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10.1016/j.jsxm.2020.01.011 http://scihub22266oqcxt.onion/10.1016/j.jsxm.2020.01.011 32171629!ä!32171629 Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=32171629&cmd=llinks): Failed to open stream: HTTP request failed! 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Correlations Among Genotype and Outcome in Chinese Male Patients With Congenital Hypogonadotropic Hypogonadism Under HCG Treatment |pdf=|usr=}}{{32171629}} gab.com Text Correlations Among Genotype and Outcome in Chinese Male Patients With Congenital Hypogonadotropic Hypogonadism Under HCG Treatment JO: J Sex Med http://www.kidney.de/pget.php?&tw=1&pmid=32171629 #FOAvip BACKGROUND: Congenital hypogonadotropic hypogonadism (CHH) is a genetically heterogeneous disorder characterized by absent or incomplete puberty and infertility, and heterogeneous responses are often observed during treatment. AIM: To investigate the role of CHH-associated variants in patients with CHH with poor responses to human chorionic gonadotropin (hCG). METHODS: This retrospective study investigated 110 Chinese male patients with CHH undergoing genetic analysis and hCG treatment. CHH-associated rare sequence variants (RSVs) were identified by using a tailored next-generation sequencing panel and were interpreted in accordance with the American College of Medical Genetics and Genomics criteria. Clinical characteristics were recorded, and Kyoto Encyclopedia of Genes and Genomes analysis was conducted to assess pathways enriched in protein networks implicated in poor responses. OUTCOMES: The outcomes include testicular volume, serum hormonal profiles, parameters of semen analysis, pathogenicity classification, and pathway enrichment. RESULTS: Among the 110 patients, 94.55% achieved normal serum testosterone and 54.55% achieved seminal spermatozoa appearance (SSA). PLXNB1, ROBO3, LHB, NRP2, CHD7, and PLXNA1 RSVs were identified in patients who had an abnormal serum testosterone level during treatment. In spermatogenesis, the number of CHH-associated RSVs was not significantly strongly associated with delayed SSA. After pathogenicity classification, pathogenic/likely pathogenic (P/LP) RSVs were identified in 30% (33/110) of patients. Patients with P/LP RSVs showed delayed SSA compared with noncarriers, and P/LP PROKR2 RSVs showed the strongest association (48, 95% CI: 34.1-61.9 months, P = .043). Enriched pathways implicated in delayed SSA included neuroactive ligand-receptor interaction; Rap1, MAPK, PI3K-Akt signaling; and regulation of actin cytoskeleton. CLINICAL IMPLICATIONS: Male patients with CHH harboring P/LP PROKR2 RSVs should be aware of a high probability of poor responses to hCG; If these patients desire fertility, it might be better to recommend hCG/human menopausal gonadotropin, hCG/recombinant follicle-stimulating hormone, or pulsatile GnRH administration before treatments start or as early as possible. STRENGTHS & LIMITATIONS: Strengths are the standardized regimen and extensive follow-up (median time of 40 months). However, included patients in the study voluntarily chose hCG treatment because of the burden of drug cost and/or little fertility desire. Therefore, human menopausal gonadotropin or follicle-stimulating hormone was not added to this cohort. Our observed correlations should be further verified in patients with CHH undergoing other treatments. CONCLUSION: Among all P/LP RSVs, P/LP PROKR2 RSVs might correlate with poor responses in CHH under hCG treatment; our study supports the pathogenicity assessment of American College of Medical Genetics and Genomics criteria in genetic counseling, to improve management of patients with CHH. Chen Y, Sun T, Niu Y, et al. Correlations AmongGenotype and Outcome in Chinese Male Patients WithCongenital Hypogonadotropic Hypogonadism Under HCG Treatment. J Sex Med 2020;17:645-657. Twit Text FOAVip Correlations Among Genotype and Outcome in Chinese Male Patients With Congenital Hypogonadotropic Hypogonadism Under HCG Treatment ????J Sex Med http://www.kidney.de/pget.php?