Clinical Significance of Sperm DNA Damage Threshold Value in the Assessment of Male Infertility

Laboratory for Molecular Reproduction and Genetics, Department of Anatomy, All India Institute of Medical Sciences, New Delhi, India.
Reproductive sciences (Thousand Oaks, Calif.) (Impact Factor: 2.23). 10/2011; 18(10):1005-13. DOI: 10.1177/1933719111401662
Source: PubMed


Sperm DNA integrity is a prerequisite for normal spermatozoal function. The aim of the study was to evaluate the role of sperm chromatin damage, its cut-off level and its effect on sperm parameters in men with idiopathic infertility by analyzing 100 idiopathic infertile men and 50 fertile controls. Semen samples were analyzed as per WHO 1999 guidelines and sperm chromatin structure assay (SCSA) was applied to measure DNA fragmentation index (DFI) in sperm. The mean DFI of infertile men (35.75) was significantly (P < .0001) higher as compared to controls (26.22). The threshold level of 30.28% was obtained as cut-off value to discriminate infertile men from fertile controls. Sperm count, forward motility, and normal morphology found to be negatively associated with DFI in overall study subjects. Infertile men with severe oligozoospermia had higher mean DFI (40.01 ± 11.31) than infertile men with oligozoospermia (35.11 ± 10.05) and normal sperm count (33.99 ± 9.96). Moreover 64% of infertile men have DFI > 30 against 6% of fertile controls (P < .0001). Higher sperm DNA fragmentation may be the underlying cause for poor semen quality in idiopathic infertile men and the threshold value of 30.28% is a clear discriminator to distinguish infertile men from fertile men of Indian population. Thus, DFI is a good prognostic marker as cases with higher sperm DFI may have poor success rate even after assisted conception and may experience recurrent pregnancy loss (RPL) and should be counseled accordingly.

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    • "For example, in three studies looking at prediction of natural fertility (Gunalp et al., 2001; Menkveld et al., 2001; Ombelet et al., 1997), sperm morphology had a specificity of about 80% and sensitivity of about 70%, with the area under the curve (AUC) for receiver operator curve (ROC) analysis of about 80%, giving it 'fair' to 'good' accuracy as a diagnostic test. Several studies have produced analogous data for DNA-F assays (Ribas-Maynou et al., 2013; Sergerie et al., 2005; Simon et al., 2011; Venkatesh et al., 2011), although only one (Venkatesh et al., 2011) had appropriate infertile and fertile study populations . The others failed to exclude female factors in the infertility cases, excluded men with normal SA (the group of greatest interest), or used infertility patients who achieved an assisted pregnancy as fertile controls. "
    Reproductive biomedicine online 12/2014; 30(2). DOI:10.1016/j.rbmo.2014.12.001 · 3.02 Impact Factor
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    • "According to the literature, the SCSA, giving a DNA fragmentation index (DFI) value, is perceived as the most statistically robust and reproducible test and is a valuable predictor of fertility (Bungum, 2012; Giwercman et al., 2010; Oleszczuk et al., 2011; Smit et al., 2007; Venkatesh et al., 2011). A valuable threshold for DFI was set by Evenson et al. (1999) at 30%, which is robustly indicative of fertility potential. "
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    ABSTRACT: DNA fragmentation is an important factor in the aetiology of male infertility. However, it is still underevaluated and its inclusion in routine semen analysis is debated. DNA fragmentation has been shown to be a robust indicator of fertility potential, more so than conventional semen parameters. Men with high DNA fragmentation levels have significantly lower odds of conceiving, naturally or through procedures such as intrauterine insemination and IVF. Couples may be counselled to proceed directly to intracytoplasmic sperm injection as it is more successful in this group, avoiding costly procedures, recurrent failures or pregnancy losses; however, this treatment is not without limitations or risks. Ideally DNA fragmentation should be minimized where possible. Oxidative stress is the major cause of DNA fragmentation in spermatozoa. Endogenous and exogenous factors that contribute to oxidative stress are discussed, and in many cases are shown to be easily modifiable. Antioxidants play a protective role, although a delicate balance of reduction and oxidation is required for essential functions, including fertilization. Reducing oxidative stress may improve a couple’s chances of conception either naturally or via assisted reproduction. Sources of oxidative stress therefore should be thoroughly examined in men with high levels of DNA fragmentation and modified where possible.
    Reproductive biomedicine online 06/2014; 28(6). DOI:10.1016/j.rbmo.2014.02.004 · 3.02 Impact Factor
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    • "Reported values for SCSA threshold vary from 20 to 30% (Evenson & Jost, 2000; Evenson et al., 2002; Larson-Cook et al., 2003; Bungum et al., 2004; Payne et al., 2005; Boe-Hansen et al., 2006; Venkatesh et al., 2011; Evenson, 2013). Our results show a threshold value of 18.9% of SDF, which is at the low end of the published range. "
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    ABSTRACT: Sperm DNA fragmentation (SDF) is becoming an important test to assess male infertility. Several different tests are available, but no consensus has yet been reached as to which tests are most predictive of infertility. Few publications have reported a comprehensive analysis comparing these methods within the same population. The objective of this study was to analyze the differences between the five most common methodologies, to study their correlations and to establish their cut-off values, sensitivity and specificity in predicting male infertility. We found differences in SDF between fertile donors and infertile patients in TUNEL, SCSA, SCD and alkaline Comet assays, but none with the neutral Comet assay. The alkaline COMET assay was the best in predicting male infertility followed by TUNEL, SCD and SCSA, whereas the neutral COMET assay had no predictive power. For our patient population, threshold values for infertility were 20.05% for TUNEL assay, 18.90% for SCSA, 22.75% for the SCD test, 45.37% for alkaline Comet and 34.37% for neutral Comet. This work establishes in a comprehensive study that the all techniques except neutral Comet are useful to distinguish fertile and infertile men.
    Andrology 07/2013; 1(5). DOI:10.1111/j.2047-2927.2013.00111.x · 2.30 Impact Factor
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