Male fertility and varicocoele: Role of immune factors

The role of antisperm antibodies (ASA) in the aetiopathogenesis of varicocoele-related male infertility remains unclear. The objective of this study was to determine whether varicocoele is associated with antisperm immune response and whether this factor provides additional affect on male fertility. We performed a multicentral, prospective study that included the clinical examination of 1639 male subjects from infertile couples and 90 fertile men, the evaluation of the absolute and relative risks of immune infertility associated with varicocoele and the impact of the autoimmune response on the semen quality. The methods used were as follows: standard examination of seminal fluid according to WHO criteria; ASA detection in seminal fluid using mixed antiglobulin reaction (MAR) and direct flow cytometry; measurement of spontaneous and ionophore-induced acrosome reactions; oxidative stress evaluation with luminal-dependent chemiluminescence method and evaluation of DNA fragmentation by sperm chromatin dispersion. The prevalence of varicocoele-related immune infertility is about 15% and does not depend on the grade of vein dilatation both in primary and secondary fertility disorders. Varicocoele is not an immediate cause of autoimmune reactions against spermatozoa, but is a cofactor increasing ASA risk; the OR of immune infertility after a testicular trauma in varicocoele patients increases twofold. In varicocoele patients, the autoimmune antisperm reaction is accompanied by a more significant decrease in the semen quality (concentration and number of progressively motile and morphologically normal spermatozoa in the ejaculate), acrosome reaction disorders (presence of pre-term spontaneous and lack of induced reactions) and an increase in the proportion of spermatozoa with DNA fragmentation. These disorders correlate with the level of sperm oxidative stress; reactive oxygen species (ROS) production in ASA-positive varicocoele patients is 2.8 and 3.5 times higher than in ASA-negative varicocoele patients and fertile men respectively. We did not find correlation between the grade of spermatic cord vein dilatation and ROS production. © 2013 American Society of Andrology and European Academy of Andrology

Functional deficit of sperm and fertility impairment in men with antisperm antibodies

Autoimmune reactions against the sperm cells play an ambiguous role in fertility impairment. The objective of this study was to characterize functional deficit of sperm conditioned by antisperm immune response in normozoospermic men. This was a multi-centric, cross-sectional, case-control study. The study subjects were 1060 infertile normozoospermic men and 107 fertile men. The main outcome measures were clinical examination, semen analysis including MAR test for antisperm antibodies (ASA), computer-aided sperm analysis, acrosome reaction (AR) detected with flow cytometry, DNA fragmentation measured with sperm chromatin dispersion, reactive oxygen species (ROS) assessed using the luminol-dependent chemiluminescence method. 2% of the fertile men had MAR-IgG ≥ 50%, but all subjects with MAR-IgG ≤ 12% were outliers; 16% infertile men had MAR-IgG ≥ 50% (p< 0.0001). There was a direct correlation between the infertility duration and MAR-IgG (R= 0.3; p< 0.0001). The ASA-positive infertile men had AR disorders 2.1 times more frequently (p< 0.02), predominantly inductivity disorders. We found signs of hyperactivation proportionate to the ASA level (p< 0.001). DNA fragmentation was more highly expressed and was 1.6 and 1.3 times more frequent compared with the fertile and the ASA-negative patients, respectively (p< 0.001 and p< 0.05). We found signs of oxidative stress (OS): ROS generation by washed ASA-positive spermatozoa was 3.7 times higher than in the fertile men (p< 0.00001) and depended on the ASA levels (R = 0.5; p< 0.0001). The ASA correlation with ROS generation in native sperm was weak (R = 0.2; p< 0.001). We concluded that autoimmune reactions against spermatozoa are accompanied by a fertility decrease in normozoospermia. This results from AR and capacitation disorders and DNA fragmentation. The pathogenesis of sperm abnormalities in immune infertility is associated with the OS of spermatozoa. © 2015 Elsevier Ireland Ltd

