A systematic review on sperm DNA fragmentation in male factor infertility: Laboratory assessment

Abstract

ObjectiveTo review sperm DNA fragmentation (SDF) testing as an important sperm function test in addition to conventional semen analysis. High SDF is negatively associated with semen quality, the fertilisation process, embryo quality, and pregnancy outcome. Over recent decades, different SDF assays have been developed and reviewed extensively to assess their applicability and accuracy as advanced sperm function tests. Amongst them, the standardisation of the terminal deoxynucleotidyl transferased UTP nick-end labelling (TUNEL) assay with a bench top flow cytometer in clinical practice deserves special mention with a threshold value of 16.8% to differentiate infertile men with DNA damage from fertile men.Materials and methodsA systematic literature search was performed through the PubMed, Medline, and ScienceDirect databases using the keywords ‘sperm DNA fragmentation’ and ‘laboratory assessment’. Non-English articles were excluded and studies related to humans were only included.ResultsOf the 618 identified, 87 studies (original research and reviews) and in addition eight book chapters meeting the selection criteria were included in this review. In all, 366 articles were rejected in the preliminary screening and a further 165 articles related to non-human subjects were excluded.ConclusionThere are pros and cons to all the available SDF assays. TUNEL is a reliable technique with greater accuracy and as an additional diagnostic test in Andrology laboratories along with basic semen analysis can predict fertility outcome, and thus direct the choice of an assisted reproductive technology procedure for infertile couples. Also, the TUNEL assay can be used as a prognostic test and results are beneficial in deciding personalised treatment for infertile men.

Diagnostics of DNA fragmentation in human spermatozoa: Are sperm chromatin structure analysis and sperm chromatin dispersion tests (SCD‐HaloSpermG2 ® ) comparable?

“…The SCD assay has also been used for a long time (Fernández et al, ), being further developed under time to attempt becoming an economical and management alternative to SCSA (Feijó & Esteves, ). As such, it has been adopted by many IVF clinics since it is simple, quick, does not require expensive or complicated instruments and, moreover, has high reproducibility (<3% intra‐assay variation; Panner Selvam & Agarwal, ; Zeqiraj et al, ). The CV for the reference sample and replicates assayed in the present study were well within these values, confirming previous studies (Erenpreiss, Bungum, et al, ).…”

“…Sperm DNA fragmentation has been evaluated with different techniques (Chohan, Griffin, Lafromboise, Jonge, & Carrell, ; Kim, ; Panner Selvam & Agarwal, ). Among these, the most popular for screening purposes is the sperm chromatin structure assay (SCSA), a 30‐year‐old flow cytometry/specific software‐linked methodology with high repeatability and low variation (1%–3%; Evenson, ), but requires specialised technicians for running it.…”

A treatment algorithm for couples with unexplained infertility based on sperm chromatin assessment

“…These various assays have untested thresholds and often lack concordance among each other [ 17 ]. Among these tests, SCSA is considered the gold standard [ 18 ] and the COMET assay is reputed to be the most sensitive and particularly useful for identifying double-stranded breaks [ 19 ] although recent meta-analysis studies have reported the TUNEL assay as having high sensitivity and specificity compared to other DNA fragmentation assays [ 17 , 20 ]. A simple and more consistent approach is to utilize in-house testing that would allow consistent, expedited, and cost-effective methods to screen couples.…”

Investigating the relationship between BRCA1 and BRCA2 genes methylation profile and sperm DNA fragmentation in infertile men

“…In the present study, we aimed to investigate the relationship between sDF and the methylation status of BRCA1 and BRCA2 gene promoters in spermatozoa of idiopathic infertile patients with OAT . sDF is known to be negatively associated with sperm quality, fertilisation rate and pregnancy success (Panner Selvam & Agarwal, ). Semen parameters such as sperm morphology and motility have been negatively correlated with increased DNA fragmentation (Evgeni, Charalabopoulos, & Asimakopoulos, ).…”