Advertisement

Sperm DNA fragmentation index as a promising predictive tool for male infertility diagnosis and treatment management – meta-analyses

  • Daniele Santi
    Affiliations
    Department of BiomedicalMetabolic and Neural SciencesUniversity of Modena and Reggio EmiliaModenaItaly

    Unit of EndocrinologyDepartment of Medical SpecialtiesAzienda Ospedaliero-Universitaria of ModenaModenaItaly
    Search for articles by this author
  • Giorgia Spaggiari
    Affiliations
    Department of BiomedicalMetabolic and Neural SciencesUniversity of Modena and Reggio EmiliaModenaItaly

    Unit of EndocrinologyDepartment of Medical SpecialtiesAzienda Ospedaliero-Universitaria of ModenaModenaItaly
    Search for articles by this author
  • Manuela Simoni
    Affiliations
    Department of BiomedicalMetabolic and Neural SciencesUniversity of Modena and Reggio EmiliaModenaItaly

    Unit of EndocrinologyDepartment of Medical SpecialtiesAzienda Ospedaliero-Universitaria of ModenaModenaItaly
    Search for articles by this author

      Abstract

      Conventional semen analyses have limitations in male infertility diagnosis and prognosis. Assessment of sperm DNA fragmentation (sDF) has been proposed to discriminate fertile from infertile men and predict FSH treatment response in infertile men, although a comprehensive evaluation of this is not available. The aims of these meta-analyses were to assess the power of sDF in male infertility diagnosis and its role in predicting FSH therapy response in infertile men. Two literature searches were conducted in MEDLINE (PubMed), Embase, the Cochrane Library, Scopus and UpToDate. First, interventional/observational clinical trials comparing fertile to infertile/subfertile men were included. Second, interventional/observational clinical trials evaluating FSH-treated infertile men were assessed. sDF levels were significantly higher in infertile men considering 28 studies (P < 0.001), independently of the sDF method applied. Receiver operator characteristics curves identified an sDF threshold of 20%, with sensitivity of 79% and specificity of 86%. Six studies showed significant sDF improvement of 4.24% (95% confidence interval: 0.24–8.25%) after 3 months of FSH treatment. These meta-analyses demonstrate the sDF relevance in male infertility, suggesting a higher accuracy in detecting sperm function than conventional semen parameters. Although larger prospective trials are needed, sDF represents a promising tool for clinical and research practice.

      Keywords

      To read this article in full you will need to make a payment

      References

        • Acosta A.A.
        • Oehninger S.
        • Ertunc H.
        • Philput C.
        Possible role of pure human follicle-stimulating hormone in the treatment of severe male-factor infertility by assisted reproduction: Preliminary report.
        Fertility and sterility. 1991; 55: 1150-1156
        • Alkhayal A.
        • San Gabriel M.
        • Zeidan K.
        • Alrabeeah K.
        • Noel D.
        • Mcgraw R.
        • Bissonnette F.
        • Kadoch I.J.
        • Zini A.
        Sperm DNA and chromatin integrity in semen samples used for intrauterine insemination.
        Journal of assisted reproduction and genetics. 2013; 30: 1519-1524
        • Atig F.
        • Kerkeni A.
        • Saad A.
        • Ajina M.
        Effects of reduced seminal enzymatic antioxidants on sperm DNA fragmentation and semen quality of tunisian infertile men.
        Journal of assisted reproduction and genetics. 2017; 34: 373-381
        • Attia A.M.
        • Abou-Setta A.M.
        • Al-Inany H.G.
        Gonadotrophins for idiopathic male factor subfertility.
        The Cochrane database of systematic reviews. 2013; CD005071
        • Attia A.M.
        • Abou-Setta A.M.
        • Al-Inany H.G.
        Gonadotrophins for idiopathic male factor subfertility.
        The Cochrane database of systematic reviews. 2013; 8CD005071
        • Avendano C.
        • Franchi A.
        • Taylor S.
        • Morshedi M.
        • Bocca S.
        • Oehninger S.
        Fragmentation of DNA in morphologically normal human spermatozoa.
        Fertility and sterility. 2009; 91: 1077-1084
        • Banks S.
        • King S.A.
        • Irvine D.S.
        • Saunders P.T.
        Impact of a mild scrotal heat stress on DNA integrity in murine spermatozoa.
        Reproduction (Cambridge, England). 2005; 129: 505-514
        • Bareh G.M.
        • Jacoby E.
        • Binkley P.
        • Chang T.C.
