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Sperm DNA fragmentation and male fertility: a retrospective study of 5114 men attending a reproductive center

  • Assisted Reproduction Technologies
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Abstract

Purpose

The sperm DNA fragmentation index (DFI) was quantitatively measured and its relationship with age, semen quality, and infertility conditions was investigated.

Methods

Semen routine test and sperm DFI were performed in 2760 infertile male and 2354 male whose spouse experienced at least one unexplained miscarriage to analyze the correlation between sperm DNA damage, semen routine parameters, and age.

Results

Sperm DFI was significantly lower from patients whose wife experienced unexplained miscarriage compared to infertility males (p = 0.000). An inverse correlation between sperm DFI and sperm progressive motility was observed (rs = − 0.465, p = 0.000) and sperm DFI was positively correlated with age (rs = 0.255, p = 0.000). However, the correlation between sperm DFI and sperm concentration, semen volume, total sperm count, and motile sperm count were not proved.

Conclusions

Sperm DFI is an important indicator for evaluating the quality of semen. Sperm DNA integrity testing is preferentially recommended to those who have decreased sperm progressive motility, especially older men. An integrative analysis of sperm DFI, sperm progressive motility, age, and infertility conditions can provide a more comprehensive assessment of male fertility.

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References

  1. Pasqualotto FF, Sobreiro BP, Hallak J, Athayde KS, Pasqualotto EB, Lucon AM. High percentage of abnormal semen parameters in a prevasectomy population. Fertil Steril. 2006;85(4):954–60. https://doi.org/10.1016/j.fertnstert.2005.09.032.

    Article  PubMed  Google Scholar 

  2. Practice Committee of the American Society for Reproductive M. Diagnostic evaluation of the infertile male: a committee opinion. Fertil Steril. 2015;103(3):e18–25. https://doi.org/10.1016/j.fertnstert.2014.12.103.

    Article  Google Scholar 

  3. Cooper TG, Noonan E, von Eckardstein S, Auger J, Baker HW, Behre HM, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16(3):231–45. https://doi.org/10.1093/humupd/dmp048.

    Article  PubMed  Google Scholar 

  4. Andersen AG, Ziebe S, Jorgensen N, Petersen JH, Skakkebaek NE, Andersen AN. Time to pregnancy in relation to semen quality assessed by CASA before and after sperm separation. Hum Reprod. 2002;17(1):173–7. https://doi.org/10.1093/humrep/17.1.173.

    Article  CAS  PubMed  Google Scholar 

  5. Buck Louis GM, Sundaram R, Schisterman EF, Sweeney A, Lynch CD, Kim S, et al. Semen quality and time to pregnancy: the Longitudinal Investigation of Fertility and the Environment Study. Fertil Steril. 2014;101(2):453–62. https://doi.org/10.1016/j.fertnstert.2013.10.022.

    Article  PubMed  Google Scholar 

  6. Santi D, Spaggiari G, Simoni M. Sperm DNA fragmentation index as a promising predictive tool for male infertility diagnosis and treatment management - meta-analyses. Reprod BioMed Online. 2018;37(3):315–26. https://doi.org/10.1016/j.rbmo.2018.06.023.

    Article  CAS  PubMed  Google Scholar 

  7. Panner Selvam MK, Agarwal A. A systematic review on sperm DNA fragmentation in male factor infertility: Laboratory assessment. Arab J Urol. 2018;16(1):65–76. https://doi.org/10.1016/j.aju.2017.12.001.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Agarwal A, Cho CL, Majzoub A, Esteves SC. The Society for Translational Medicine: clinical practice guidelines for sperm DNA fragmentation testing in male infertility. Transl Androl Urol. 2017;6(Suppl 4):S720–S33. https://doi.org/10.21037/tau.2017.08.06.

    Article  PubMed  PubMed Central  Google Scholar 

  9. Oliva R. Protamines and male infertility. Hum Reprod Update. 2006;12(4):417–35. https://doi.org/10.1093/humupd/dml009.

    Article  CAS  PubMed  Google Scholar 

  10. Sakkas D, Alvarez JG. Sperm DNA fragmentation: mechanisms of origin, impact on reproductive outcome, and analysis. Fertil Steril. 2010;93(4):1027–36. https://doi.org/10.1016/j.fertnstert.2009.10.046.

