Clinical correlates of the biological variation of sperm DNA fragmentation in infertile men attending an andrology outpatient clinic

Abstract

Determination of sperm DNA fragmentation, as assessed by the sperm chromatin structure assay (SCSA), has become an important tool for the evaluation of semen quality. The aim of the present study was to describe the biological variation of sperm DNA fragmentation in men attending an andrology clinic and to identify clinical correlates of the biological variation of sperm DNA fragmentation. For this study, two consecutive semen samples from 100 patients attending our andrology outpatient clinic were subjected to semen analysis, performed in parallel according to WHO guidelines and by SCSA. A good agreement between pairs of samples was found for SCSA-derived variables, as indicated by a significantly lower median coefficient of variation (CV) of the DNA Fragmentation Index (DFI) and the high DNA stainability (HDS) compared with WHO semen parameters. In half of the men attending our andrology clinic, however, the individual biological variation of DFI and HDS, expressed as CV of two samples, exceeded 10%. Dysregulation of spermatogenesis, as seen as testicular insufficiency or varicocele, was not associated with increased variability of DFI or HDS. A backward multiple linear regression analysis, however, indicated that the biological variation of DFI may be more profound in men with characteristics of normal spermatogenesis. In conclusion, we confirm previous reports that sperm DNA fragmentation has a lower biological variability than classical semen parameters. We hypothesize that the sperm chromatin structure may be more influenced in patients with normal spermatogenesis, whereas in men with disturbed spermatogenesis, the chromatin structure may be already so impaired that the effect of unidentified factors leading to variability of sperm DNA fragmentation in time may not be as profound.

Are varicoceles associated with increased deoxyribonucleic acid fragmentation?

“…Thus a primary defect in spermatogenesis can also result in oxidative stress. Impairment of sperm chromatin structure can be found to a variable degree in the majority of men with abnormal semen parameters, irrespective of the etiology of the semen abnormalities (6). Sperm DNA damage is probably the reflection of disrupted spermatogenesis due to several factors, including the presence of a varicocele.…”

“…Recently, studies have shown an increase in both reactive oxygen species (ROS) and apoptosis markers in semen of infertile men with a varicocele (5). Whether these substances play an etiologic role in the molecular mechanism by which varicoceles affect spermatogenesis is not clarified yet: they could simply be a consequence of defective spermatogenesis because they are also frequently found in semen of infertile men without a varicocele (6).…”

Significant improvement of sperm DNA quality after microsurgical repair of varicocele

“…It is suggested that this variability may explain the apparent different results when studies are compared. Sperm DNA fragmentation had a lower biological variability than classic semen parameters [Smit et al 2007]. It provides additional information about sperm quality and the ability of a couple to conceive.…”

“…SCSA based on flowcytometric method is a validated method for studying sperm DNA integrity [Evenson et al 1999]. Smit et al [2007] reported that the biological variation reported by the DFI is much lower than that of conventional semen parameters and DFI variability is not increased by varicocele. In the current study, we have shown that microsurgical repair is associated with a significant improvement over the classic semen parameters.…”

Antioxidant therapy in male infertility: fact or fiction?

“…15,22,29,53,[62][63][64][65][66][67][68][69] In addition, sperm DNA damage is a more reliable outcome measure than sperm concentration or motility because measures of sperm DNA damage exhibit a lower degree of biological variability than conventional semen parameters. [70][71][72] Treatment with oral antioxidants has generally been associated with improvement in sperm DNA integrity and in some cases pregnancy rates after assisted reproduction, although most of these studies are small and few are randomized placebo-controlled trials ( Table 3).…”