        • Schenken R.S.
        • Robinson R.D.
        Sperm deoxyribonucleic acid fragmentation assessment in normozoospermic male partners of couples with unexplained recurrent pregnancy loss: A prospective study.
        Fertility and sterility. 2016; 105 (e1): 329-336
        • Ben-Rafael Z.
        • Farhi J.
        • Feldberg D.
        • Bartoov B.
        • Kovo M.
        • Eltes F.
        • Ashkenazi J.
        Follicle-stimulating hormone treatment for men with idiopathic oligoteratoasthenozoospermia before in vitro fertilization: The impact on sperm microstructure and fertilization potential.
        Fertility and sterility. 2000; 73: 24-30
        • Binsaleh S.
        • Al-Qahtani R.
        • Madbouly K.
        • Isa A.M.
        • Abu-Rafea B.
        Evaluation of sperm DNA damage in men from infertile saudi couples.
        The Journal of reproductive medicine. 2015; 60: 135-140
        • Bjorndahl L.
        What is normal semen quality? On the use and abuse of reference limits for the interpretation of semen analysis results.
        Human fertility (Cambridge, England). 2011; 14: 179-186
        • Bjorndahl L.
        • Barratt C.L.
        • Mortimer D.
        • Jouannet P.
        ‘How to count sperm properly’: Checklist for acceptability of studies based on human semen analysis.
        Human reproduction (Oxford, England). 2016; 31: 227-232
        • Borini A.
        • Tarozzi N.
        • Bizzaro D.
        • Bonu M.A.
        • Fava L.
        • Flamigni C.
        • Coticchio G.
        Sperm DNA fragmentation: Paternal effect on early post-implantation embryo development in art.
        Human reproduction (Oxford, England). 2006; 21: 2876-2881
        • Brahem S.
        • Mehdi M.
        • Elghezal H.
        • Saad A.
        Detection of DNA fragmentation and meiotic segregation in human with isolated teratozoospermia.
        Journal of assisted reproduction and genetics. 2011; 28: 41-48
        • Brahem S.
        • Mehdi M.
        • Elghezal H.
        • Saad A.
        The effects of male ageing on semen quality, sperm DNA fragmentation and chromosomal abnormalities in an infertile population.
        Journal of assisted reproduction and genetics. 2011; 28: 425-432
        • Bungum M.
        • Humaidan P.
        • Axmon A.
        • Spano M.
        • Bungum L.
        • Erenpreiss J.
        • Giwercman A.
        Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome.
        Human reproduction (Oxford, England). 2007; 22: 174-179
        • Burrello N.
        • Arcidiacono G.
        • Vicari E.
        • Asero P.
        • Di Benedetto D.
        • De Palma A.
        • Romeo R.
        • D'agata R.
        • Calogero A.E.
        Morphologically normal spermatozoa of patients with secretory oligo-astheno-teratozoospermia have an increased aneuploidy rate.
        Human reproduction (Oxford, England). 2004; 19: 2298-2302
        • Carlini T.
        • Paoli D.
        • Pelloni M.
        • Faja F.
        • Dal Lago A.
        • Lombardo F.
        • Lenzi A.
        • Gandini L.
        Sperm DNA fragmentation in italian couples with recurrent pregnancy loss.
        Reproductive biomedicine online. 2017; 34: 58-65
        • Caroppo E.
        • Niederberger C.
        • Vizziello G.M.
        • D′amato G.
        Recombinant human follicle-stimulating hormone as a pretreatment for idiopathic oligoasthenoteratozoospermic patients undergoing intracytoplasmic sperm injection.
        Fertility and sterility. 2003; 80: 1398-1403
        • Carrell D.T.
        • De Jonge C.J.
        The troubling state of the semen analysis.
        Andrology. 2016; 4: 761-762
        • Casamonti E.
        • Vinci S.
        • Serra E.
        • Fino M.G.
        • Brilli S.
        • Lotti F.
        • Maggi M.
        • Coccia M.E.
        • Forti G.
        • Krausz C.
        Short-term fsh treatment and sperm maturation: A prospective study in idiopathic infertile men.
        Andrology. 2017; 5: 414-422
        • Chenlo P.H.
        • Curi S.M.
        • Pugliese M.N.
        • Ariagno J.I.
        • Sardi-Segovia M.
        • Furlan M.J.
        • Repetto H.E.
        • Zeitler E.
        • Cohen M.
        • Mendeluk G.R.
        Fragmentation of sperm DNA using the tunel method.
