Controversy and Consensus on the Management of Elevated Sperm DNA Fragmentation in Male Infertility: A Global Survey, Current Guidelines, and Expert Recommendations

Preamble:
The assessment of male infertility relies primarily on conventional semen analysis. However, 15% of infertile men have normal semen parameters, and hence the semen analysis may be insufficient to detect all causes of male infertility. New tests are proposed to assess the functional competence of spermatozoa, including sperm DNA fragmentation (SDF) testing, which has been included and highlighted as a promising biomarker in the Sixth Edition of
the World Health Organization (WHO) Laboratory Manual for the Examination and Processing of Human Semen. Sperm DNA integrity is an important factor that can have a direct bearing on male fertility potential and sperm DNA strand breaks have been negatively correlated with fertilization rates in couples suffering from unexplained infertility and poorer outcomes during assisted reproductive treatments. Approaches such as offering antioxidants, short ejaculatory abstinence, weight loss, and using testicular sperm for intracytoplasmic sperm injection (ICSI) are demonstrated to benefit infertile men with elevated SDF. (Contributor: Zhongwei H, MBBS, PhD)

Briefly what is our vision:
To provide expert recommendations on the management of infertile men with elevated SDF based on the integration of best practices from available evidence in the literature, trendsi in global practices and current recommendations from professional society guidelines. (Contributor: Zhongwei H, MBBS, PhD)

Why do we do what we do?
The evidence from literature remains divided on the routine clinical use of sperm DNA fragmentation during male infertility assessment. Importantly, many professional societies recommended lifestyle modifications and antioxidant use for men with purported high sperm DNA fragmentation. Physiologically, men continuously produce spermatozoa and spermatogenesis occur on average every 70 days, therefore it is prudent to consider lifestyle modifications and antioxidant use to improve SDF. Hence, this clinical survey was done to understand globally about the clinical practices of professionals who provide care for men with fertility issues and the clinical impact of detecting SDF. The results of this survey offer novel information that will integrate with professional society guidelines and published evidence to provide sound clinical practice recommendations. (Contributor: Zhongwei H, MBBS, PhD)

Capsule:
A Reproductive Endocrinologist’s Viewpoint:
This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. A total of 436 experts from 55 different countries submitted responses to the survey on their practices for infertile men with elevated SDF. The majority of the experts recommend lifestyle modifications and prescribe empiric antioxidants. Most respondents will refer men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF for ART after 6 months’ failure of conservative and empiric medical management. However, for most questions, heterogenous practices were demonstrated - for example, duration of antioxidant treatments, other sperm selection techniques, indications for varicocele repair and testicular sperm extraction. Hence, this demonstrates the scarcity of professional society guidelines in this regard and this paper attempts to highlight the relevant evidence and offers expert recommendations to guide clinicians on management of infertile men who are detected to have elevated SDF. [Contributor: Zhongwei Huang, MBBS, PhD (Oxon) MRCOG (UK) is a Consultant in the Division of Reproductive Endocrinology and Infertility, Department of Ob-Gyn, National University of Singapore, Singapore]

A Reproductive Urologist’s Viewpoint:
Most if not all of us practicing clinical andrologists have differing views on elevated sperm DNA fragmentation (SDF) in terms of interpretation with regards to its predictive value of male infertility as well as its treatment options. A lot of patients who seek medical attention with regards to male infertility often request for SDF to be evaluated in addition to the runof-the-mill semen analysis. However, are there scientifically proven treatments or lifestyle modifications that can truly lower elevated SDF and if so, would lowering elevated SDF result in successful conception?

Can elevated SDF be contributed by the presence of varicoceles and would varicocele repair lower the elevated SDF to improve the chances of successful conception should the rest of the semen analysis parameters appear not to be affected? Does elevated SDF then become an indication for varicocele repair? What about reduced ejaculatory abstinence of 12-24 hours before attempting conception? Is that a recommended practice, knowing that this can result in additional stress to the couple and result in psychogenic erectile dysfunction in men due to performance anxiety?

This article gives a good overview of a global survey, current guidelines and ends off with expert recommendations regarding the controversy and consensus on the management of elevated SDF in male infertility. [Contributor: Ronny Tan, MBBS, MRCSEd, M Med (Surgery), FAMS (Urology), Advanced Urology Associates, Singapore]