relationship at a time when activation of hypothalamic-pituitary interaction is emerging. This notion is underscored by the association of obesity with an earlier onset of puberty and precocity, increased risk of chronic anovulation with menstrual irregularities, and greater likelihood of PCOS. The last of these conditions commonly manifests clinical symptomatology during or soon after puberty. In this issue of JCEM, McCartney et al. (7) have extended their efforts to define the role of obesity on gonadotropin secretion during pubertal development. In previous studies using a cross-sectional design, they showed that during early puberty (Tanner 1–3), obese girls had significantly increased serum total and free testosterone levels compared with nonobese controls accompanied by corresponding decreases of circulating LH concentrations (8, 9). In addition, obese girls exhibited hyperinsulinemia and increased homeostasis model of assessment values compared with that of normal-weight controls, which may have accounted, in part, for hyperandrogenemia in the presence of lowered serum LH. In early pubertal girls, diurnal variation was observed for both testosterone and progesterone with levels lower at night and rising in the early morning hours. The incremental change in both hormones was significant in nonobese girls but failed to achieve statistical significance in obese girls likely because of too few numbers. Nevertheless, the heightened level of progesterone in obese girls may have contributed to reduced LH levels in early puberty. This notion relates to the insensitivity of the GnRH pulse generator to progesterone negative feedback in women with PCOS. In normal women, progesterone administration inhibits LH secretion, e.g. pulse frequency. Prior studies by this group have shown that androgen may interfere with this feedback mechanism as suggested by reduction of rapid LH release in response to progesterone administration in women with PCOS treated with an antiandrogen, which implies that hyperandrogenemia may contribute to increased LH secretion in this disorder. This proposed mechanism is suggested in young adolescents because some girls with PCOS treated with progesterone failed to exhibit a reduced rate of LH release (10). Because their earlier studies had been restricted to basal serum LH measurements, McCartney et al. (7) proceeded to conduct an extensive frequent sampling study of obese [body mass index (BMI) 95th percentile] and nonobese (BMI 95th percentile) girls at Tanner stages 1–5 and found differences in LH secretion within and between groups during early puberty (11). The experimental design employed a sampling interval of 1900–2300 h to denote daytime secretion and 2300–0300 h and 0300– 0700 h to reflect nighttime release. As expected, LH pulse frequency, amplitude, and mean concentrations in nonobese Tanner 1–2 girls were, in general, greater with sleep than values observed in awake subjects. In Tanner 1–2 obese girls, there was little change in LH secretion over the same intervals of study.

In-vitro maturation (IVM) and vitrification of oocytes retrieved at the luteal phase in cancer patients facing urgent gonadotoxic treatment

To describe successful in-vitro maturation (IVM) and vitrification of oocytes retrieved at the luteal phase. Three cancer patients aged 21, 30 and 40 years, facing urgent gonadotoxic treatment, who were unable to undergo hormonal ovarian stimulation for fertility preservation. Women had regular menstrual cycles and basal serum FSH, LH and estradiol levels within normal range. None had a male partner. They were first seen at our clinic during the luteal phase of the menstrual cycle and were to undergo gonadotoxic treatment imminently. They expressed their desire to cryopreserve as many oocytes as possible during this short period of time. Treatment results are summarized in Table 1. In two women, we were able to perform luteal phase collection followed by a follicular phase collection in the following menstrual cycle. Case number 3 wished to use donor sperm following follicular-phase retrieval in order to fertilize her oocytes, therefore intracytoplasmic sperm injection (ICSI) was performed. Only the oocytes that were matured at the day of collection cleaved. Therefore, 5 MII stage oocytes were vitrified following the luteal phase retrieval and additional two embryos were vitrified following the follicular phase retrieval.Table 1In-vitro maturation (IVM) and vitrification of oocytes retrieved from three cancer patients, facing urgent gonadotoxic treatment, who were unable to undergo hormonal ovarian stimulation for fertility preservationWoman ageCycle day at oocyte retrievalOocytes retrieved (no.)MII stage oocytes at retrieval day (no.)MII stage oocytes after 24 hours (no.)MII stage oocytes after 48 hours (no.)MII stage oocytes vitrified (no.)Case 1213070235Case 2 (luteal collection)302350303Case 2 (follicular phase collection)102137616Case 3 (luteal collection)401570235Case 3 (follicular phase l collection)1152202 embryos∗∗Oocytes were fertilized with donor sperm. Open table in a new tab ∗Oocytes were fertilized with donor sperm. Our result suggests that in vitro maturation of immature oocytes retrieved during the luteal phase is feasible. This option can be considered for fertility preservation in women facing imminente gonadotoxic treatment who are not able to undergo hormonal ovarian stimulation. Moreover, aspiration of oocytes at the luteal phase may not impair the ability to retrieve oocytes during the following follicular phase. Therefore, in women facing gonadotoxic treatment more than one procedure of oocyte retrieval may be performed in a short time period.

