Serum Follicle-stimulating Hormone Research Articles

O-138 Factors influencing sperm retrieval rate of microdissection testicular sperm extraction in nonobstructive azoospermia patients with different etiologies: a retrospective study of 3104 patients

Abstract Study question What are predictors of successful sperm retrieval (SRR) with microdissection testicular sperm extraction (mTESE) in men with non-obstructive azoospermia (NOA) according to different etiologies? Summary answer Predictors for SRR were different in patients with various etiologies and effects of age on SRR in idiopathic NOA and KS patients were opposite. What is known already NOA patients due to spermatogenic dysfunction, accounting for about 60 percent of the total azoospermia cases, may have opportunities to obtain sperm by mTESE and overall SRR of mTESE in NOA patients is about 50%. There were some of predictive factors for SRR at mTESE including age, testis volume, serum follicle stimulating hormone (FSH), testosterone (T), inhibin B, anti-Mullerian hormone and testicular histopathology, while the predictive factors of SRR remains underappreciated, especially in accordance with different type of etiology. Most notably, there are some controversies about the relationship between SSR and age at mTESE surgery. Study design, size, duration This retrospective study involved 3104 NOA patients with different etiologies treated with the first mTESE at the Reproductive Medical Centre of Peking University Third Hospital from March 2012 to December 2022. Participants/materials, setting, methods 3104 NOA patients were classified into seven groups according to etiologies including 1530 males with idiopathic NOA (iNOA), 763 males with Klinefelter syndrome (KS), 345 males with microdeletion of the AZFc, 177 cases with the history of cryptorchidism, 131 with a history of mumps orchitis, 89 males with cryptozoospermia and 69 cases with other causes. The end-point was the presence of one or more sperm. Multi-variable logistic regression was used to analyze sperm retrieval outcome. Main results and the role of chance Overall SRR was 43.46%, and there were different SRR in NOA patients with various etiologies with highest SRR of 89.31% in patients with a history of mumps orchitis and lowest SRR of 29.35% in iNOA patients. For patients with a history of mumps orchitis, there was a negative relationship between T and SRR (0.805 [0.654, 0.991] p = 0.041). For cryptozoospermia patients, shorter infertility duration was predictive for successful SRR (0.837 [0.704, 0.995], p = 0.044). Males with bigger testes had more likelihood of positive SRR (1.077 [1.005; 1.153], p = 0.035) in patients with cryptorchidism. BMI was an independent factor of SRR in AZFc-deleted patients (1.084 [1.013, 1.161], p = 0.020). For KS patients, lower male age (0.938 [0.898, 0.979], p = 0.004) and bigger testes (1.214[1.099, 1.342], p＜0.001) were predictive for successful SRR. Lower levels of FSH (0.984[0.970, 0.998] p = 0.025) and higher male age(1.079[1.050, 1.110], p＜0.001) were predictive for successful sperm retrieval in iNOA patients. So, the optimum age range of iNOA male undergoing mTESE should be 30 to 35 years old with the SRR of 29.13% when considering low SRR of iNOA males aged＜30 years (23.96%) and the negative effect of female age on ICSI outcome. Limitations, reasons for caution Surgeon performing mTESE maybe another predictor for SRR which is a potential selection bias. Inhibin B and Anti-Müllerian hormone weren’t included due to limited information in our database. We couldn’t verify the conclusion in more population from multicenter despite the current study with the large sample size so far. Wider implications of the findings Our results provide valuable information for NOA patients who want to counsel surgeons about their treatments to help patients and surgeons to perform a shared decision-making for optimal therapy methods, especially about optimal age treated with mTESE in iNOA and KS patients. Trial registration number not applicable

O-140 studying the effect of mosaicism on the outcome of micro-TESE among Klinefelter syndrome patients

Abstract Study question Does mosaicism affect sperm retrieval rate in Klinefelter patients? Summary answer Patients with mosaic Klinefelter syndrome (KS) have a higher success rate of sperm retrieval than those with non-mosaic KS. What is known already Klinefelter syndrome is characterised by the presence of an extra X chromosome in male individuals leading to a 47XXY karyotype and rarely to 46XY/47XXY Mosaicism; it is the most common sex chromosomal aneuploidy and the most common genetic cause of Azoospermia (Kanakis GA et al., 2018 and Gravholt CH et al.,2018). It accounts for 3–4% of male infertility cases and 10–12% of men with Azoospermia (Winters SJ,2018). Study design, size, duration After approval of the ethical committee of the faculty of medicine at Cairo University, This prospective study was conducted where 70 men who complained of primary infertility and azoospermia and were diagnosed with Klinefelter Syndrome were recruited for this study between 1/11/2021 and 30/11/2022. Patients with previous testicular disease (torsion, trauma) or who had a history of undescended testes or received chemotherapy or radiotherapy were excluded. Participants/materials, setting, methods Seventy patients (n = 70) aged between 20 and 50 who fit the inclusion criteria were recruited and underwent micro_TESE. Semen analysis (Azoospermia), hormonal profile, scrotal colour doppler ultrasonography, Karyotyping and FISH for Y and X chromosomes were performed. Statistical analysis was conducted using SPSS 22nd edition. Main results and the role of chance Our study groups comprised 14 patients with mosaic KS and 56 with non-mosaic KS. The clinical characteristics were not significantly different statistically between the two groups. Micro_TESE was performed in all 70 patients; in 26 patients (37.1%), mature sperm were found in the wet preparation. No statistically significant correlation was found between the presence of spermatozoa in the extraction specimen and age, serum follicle-stimulating hormone, serum testosterone, prolactin or oestradiol. The statistically significant predictor variable for sperm extraction was mosaicism, luteinising hormone, testicular volume and FISH. The sperm retrieval rate of the patients with mosaic and non-mosaic KS was 57.1% and 32.1%, respectively. Limitations, reasons for caution 1) Larger (n) number of patients was needed. 2) Despite our valuable findings, further studies should be performed to illuminate the relation between FISH for X and Y chromosomes and sperm retrieval rate success. Wider implications of the findings Klinefelter patients with mosaicism should be offered high sperm retrieval rate during IVF counselling. Trial registration number n/a

