Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility

Abstract

Sperm is not a simple carrier of paternal genetic information but its role extends clearly beyond fertilization. Integrity of sperm genome is an essential pre-requisite for birth of healthy offspring and evaluation of sperm should entail DNA integrity analysis. DNA integrity analysis is a better diagnostic and prognostic marker of sperm reproductive potential. Conventional semen analysis emphasizes on sperm concentration, viability, motility and morphology and has been proven to be a poor indicator of reproductive potential and pregnancy outcome. To overcome the drawbacks associated with conventional semen analysis more useful fertility tests and molecular biomarkers have been explored. Among the different tests which have evolved for assessing the sperm reproductive potential, tests for sperm DNA quality are most promising. Sperm DNA damage has been closely associated with numerous indicators of reproductive health including fertilization, embryo quality, implantation, spontaneous abortion, congenital malformations and childhood diseases. It therefore has great potential as a prognostic test for both in vitro and in vivo conception. This review presents an updated account of tests that have better diagnostic and prognostic implications in the evaluation of sperm DNA damage. The basic principles, outline of methodology, advantage, disadvantage, clinical significance of each technique and implications of these tests have been discussed. The logistics of each test with respect to available resources and equipment in an andrology laboratory, the feasibility of performing these tests in routine diagnostic workup of infertile men and the opportunities and challenges provided by DNA testing in male fertility determination are also presented.

Sperm DNA Fragmentation Assays Correlate with Sperm Abnormal Morphology and the Pregnancy Outcome

“…In IVF centres, potential infertile men are screened for the sperm quality by semen analysis, in particular investigating concentration, motility and morphology according to WHO guidelines [1]. However, at present, these parameters appear to be poor predictors of the fertilization success since infertile men may often show normal semen analysis [2]. For these reasons, it is claimed that, due to poor diagnostic methods and no fully effective infertility treatments, the use of sperm functionality test should be mandatory and routinely associated to conventional semen analysis [3][4][5].…”

“…Defective sperm chromatin packaging, abortive apoptosis and oxidative stress have been suggested among the etiologies of DNA strand breaks [2,17].…”

The Relationship between the Halosperm Assay and Semen Analysis Performed According to the 4th and the 5th Editions of the World Health Organization Guidelines

“…The Relationship between the Halosperm Assay and Semen Analysis Performed According to the 4 th and the 5 th Editions of the World Health Organization Guidelines men [10][11][12][13][14], poor fertilization rates [15,16], specific semen defects [17], miscarriage and poor artificial reproductive technology results [18]. Furthermore, infertile men have been shown to have substantially higher levels of DNA fragmentation than fertile men [13] and hence DNA fragmentation testing has been proposed as a valuable adjunct to routine semen analysis when considering the fertility potential of a man [16].…”

Engaging Practicing Gynecologists in the Management of Infertile Men

“…Sperm DNA damage is the loss of DNA integrity, and it may occur at any level in vivo during spermatogenesis, spermiogenesis, epididymis transit, or in vitro when spermatozoa are prepared for assisted conception [59]. Sperm DNA damage is a broad term that accounts for many defects in the DNA structure including single or double DNA strand breaks, base deletion or modification, interstrand or intrastrand DNA crosslinkage, and protamine mispackage via defective DNA-protein crosslinking [60].…”

“…Several assays used to measure sperm DNA damage are based on different principles and therefore differ in their ability to detect DNA damage [59,70]. In Table 4, we summarize the principles and interpretations of the most commonly used assays.…”