Contribution of all exome analyzes to explaining unexplained male infertility

Objective: It is aimed to investigate the genetic etiology of the male factor without chromosomal and Y microdeletion anomaly in couples with a history of recurrent pregnancy loss (≥2) or secondary infertility by next generation sequencing method. Method: From the couples who applied to Istanbul University, Istanbul Faculty of Medicine, Department of Medical Genetics between 2014-2020, who experienced primary/secondary infertility and recurrent pregnancy loss, 34 expectant mothers were previously consulted with Dr. Ezgi Gizem Berkay, within the scope of doctoral thesis, whole exome sequence analysis was performed and 10 father candidates whose etiogenesis could not be clarified were selected among these couples. Results: Within the scope of the study, 14 variants in genes that may be associated with the phenotype were detected in 8 cases. In two cases, no variants were detected in candidate genes associated with infertility/TGK. Etiology was clarified in one case (Case 1) (10%) with a pathogenic variant detected in the TCC21B gene. Carriage associated with the CFTR gene (40%), defined as pathogenic, or pathogenicity of which has not yet been fully elucidated in the databases, was detected in four cases. In seven cases, the relationship with infertility and RPL was not clearly explained, but variants among the candidate genes were detected (70%). In our series, pathogenic variants were found in 2 genes that were not directly associated with infertility (20%). One of these diseases was dermatological (ichthyosis vulgaris) and the other was associated with BMD. Conclusion: Identification of candidate genes associated with infertility/TGK strengthened the phenotype-genotype relationship of these genes. The detection of clinical conditions other than the purpose of research in 2 cases shows the importance of genetic counseling in cases where TED analysis will be performed for diagnostic or research purposes. Keywords: recurrent pregnancy loss, infertility, next generation sequencing The present work was supported by the Research Fund of Istanbul University. Project No: 36968