Zinc improves sexual performance and erectile function by preventing penile oxidative injury and upregulating circulating testosterone in lead-exposed rats

ABSTRACTAim:The present study evaluated the effect of lead exposure with and without zinc therapy on male sexual and erectile function.Methods:Twenty male Wistar rats were randomly assigned into four groups; the control, zinc-treated, lead-exposed, lead + zinc-treated groups. Administrations were per os daily for 28 days.Results:Zinc co-administration significantly improved absolute and relative penile weights and the latencies and frequencies of mount, intromission, and ejaculation in lead-exposed rats. Also, zinc ameliorated lead-induced reductions in motivation to mate and penile reflex/erection. These findings were accompanied by attenuation of lead-induced suppression of circulating nitric oxide (NO), penile cyclic guanosine monophosphate (cGMP), dopamine, serum luteinizing hormone, follicle-stimulating hormone, and testosterone. In addition, zinc alleviated lead-induced upregulation of penile activities of acetylcholinesterase and xanthine oxidase (XO), and uric acid (UA) and malondialdehyde (MDA) levels. Furthermore, zinc ameliorated the lead-induced decline in penile nuclear factor erythroid 2-related factor 2 (Nrf2) and reduced glutathione (GSH) levels, and catalase, superoxide dismutase (SOD), glutathione peroxidase (GPx), and glutathione-S-transferase (GST) activities.Conclusion:This study revealed that co-administration of zinc improves lead-induced sexual and erectile dysfunction by suppressing XO/UA-driven oxidative stress and upregulating testosterone via Nrf2-mediated signaling.

O-015 Spontaneous alterations in semen parameters are associated with age, accessory gland function and the FSHB c.-211G>T variant

Abstract Study question Which parameters are associated with spontaneous alterations in semen analysis in infertile men? Summary answer Changes in semen parameters are modulated by abstinence time, accessory gland function and fluctuations in FSH serum concentration, which is bound to FSHB c.-211G>T variant. What is known already There is a strong within-subject alteration of semen parameters in men with infertility. The WHO therefore recommends two ejaculate analyses. However, it remains unknown in which subgroup variations are likely to occur and which semen parameters are affected. We assume that in some men with idiopathic infertility, ejaculate parameters may spontaneously change without interventional medication apart from regression to the mean effects. The study aims to identify factors in conventional semen analysis based on the patients’ clinical data, including reproductive hormones like follicle stimulating hormone (FSH), and factors impacting endocrine activity, like the FSHB-211 promoter gene. Study design, size, duration In this retrospective longitudinal study we selected 3456 deeply phenotyped men with idiopathic infertility who had visited our centre for fertility workup from 2010-2020. The patients were selected from our well curated database Androbase© for analysis of repeated ejaculate samples. Participants/materials, setting, methods Men with idiopathic infertility and at least two ejaculate analyses (70-90 days distance) were included. Exclusion criteria comprised: sperm concentration <1 million/ml, abnormal FSH or low testosterone, bitesticular volume (bTV) <10ml, orchiectomy, cryptorchidism, varicocele testis, oncological disease, genetic findings (i.e. abnormal karyotype, AZF deletions), medication affecting spermatogenesis. Grouped linear 2-level nested mixed-effect models were applied. Analyzed parameters included: somatic, hormonal (including FSH and FSHB c.-211 variants), and semen parameters (including abstinence time, accessory gland markers). Main results and the role of chance Groups were built according to sperm concentration: A (n = 397): ≥1.0 to < 5.0 mill/ml, B (n = 708): ≥5.0 to < 15.0 mill/ml, C (n = 2351): ≥15.0 mill/ml. A, B and C: changes in ejaculate volume were associated with alterations in total sperm count and motility (p < 0.003). Changes were, controlled for abstinence time (p < 0.001), related to alpha-glucosidase, fructose or zinc (p = 0.005-0.02). A+B: fluctuations in FSH concentration influenced sperm concentration/count (p = 0.004-0.02), albeit only in men with FSHB c.-211 GG (p = 0.007-0.02). T-allele carriers did not show changes in FSH concentration (p > 0.1). B: age <50 years (p = 0.007-0.01) and normal bTV (p = 0.008-0.02) were associated with spontaneous increases of sperm concentration, count and motility. Semen parameters exhibit intra-individual alterations associated with organic, hormonal and genetic variables. Changes are pronounced in younger men with normal bTV and oligo- to almost normozoospermia. The effect is modulated by abstinence time, accessory gland function and fluctuations in FSH concentrations which, in turn, are bound to the FSHB-211 promotor gene polymorphism. Limitations, reasons for caution A limitation of our approach is the retrospective nature of the study, which cannot exclude the possibility of bias within the data set. Wider implications of the findings Judgement of semen analysis should be based on two semen samples, with abstinence time between 4-5 days. In future clinical trials, abstinence time should be kept constant. It might be investigated if younger men with normal bTV and FSHB c.-211 GT/TT benefit from improving accessory gland function and increasing FSH. Trial registration number not applicable