    Article  CAS  PubMed  Google Scholar 

  11. Lu JC, Jing J, Chen L, Ge YF, Feng RX, Liang YJ, et al. Analysis of human sperm DNA fragmentation index (DFI) related factors: a report of 1010 subfertile men in China. Reprod Biol Endocrinol. 2018;16(1):23. https://doi.org/10.1186/s12958-018-0345-y.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Sergerie M, Laforest G, Bujan L, Bissonnette F, Bleau G. Sperm DNA fragmentation: threshold value in male fertility. Hum Reprod. 2005;20(12):3446–51. https://doi.org/10.1093/humrep/dei231.

    Article  CAS  PubMed  Google Scholar 

  13. Schulte RT, Ohl DA, Sigman M, Smith GD. Sperm DNA damage in male infertility: etiologies, assays, and outcomes. J Assist Reprod Genet. 2010;27(1):3–12. https://doi.org/10.1007/s10815-009-9359-x.

    Article  PubMed  Google Scholar 

  14. Agarwal A, Said TM. Role of sperm chromatin abnormalities and DNA damage in male infertility. Hum Reprod Update. 2003;9(4):331–45. https://doi.org/10.1093/humupd/dmg027.

    Article  CAS  PubMed  Google Scholar 

  15. Robinson L, Gallos ID, Conner SJ, Rajkhowa M, Miller D, Lewis S, et al. The effect of sperm DNA fragmentation on miscarriage rates: a systematic review and meta-analysis. Hum Reprod. 2012;27(10):2908–17. https://doi.org/10.1093/humrep/des261.

    Article  CAS  PubMed  Google Scholar 

  16. Tesarik J, Greco E, Mendoza C. Late, but not early, paternal effect on human embryo development is related to sperm DNA fragmentation. Hum Reprod. 2004;19(3):611–5. https://doi.org/10.1093/humrep/deh127.

    Article  CAS  PubMed  Google Scholar 

  17. Qiu Y, Yang H, Li C, Xu C. Progress in research on sperm DNA fragmentation. Med Sci Monit. 2020;26:e918746. https://doi.org/10.12659/MSM.918746.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Evenson DP, Darzynkiewicz Z, Melamed MR. Relation of mammalian sperm chromatin heterogeneity to fertility. Science. 1980;210(4474):1131–3. https://doi.org/10.1126/science.7444440.

    Article  CAS  PubMed  Google Scholar 

  19. Giwercman A, Lindstedt L, Larsson M, Bungum M, Spano M, Levine RJ, et al. Sperm chromatin structure assay as an independent predictor of fertility in vivo: a case–control study. Int J Androl. 2010;33(1):e221–e7. https://doi.org/10.1111/j.1365-2605.2009.00995.x.

    Article  PubMed  Google Scholar 

  20. Oleszczuk K, Augustinsson L, Bayat N, Giwercman A, Bungum M. Prevalence of high DNA fragmentation index in male partners of unexplained infertile couples. Andrology. 2013;1(3):357–60. https://doi.org/10.1111/j.2047-2927.2012.00041.x.

    Article  CAS  PubMed  Google Scholar 

  21. 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 center. J Assist Reprod Genet. 2009;26(1):41–6. https://doi.org/10.1007/s10815-008-9277-3.

    Article  PubMed  Google Scholar 

  22. Colin A, Barroso G, Gomez-Lopez N, Duran EH, Oehninger S. The effect of age on the expression of apoptosis biomarkers in human spermatozoa. Fertil Steril. 2010;94(7):2609–14. https://doi.org/10.1016/j.fertnstert.2010.04.043.

    Article  CAS  PubMed  Google Scholar 

  23. Brahem S, Mehdi M, Elghezal H, Saad A. The effects of male aging on semen quality, sperm DNA fragmentation and chromosomal abnormalities in an infertile population. J Assist Reprod Genet. 2011;28(5):425–32. https://doi.org/10.1007/s10815-011-9537-5.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Sloter ED, Marchetti F, Eskenazi B, Weldon RH, Nath J, Cabreros D, et al. Frequency of human sperm carrying structural aberrations of chromosome 1 increases with advancing age. Fertil Steril. 2007;87(5):1077–86. https://doi.org/10.1016/j.fertnstert.2006.08.112.

