Eight tests for sperm DNA fragmentation and their roles in the clinic

Ward, W. Steven

doi:10.21037/tau.2017.03.78

Cited by 8 publications

(8 citation statements)

References 15 publications

(18 reference statements)

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“…Lastly, the question of whether or not doctors should ask patients to spend more money to obtain a diagnosis of the status of DNA damage in the sperm as a tool for both the patient and clinician to decide on a course of treatment should be put in the right perspective ( 68 ). Given the evidence indicating that SDF is associated with reproductive health issues in the male and the embryo, the question we as individuals and as a medical community must ultimately consider is if we are providing the best care to the infertile couple and the offspring by ignoring the “health” of the sperm ( 61 ).…”

Section: Discussionmentioning

confidence: 99%

A Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis on the clinical utility of sperm DNA fragmentation testing in specific male infertility scenarios

Esteves¹,

Agarwal

Cho

et al. 2017

Transl. Androl. Urol.

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BackgroundSperm DNA fragmentation (SDF) is recognized as a leading cause of male infertility because it can impair the paternal genome through distinct pathophysiological mechanisms. Current evidence supports SDF as a major factor in the pathophysiology of several conditions, including varicocele, unexplained infertility, assisted reproductive technology failure, and environmental lifestyle factors, although the mechanisms involved have not been fully described yet. Measurement of the levels of DNA fragmentation in semen provides valuable information on the integrity of paternal chromatin and may guide therapeutic strategies. A recently published clinical practice guideline (CPG) highlighted how to use the information provided by SDF testing in daily practice, which triggered a series of commentaries by leading infertility experts. These commentaries contained an abundance of information and conflicting views about the clinical utility of SDF testing, which underline the complex nature of SDF.MethodsA search of papers published in response to the CPG entitled “Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios” was performed within the Translational Andrology and Urology (TAU) website (http://tau.amegroups.com/). The start and end dates for the search were May 2017 and August 2017, respectively. Each commentary meeting our inclusion criteria was rated as “supportive without reservation”, “supportive with reservation”, “not supportive” or “neutral”. We recorded whether articles discussed either SDF characteristics as a laboratory test method or clinical scenarios, or both. Subsequently, we extracted the particulars from each commentary and utilized the ‘Strengths-Weaknesses-Opportunities-Threats’ (SWOT) analysis to understand the perceived advantages and drawbacks of SDF as a specialized sperm function method in clinical practice.ResultsFifty-eight fertility experts from six continents and twenty-two countries contributed commentaries. Overall, participants (87.9%; n=51) were supportive of the recommendations provided by the CPG on the utility of SDF testing based on clinical scenarios. The majority of participants made explicit remarks about both the clinical scenarios and SDF assays’ characteristics. Among ‘not supportive’ and ‘supportive with reservation’ participants, 75% (n=30/40) and 77.5% (n=31/40) expressed concerns related to technical limitations of SDF testing methods and clinical utility of the test in one or more clinical scenarios discussed in the CPG, respectively. The SWOT analysis revealed that the CPG provides a reasonable evidence-based proposal for integration of SDF testing in the routine daily practice. It also uncovered gaps of knowledge and threats limiting the widespread application of SDF in everyday practice, thus allowing the identification of opportunities to further refine SDF testing and its clinical utility.ConclusionsThe understanding of the role of SDF in male infertility requires an in-depth analysis of the multifactorial pat...

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Section: Discussionmentioning

confidence: 99%

A Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis on the clinical utility of sperm DNA fragmentation testing in specific male infertility scenarios

Esteves¹,

Agarwal

Cho

et al. 2017

Transl. Androl. Urol.

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“…In addition to DFI, another parameter, the percentage of sperm with high DNA stainability (HDS), is provided by the SCSA® flow cytometer-assisted assessment. HDS has been hypothesized to reflect the immaturity of the sperm nucleus, which has been proposed to be due to a sub-optimal histone to protamine ratio that affects sperm nucleus compaction and therefore makes it susceptible to DNA damage [32,33,46].…”

Section: Introductionmentioning

confidence: 99%

“…The Comet assay assesses DNA fragmentation based on electrophoretic characteristics [ 30 ]. The Sperm Chromatin Structure Assay (SCSA ® ) uses acridine orange (AO: a cell-permeable nucleic acid binding dye that fluoresces green when bound to double-stranded DNA [dsDNA] and red when bound to single-stranded DNA [ssDNA]) to stain sperm DNA that may be denatured by acid treatment or temperature [ 31 – 33 ]. The use of a low pH in the SCSA ® assay opens the DNA strand at break sites, allowing the AO to access the single-stranded DNA.…”

Section: Introductionmentioning

confidence: 99%

Could high DNA stainability (HDS) be a valuable indicator of sperm nuclear integrity?