        Actas urologicas espanolas. 2014; 38: 608-612
        • Colacurci N.
        • Monti M.G.
        • Fornaro F.
        • Izzo G.
        • Izzo P.
        • Trotta C.
        • Mele D.
        • De Franciscis P.
        Recombinant human fsh reduces sperm DNA fragmentation in men with idiopathic oligoasthenoteratozoospermia.
        Journal of andrology. 2012; 33: 588-593
        • Cooper T.G.
        • Noonan E.
        • Von Eckardstein S.
        • Auger J.
        • Baker H.W.
        • Behre H.M.
        • Haugen T.B.
        • Kruger T.
        • Wang C.
        • Mbizvo M.T.
        • Vogelsong K.M.
        World health organization reference values for human semen characteristics.
        Human reproduction update. 2010; 16: 231-245
        • De Paula T.S.
        • Bertolla R.P.
        • Spaine D.M.
        • Cunha M.A.
        • Schor N.
        • Cedenho A.P.
        Effect of cryopreservation on sperm apoptotic deoxyribonucleic acid fragmentation in patients with oligozoospermia.
        Fertility and sterility. 2006; 86: 597-600
        • Ding X.
        • Zhang J.
        [the association study between eppin gene polymorphisms and idiopathic male infertility].
        Zhonghua yu fang yi xue za zhi [Chinese journal of preventive medicine]. 2014; 48: 1072-1077
        • Dorostghoal M.
        • Kazeminejad S.R.
        • Shahbazian N.
        • Pourmehdi M.
        • Jabbari A.
        Oxidative stress status and sperm DNA fragmentation in fertile and infertile men.
        Andrologia. 2017; 49
        • Efesoy O.
        • Cayan S.
        • Akbay E.
        The efficacy of recombinant human follicle-stimulating hormone in the treatment of various types of male-factor infertility at a single university hospital.
        Journal of andrology. 2009; 30: 679-684
        • Evenson D.
        • Wixon R.
        Meta-analysis of sperm DNA fragmentation using the sperm chromatin structure assay.
        Reproductive biomedicine online. 2006; 12: 466-472
        • Evgeni E.
        • Lymberopoulos G.
        • Gazouli M.
        • Asimakopoulos B.
        Conventional semen parameters and DNA fragmentation in relation to fertility status in a greek population.
        European journal of obstetrics, gynecology, reproductive biology. 2015; 188: 17-23
        • Evgeni E.
        • Lymberopoulos G.
        • Touloupidis S.
        • Asimakopoulos B.
        Sperm nuclear DNA fragmentation and its association with semen quality in greek men.
        Andrologia. 2015; 47: 1166-1174
        • Fernandez J.L.
        • Muriel L.
        • Rivero M.T.
        • Goyanes V.
        • Vazquez R.
        • Alvarez J.G.
        The sperm chromatin dispersion test: A simple method for the determination of sperm DNA fragmentation.
        Journal of andrology. 2003; 24: 59-66
        • Filimberti E.
        • Degl'innocenti S.
        • Borsotti M.
        • Quercioli M.
        • Piomboni P.
        • Natali I.
        • Fino M.G.
        • Caglieresi C.
        • Criscuoli L.
        • Gandini L.
        • Biggeri A.
        • Maggi M.
        • Baldi E.
        High variability in results of semen analysis in andrology laboratories in tuscany (italy): The experience of an external quality control (eqc) programme.
        Andrology. 2013; 1: 401-407
        • Foresta C.
        • Bettella A.
        • Garolla A.
        • Ambrosini G.
        • Ferlin A.
        Treatment of male idiopathic infertility with recombinant human follicle-stimulating hormone: A prospective, controlled, randomized clinical study.
        Fertility and sterility. 2005; 84: 654-661
        • Foresta C.
        • Bettella A.
        • Merico M.
        • Garolla A.
        • Ferlin A.
        • Rossato M.
        Use of recombinant human follicle-stimulating hormone in the treatment of male factor infertility.
        Fertility and sterility. 2002; 77: 238-244
        • Garcia-Peiro A.
        • Martinez-Heredia J.
        • Oliver-Bonet M.
        • Abad C.
        • Amengual M.J.
        • Navarro J.
        • Jones C.
        • Coward K.
        • Gosalvez J.
        • Benet J.
        Protamine 1 to protamine 2 ratio correlates with dynamic aspects of DNA fragmentation in human sperm.
        Fertility and sterility. 2011; 95: 105-109
        • Garolla A.
        • Cosci I.
        • Bertoldo A.
