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      A Strengths-Weaknesses-Opportunities-Threats (SWOT) analysis on the clinical utility of sperm DNA fragmentation testing in specific male infertility scenarios

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          Abstract

          Background

          Sperm DNA fragmentation (SDF) is recognized as a leading cause of male infertility because it can impair the paternal genome through distinct pathophysiological mechanisms. Current evidence supports SDF as a major factor in the pathophysiology of several conditions, including varicocele, unexplained infertility, assisted reproductive technology failure, and environmental lifestyle factors, although the mechanisms involved have not been fully described yet. Measurement of the levels of DNA fragmentation in semen provides valuable information on the integrity of paternal chromatin and may guide therapeutic strategies. A recently published clinical practice guideline (CPG) highlighted how to use the information provided by SDF testing in daily practice, which triggered a series of commentaries by leading infertility experts. These commentaries contained an abundance of information and conflicting views about the clinical utility of SDF testing, which underline the complex nature of SDF.

          Methods

          A search of papers published in response to the CPG entitled “Clinical utility of sperm DNA fragmentation testing: practice recommendations based on clinical scenarios” was performed within the Translational Andrology and Urology ( TAU) website ( http://tau.amegroups.com/). The start and end dates for the search were May 2017 and August 2017, respectively. Each commentary meeting our inclusion criteria was rated as “supportive without reservation”, “supportive with reservation”, “not supportive” or “neutral”. We recorded whether articles discussed either SDF characteristics as a laboratory test method or clinical scenarios, or both. Subsequently, we extracted the particulars from each commentary and utilized the ‘Strengths-Weaknesses-Opportunities-Threats’ (SWOT) analysis to understand the perceived advantages and drawbacks of SDF as a specialized sperm function method in clinical practice.

          Results

          Fifty-eight fertility experts from six continents and twenty-two countries contributed commentaries. Overall, participants (87.9%; n=51) were supportive of the recommendations provided by the CPG on the utility of SDF testing based on clinical scenarios. The majority of participants made explicit remarks about both the clinical scenarios and SDF assays’ characteristics. Among ‘not supportive’ and ‘supportive with reservation’ participants, 75% (n=30/40) and 77.5% (n=31/40) expressed concerns related to technical limitations of SDF testing methods and clinical utility of the test in one or more clinical scenarios discussed in the CPG, respectively. The SWOT analysis revealed that the CPG provides a reasonable evidence-based proposal for integration of SDF testing in the routine daily practice. It also uncovered gaps of knowledge and threats limiting the widespread application of SDF in everyday practice, thus allowing the identification of opportunities to further refine SDF testing and its clinical utility.

          Conclusions

          The understanding of the role of SDF in male infertility requires an in-depth analysis of the multifactorial pathophysiological processes and the theories involved. The SWOT analysis allowed an objective evaluation of CPG on the clinical utility of SDF testing based on clinical scenarios and its accompanying commentaries written by global experts in all possible angles. Implementation of SDF testing in the clinic may not only increase the outcome of ART but more importantly improve the health of both fathers to be and resulting offspring.

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          Most cited references228

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

          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 fragmentation: mechanisms of origin, impact on reproductive outcome, and analysis.

            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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              Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988-1989).

              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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                Author and article information

                Journal
                Transl Androl Urol
                Transl Androl Urol
                TAU
                Translational Andrology and Urology
                AME Publishing Company
                2223-4691
                September 2017
                September 2017
                : 6
                : Suppl 4
                : S734-S760
                Affiliations
                [1 ]ANDROFERT, Andrology and Human Reproduction Clinic, Referral Center for Male Reproduction , Campinas, SP, Brazil;
                [2 ]Division of Urology, Department of Surgery, Universtity of Campinas (UNICAMP), SP, Brazil;
                [3 ]Faculty of Health, Department of Clinical Medicine, Aarhus University , Aarhus, Denmark;
                [4 ]American Center for Reproductive Medicine, Cleveland Clinic , Cleveland, OH, USA;
                [5 ]Division of Urology, Department of Surgery, Kwong Wah Hospital, Hong Kong, China;
                [6 ]Department of Urology, Hamad Medical Corporation , Doha, Qatar
                Author notes

                Contributions: (I) Conception and design: SC Esteves; (II) Administrative support: None; (III) Provision of study materials or patients: None; (IV) Collection and assembly of data: SC Esteves; (V) Data analysis and interpretation: SC Esteves, CL Cho, A Majzoub, A Agarwal; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

                Correspondence to: Sandro C. Esteves. Director, ANDROFERT, Andrology and Human Reproduction Clinic, Referral Center for Male Reproduction, Campinas, SP, Brazil. Email: s.esteves@ 123456androfert.com.br .
                Article
                tau-06-S4-S734
                10.21037/tau.2017.08.20
                5643602
                68d9811a-81f8-47ce-a140-be45026009a3
                2017 Translational Andrology and Urology. All rights reserved.
                History
                : 22 August 2017
                : 24 August 2017
                Categories
                Original Article

                assisted reproductive technology,male infertility,sperm dna fragmentation (sdf),semen analysis,varicocele,unexplained infertility,strengths-weaknesses-opportunities-threats analysis (swot analysis)

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