Effects of Liver-Regulating Herb Compounds on Varicocele-Associated Testicular Dysfunction Through Restoring Hormones and Spermatocytes Apoptosis.

Varicocele is considered as one of the causes for male infertility. Though varicocelectomy is suppose to improve semen parameters in adult infertile men, some patients with varicocele were still infertile after varicocelectomy.. Previous studies showed Traditional Chinese Medicine, Liver-regulating herb compounds (LRHC) could improve the semen quality and increase fertility rates of infertile patients with varicocele. This study aimed to throw light on the mechanism of LRHC on varicocele-associated infertility. Materials and methods: Rats with varicocele-induced were treated with LRHC at dosage of 1mL/100g by intragastric administration for 90 days. The effects of LRHC on hormones and spermatocytes apoptosis were examined using ELISA assay, Western blotting, and flow cytometry. Rats induced with varicocele showed higher level of follicle stimulating hormone (FSH) in serum, which was brought back to normal level by LRHC. After treating with LRHC, both testicular tissue in vivo and Sertoli cell TM4 cells in vitro showed elevated expressions of FSHR. Cell viabilities of TM4 cells and spermatocyte GC-2 cells were improved by LRHC treatment under normoxia and hypoxia condition. Moreover, LRHC protected GC-2 cells from apoptosis induced by hypoxia. The expression of Bax reduced, while that of Bcl-2 increased after treating with LRHC. This study revealed that LRHC had protective effects on spermatogenic disturbance caused by varicocele through regulating hormones and reducing spermatogenic cell apoptosis under hpoxia condition.

Testicular Effect of Selenium Nanoparticles on Monosodium Glutamate Induced Alteration in Male Albino Rats.

<b>Background and Objective:</b> The flavor enhancer Monosodium Glutamate (MSG) is mostly utilized in Asian and West African cuisines, especially in West African and Asian dishes. However, due to its availability, largely without labeling, in many food products, unintentional overuse of this food additive may occur. The objective of this study was to find out how selenium nanoparticles affected the toxicity of MSG in male albino rats' testicles. <b>Materials and Methods:</b> As 35 Wistar male rats partitioned into 5 groups: G1: Control rats, G2: Received Se-NPs at 0.4 mg kg<sup>1</sup> b.wt., orally, G3: Injected with MSG at a daily dose of 4 g kg<sup>1</sup> b.wt., intraperitoneally (IP), G4: Ingested a daily oral dose of Se-NPs for 7 successive days and on the 7th day, received the first dose of MSG IP 4 g kg<sup>1</sup> b.wt., then received both treatments till the end of the study and G5: Administered a daily oral dose of 4 g kg<sup>1</sup> MSG, followed by Se-NPs at a daily dose of 0.4 mg kg<sup>1</sup> b.wt., the experiment continued for 28 days. Serum testosterone hormone, Follicle Stimulating Hormone (FSH), Luteinizing Hormone (LH), the levels of serum lipid peroxidation (MDA), reduced Glutathione (GSH), Glutathione Peroxidase (GSH-Px), superoxide dismutase (SOD) and Lactate Dehydrogenase (LDH) were estimated and samples from testis were separated for histological analysis. <b>Results:</b> The MSG treatment induced a significant decline in the values of serum testosterone, FSH, LH, GSH, GSH-Px and SOD. It also increased the values of serum MDA and LDH and spermatic arrest. While, the administration of Se-NPs orally before MSG treatment resulted in a decline in the values of serum MDA and LDH, an elevation in the values of serum GSH, GSH-PX and SOD, testosterone, FSH, LH and reappearance of sperm. <b>Conclusion:</b> The use of Se-NPs as a protector exhibited more improvement in values of estimated hormones and oxidative stress markers than using it as a therapy.

Clinical profile and cytogenetic correlations in females with primary amenorrhea.