        • Sartini B.
        • Boudjema E.
        • Foresta C.
        DNA double strand breaks in human spermatozoa can be predictive for assisted reproductive outcome.
        Reproductive biomedicine online. 2015; 31: 100-107
        • Garolla A.
        • Ghezzi M.
        • Cosci I.
        • Sartini B.
        • Bottacin A.
        • Engl B.
        • Di Nisio A.
        • Foresta C.
        Fsh treatment in infertile males candidate to assisted reproduction improved sperm DNA fragmentation and pregnancy rate.
        Endocrine. 2017; 56: 416-425
        • Garolla A.
        • Selice R.
        • Engl B.
        • Bertoldo A.
        • Menegazzo M.
        • Finos L.
        • Lenzi A.
        • Foresta C.
        Spermatid count as a predictor of response to fsh therapy.
        Reproductive biomedicine online. 2014; 29: 102-112
        • Gorczyca W.
        • Traganos F.
        • Jesionowska H.
        • Darzynkiewicz Z.
        Presence of DNA strand breaks and increased sensitivity of DNA in situ to denaturation in abnormal human sperm cells: Analogy to apoptosis of somatic cells.
        Experimental cell research. 1993; 207: 202-205
        • Guzick D.S.
        • Overstreet J.W.
        • Factor-Litvak P.
        • Brazil C.K.
        • Nakajima S.T.
        • Coutifaris C.
        • Carson S.A.
        • Cisneros P.
        • Steinkampf M.P.
        • Hill J.A.
        • Xu D.
        • Vogel D.L.
        Sperm morphology, motility, and concentration in fertile and infertile men.
        The New England journal of medicine. 2001; 345: 1388-1393
        • Guzick D.S.
        • Sullivan M.W.
        • Adamson G.D.
        • Cedars M.I.
        • Falk R.J.
        • Peterson E.P.
        • Steinkampf M.P.
        Efficacy of treatment for unexplained infertility.
        Fertility and sterility. 1998; 70: 207-213
        • Hoeijmakers J.H.
        DNA damage, ageing, and cancer.
        The New England journal of medicine. 2009; 361: 1475-1485
        • Host E.
        • Lindenberg S.
        • Smidt-Jensen S.
        DNA strand breaks in human spermatozoa: Correlation with fertilization in vitro in oligozoospermic men and in men with unexplained infertility.
        Acta obstetricia et gynecologica Scandinavica. 2000; 79: 189-193
        • Jurewicz J.
        • Radwan M.
        • Sobala W.
        • Radwan P.
        • Bochenek M.
        • Hanke W.
        Dietary patterns and their relationship with semen quality.
        American journal of men's health. 2016;
        • Kamischke A.
        • Behre H.M.
        • Bergmann M.
        • Simoni M.
        • Schafer T.
        • Nieschlag E.
        Recombinant human follicle stimulating hormone for treatment of male idiopathic infertility: A randomized, double-blind, placebo-controlled, clinical trial.
        Human reproduction (Oxford, England). 1998; 13: 596-603
        • Kefer J.C.
        • Agarwal A.
        • Sabanegh E.
        Role of antioxidants in the treatment of male infertility.
        International journal of urology: official journal of the Japanese Urological Association. 2009; 16: 449-457
        • Khalili M.A.
        • Aghaie-Maybodi F.
        • Anvari M.
        • Talebi A.R.
        Sperm nuclear DNA in ejaculates of fertile and infertile men: Correlation with semen parameters.
        Urology journal. 2006; 3: 154-159
        • Larson K.L.
        • Dejonge C.J.
        • Barnes A.M.
        • Jost L.K.
        • Evenson D.P.
        Sperm chromatin structure assay parameters as predictors of failed pregnancy following assisted reproductive techniques.
        Human reproduction (Oxford, England). 2000; 15: 1717-1722
        • Lewis S.E.
        • Agbaje I.
        • Alvarez J.
        Sperm DNA tests as useful adjuncts to semen analysis.
        Systems biology in reproductive medicine. 2008; 54: 111-125
        • Li Z.
        • Wang L.
        • Cai J.
        • Huang H.
        Correlation of sperm DNA damage with ivf and icsi outcomes: A systematic review and meta-analysis.
        Journal of assisted reproduction and genetics. 2006; 23: 367-376
        • Liu J.
        • Zhu P.
        • Wang W.T.
        • Li N.
        • Liu X.
        • Shen X.F.
        • Wang Y.W.
        • Li Y.
