Comprehensive genetic examination of azoospermiс and severe oligozoospermiс patients

Background. Severe forms of reproduction disorders are often associated with genetic factors. However, for a number of reasons, medical and genetic examination and counseling of infertile patients are not effective enough, and the contribution of many genetic factors to the genesis of fertility disorders remains insufficiently studied. An integrated approach using various clinical, cytogenetic and molecular genetic methods in the examination makes it possible to improve the diagnosis of genetically determined forms of fertility disorders, in particular those associated with severe azoospermia or oligozoospermia. Aim: improving the effectiveness of medical and genetic examination and counseling of patients with severe azoospermia and oligozoospermia. Methods. The selected sample included 200 men with azoospermia (n=172) and severe oligozoospermia (n=28). The patients underwent clinical, andrological and laboratory-instrumental examination: ultrasound of the scrotum, spermatological, hormonal, cytogenetic, molecular cytogenetic (FISH) and molecular genetic examination of loci or genes associated with male fertility disorders (AZF, CFTR, AR). Results. Various genetic factors of male infertility were found in 99 (49.5%) of 200 patients, including 76 (45.7%) men with azoospermia and 23 (82.1%) patients with severe oligozoospermia. Cystic fibrosis and CBAVD syndrome were diagnosed in 4.5% of patients, congenital hypogonadotropic hypogonadism - in 7.5% of men. Karyotype abnormalities were found in 52 (26.8%) patients, including Klinefelter syndrome (47,XXY; n=34), disomy Y (47,XYY; n=6), 46,XX-testicular disorder of sex development (n=3), balanced autosomal abnormalities (n=9). According to the results of the FISH analysis, no cryptic mosaicism was found in patients with sex chromosomes aneuploidy. Pathogenic Y chromosome microdeletions in the AZF locus (Y q11.2) were found in 16 (8%) patients. Pathogenic variants of the CFTR gene were detected in 9 patients with cystic fibrosis and CBAVD syndrome. Conclusions. Comprehensive genetic examination can significantly improve the effectiveness of the diagnosis of genetically determined forms of male infertility associated with severe pathozoospermia. To identify rare non-syndromic genetic forms of male fertility associated with gene variants and copy number variations, it is necessary to use massive parallel sequencing, array comparative genomic hybridization and other genomic analysis methods.

male infertility, azoospermia, oligozoospermia, hypogonadism, chromosome anomalies, Klinefelter syndrome, AZF, CBAVD, cystic fibrosis, microdeletions, Y-chromosome

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