Male fertility and varicocoele: Role of immune factors

The role of antisperm antibodies (ASA) in the aetiopathogenesis of varicocoele-related male infertility remains unclear. The objective of this study was to determine whether varicocoele is associated with antisperm immune response and whether this factor provides additional affect on male fertility. We performed a multicentral, prospective study that included the clinical examination of 1639 male subjects from infertile couples and 90 fertile men, the evaluation of the absolute and relative risks of immune infertility associated with varicocoele and the impact of the autoimmune response on the semen quality. The methods used were as follows: standard examination of seminal fluid according to WHO criteria; ASA detection in seminal fluid using mixed antiglobulin reaction (MAR) and direct flow cytometry; measurement of spontaneous and ionophore-induced acrosome reactions; oxidative stress evaluation with luminal-dependent chemiluminescence method and evaluation of DNA fragmentation by sperm chromatin dispersion. The prevalence of varicocoele-related immune infertility is about 15% and does not depend on the grade of vein dilatation both in primary and secondary fertility disorders. Varicocoele is not an immediate cause of autoimmune reactions against spermatozoa, but is a cofactor increasing ASA risk; the OR of immune infertility after a testicular trauma in varicocoele patients increases twofold. In varicocoele patients, the autoimmune antisperm reaction is accompanied by a more significant decrease in the semen quality (concentration and number of progressively motile and morphologically normal spermatozoa in the ejaculate), acrosome reaction disorders (presence of pre-term spontaneous and lack of induced reactions) and an increase in the proportion of spermatozoa with DNA fragmentation. These disorders correlate with the level of sperm oxidative stress; reactive oxygen species (ROS) production in ASA-positive varicocoele patients is 2.8 and 3.5 times higher than in ASA-negative varicocoele patients and fertile men respectively. We did not find correlation between the grade of spermatic cord vein dilatation and ROS production. © 2013 American Society of Andrology and European Academy of Andrology

Functional deficit of sperm and fertility impairment in men with antisperm antibodies

Autoimmune reactions against the sperm cells play an ambiguous role in fertility impairment. The objective of this study was to characterize functional deficit of sperm conditioned by antisperm immune response in normozoospermic men. This was a multi-centric, cross-sectional, case-control study. The study subjects were 1060 infertile normozoospermic men and 107 fertile men. The main outcome measures were clinical examination, semen analysis including MAR test for antisperm antibodies (ASA), computer-aided sperm analysis, acrosome reaction (AR) detected with flow cytometry, DNA fragmentation measured with sperm chromatin dispersion, reactive oxygen species (ROS) assessed using the luminol-dependent chemiluminescence method. 2% of the fertile men had MAR-IgG ≥ 50%, but all subjects with MAR-IgG ≤ 12% were outliers; 16% infertile men had MAR-IgG ≥ 50% (p< 0.0001). There was a direct correlation between the infertility duration and MAR-IgG (R= 0.3; p< 0.0001). The ASA-positive infertile men had AR disorders 2.1 times more frequently (p< 0.02), predominantly inductivity disorders. We found signs of hyperactivation proportionate to the ASA level (p< 0.001). DNA fragmentation was more highly expressed and was 1.6 and 1.3 times more frequent compared with the fertile and the ASA-negative patients, respectively (p< 0.001 and p< 0.05). We found signs of oxidative stress (OS): ROS generation by washed ASA-positive spermatozoa was 3.7 times higher than in the fertile men (p< 0.00001) and depended on the ASA levels (R = 0.5; p< 0.0001). The ASA correlation with ROS generation in native sperm was weak (R = 0.2; p< 0.001). We concluded that autoimmune reactions against spermatozoa are accompanied by a fertility decrease in normozoospermia. This results from AR and capacitation disorders and DNA fragmentation. The pathogenesis of sperm abnormalities in immune infertility is associated with the OS of spermatozoa. © 2015 Elsevier Ireland Ltd

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