Future direction in sperm DNA fragmentation testing

tau.amegroups.com © Translational Andrology and Urology. All rights reserved. Dr. Rey, in his commentary (1), has provided us with a comprehensive summary of the practice recommendations proposed by Agarwal et al. (2) with additional discussion on the basic physiology of sperm DNA structure. The pros and cons of the eight available sperm DNA fragmentation (SDF) tests were listed by the author. Dr. Rey correctly pointed out that Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) test is relatively simple, sensitive, reliable and has very low interobserver variability. In fact, the standardization of the assay between laboratories has been established recently by a multicenter study. By using identical instruments and protocols between two laboratories at Cleveland, USA, and Basel, Switzerland, a high correlation in TUNEL results could be achieved when the same set of semen samples was independently analyzed (3). Although all SDF tests currently suffer from the common pitfall that the nature and type of DNA damage are unclear (4), numerous studies have illustrated the prognostic value of SDF tests irrespective of the testing method used (5). The evolving knowledge and continuous effort from researchers in refining SDF tests will certainly enhance the performance of these advanced sperm function tests in the near future. The evidence-based indications of SDF testing put forward by Agarwal et al. was supported by Dr. Rey. In fact, the indications proposed represent the first step in promoting the clinical application of SDF tests. The use of SDF tests should not be limited by the practice recommendations. Expanded indications should apply with an understanding of the principles of the assay. We would like to further illustrate this point in the following paragraphs. The use of SDF tests in better stratification of patients in varicocele treatment and assisted reproductive technology (ART) are discussed. Search for advanced diagnostic and assessment tests continues in view of a lack of reliable prognostic factors for varicocele repair. The decision to repair a varicocele with reference to professional society guidelines based on presence of clinical varicocele and abnormal conventional semen parameters does not predict treatment success (6). Recent evidence clearly supported the association between varicocele and SDF, and the negative implication of SDF on pregnancy outcomes is increasingly being unmasked (7). The effect of varicocelectomy in ameliorating SDF has also been demonstrated (8-10). Therefore, the potential role of SDF tests in identification of suitable surgery candidates is valid. It is suggested in the practice recommendations that SDF is recommended in patients with grade 2/3 varicocele with normal conventional semen parameters and in patients with grade 1 varicocele with borderline/ abnormal conventional semen parameters (2). The essence is to introduce the use of SDF tests in providing additional information in case of ambiguity based on clinical grading of varicocele and conventional semen parameters. We believe that the statement based on current best evidence is a relatively conservative one. With ever expanding evidence on the clinical use of SDF in clinical practice, we foresee the incorporation of SDF test results, together with other factors, as one of the essential predictors of postvaricocelectomy outcome in a prognostic model/nomogram. In patients with unexplained infertility and total motile sperm count of over 5 million, intrauterine insemination Editorial