        Tat-peroxiredoxin 2 fusion protein supplementation improves sperm motility and DNA integrity in sperm samples from asthenozoospermic men.
        The Journal of urology. 2016; 195: 706-712
        • Mac L.J.
        The male factor in fertility and infertility; an analysis of ejaculate volume in 800 fertile men and in 600 men in infertile marriage.
        Fertility and sterility. 1950; 1: 347-361
        • Malic Voncina S.
        • Golob B.
        • Ihan A.
        • Kopitar A.N.
        • Kolbezen M.
        • Zorn B.
        Sperm DNA fragmentation and mitochondrial membrane potential combined are better for predicting natural conception than standard sperm parameters.
        Fertility and sterility. 2016; 105 (e1): 637-644
        • Manente L.
        • Pecoraro S.
        • Picillo E.
        • Gargiulo U.
        • Gargiulo P.
        • De Luca A.
        • Politano L.
        Molecular evidence of apoptotic pathway activation in semen samples with high DNA fragmentation.
        In vivo (Athens, Greece). 2015; 29: 289-294
        • Mangiarini A.
        • Paffoni A.
        • Restelli L.
        • Ferrari S.
        • Guarneri C.
        • Ragni G.
        • Somigliana E.
        Specific sperm defects are differentially correlated with DNA fragmentation in both normozoospermic and teratozoospermic subjects.
        Andrology. 2013; 1: 838-844
        • Mcpherson S.
        • Longo F.J.
        Chromatin structure-function alterations during mammalian spermatogenesis: DNA nicking and repair in elongating spermatids.
        European journal of histochemistry: EJH. 1993; 37: 109-128
        • Mehdi M.
        • Khantouche L.
        • Ajina M.
        • Saad A.
        Detection of DNA fragmentation in human spermatozoa: Correlation with semen parameters.
        Andrologia. 2009; 41: 383-386
        • Moustafa M.H.
        • Sharma R.K.
        • Thornton J.
        • Mascha E.
        • Abdel-Hafez M.A.
        • Thomas Jr., A.J.
        • Agarwal A.
        Relationship between ros production, apoptosis and DNA denaturation in spermatozoa from patients examined for infertility.
        Human reproduction (Oxford, England). 2004; 19: 129-138
        • Muratori M.
        • Marchiani S.
        • Tamburrino L.
        • Cambi M.
        • Lotti F.
        • Natali I.
        • Filimberti E.
        • Noci I.
        • Forti G.
        • Maggi M.
        • Baldi E.
        DNA fragmentation in brighter sperm predicts male fertility independently from age and semen parameters.
        Fertility and sterility. 2015; 104 (e4): 582-590
        • Ni K.
        • Steger K.
        • Yang H.
        • Wang H.
        • Hu K.
        • Zhang T.
        • Chen B.
        A comprehensive investigation of sperm DNA damage and oxidative stress injury in infertile patients with subclinical, normozoospermic, and astheno/oligozoospermic clinical varicocoele.
        Andrology. 2016; 4: 816-824
        • Nicopoullos J.D.
        • Gilling-Smith C.
        • Almeida P.A.
        • Homa S.
        • Norman-Taylor J.Q.
        • Ramsay J.W.
        Sperm DNA fragmentation in subfertile men: The effect on the outcome of intracytoplasmic sperm injection and correlation with sperm variables.
        BJU international. 2008; 101: 1553-1560
        • O′flaherty C.
        • Vaisheva F.
        • Hales B.F.
        • Chan P.
        • Robaire B.
        Characterization of sperm chromatin quality in testicular cancer and hodgkin's lymphoma patients prior to chemotherapy.
        Human reproduction (Oxford, England). 2008; 23: 1044-1052
        • Ollero M.
        • Gil-Guzman E.
        • Lopez M.C.
        • Sharma R.K.
        • Agarwal A.
        • Larson K.
        • Evenson D.
        • Thomas Jr., A.J.
        • Alvarez J.G.
        Characterization of subsets of human spermatozoa at different stages of maturation: Implications in the diagnosis and treatment of male infertility.
        Human reproduction (Oxford, England). 2001; 16: 1912-1921
        • Omran H.M.
        • Bakhiet M.
        • Dashti M.G.
        DNA integrity is a critical molecular indicator for the assessment of male infertility.
        Molecular medicine reports. 2013; 7: 1631-1635
        • Palomba S.
        • Falbo A.
        • Espinola S.
        • Rocca M.
        • Capasso S.
        • Cappiello F.
        • Zullo F.