Effect of increasing levels of undegradable intake protein on metabolic and endocrine factors in estrous cycling beef heifers.

To determine the influence of three levels of undegradable intake protein (UIP) supplementation on metabolic and endocrine factors that influence reproduction, 23 yearling crossbred heifers (body condition score = 4.5 +/- 0.5; initial BW = 362 +/- 12 kg) were stratified by BW and assigned randomly to one of three supplements: 1) low UIP (1,135 g x heifer(-1) x d(-1); 30% CP, 115 g UIP, n = 7); 2) mid UIP (1,135 g x heifer(-1) x d(-1); 38% CP, 216 g UIP, n = 8); or 3) high UIP (1,135 g x heifer(-1) x d(-1); 46% CP, 321 g UIP, n = 8). Heifers were estrually synchronized before initiation of supplementation. Supplement was individually fed daily for 30 to 32 d, at which time heifers were slaughtered (d 12 to 14 of the estrous cycle) and tissues collected. Heifers were fed a basal diet of sudan grass hay (6.0% CP) ad libitum. On d 28 of supplementation (d 10 of the estrous cycle), no differences were observed (P > 0.10) in serum insulin or IGF-I among treatments. At slaughter (d 10 to 12 of the estrous cycle), treatments did not influence corpus luteum weight, cerebral spinal fluid leptin, or IGFBP; serum estradiol-17beta, progesterone, leptin, IGF-I, and IGFBP; or anterior pituitary content of IGFBP (P > 0.10). Follicular fluid IGFBP-2 and IGFBP-4 were greater in high-UIP heifers than low- or mid-UIP heifers on d 12 to 14 of the estrous cycle (P < 0.05). Basal serum LH concentrations and LH area under the curve (every 15 min for 240 min) did not differ (P > 0.10) following 28 d of supplementation (d 10 of the estrous cycle); however, basal serum FSH concentrations were greater (P = 0.06) in low- and mid- vs. high-UIP heifers (5.2 and 5.2 vs. 4.6 ng/mL, respectively), and FSH area under the curve was greater (P = 0.03) in low- vs. high-UIP heifers. At slaughter (d 12 to 14 of the estrous cycle), anterior pituitary LH and FSH content and steady-state mRNA encoding alpha, LHbeta, and GnRH receptor did not differ (P > 0.10) among treatments. However, FSHbeta mRNA was increased approximately twofold (P = 0.03) in mid vs. low UIP. In summary, low and mid levels of UIP supplements fed to estrous cycling beef heifers seemed to enhance pituitary expression and/or secretion of FSH relative to high levels of UIP. Moreover, high-UIP supplementation was associated with increased low-molecular-weight IGFBP compared with supplementation of low and mid levels of UIP. These data suggest that differing levels of UIP supplementation may alter pituitary and ovarian function, thereby influencing reproductive performance in beef heifers.