This study was conducted to investigate chromosomal abnormalities and their correlations with clinical and radiological findings in females with primary amenorrhea (PA). Detailed forms were recorded for 470 females, including the construction of three-generation pedigrees. Peripheral venous blood was drawn, with informed consent, for cytogenetic analysis. An abnormal karyotype was found in 16.38% of participants. The incidence of structural abnormalities (6.8%) exceeded that of numerical abnormalities (6.15%). Turner syndrome represented 45% of all numerical abnormalities. Furthermore, the Y chromosome was detected in 5% of females with PA. Among the structural chromosomal abnormalities detected (n=32) were mosaicism (25%), deletions (12.5%), isochromosomes (18.75%), fragile sites (3.12%), derivatives (3.12%), marker chromosomes (3.12%), and normal variants (29.125%). An examination of secondary sexual characteristics revealed that 29.6% of females had a complete absence of breast development, 29.78% lacked pubic hair, and 36.88% exhibited no axillary hair development. Radiological findings revealed that 51.22% of females had a hypoplastic uterus and 26.66% had a completely absent uterus. Abnormal ovarian development, such as the complete absence of both ovaries, absence of one ovary, one absent and other streak, or both streak ovaries, was observed in 69.47% of females with PA. Additionally 43.1%, 36.1%, 67.4%, and 8% of females had elevated levels of serum follicle-stimulating hormone, luteinizing hormone, thyroid-stimulating hormone, and prolactin, respectively. This study underscores the importance of karyotyping as a fundamental diagnostic tool for assessing PA. The cytogenetic correlation with these profiles will aid in genetic counseling and further management of the condition.

The possible protective effect of the nuclear factor kappa B inhibitor pyrrolidine dithiocarbamate on tramadol-induced testicular damage in rats

BackgroundTramadol provokes oxidative stress that gives rise to apoptosis with alterations in the cellular structure and adversely influences male fertility. A specific inhibitor of nuclear factor kappa B (NF-κB), pyrrolidine dithiocarbamate (PDTC), has observable antioxidant and anti-inflammatory characteristics and enhances the improvement of organs damage caused by various agents. The impact of PDTC on testicular damage caused by tramadol has not been previously examined.ObjectiveThis study was designed to investigate the potential impact of pyrrolidine dithiocarbamate on testicular damage provoked by chronic tramadol usage.Materials and methodsForty healthy adult male albino rats were included in this study. Rats were randomly and equally divided into 4 groups: group (I), control group; group (II), pyrrolidine dithiocarbamate (PDTC) group; group (III), tramadol (Tr) group; and group (IV), Tr + PDTC group. This study measured serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and free testosterone levels. Testicular malondialdehyde (MDA), interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) levels, and superoxide dismutase (SOD), glutathione peroxidase (GPX), and caspase-8 and caspase-3 activities were also detected. Immuno-histochemical evaluation of inducible NOS (iNOS) expression in testicular tissue along with histopathological examination of testicular tissue has been studied.ResultsTramadol caused a significant reduction in serum FSH, LH and testosterone levels, epididymal sperm count, and motility, as well as testicular GPX and SOD activities. On the other hand, a significant elevation of testicular MDA, IL-1β, IL-6, and TNF-α levels and caspase-8 and caspase-3 activities were found. However, PDTC administration with tramadol showed significantly increased sperm production and motility and alleviated tramadol-induced disturbance in other measured parameters in the Tr + PDTC group compared to the Tr group. Moreover, co-administration of PDTC with tramadol significantly alleviated the histopathological structure of testicular tissue and the increased iNOS expressions noticed in the tramadol-treated group.ConclusionConsidering the protective effects of PDTC against the reproductive toxicity induced by tramadol, this compound can be used as a possible protective and treating target for tramadol-induced reproductive toxicity.

Effect of citalopram on sex hormones and testicular histomorphology in male albino rats

Introduction: Citalopram, a selective serotonin reuptake inhibitor (SSRI), is commonly used as a first-line treatment for depression. However, the potential effects of Citalopram on testicular histo-morphology and hormone levels have not been extensively studied. This study aimed to evaluate the impact of Citalopram on the microscopic structure of the testes and the levels of serum testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) in male albino rats. Aims: The primary objective of this study was to assess the effects of Citalopram on testicular histo-morphology using the Johnson scoring system. The secondary objective was to measure the levels of serum testosterone, LH, and FSH in rats treated with varying doses of Citalopram. Methodology: A total of 25 healthy male albino rats were divided into five groups: control, group I, group II, group III, and group IV. The rats in groups I to IV were orally administered 10 mg, 20 mg, 30 mg, and 40 mg of Citalopram, respectively, while the control group received oral distilled water. The dosages were adjusted based on the suggested doses for humans and scaled according to the rats' weight.

Characterization of the volatile profile and its estrogenic activity in Kadsura coccinea fruit.

The fruit of Kadsura coccinea (Lem.) A. C. Smith is an ethnomedicine used to treat abnormal menstruation, menopausal syndrome, and female infertility among the Dong Nationality in China. Our study aimed to identify the volatile oil profiles of the K. coccinea fruit and elucidate their estrogenic activity. The peel volatile oil (PeO), pulp volatile oil (PuO), and seed volatile oil (SeO) of K. coccinea were extracted using hydrodistillation and qualitatively analyzed using gas chromatography-mass spectrometry (GC-MS). Estrogenic activity was evaluated in vitro using cell assay and in vivo using immature female rats. Serum 17β-Estradiol (E2) and follicle-stimulating hormone (FSH) levels were detected using ELISA. In total, 46 PeO, 27 PuO, and 42 SeO components representing 89.96%, 90.19%, and 97% of the total composition, respectively, were identified. The compounds with the highest content in PeO, PuO, and SeO were β-caryophyllene, γ-amorphene, and n-hexadecanoic acid, respectively. PeO induced proliferation of MCF-7cells with an EC50 of 7.40μg/mL. Subcutaneous administration of 10mg/kg PeO significantly increased the weight of the uteri in immature female rats, with no effect on serum E2 and FSH levels. PeO acted as an agonist of ERα and ERβ. PuO and SeO showed no estrogenic activity. The chemical compositions of PeO, PuO, and SeO of K. coccinea are different. PeO is the main effective fraction for estrogenic activities, providing a new source of phytoestrogen for the treatment of menopausal symptoms.