        Effects of highly purified follicle-stimulating hormone on sperm DNA damage in men with male idiopathic subfertility: A pilot study.
        Journal of endocrinological investigation. 2011; 34: 747-752
        • Paradisi R.
        • Busacchi P.
        • Seracchioli R.
        • Porcu E.
        • Venturoli S.
        Effects of high doses of recombinant human follicle-stimulating hormone in the treatment of male factor infertility: Results of a pilot study.
        Fertility and sterility. 2006; 86: 728-731
        • Paradisi R.
        • Natali F.
        • Fabbri R.
        • Battaglia C.
        • Seracchioli R.
        • Venturoli S.
        Evidence for a stimulatory role of high doses of recombinant human follicle-stimulating hormone in the treatment of male-factor infertility.
        Andrologia. 2014; 46: 1067-1072
        • Perrin A.
        • Basinko A.
        • Douet-Guilbert N.
        • Gueganic N.
        • Le Bris M.J.
        • Amice V.
        • De Braekeleer M.
        • Morel F.
        Aneuploidy and DNA fragmentation in sperm of carriers of a constitutional chromosomal abnormality.
        Cytogenetic and genome research. 2011; 133: 100-106
        • Plastira K.
        • Msaouel P.
        • Angelopoulou R.
        • Zanioti K.
        • Plastiras A.
        • Pothos A.
        • Bolaris S.
        • Paparisteidis N.
        • Mantas D.
        The effects of age on DNA fragmentation, chromatin packaging and conventional semen parameters in spermatozoa of oligoasthenoteratozoospermic patients.
        Journal of assisted reproduction and genetics. 2007; 24: 437-443
        • Punjabi U.
        • Wyns C.
        • Mahmoud A.
        • Vernelen K.
        • China B.
        • Verheyen G.
        Fifteen years of belgian experience with external quality assessment of semen analysis.
        Andrology. 2016; 4: 1084-1093
        • Ramos L.
        • De Boer P.
        • Meuleman E.J.
        • Braat D.D.
        • Wetzels A.M.
        Chromatin condensation and DNA damage of human epididymal spermatozoa in obstructive azoospermia.
        Reproductive biomedicine online. 2004; 8: 392-397
        • Ramzan M.H.
        • Ramzan M.
        • Khan M.M.
        • Ramzan F.
        • Wahab F.
        • Khan M.A.
        • Jillani M.
        • Shah M.
        Human semen quality and sperm DNA damage assessed by comet assay in clinical groups.
        Turkish journal of medical sciences. 2015; 45: 729-737
        • Rathke C.
        • Baarends W.M.
        • Awe S.
        • Renkawitz-Pohl R.
        Chromatin dynamics during spermiogenesis.
        Biochimica et biophysica acta. 2014; 1839: 155-168
        • Robinson L.
        • Gallos I.D.
        • Conner S.J.
        • Rajkhowa M.
        • Miller D.
        • Lewis S.
        • Kirkman-Brown J.
        • Coomarasamy A.
        The effect of sperm DNA fragmentation on miscarriage rates: A systematic review and meta-analysis.
        Human reproduction (Oxford, England). 2012; 27: 2908-2917
        • Rubes J.
        • Selevan S.G.
        • Sram R.J.
        • Evenson D.P.
        • Perreault S.D.
        Gstm1 genotype influences the susceptibility of men to sperm DNA damage associated with exposure to air pollution.
        Mutation research. 2007; 625: 20-28
        • Ruvolo G.
        • Roccheri M.C.
        • Brucculeri A.M.
        • Longobardi S.
        • Cittadini E.
        • Bosco L.
        Lower sperm DNA fragmentation after r-fsh administration in functional hypogonadotrophic hypogonadism.
        Journal of assisted reproduction and genetics. 2013; 30: 497-503
        • Sakkas D.
        • Alvarez J.G.
        Sperm DNA fragmentation: Mechanisms of origin, impact on reproductive outcome, and analysis.
        Fertility and sterility. 2010; 93: 1027-1036
        • Sakkas D.
        • Moffatt O.
        • Manicardi G.C.
        • Mariethoz E.
        • Tarozzi N.
        • Bizzaro D.
        Nature of DNA damage in ejaculated human spermatozoa and the possible involvement of apoptosis.
        Biology of reproduction. 2002; 66: 1061-1067
        • Saleh R.A.
        • Agarwal A.
        • Nada E.A.
        • El-Tonsy M.H.
        • Sharma R.K.
        • Meyer A.
        • Nelson D.R.
        • Thomas A.J.
