Potential adverse effect of sperm DNA damage on embryo quality after ICSI

Zini, Armand; Meriano, Jim; Kader, Karim; Jarvi, Keith; Laskin, Carl A.; Cadesky, Ken

doi:10.1093/humrep/dei266

Cited by 164 publications

(115 citation statements)

References 39 publications

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“…As with IVF studies, these ICSI studies are quite heterogeneous in terms of design, inclusion/exclusion criteria, and the sperm DNA damage test employed. In keeping with a recent analysis [Collins et al 2008], the results of this updated meta-analysis on ICSI studies indicate that sperm DNA damage is not related to ICSI pregnancy rates (combined OR of 1.15, 95% 0.90, 1.55, p = 0.65) [Benchaib et al 2007;Boe-Hansen et al 2006;Borini et al 2006;Bungum et al 2007;Check et al 2005;Gandini et al 2004;Hammadeh et al 1996;Henkel et al 2003;Host et al 2000;Huang et al 2005;Lin et al 2008;Micinski et al 2009;Tarozzi et al 2009;Zini et al 2005]. The characteristics of the 14 ICSI studies that could be evaluated are shown in Tables 4 and 5.…”

Section: In Vitro Fertilization With Intracytoplasmic Sperm Injectionsupporting

confidence: 63%

Are sperm chromatin and DNA defects relevant in the clinic?

Zini

2011

Systems Biology in Reproductive Medicine

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228

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There has been an increase in the use of sperm DNA and chromatin integrity tests in the evaluation of the infertile man with the hypothesis that these tests may better diagnose infertility and predict reproductive outcomes. This review discusses the etiology of sperm DNA damage, briefly describing the tests of sperm DNA damage, and evaluates the relationship between sperm DNA damage and reproductive outcomes. A systematic review of the literature allows us to conclude that sperm DNA damage is associated with lower natural, intra-uterine insemination (IUI), and in vitro fertilization (IVF) pregnancy rates. Studies to date have not shown a clear association between sperm DNA and chromatin defects and pregnancy outcomes after intra-cytoplasmic sperm injection (ICSI). However, we cannot exclude the possibility that very high levels of DNA damage will impact on ICSI outcomes. In couples undergoing IVF or ICSI, there is evidence to show that sperm DNA damage is associated with an increased risk of pregnancy loss. A limitation of this systematic review and meta-analysis is that it does not address the heterogeneity of the individual study characteristics. Although the clinical utility of tests of sperm DNA damage remains to be firmly established, the data suggest that there is clinical value in testing couples prior to assisted reproductive technologies (ARTs IUI, IVF, and ICSI) and in those couples with recurrent miscarriages. Additional, well-designed prospective studies are needed before testing becomes a routine part of patient care.

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Section: In Vitro Fertilization With Intracytoplasmic Sperm Injectionsupporting

confidence: 63%

Are sperm chromatin and DNA defects relevant in the clinic?

Zini

2011

Systems Biology in Reproductive Medicine

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228

196

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“…In a yet unpublished study from our laboratory, we have found shorter sperm telomere length secondary to oxidative damage and high sperm DFI in cases with iRPL. Zini and colleague [48] reported that percentage of sperm with denatured and fragmented DNA was 25 to 28 % in infertile men as compared to 10 to 13 % in fertile men. They also reported that infertile men have >30 % denatured DNA and is associated with poor embryo quality and miscarriage.…”

Section: Discussionmentioning

confidence: 99%

Predictive value of DNA integrity analysis in idiopathic recurrent pregnancy loss following spontaneous conception

Kumar

Deka

Singh

et al. 2012

J Assist Reprod Genet

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Purpose Standard semen parameters are poor predictors of fertility potential. To date, apart from, paternal karyotyping sperm factors are not evaluated in recurrent pregnancy loss (RPL), only recent studies have emphasized the role of sperm factors in early embryonic development as sperm transcribes genes critical for early embryonic development. Sperm DNA integrity is useful diagnostic and prognostic marker and has clinical implications in idiopathic recurrent pregnancy loss (iRPL) following spontaneous conception. The aim of this study was to assess DNA integrity in cases experiencing iRPL following spontaneous conception. Methods Semen samples from 45 patients and 20 controls were analyzed as per WHO 1999 guidelines and sperm chromatin structure assay (SCSA) was used to measure DNA fragmentation index (DFI). Results By applying receiver operating curve (ROC) analysis, sperm DFI of approximately 26 % was found in male partner of couples experiencing iRPL. Conclusions Our data indicate that sperm from men with a history of iRPL have a higher percentage of DNA damage as compared to control group, and this can explain pregnancy loss in these patients. Men with higher DFI are infertile whereas men with lower DFI (26 %) are able to conceive but experience recurrent pregnancy loss. Thus it is important to evaluate sperm DFI in couples experiencing iRPL to understand exact aetiology of RPL and determine prognosis and management.

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“…Sperm DNA fragmentation index (DFI) Sperm DNA damage was assessed by the sperm chromatin structure assay (SCSA) and the results were expressed as sperm % DFI (an index of DNA damage), as previously described [13,39]. Stored semen samples were thawed on ice and treated for 30 s with 400 μL of a solution of 0.1 % Triton X-100, 0.15 M NaCl, and 0.08 N HCl, pH 1.2.…”

Section: Methodsmentioning

confidence: 99%

High prevalence of isolated sperm DNA damage in infertile men with advanced paternal age

Das

Alhathal

San-Gabriel

et al. 2013

J Assist Reprod Genet

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Background Sperm DNA damage is associated with male infertility, lower pregnancy rates and pregnancy loss. Objective The primary aim of our study was to evaluate the prevalence of sperm DNA damage in younger and older men with normozoospermia. Design, Setting and Participants We obtained semen from 277 consecutive non-azoospermic men presenting for sperm DNA testing. Outcome Measurements and Statistical Analysis The main outcome measures included sperm % DNA fragmentation index (%DFI, using sperm chromatin structure assay), sperm concentration, motility and morphology, and, paternal age.Results and Limitations Sperm % DFI was positively correlated with paternal age (r=0.20, P<0.001) and inversely correlated % progressive motility (r=−0.16, P=0.01). Sperm %DFI was significantly higher in older (≥40 years) compared to younger (<40 years) normozoospermic men (17±13 vs. 12±8, respectively P=0.008), whereas, sperm concentration, progressive motility and morphology were not significantly different in these two groups. Moreover, the prevalence of high levels of sperm DNA damage (>30 % DFI) was significantly higher in older compared to younger normozoospermic men (17 % vs. 3 %, respectively, P<0.001). Conclusion The data indicate that a conventional semen analysis can often fail to detect a defect in spermatogenesis (high %DFI) in older men and suggest that infertile couples with advanced paternal age, including those with normal semen parameters, should consider sperm DNA testing as part of the couple evaluation.

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Potential adverse effect of sperm DNA damage on embryo quality after ICSI

Abstract: Although we did not observe significant relationships between sperm DNA damage and either fertilization or pregnancy rates, the potential adverse effect of sperm DNA damage on embryo quality and spontaneous pregnancy loss is concerning.

Cited by 164 publications

References 39 publications

Are sperm chromatin and DNA defects relevant in the clinic?

Are sperm chromatin and DNA defects relevant in the clinic?

Predictive value of DNA integrity analysis in idiopathic recurrent pregnancy loss following spontaneous conception

High prevalence of isolated sperm DNA damage in infertile men with advanced paternal age

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