Effect of induced molting on ovarian function remodeling in laying hens

Induced molting (IM) can restore the laying rate of aged laying hens to the peak level of laying and rejuvenate ovarian function for the second laying cycle. To explore the mechanism of ovarian function remodeling during IM in laying hens, in this study, ninety 71-wk-old laying lady hens with 60% laying rate and uniform weight were selected for molting induction by fasting. Samples (serum and fresh ovarian tissue) were collected on the day before fasting (F0), the 3rd and 16th days of fasting (F3, F16), and the 6th, 15th, 32nd days of refeeding (R6, R15, and R32), and the number of follicles in each period was counted. Then, the reproductive hormone levels in serum and antioxidant levels in ovarian tissues were detected at different stages, and the gene expression of the KIT-PI3K-PTEN-AKT pathway and GDF-9 in ovaries was measured by qRT-PCR. The results showed that the laying rate increased rapidly after refeeding and returned to the prefasting level by R32. At F16 and R6, the number of mature follicles significantly decreased; the number of primary and secondary follicles significantly increased; the contents of follicle stimulating hormone (FSH), luteinizing hormone (LH), estradiol (E2), and progesterone (P4) in serum decreased; the relative expression of KIT, PI3K, AKT, and GDF-9 significantly increased; and that of PTEN significantly decreased. At R15 and R32, except for GDF-9, which maintained a high expression state, other indicators showed opposing trends to those observed at F16 and R6. In conclusion, IM activated the KIT-PI3K-PTEN-AKT signaling pathway and promoted the activation of primordial follicles during the fasting period and early resumption of feeding; gonadotropin secretion increased gradually, which promoted the rapid development of primary and secondary follicles to mature follicles and ovulation. This study explained the mechanism of ovarian function remodeling in the process of IM and provided a theoretical basis for improving the ovarian function of laying hens and optimizing the IM program.

Delayed puberty: How to approach?

Disorders of puberty can profoundly impact physical and psychosocial well-being. Delayed puberty is the absence of breast development in girls by 13 years of age and absence of testicular growth to at least 4 mL in volume or 2.5 cm in length in boys by 14 years of age. Hypogonadism occurs when there is a disruption in the hypothalamic-pituitary-gonadal axis. Two categories of delayed puberty are: hypergonadotropic (primary) hypogonadism and hypogonadotropic (secondary) hypogonadism. The etiology of delayed puberty varies from relatively benign to life threatening conditions, which may be either congenital or acquired. Constitutional delay of growth and puberty is the commonest cause of delayed puberty, which is a diagnosis of exclusion. There is a notable delay in puberty but eventually progress through normal stages of puberty. History concerns about stature are often present and a familial pattern of inheritance is usually present. Delayed bone age but corresponding to height age helps in diagnosis. Reversible hypogonadotropic hypogonadism may be observed due to associated conditions including chronic malnutrition, systemic disease, untreated hypothyroidism, hyperprolactinemia, anorexia nervosa. Permanent causes include structural damage either to hypothalamic-pituitary axis or linked to the sexual organs of the individual. Complete physical examination should include proper anthropometry, pubertal staging and assessment to look for any signs of chronic illness or stigmata of syndromes. In laboratory analysis, hypogonadotropichypogonadism (pHH) showing low serum testosterone or estradiol and blunted follicle-stimulating hormones (FSH) and luteinizing hormones (LH) levels may be due to abnormalities in the central nervous system. Magnetic resonance imaging is necessary to exclude morphological abnormalities and neoplasia. Low serum testosterone in male patients and low estradiol values in female patients, associated with high serum FSH and LH levels, suggest a diagnosis of hypergonadotropic hypogonadism due to dysfunction of peripheral sex organs. Abnormal growth velocity necessitates assessment of serum thyroid function, prolactin, and insulin like growth factor-1. Karyotyping can reveal a chromosomal abnormality like Turner syndrome or Klinefelter syndrome. Beside reassurance, in cases where the adolescent with CDGP is experiencing psychological difficulties, short courses of sex hormones may be used to allow individuals to catch up with their peers. Definitive treatment for underlying cause is worthy where possible. Long-term hormone replacement therapy is recommended for permanent causes of delayed puberty. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 192

Repeat Microdissection Testicular Sperm Extraction in Azoospermic Men with Nonmosaic Klinefelter Syndrome