        Negative effects of increased sperm DNA damage in relation to seminal oxidative stress in men with idiopathic and male factor infertility.
        Fertility and sterility. 2003; 79 Suppl 3: 1597-1605
        • Saleh R.A.
        • Agarwal A.
        • Nelson D.R.
        • Nada E.A.
        • El-Tonsy M.H.
        • Alvarez J.G.
        • Thomas Jr., A.J.
        • Sharma R.K.
        Increased sperm nuclear DNA damage in normozoospermic infertile men: A prospective study.
        Fertility and sterility. 2002; 78: 313-318
        • Santi D.
        • Granata A.R.
        • Simoni M.
        Fsh treatment of male idiopathic infertility improves pregnancy rate: A meta-analysis.
        Endocrine connections. 2015; 4: R46-R58
        • Santi D.
        • Vezzani S.
        • Granata A.R.
        • Roli L.
        • De Santis M.C.
        • Ongaro C.
        • Donati F.
        • Baraldi E.
        • Trenti T.
        • Setti M.
        • Simoni M.
        Sperm quality and environment: A retrospective, cohort study in a northern province of italy.
        Environmental research. 2016; 150: 144-153
        • Seli E.
        • Gardner D.K.
        • Schoolcraft W.B.
        • Moffatt O.
        • Sakkas D.
        Extent of nuclear DNA damage in ejaculated spermatozoa impacts on blastocyst development after in vitro fertilization.
        Fertility and sterility. 2004; 82: 378-383
        • Selice R.
        • Garolla A.
        • Pengo M.
        • Caretta N.
        • Ferlin A.
        • Foresta C.
        The response to fsh treatment in oligozoospermic men depends on fsh receptor gene polymorphisms.
        International journal of andrology. 2011; 34: 306-312
        • Sergerie M.
        • Laforest G.
        • Bujan L.
        • Bissonnette F.
        • Bleau G.
        Sperm DNA fragmentation: Threshold value in male fertility.
        Human reproduction (Oxford, England). 2005; 20: 3446-3451
        • Shamsi M.B.
        • Imam S.N.
        • Dada R.
        Sperm DNA integrity assays: Diagnostic and prognostic challenges and implications in management of infertility.
        Journal of assisted reproduction and genetics. 2011; 28: 1073-1085
        • Sharma R.
        • Ahmad G.
        • Esteves S.C.
        • Agarwal A.
        Terminal deoxynucleotidyl transferase dutp nick end labelling (tunel) assay using bench top flow cytometer for evaluation of sperm DNA fragmentation in fertility laboratories: Protocol, reference values, and quality control.
        Journal of assisted reproduction and genetics. 2016; 33: 291-300
        • Sharma R.K.
        • Sabanegh E.
        • Mahfouz R.
        • Gupta S.
        • Thiyagarajan A.
        • Agarwal A.
        Tunel as a test for sperm DNA damage in the evaluation of male infertility.
        Urology. 2010; 76: 1380-1386
        • Shoukir Y.
        • Chardonnens D.
        • Campana A.
        • Sakkas D.
        Blastocyst development from supernumerary embryos after intracytoplasmic sperm injection: A paternal influence?.
        Human reproduction (Oxford, England). 1998; 13: 1632-1637
        • Simoni M.
        • Santi D.
        • Negri L.
        • Hoffmann I.
        • Muratori M.
        • Baldi E.
        • Cambi M.
        • Marcou M.
        • Greither T.
        • Baraldi E.
        • Tagliavini S.
        • Carra D.
        • Lombardo F.
        • Gandini L.
        • Pallotti F.
        • Krausz C.
        • Rastrelli G.
        • Ferlin A.
        • Menegazzo M.
        • Pignatti E.
        • Linari F.
        • Marino M.
        • Benaglia R.
        • Levi-Setti P.E.
        • Behre H.M.
        Treatment with human, recombinant fsh improves sperm DNA fragmentation in idiopathic infertile men depending on the fsh receptor polymorphism p.N680s: A pharmacogenetic study.
        Human reproduction (Oxford, England). 2016; 31: 1960-1969
        • Singh N.P.
        • Danner D.B.
        • Tice R.R.
        • Mccoy M.T.
        • Collins G.D.
        • Schneider E.L.
        Abundant alkali-sensitive sites in DNA of human and mouse sperm.
        Experimental cell research. 1989; 184: 461-470
        • Spano M.
        • Bonde J.P.
        • Hjollund H.I.
        • Kolstad H.A.
        • Cordelli E.