    Article  PubMed  Google Scholar 

  25. Bojar I, Witczak M, Wdowiak A. Biological and environmental conditionings for a sperm DNA fragmentation. Ann Agric Environ Med. 2013;20(4):865–8.

    PubMed  Google Scholar 

  26. Das M, Al-Hathal N, San-Gabriel M, Phillips S, Kadoch IJ, Bissonnette F, et al. High prevalence of isolated sperm DNA damage in infertile men with advanced paternal age. J Assist Reprod Genet. 2013;30(6):843–8. https://doi.org/10.1007/s10815-013-0015-0.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Pino V, Sanz A, Valdes N, Crosby J, Mackenna A. The effects of aging on semen parameters and sperm DNA fragmentation. JBRA Assist Reprod. 2020;24(1):82–6. https://doi.org/10.5935/1518-0557.20190058.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Plastira K, Msaouel P, Angelopoulou R, Zanioti K, Plastiras A, Pothos A, et al. The effects of age on DNA fragmentation, chromatin packaging and conventional semen parameters in spermatozoa of oligoasthenoteratozoospermic patients. J Assist Reprod Genet. 2007;24(10):437–43. https://doi.org/10.1007/s10815-007-9162-5.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Potts RJ, Notarianni LJ, Jefferies TM. Seminal plasma reduces exogenous oxidative damage to human sperm, determined by the measurement of DNA strand breaks and lipid peroxidation. Mutat Res. 2000;447(2):249–56. https://doi.org/10.1016/s0027-5107(99)00215-8.

    Article  CAS  PubMed  Google Scholar 

  30. Baumber J, Ball BA, Linfor JJ, Meyers SA. Reactive oxygen species and cryopreservation promote DNA fragmentation in equine spermatozoa. J Androl. 2003;24(4):621–8. https://doi.org/10.1002/j.1939-4640.2003.tb02714.x.

    Article  CAS  PubMed  Google Scholar 

  31. Guthrie HD, Welch GR. Effects of reactive oxygen species on sperm function. Theriogenology. 2012;78(8):1700–8. https://doi.org/10.1016/j.theriogenology.2012.05.002.

    Article  CAS  PubMed  Google Scholar 

  32. Andolz P, Bielsa MA, Vila J. Evolution of semen quality in North-eastern Spain: a study in 22 759 infertile men over a 36 year period. Hum Reprod. 1999;14(3):731–5. https://doi.org/10.1093/humrep/14.3.731.

    Article  CAS  PubMed  Google Scholar 

  33. Fisch H, Goluboff ET, Olson JH, Feldshuh J, Broder SJ, Barad DH. Semen analyses in 1,283 men from the United States over a 25-year period: no decline in quality. Fertil Steril. 1996;65(5):1009–14. https://doi.org/10.1016/s0015-0282(16)58278-8.

    Article  CAS  PubMed  Google Scholar 

  34. Levitas E, Lunenfeld E, Weisz N, Friger M, Potashnik G. Relationship between age and semen parameters in men with normal sperm concentration: analysis of 6022 semen samples. Andrologia. 2007;39(2):45–50. https://doi.org/10.1111/j.1439-0272.2007.00761.x.

    Article  CAS  PubMed  Google Scholar 

  35. Gu XL, Li HG, Xiong CL. [Correlation of sperm DNA fragmentation index with age and semen parameters in infertile men]. Zhonghua nan ke xue =. Natl J Androl. 2018;24(7):608–12.

    Google Scholar 

  36. Spano M, Kolstad AH, Larsen SB, Cordelli E, Leter G, Giwercman A, et al. The applicability of the flow cytometric sperm chromatin structure assay in epidemiological studies. Asclepios. Hum Reprod. 1998;13(9):2495–505. https://doi.org/10.1093/humrep/13.9.2495.