&tw=1&pmid=32171629 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32171629 #FOAvip English Wikipedia <ref>{{Cite pmid|32171629}}</ref> Correlations Among Genotype and Outcome in Chinese Male Patients With Congenital Hypogonadotropic Hypogonadism Under HCG Treatment #MMPMID32171629 Chen Y; Sun T; Niu Y; Wang D; Xiong Z; Li C; Liu K; Qiu Y; Sun Y; Gong J; Wang T; Wang S; Xu H; Liu J J Sex Med 2020[Apr]; 17 (4): 645-657 PMID32171629show ga BACKGROUND: Congenital hypogonadotropic hypogonadism (CHH) is a genetically heterogeneous disorder characterized by absent or incomplete puberty and infertility, and heterogeneous responses are often observed during treatment. AIM: To investigate the role of CHH-associated variants in patients with CHH with poor responses to human chorionic gonadotropin (hCG). METHODS: This retrospective study investigated 110 Chinese male patients with CHH undergoing genetic analysis and hCG treatment. CHH-associated rare sequence variants (RSVs) were identified by using a tailored next-generation sequencing panel and were interpreted in accordance with the American College of Medical Genetics and Genomics criteria. Clinical characteristics were recorded, and Kyoto Encyclopedia of Genes and Genomes analysis was conducted to assess pathways enriched in protein networks implicated in poor responses. OUTCOMES: The outcomes include testicular volume, serum hormonal profiles, parameters of semen analysis, pathogenicity classification, and pathway enrichment. RESULTS: Among the 110 patients, 94.55% achieved normal serum testosterone and 54.55% achieved seminal spermatozoa appearance (SSA). PLXNB1, ROBO3, LHB, NRP2, CHD7, and PLXNA1 RSVs were identified in patients who had an abnormal serum testosterone level during treatment. In spermatogenesis, the number of CHH-associated RSVs was not significantly strongly associated with delayed SSA. After pathogenicity classification, pathogenic/likely pathogenic (P/LP) RSVs were identified in 30% (33/110) of patients. Patients with P/LP RSVs showed delayed SSA compared with noncarriers, and P/LP PROKR2 RSVs showed the strongest association (48, 95% CI: 34.1-61.9 months, P = .043). Enriched pathways implicated in delayed SSA included neuroactive ligand-receptor interaction; Rap1, MAPK, PI3K-Akt signaling; and regulation of actin cytoskeleton. CLINICAL IMPLICATIONS: Male patients with CHH harboring P/LP PROKR2 RSVs should be aware of a high probability of poor responses to hCG; If these patients desire fertility, it might be better to recommend hCG/human menopausal gonadotropin, hCG/recombinant follicle-stimulating hormone, or pulsatile GnRH administration before treatments start or as early as possible. STRENGTHS & LIMITATIONS: Strengths are the standardized regimen and extensive follow-up (median time of 40 months). However, included patients in the study voluntarily chose hCG treatment because of the burden of drug cost and/or little fertility desire. Therefore, human menopausal gonadotropin or follicle-stimulating hormone was not added to this cohort. Our observed correlations should be further verified in patients with CHH undergoing other treatments. CONCLUSION: Among all P/LP RSVs, P/LP PROKR2 RSVs might correlate with poor responses in CHH under hCG treatment; our study supports the pathogenicity assessment of American College of Medical Genetics and Genomics criteria in genetic counseling, to improve management of patients with CHH. Chen Y, Sun T, Niu Y, et al. Correlations AmongGenotype and Outcome in Chinese Male Patients WithCongenital Hypogonadotropic Hypogonadism Under HCG Treatment. J Sex Med 2020;17:645-657. |*Spermatogenesis[MESH] |Adolescent[MESH] |Adult[MESH] |Chorionic Gonadotropin/*administration & dosage[MESH] |Cohort Studies[MESH] |Genotype[MESH] |Gonadotropin-Releasing Hormone/therapeutic use[MESH] |Humans[MESH] |Hypogonadism/*drug therapy[MESH] |Infertility/etiology[MESH] |Male[MESH] |Phosphatidylinositol 3-Kinases/metabolism[MESH] |Retrospective Studies[MESH]Correlations Among Genotype and Outcome in Chinese Male Patients With (epmc).pdf DeepDyve Pubget Overpricing