Introduction. To investigate the predictive factors for successful repeat microdissection testicular sperm extraction attempts in patients with Klinefelter syndrome. Methods. A total of 28 azoospermic men with nonmosaic Klinefelter syndrome who have received microdissection testicular sperm extraction twice with successful initial microdissection testicular sperm extraction attempts in our institute were studied. Outcome variables (age, serum follicle-stimulating hormone, luteinizing hormone, testosterone, prolactin, and estradiol) of azoospermic men with nonmosaic Klinefelter syndrome and a successful 2nd surgical sperm retrieval attempt (group A) were compared to those with an unsuccessful 2nd sperm retrieval attempt (group B). Results. Twenty-one patients (75%) had successful sperm recovery at the 2nd microdissection testicular sperm extraction attempt. The mean testosterone level at baseline and before the 1st microdissection testicular sperm extraction attempt was higher in group A than in group B (2.7 vs. 0.9 ng/mL, p < 0.01 , and 3.9 vs. 1.1 ng/mL, p = 0.02 ). Receiver operating characteristic curve analysis identified the threshold baseline testosterone concentration (1.5 ng/mL) of patients with Klinefelter syndrome in predicting successful 2nd sperm retrieval attempts and revealed positive and negative predictive values of 94.44% and 60%, respectively. Conclusion. Azoospermic men with Klinefelter syndrome presenting with low testosterone levels and successful sperm recovery during the first microdissection testicular sperm extraction procedure are unlikely to retrieve sperm on the 2nd microdissection testicular sperm extraction attempt. Hence, these patients should be properly counseled before sperm retrieval.

LCZ696 (sacubitril/valsartan) mitigates cyclophosphamide-induced premature ovarian failure in rats; the role of TLR4/NF-κB/NLRP3/Caspase-1 signaling pathway

AimCyclophosphamide (CP) is used to treat a variety of cancers and autoimmune illnesses. CP has been found to frequently cause premature ovarian failure (POF). The study's objective was to assess LCZ696's potential for protection against CP-induced POF in a rat model. Main methodsRats were randomly assigned into seven groups as follows: control, valsartan (VAL), LCZ696, CP, CP + VAL, CP + LCZ696, and CP + triptorelin (TRI). Ovarian malondialdehyde (MDA), reduced glutathione (GSH), superoxide dismutase (SOD), interleukin-18 (IL-18), IL-1β, and tumor necrosis factor-alpha (TNF-α) were assessed using ELISA. Serum anti-mullerian hormone (AMH), estrogen, follicle-stimulating hormone (FSH), and luteinizing hormone (LH) were also measured using ELISA. The expression of NLRP3/Caspase-1/GSDMD C-NT and TLR4/MYD88/NF-B P65 proteins was estimated using western blot assay. The histopathology of the ovaries was also investigated. The estrous cycle, body, and ovarian weights were also monitored. Key findingsCP treatment significantly elevated levels of MDA, IL-18, IL-1β, TNF-α, FSH, LH, and up-regulated TLR4/NF-κB/NLRP3/Caspase-1 proteins, as compared to the control group, however, ovarian follicles count, and levels of GSH, SOD, AMH, and estrogen were reduced with CP administration. All the aforementioned biochemical and histological abnormalities were considerably alleviated by the LCZ696 therapy compared to valsartan alone. SignificanceLCZ696 effectively mitigated CP-induced POF, offering promising protection that could be related to its suppression power on NLRP3-induced pyroptosis and TLR4/NF-B P65 pathway.

Disordered hypothalamus-pituitary-ovary axis in heterotopic extraovarian sex cord-stromal proliferation: a case report of fallopian tube serous adenofibroma

BackgroundFallopian tube serous adenofibromas are uncommon tumors of the female genital tract, only dozens of cases have ever been reported. Earlier study indicated that they might be derived from embryonic remnants of the Müllerian duct. Clinical presentation of these tumors is usually asymptomatic. Small cysts of 0.5–3 cm in diameter are mostly incidentally found at the fimbriae end, with coarse papillary excrescences lined by epithelial cells and connective tissue stroma without nuclear pleomorphism or mitosis.Case presentationA 23-year-old woman with normal secondary sexual characters and 46, XX karyotype, presented to the gynecology clinic complaining of irregular menstrual cycles. Laboratory studies reported unique discrepancy of hormone levels; anti-Müllerian hormone (AMH): 6.05 ng/mL (The normal range of AMH is 1.70–5.63 ng/mL in women aged under 35 years old), follicle stimulating hormone (FSH): 31.9 mIU/mL (reference range: 3.85–8.78, follicular phase; 4.54–22.51, ovulatory phase; 1.79–5.12, luteal phase; 16.74-113.59, menopause), and luteinizing hormone (LH): 52.0 mIU/mL (reference range: 2.12–10.89, follicular phase; 19.18-103.03, ovulatory phase; 1.20-12.86, luteal phase; 10.87–58.64, menopause), mimicking gonadotropin-resistant ovary syndrome. The ultrasound reported a right adnexal cyst of 10.4 × 7.87 × 6.7 cm. Laparoscopic evaluation was performed; pathology revealed serous adenofibroma of the fallopian tube with ovarian stroma contents. Heterotopic extraovarian sex cord-stromal proliferations was most probable. The patient’s hormone levels returned to the reproductive status two weeks after surgery; FSH: 7.9 mIU/mL, LH: 3.59 mIU/mL,and AMH: 4.32 ng/mL. The patient’s menstrual cycles have resumed to normal for over two years after removal of the fallopian tube cyst.ConclusionsThis case of fallopian tube serous adenofibromas presented a discrepancy of serum AMH and FSH mimicking gonadotropin-resistant ovary syndrome. The clinical picture derived from heterotopic extraovarian sex cord-stromal proliferation indicated a disordered hypothalamus-pituitary-ovary axis.

