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      Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios

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          Abstract

          Sperm DNA fragmentation (SDF) has been generally acknowledged as a valuable tool for male fertility evaluation. While its detrimental implications on sperm function were extensively investigated, little is known about the actual indications for performing SDF analysis. This review delivers practice based recommendations on commonly encountered scenarios in the clinic. An illustrative description of the different SDF measurement techniques is presented. SDF testing is recommended in patients with clinical varicocele and borderline to normal semen parameters as it can better select varicocelectomy candidates. High SDF is also linked with recurrent spontaneous abortion (RSA) and can influence outcomes of different assisted reproductive techniques. Several studies have shown some benefit in using testicular sperm rather than ejaculated sperm in men with high SDF, oligozoospermia or recurrent in vitro fertilization (IVF) failure. Infertile men with evidence of exposure to pollutants can benefit from sperm DNA testing as it can help reinforce the importance of lifestyle modification (e.g., cessation of cigarette smoking, antioxidant therapy), predict fertility and monitor the patient’s response to intervention.

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          Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome.

          M Bungum, P Humaidan, A Axmon … (2007)
          The sperm chromatin structure assay (SCSA) has been suggested as a predictor of fertility in vivo as well as in vitro. The available data however, have been based on limited numbers of treatments. We aimed to define the clinical role of SCSA in assisted reproduction. A total of 998 cycles [387 intrauterine insemination (IUI), 388 IVF and 223 ICSI] from 637 couples were included. SCSA results were expressed as DNA fragmentation index (DFI) and high DNA stainable (HDS) cell fractions. Outcome parameters were biochemical pregnancy (BP), clinical pregnancy (CP) and delivery (D). For IUI, the odds ratios (ORs) for BP, CP and D were significantly lower for couples with DFI >30% as compared with those with DFI 30% group, the results of ICSI were significantly better than those of IVF. DFI can be used as an independent predictor of fertility in couples undergoing IUI. As a result, we propose that all infertile men should be tested with SCSA as a supplement to the standard semen analysis. When DFI exceeds 30%, ICSI should be the method of choice.
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            Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988-1989).

            Patrick Thonneau, Sophie Marchand, Anne Tallec … (1991)
            To estimate the prevalence and main causes of infertility, a multicentre survey was conducted over 1 year (July 1988-June 1989) in three regions of France. All the 1686 couples in these regions, who consulted a practitioner for primary or secondary infertility during this period, were included in the investigation. The prevalence rate of infertility was found to be 14.1%, indicating that one woman out of seven in France will consult a doctor for an infertility problem during her reproductive life. The main causes of female infertility were ovulation disorders (32%) and tubal damage (26%), and of male infertility oligo-terato-asthenozoospermia (21%), asthenozoospermia (17%), teratozoospermia (10%) and azoospermia (9%). Infertility was also found to be caused by disorders in both the male and female partners together; thus in 39% of cases both the man and woman presented with disorders. The woman alone was responsible for infertility in one-third of cases and the man alone in one-fifth. Unexplained infertility was found in 8% of the couples surveyed.
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              Sperm DNA fragmentation: mechanisms of origin, impact on reproductive outcome, and analysis.

              Denny Sakkas, Juan G Alvarez (2010)
              To review the mechanisms responsible for DNA fragmentation in human sperm, including those occurring during spermatogenesis and transport through the reproductive tract. The mechanisms examined include: apoptosis in the seminiferous tubule epithelium, defects in chromatin remodeling during the process of spermiogenesis, oxygen radical-induced DNA damage during sperm migration from the seminiferous tubules to the epididymis, the activation of sperm caspases and endonucleases, damage induced by chemotherapy and radiotherapy, and the effect of environmental toxicants. The different tests currently used for sperm DNA fragmentation analysis and the factors that determine the predictive value of sperm DNA fragmentation testing and their implications in the diagnosis and treatment of infertility are also discussed. Finally, we also scrutinize how the presence in the embryonic genome of DNA strand breaks or modifications of DNA nucleotides inherited from the paternal genome could impact the embryo and offspring. In particular we discuss how abnormal sperm could be dealt with by the oocyte and how sperm DNA abnormalities, which have not been satisfactorily repaired by the oocyte after fertilization, may interfere with normal embryo and fetal development. Sperm DNA can be modified through various mechanisms. The integrity of the paternal genome is therefore of paramount importance in the initiation and maintenance of a viable pregnancy both in a natural conception and in assisted reproduction. The need to diagnose sperm at a nuclear level is an area that needs further understanding so that we can improve treatment of the infertile couple. Copyright 2010 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Transl Androl Urol
                Journal ID (iso-abbrev): Transl Androl Urol
                Journal ID (publisher-id): TAU
                Title: Translational Andrology and Urology
                Publisher: AME Publishing Company
                ISSN (Electronic): 2223-4691
                Publication date (Print and electronic): December 2016
                Publication date (Print): December 2016
                Volume: 5
                Issue: 6
                Pages: 935-950
                Affiliations
                [1 ]American Center for Reproductive Medicine, Cleveland Clinic, Cleveland, OH, USA;
                [2 ]Department of Urology, Glickman Urological and kidney Institute, Cleveland Clinic, Cleveland, OH, USA;
                [3 ]ANDROFERT, Andrology and Human Reproduction Clinic, Referral Center for Male Reproduction, Campinas, SP, Brazil;
                [4 ]Department of Urology, Loma Linda University, Loma Linda, California, USA;
                [5 ]Department of Urology, University of Miami, Miami, Florida, USA;
                [6 ]Department of Urology, McGill University, Montreal, Canada
                Author notes
                Correspondence to: Dr. Ashok Agarwal. Professor and Director, American Center for Reproductive Medicine, Cleveland Clinic, Mail Code X-11, 10681 Carnegie Avenue, Cleveland, OH 44195, USA. Email: AGARWAA@ 123456ccf.org .
                Article
                Publisher ID: tau-05-06-935
                DOI: 10.21037/tau.2016.10.03
                PMC ID: 5182232
                PubMed ID: 28078226
                SO-VID: 2a76db6c-47d0-4fb3-80b6-06a5c0b302bf
                Copyright © 2016 Translational Andrology and Urology. All rights reserved.
                History
                Date received : 29 September 2016
                Date accepted : 14 October 2016
                Categories
                Subject: Guideline

                Keywords: sperm dna fragmentation (sdf),male infertility,varicocele,unexplained infertility,assisted reproductive technology (art)
                Data availability:
                Keywords: sperm dna fragmentation (sdf), male infertility, varicocele, unexplained infertility, assisted reproductive technology (art)

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