Mohammadi

Tavalaee

Gharagozloo

et al. 2020

Basic Clin. Androl.

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Background: The Sperm Chromatin Structure Assay (SCSA®), in addition to identifying the DNA Fragmentation Index (DFI) also identifies High DNA satiability (HDS), supposed to reflect the nuclear compaction of spermatozoa. However, data on what exactly this parameter reveals, its relevance and usefulness are contradictory. In order to shed light on this situation, spermatozoa of a cohort (N = 397) of infertile men were subjected to the SCSA®, TUNEL (terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling) and CMA3 (Chromomycin A3) tests. In a smaller subcohort (N = 100), aniline blue (AB) and toluidine blue (TB) staining were performed in addition. The objective of this study was thus to answer the question of whether HDS is a relevant and reliable parameter to be taken into account? Results: HDS does not appear to be a reliable indicator of nuclear immaturity because it shows a weak correlation with the CMA3, AB and TB stains. The low correlation of HDS with sperm DNA fragmentation (TUNEL and SCSA®) and DNA condensation (CMA3, AB and TB) tests suggests that these two parameters could be decoupled. Unlike DFI and TUNEL, HDS has not been shown to correlate with classic clinical situations of male infertility (asthenozoospermia, teratozoospermia or astheno-teratozoospermia). Conclusion: HDS correlates poorly with most tests that focus specifically on the level of maturity of the sperm nucleus. To our knowledge, this study is the first to compare SCSA®, TUNEL, AB, TB and CMA3 assays on identical samples. It shows the potency, consistency and limitations of each test and the care that must be taken in their interpretation.

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“…Sperm DNA fragmentation (SDF) can be analyzed using different direct and indirect methodologies, as Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL), Comet assay, Sperm Chromatin Dispersion (SCD) test or Sperm Chromatin Structure Assay (SCSA), among others. The respective advantages and disadvantages of these different methods have been widely reviewed by multiple authors [ 6 , 7 , 8 ]. Despite the effectiveness of SDF testing for the prediction natural fertility and intra-uterine insemination outcomes, current scientific evidence is has not reached a consensus regarding if SDF is associated to pregnancy rates after ICSI cycles [ 9 ], the fact that is probably associated with a lack of standardization of some methodologies among laboratories around the world [ 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

Proteomic Analysis in Seminal Plasma of Fertile Donors and Infertile Patients with Sperm DNA Fragmentation

Fernández-Encinas

García-Peiró²,

Rey

et al. 2020

IJMS

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Seminal plasma proteomics studies could represent a new approach for the determination of molecular elements driving male infertility, resulting in a better male infertility characterization. The aim of this study is to investigate proteomic differences in seminal plasma samples from fertile and infertile individuals. For that, semen samples were selected according to semen analysis, clinical pathology, and values of sperm DNA fragmentation (alkaline and neutral Comet assay and Sperm Chromatin Dispersion test). A total of 24 seminal plasma samples classified in four groups were processed: fertile donors (FD), recurrent miscarriage patients (RM), asthenoteratozoospermic patients (ATZ), and asthenoteratozoospermic patients with varicocele (ATZ-VAR). Results obtained by 2D-differential gel electrophoresis (2D-DIGE) revealed 26 spots significantly increased in fertile donors when compared to patient groups. Also, eight spots in the ATZ group and two in the ATZ-VAR group were decreased compared to the other groups. Twenty-eight proteins were identified by mass spectrometry (MS), most of them involved in metabolic and cellular processes and with a catalytic or binding function. Protein–protein interactions through Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) tool suggest that a large part of them were associated with each other. Furthermore, most of them were associated with ubiquitin C, indicating that it could play an important regulation role, resulting in a potential male infertility biomarker.

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Eight tests for sperm DNA fragmentation and their roles in the clinic

Cited by 8 publications

References 15 publications

A Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis on the clinical utility of sperm DNA fragmentation testing in specific male infertility scenarios

A Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis on the clinical utility of sperm DNA fragmentation testing in specific male infertility scenarios

Could high DNA stainability (HDS) be a valuable indicator of sperm nuclear integrity?

Proteomic Analysis in Seminal Plasma of Fertile Donors and Infertile Patients with Sperm DNA Fragmentation

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