Gonadal development and function after immature testicular tissue banking as part of high-risk gonadotoxic treatment.

Experimental fertility preservation programs have been started to safeguard the future fertility of prepubertal and pubertal males requiring high-risk gonadotoxic treatment protocols. However, long-term follow-up studies evaluating the effects on their gonadal development and function related to the testicular biopsy procedure are rather limited. This two-center follow-up study (between 2002 and 2020) evaluated the gonadal development and function of a cohort of 59 prepubertal and pubertal males who have been offered immature testicular tissue banking (TTB) prior to conventional high-risk chemo- and/or radiotherapy (HR-C/R) or conditioning therapy before hematopoietic stem cell transplantation (CT-HSCT). The aim is to investigate the long-term impact of the testicular biopsy procedure and the high-risk gonadotoxic treatment. Testicular growth and the reproductive hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and inhibin B (INHB) were analyzed after treatment completion, and compared between males accepting TTB and those refusing TTB (control) as well as between HR-C/R and CT-HSCT treatment protocols. Of the 59 prepubertal and pubertal males included, 25 were treated by HR-C/R and 34 required CT-HSCT. TTB was accepted for 39 males and refused for 20 males. Most patients were prepubertal at diagnosis (85%), at TTB (79%), and at treatment completion (76%), and pubertal or postpubertal at their last follow-up visit (66%). After 5.0 (1.0-13.0) years post treatment, most patients show normal testicular volumes (83%) and normal LH (89%), FSH (87%), T (87%), and INHB (79%) serum levels. The testicular biopsy procedure did not have an effect on testicular growth, LH, FSH, T, and INHB. Significantly more small postpubertal testicular volumes (p=.0278) and low INHB serum levels (p=.0130) were recorded after CT-HSCT, especially after myeloablative conditioning. The clinical follow-up data demonstrate no effect related to the biopsy procedure, but a substantial risk for impaired gonadal development after high-risk gonadotoxic treatment, in particular myeloablative CT-HSCT. Longer follow-up studies with a larger study population are needed to confirm these preliminary findings.

The Mood of Menopausal Women is Affected by Stress Levels and Symptoms of Anxiety and Depression

Introduction: Menopause is a period of vulnerability to psychological manifestations and can increase the sensitivity of emotions to stress and mood. Studies have analyzed factors associated with stress and symptoms of anxiety and depression, however, it is still scarce in the literature whether the mood changes these symptoms in menopausal women. Objective: To analyze the relationship between mood and stress and depressive symptoms and anxiety in menopausal women. Methods: Cross-sectional study composed of 90 menopausal women aged 40 to 59 years (52.6±4.1), one year without menstruation, with serum FSH (Follicle Stimulating Hormone) levels ≥25IU/ml, and with a positive score to the Menopause Rating Scale (MRS) questionnaire. The questionnaires were composed of sociodemographic and clinical aspects, Brunel’s Mood Scale (BRUMS), Perceived Stress Scale (PSS) and Hospital Anxiety and Depression Scale (HADS). Results: Women who showed symptoms of anxiety and depression scored more on the subscales of negative mood (p<0,001), and less on the subscale of positive mood (p<0,001) for depression and anxiety (p=0,005); besides that they were more stressed than those without symptoms of anxiety and depression. Multiple linear regression analysis showed that mental confusion, fatigue and vigor have a predictive power of 33% in the stress of menopausal women. Conclusions: The mood of women in menopause seems to be affected by those with high levels of stress and symptoms of anxiety and depression.

Association of follicle-stimulating hormone with bone turnover markers and bone mineral density in Chinese women across the menopausal transition.

Elevated follicle-stimulating hormone (FSH) is associated with an increased risk of postmenopausal osteoporosis. This study investigated the association of serum FSH with bone turnover markers (BTMs) and bone mineral density (BMD) in healthy women undergoing menopausal transition. A total of 487 healthy women (age 35-65 years, 50 ± 8.5 years) were enrolled in this study. Serum FSH, BTMs, and BMD at lumbar spine and total hip were measured in these subjects. Follicle-stimulating hormone was positively correlated with various BTMs (r = 0.339-0.583, all p < 0.001) and negatively correlated with lumbar spine and total hip BMD (r = -0.629 and -0.514, all p < 0.001). After adjusting for age and body mass index, the partial correlation coefficients of FSH with BTMs and BMD remained significant. Estimating from the regression equation, for every 10 IU/L increase in serum FSH, BTMs increased by 0.38-3.6 units, and BMD decreased by 0.03-0.05 g/cm2 , respectively. Multiple linear regression analysis showed that FSH was a positive factor for serum bone-specific alkaline phosphatase, osteocalcin, and N-telopeptide of collagen type 1 (β = 0.188-0.403, all p < 0.001), and a negative factor for lumbar spine BMD and serum C-telopeptide of collagen type 1 (β = -0.629 and -0.183, all p < 0.001). This study suggests that serum FSH levels are an independent risk factor for BTMs and BMD in menopause-transitioning women, particularly for serum BAP and lumbar spine BMD.

