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Causes and Clinical Features of Infertile Men With Nonobstructive Azoospermia and Histopathologic Diagnosis of Hypospermatogenesis.

Urology 2017 July
OBJECTIVE: To analyze the causes and the clinical features of infertile men with nonobstructive azoospermia and hypospermatogenesis (HS).

MATERIALS AND METHODS: This retrospective cohort study included 100 patients with nonobstructive azoospermia and HS and 8 patients with obstructive azoospermia and normal spermatogenesis. The severity of HS was subdivided into 3 groups (mild, moderate, and severe) based on spermatogenic score. Data of history, physical findings, serum hormone profiles, genetic studies, and sperm retrieval rate were collected. Whole genome DNA methylation analysis and microarray mRNA expression analysis were used to identify the candidate genes of methylation dysregulation in HS.

RESULTS: Thirty-two (32%) patients had at least 1 prior/current testicular insults and 13 (13%) patients had genetic anomalies. Fifty-five (55%) patients were categorized as idiopathic HS. Patients with mild HS had a higher frequency of testicular insults, and patients with severe HS had a significantly higher frequency of genetic anomalies. Sperm retrieval rate was 100%, 100%, and 88.4% for patients with mild, moderate, and severe HS, respectively. Four sterility-related genes, including BOLL, DDX4, HORMAD1, and MAEL, were found to have increased methylation at CpGs of the promoter regions and decreased mRNA expressions in HS testis.

CONCLUSION: The causes of HS are complex and multifactorial. The main causes of HS were prior or current testicular insults and chromosomal or genetic anomalies. More than half of the patients were categorized as idiopathic HS. With high throughput analysis, methylation dysregulations of BOLL, DDX4, HORMAD1, and MAEL are believed to be associated with HS.

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