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While the latest European Society of Human Reproduction and Embryology (ESHRE) position report concluded that DNA damage negatively affects assisted reproduction outcomes, the Practice Committee of the American Society for Reproductive Medicine (ASRM) does not recommend the routine testing of DNA damage for in vitro<\/jats:italic> fertilization (IVF) or intracytoplasmic sperm injection (ICSI). Herein, our aim was to perform a systematic review and meta\u2010analysis of studies investigating whether sperm DNA damage affects clinical outcomes in IVF and ICSI, in order to contribute objectively to a consistent clinical recommendation. A comprehensive systematic search was conducted according to PRISMA guidelines from the earliest available online indexing year until March 2020, using the MEDLINE\u2010PubMed and EMBASE databases. We included studies analysing IVF and\/or ICSI treatments performed in infertile couples in which sperm DNA damage was well defined and assessed. Studies also had to include information about pregnancy, implantation or live birth rates as primary outcomes. The NHLBI\u2010NIH quality assessment tool was used to assess the quality of each study. Meta\u2010analyses were conducted using the Mantel\u2013Haenszel method with random\u2010effects models to evaluate the Risk Ratio (RR) between high\u2010DNA\u2010damage and control groups, taking into account the 95% confidence intervals. Heterogeneity among studies was evaluated using the I<\/jats:italic>2<\/jats:sup> statistic. We also conducted sensitivity analyses and post\u2010hoc<\/jats:italic> subgroup analyses according to different DNA fragmentation assessment techniques. We identified 78 articles that met our inclusion and quality criteria and were included in the qualitative analysis, representing a total of 25639 IVF\/ICSI cycles. Of these, 32 articles had sufficient data to be included in the meta\u2010analysis, comprising 12380 IVF\/ICSI cycles. Meta\u2010analysis revealed that, considering IVF and ICSI results together, implantation rate (RR\u00a0=\u00a00.74; 95% CI\u00a0=\u00a00.61\u20130.91; I<\/jats:italic>2<\/jats:sup>\u00a0=\u200969) and pregnancy rate (RR\u00a0=\u00a00.83; 0.73\u20130.94; I<\/jats:italic>2<\/jats:sup>\u00a0=\u200958) are negatively influenced by sperm DNA damage, although after adjustment for publication bias the relationship for pregnancy rate was no longer significant. The results showed a non\u2010significant but detrimental tendency (RR\u00a0=\u00a00.78; 0.58\u20131.06; I<\/jats:italic>2<\/jats:sup>\u00a0=\u200972) on live birth rate. Meta\u2010analysis also showed that IVF outcomes are negatively influenced by sperm DNA damage, with a statistically significant impact on implantation (RR\u00a0=\u00a00.68; 0.52\u20130.89; I<\/jats:italic>2<\/jats:sup>\u00a0=\u200950) and pregnancy rates (RR\u00a0=\u00a00.72; 0.55\u20130.95; I<\/jats:italic>2<\/jats:sup>\u00a0=\u200972), although the latter was no longer significant after correction for publication bias. While it did not quite meet our threshold for significance, a negative trend was also observed for live birth rate (RR\u00a0=\u00a00.48; 0.22\u20131.02; I<\/jats:italic>2<\/jats:sup>\u00a0=\u200979). In the case of ICSI, non\u2010significant trends were observed for implantation (RR\u00a0=\u00a00.79; 0.60\u20131.04; I<\/jats:italic>2<\/jats:sup>\u00a0=\u200972) or pregnancy rates (RR\u00a0=\u00a00.89; 0.78\u20131.02; I<\/jats:italic>2<\/jats:sup>\u00a0=\u200944), and live birth rate (RR\u00a0=\u00a00.92; 0.67\u20131.27; I<\/jats:italic>2<\/jats:sup>\u00a0=\u200970). The current review provides the largest evidence to date supporting a negative association between sperm DNA damage and conventional IVF treatments, significantly reducing implantation and pregnancy rates. The routine use of sperm DNA testing is therefore justified, since it may help improve the outcomes of IVF treatments and\/or allow a given couple to be advised on the most suitable treatment. Further well\u2010designed controlled studies on a larger number of patients are required to allow us to reach more precise conclusions, especially in the case of ICSI treatments.<\/jats:p>","DOI":"10.1111\/brv.12700","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T08:50:07Z","timestamp":1614588607000},"page":"1284-1300","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":143,"title":["Clinical implications of sperm DNA<\/scp> damage in IVF<\/scp> and ICSI<\/scp>: updated systematic review and meta\u2010analysis"],"prefix":"10.1111","volume":"96","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9101-2044","authenticated-orcid":false,"given":"Jordi","family":"Ribas\u2010Maynou","sequence":"first","affiliation":[{"name":"Biotechnology of Animal and Human Reproduction (TechnoSperm), Institute of Food and Agricultural Technology University of Girona Jaume Casadamont Building, Door E, 15 Pic de Peguera St Girona ES\u201017003 Spain"},{"name":"Unit of Cell Biology, Department of Biology, Faculty of Sciences University of Girona Sciences Building, 69 Maria Aur\u00e8lia Capmany Girona ES\u201017003 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Yeste","sequence":"additional","affiliation":[{"name":"Biotechnology of Animal and Human Reproduction (TechnoSperm), Institute of Food and Agricultural Technology University of Girona Jaume Casadamont Building, Door E, 15 Pic de Peguera St Girona ES\u201017003 Spain"},{"name":"Unit of Cell Biology, Department of Biology, Faculty of Sciences University of Girona Sciences Building, 69 Maria Aur\u00e8lia Capmany Girona ES\u201017003 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nerea","family":"Becerra\u2010Tom\u00e1s","sequence":"additional","affiliation":[{"name":"Universitat Rovira i Virgili, Departament de Bioqu\u00edmica i Biotecnologia Unitat de Nutrici\u00f3 St\/Sant Lloren\u00e7, 21 Reus ES\u201043201 Spain"},{"name":"Institut d'Investigaci\u00f3 Sanit\u00e0ria Pere Virgili (IISPV) Reus Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red Fisiopatolog\u00eda de la Obesidad y la Nutrici\u00f3n (CIBEROBN) Institute of Health Carlos III Madrid Spain"},{"name":"Department of Preventive Medicine and Public Health, School of Medicine University of Valencia Valencia ES\u201046010 Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenneth I.","family":"Aston","sequence":"additional","affiliation":[{"name":"Andrology and IVF Laboratory, Division of Urology, Department of Surgery University of Utah School of Medicine 675 Arapeen Drive Salt Lake City UT US\u201084108 U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma R.","family":"James","sequence":"additional","affiliation":[{"name":"Andrology and IVF Laboratory, Division of Urology, Department of Surgery University of Utah School of Medicine 675 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