        • Leter G.
        Sperm chromatin damage impairs human fertility. The danish first pregnancy planner study team.
        Fertility and sterility. 2000; 73: 43-50
        • Van Der Steeg J.W.
        • Steures P.
        • Eijkemans M.J.
        • Jd F.H.
        • Hompes P.G.
        • Kremer J.A.
        • Van Der Leeuw-Harmsen L.
        • Bossuyt P.M.
        • Repping S.
        • Silber S.J.
        • Mol B.W.
        • Van Der Veen F.
        Role of semen analysis in subfertile couples.
        Fertility and sterility. 2011; 95: 1013-1019
        • Van Weert J.M.
        • Repping S.
        • Van Der Steeg J.W.
        • Steures P.
        • Van Der Veen F.
        • Mol B.W.
        A prediction model for ongoing pregnancy after in vitro fertilization in couples with male subfertility.
        The Journal of reproductive medicine. 2008; 53: 250-256
        • Varghese A.C.
        • Bragais F.M.
        • Mukhopadhyay D.
        • Kundu S.
        • Pal M.
        • Bhattacharyya A.K.
        • Agarwal A.
        Human sperm DNA integrity in normal and abnormal semen samples and its correlation with sperm characteristics.
        Andrologia. 2009; 41: 207-215
        • Venkatesh S.
        • Singh A.
        • Shamsi M.B.
        • Thilagavathi J.
        • Kumar R.
        • Mitra D.K.
        • Dada R.
        Clinical significance of sperm DNA damage threshold value in the assessment of male infertility.
        Reproductive sciences (Thousand Oaks, Calif.). 2011; 18: 1005-1013
        • Wdowiak A.
        • Raczkiewicz D.
        • Stasiak M.
        • Bojar I.
        Levels of fsh, lh and testosterone, and sperm DNA fragmentation.
        Neuro endocrinology letters. 2014; 35: 73-79
        • Who W.H.O.
        Who laboratory manual for the examination and processing of human semen.
        5th ed. 2010
        • Winkle T.
        • Rosenbusch B.
        • Gagsteiger F.
        • Paiss T.
        • Zoller N.
        The correlation between male age, sperm quality and sperm DNA fragmentation in 320 men attending a fertility centre.
        Journal of assisted reproduction and genetics. 2009; 26: 41-46
        • Wiweko B.
        • Utami P.
        Predictive value of sperm deoxyribonucleic acid (DNA) fragmentation index in male infertility.
        Basic and clinical andrology. 2017; 27: 1
        • Zalata A.
        • El-Samanoudy A.Z.
        • Shaalan D.
        • El-Baiomy Y.
        • Mostafa T.
        In vitro effect of cell phone radiation on motility, DNA fragmentation and clusterin gene expression in human sperm.
        International journal of fertility and sterility. 2015; 9: 129-136
        • Zandieh Z.
        • Vatannejad A.
        • Doosti M.
        • Zabihzadeh S.
        • Haddadi M.
        • Bajelan L.
        • Rashidi B.
        • Amanpour S.
        Comparing reactive oxygen species and DNA fragmentation in semen samples of unexplained infertile and healthy fertile men.
        Irish journal of medical science. 2017;
        • Zhao J.
        • Zhang Q.
        • Wang Y.
        • Li Y.
        Whether sperm deoxyribonucleic acid fragmentation has an effect on pregnancy and miscarriage after in vitro fertilization/intracytoplasmic sperm injection: A systematic review and meta-analysis.
        Fertility and sterility. 2014; 102 (e8): 998-1005
        • Zini A.
        • Bielecki R.
        • Phang D.
        • Zenzes M.T.
        Correlations between two markers of sperm DNA integrity, DNA denaturation and DNA fragmentation, in fertile and infertile men.
        Fertility and sterility. 2001; 75: 674-677
        • Zribi N.
        • Chakroun N.F.
        • Elleuch H.
        • Abdallah F.B.
        • Ben Hamida A.S.
        • Gargouri J.
        • Fakhfakh F.
        • Keskes L.A.
        Sperm DNA fragmentation and oxidation are independent of malondialdheyde.
        Reproductive biology and endocrinology: RB and E. 2011; 9: 47

      Biography

      Daniele Santi obtained his Medical Doctor degree at the University of Modena and Reggio Emilia in 2008. He obtained a specialization in Endocrinology in 2014 and a PhD in Clinical and Experimental Medicine in 2017. He currently works at the Unit of Endocrinology, University of Modena and Reggio Emilia, Italy.