Electroacupuncture promotes expression of glutathione related regulatory enzymes in ovary tissue of rats with diminished ovarian reserve

To observe the effect of electroacupuncture (EA) on ovarian function and expression of glutathione (GSH) related regulatory enzymes γ-glutamylcysteine synthetase (γ-GCS), glutathione reductase (GR) protein and gene in rats with diminished ovarian reserve (DOR), so as to explore its mechanisms underlying up-regulation of antioxidant stress ability. A total of 30 female SD rats with normal estrous cycle were randomly divided into blank control, model and EA groups, with 10 rats in each group. The DOR model was established by gavage of tripterygium wilfordii polyglycoside suspension (50 mg·kg-1·d-1) for 14 consecutive days, while the rats in the blank group were given equal volume of 0.9% sodium chloride solution. One hour after daily gavage, EA (1.0 mA, 100 Hz) was applied alternately to bilateral "Shenshu"(BL23), and "Zhongwan"(CV12)+"Guanyuan"(CV4) for 10 min, for 14 consecutive days. Estrous cycles of rats in each group were observed and recorded daily during intervention.After the intervention, H.E.staining was used to observe histopathological changes of the ovarian tissue. The contents of serum sex hormones ［follicle stimulating hormone (FSH), anti-mullerian hormone (AMH), estradiol (E2)］ and oxidative damage markers ［8-hydroxydeoxyguanosine (8-OHDG) and nitrotyrosine (NTY)］ were determined by ELISA. The contents of GSH and oxidized glutathione (GSSG) in the liver tissue were determined by colorimetry, and their ratios were calculated. Immunohistochemistry and real-time fluorescence quantitative PCR were used to detect the immunoactivity and gene expression levels of γ-GCS and GR in the ovarian tissues, respectively. Compared with the blank group, the model group had a marked increase in the disorder rate of estrous cycle, serum FSH, 8-OHDG and NTY contents (P<0.01) and a considerable decrease in the levels of serum AMH and E2, liver GSH and GSSG contents and GSH/GSSG ratio, ovarian optical density and cell number as well as the expression of γ-GCS and GR mRNAs (P<0.05, P<0.01). After EA intervention, the increase of the disorder rate of estrous cycle, serum FSH, 8-OHDG and NTY contents and the decrease of serum AMH and E2, liver GSH and GSSG contents and GSH/GSSG ratio, ovarian optical density and cell number of γ-GCS and GR as well as the expression of γ-GCS genes were all reversed (P<0.01, P<0.05). H.E. staining showed degenerative changes of the ovarian tissue, fewer follicles at every level and increase of atretic follicles, disarrangement and layer number decrease of granulosa cells, and atrophy of corpus luteum in the model group, which were relatively milder in the EA group. EA can improve ovarian function, and reduce oxidative stress damage in DOR rats, which may be associated with its functions in up-regulating the expression of γ-GCS and GR protein and gene in the ovarian tissue.

Effects of electroacupuncture on pregnancy outcome in poor ovarian response patients of kidney essence deficiency and undergoing in vitro fertilization-embryo transfer

To observe the effects of electroacupuncture (EA) on ovarian reaction, egg and embryo quality, as well as pregnancy rate in poor ovarian response (POR) patients of kidney essence deficiency and undergoing in vitro fertilization-embryo transfer (IVF-ET). Ninety-six patients who met the inclusion criteria were randomly divided into an EA group and a control group, with 48 cases in each group. Before IVF-ET, the patients in the EA group received EA, once daily, 2 or 3 treatments a week for 12 weeks. Before and after the treatment, traditional Chinese medicine (TCM) syndrome score and clinical pregnancy rate were assessed in two groups. The concentrations of serum follicle-stimulating hormone (FSH), luteinsing hormone, estradiol, progesterone and anti-mullerian hormone were detected by chemiluminescence; the contents of serum insulin-like growth factor-1, serum inhibin B (INHB) and Kisspeptin in follicular fluid were determined by enzyme linked immunosorbent assay (ELISA); the antral follicle counting (AFC) was detected by color Doppler ultrasonography; and the egg and embryo conditions were observed under microscope. Fourteen days after embryo transfer, the positive rate of serum hemchoriconic gonadotropin (HCG) and clinical pregnancy rate were calculated. After the treatment, the TCM syndrome score and level of serum FSH were reduced (P<0.05); the INHB in serum and AFC were increased (P<0.05) when compared with those before the treatment in the EA group. After the treatment, in comparison with the control group, the TCM syndrome score and level of serum FSH were lower (P<0.05); and the contents of serum INHB, AFC, the numbers of MⅡ eggs and high-quality embryos, as well as serum HCG positive rate were all increased (P<0.05) in the EA group. EA can relieve the clinical symptoms of TCM in POR patients of kidney essence deficiency and undergoing IVF-ET, increase the ovarian reserve, reduce the serum FSH level, and improve the content of serum INHB, and the quality of eggs and embryos. This therapy tends to improve the clinical pregnancy rate and clinical pregnancy outcome.