Sperm DNA Fragmentation: A New Guideline for Clinicians
Sperm DNA Fragmentation: A New Guideline for Clinicians
Sperm DNA integrity is crucial for fertilization and development of healthy offspring. The spermatozoon undergoes extensive molecular remodeling of its nucleus during later phases of spermatogenesis, which imparts compaction and protects the genetic content. Testicular (defective maturation and abortive apoptosis) and post-testicular (oxidative stress) mechanisms are implicated in the etiology of sperm DNA fragmentation (SDF), which affects both natural and assisted reproduction. Several clinical and environmental factors are known to negatively impact sperm DNA integrity. An increasing number of reports emphasizes the direct relationship between sperm DNA damage and male infertility. Currently, several assays are available to assess sperm DNA damage, however, routine assessment of SDF in clinical practice is not recommended by professional organizations. This article provides an overview of SDF types, origin and comparative analysis of various SDF assays while primarily focusing on the clinical indications of SDF testing. Importantly, we report four clinical cases where SDF testing had played a significant role in improving fertility outcome. In light of these clinical case reports and recent scientific evidence, this review provides expert recommendations on SDF testing and examines the advantages and drawbacks of the clinical utility of SDF testing using Strength-Weaknesses-Opportunities-Threats (SWOT) analysis.
INTRODUCTION
INTRODUCTION
Infertility is defined as the failure of a couple to achieve a clinical pregnancy after one year of regular, unprotected sexual intercourse . Infertility affects more than 15% of couples globally with male factors alone or in combination with female factors, contributing to 50% of the cases . Evaluation of infertile men still relies on conventional semen analysis, though it alone does not accurately predict male fertility potential and success of assisted reproductive technology (ART) . In fact, about 15% of infertile patients have a normal semen analysis . However, assessment of sperm concentration, motility and morphology may not fully reflect impaired sperm DNA integrity , which is detrimental for normal fertilization, embryo development and success of ART .
Sperm DNA fragmentation (SDF) can be caused by extrinsic factors (i.e., heat exposure, smoking, environmental pollutants, and chemotherapeutics) as well as intrinsic factors (i.e., defective germ cell maturation, abortive apoptosis, and oxidative stress [OS] ) Compelling evidence demonstrates that OS is a major contributor to male infertility . Reactive oxygen species (ROS) are vital for physiological processes such as apoptosis and capacitation, but an overproduction leads to various deleterious consequences including SDF Types of DNA damage include mismatch of bases, loss of base (abasic site), base modifications, DNA adducts and crosslink, pyrimidine dimers and single strand breaks (SSB) and double strand breaks (DSB) (Fig. 1. Any of these alterations can induce SDF and compromise natural conception or ART outcomes.
Since 1999, there has been a significant increase in the number of studies reporting an association between SDF and male infertility. According to a recent scientometric analysis, the primary focus of SDF research in the past 20 years has emphasized lifestyle factors, varicocele, and asthenozoospermia . Increased SDF levels have been implicated in male infertility while being associated with conditions such as varicocele, male accessory gland infection, advanced paternal age, cancer, chronic illness, exposure to environmental toxins and lifestyle factors
Moreover, numerous studies have found that increased SDF adversely impacts conception rates . Evidence shows that DNA damage in spermatozoa can affect the health and well-being of offspring . Consequently, the negative impact of SDF on the male fertility potential may encourage more clinicians to utilize
SDF testing in the clinical setting . Interventions have also been explored to improve fertility outcomes and promote healthy offspring.
The present article aims to highlight the clinical utility of SDF testing by providing current evidence for its use in the management of the infertile male. This review begins by examining the underlying mechanisms and risk factors of SDF. It then describes the clinical tests associated with different types of DNA fragmentation, followed by the clinical indications for SDF testing. Finally, male infertility case scenarios with high SDF are presented along with expert recommendations on its management and an illustration of strengths, weaknesses, opportunities and threats (SwOT) of SDF testing.