    Article  CAS  PubMed  Google Scholar 

  37. Zhang LH, Qiu Y, Wang KH, Wang Q, Tao G, Wang LG. Measurement of sperm DNA fragmentation using bright-field microscopy: comparison between sperm chromatin dispersion test and terminal uridine nick-end labeling assay. Fertil Steril. 2010;94(3):1027–32. https://doi.org/10.1016/j.fertnstert.2009.04.034.

    Article  CAS  PubMed  Google Scholar 

  38. Gandini L, Lombardo F, Paoli D, Caruso F, Eleuteri P, Leter G, et al. Full-term pregnancies achieved with ICSI despite high levels of sperm chromatin damage. Hum Reprod. 2004;19(6):1409–17. https://doi.org/10.1093/humrep/deh233.

    Article  CAS  PubMed  Google Scholar 

  39. Zini A, Boman JM, Belzile E, Ciampi A. Sperm DNA damage is associated with an increased risk of pregnancy loss after IVF and ICSI: systematic review and meta-analysis. Hum Reprod. 2008;23(12):2663–8. https://doi.org/10.1093/humrep/den321.

    Article  CAS  PubMed  Google Scholar 

  40. Bungum M, Humaidan P, Axmon A, Spano M, Bungum L, Erenpreiss J, et al. Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. Hum Reprod. 2007;22(1):174–9. https://doi.org/10.1093/humrep/del326.

    Article  CAS  PubMed  Google Scholar 

  41. Giwercman A, Richthoff J, Hjøllund H, Bonde JP, Jepson K, Frohm B, et al. Correlation between sperm motility and sperm chromatin structure assay parameters. Fertil Steril. 2003;80(6):1404–12. https://doi.org/10.1016/s0015-0282(03)02212-x.

    Article  PubMed  Google Scholar 

  42. McQueen DB, Zhang J, Robins JC. Sperm DNA fragmentation and recurrent pregnancy loss: a systematic review and meta-analysis. Fertil Steril. 2019;112(1):54–60 e3. https://doi.org/10.1016/j.fertnstert.2019.03.003.

    Article  PubMed  Google Scholar 

  43. Tan J, Taskin O, Albert A, Bedaiwy MA. Association between sperm DNA fragmentation and idiopathic recurrent pregnancy loss: a systematic review and meta-analysis. Reprod BioMed Online. 2019;38(6):951–60. https://doi.org/10.1016/j.rbmo.2018.12.029.

    Article  CAS  PubMed  Google Scholar 

  44. Simon L, Murphy K, Shamsi MB, Liu L, Emery B, Aston KI, et al. Paternal influence of sperm DNA integrity on early embryonic development. Hum Reprod. 2014;29(11):2402–12. https://doi.org/10.1093/humrep/deu228.

    Article  CAS  PubMed  Google Scholar 

  45. Katib AA, Al-Hawsawi K, Motair W, Bawa AM. Secondary infertility and the aging male, overview. Cent Eur J Urol. 2014;67(2):184–8. https://doi.org/10.5173/ceju.2014.02.art13.

    Article  Google Scholar 

  46. Singh NP, Muller CH, Berger RE. Effects of age on DNA double-strand breaks and apoptosis in human sperm. Fertil Steril. 2003;80(6):1420–30. https://doi.org/10.1016/j.fertnstert.2003.04.002.

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors would like to thank their grant sponsors, National Key R&D Program of China(2018YFC1004302), Open Project of the Key Laboratory of Male Reproductive Medicine and Genetics, National Health Commission of the People’s Republic of China (grant no: KF201708), and National Natural Science Foundation (grant nos. 81471495).

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Authors and Affiliations

  1. Department of Reproductive Endocrinology, Women’s Hospital, School of Medicine, Zhejiang University, Zhejiang, 310006, Hangzhou, China

    Fengbin Zhang, Jingping Li, Zhongyan Liang, Jinggen Wu, Lejun Li, Chong Chen, Fan Jin & Yonghong Tian

  2. Key Laboratory of Reproductive Genetics, Ministry of Education, Hangzhou, China

    Fan Jin & Yonghong Tian

Authors
  1. Fengbin Zhang
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  2. Jingping Li
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  3. Zhongyan Liang
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  4. Jinggen Wu
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  5. Lejun Li
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  7. Fan Jin
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Contributions

Yonghong Tian and Fan Jin conceived the idea and designed the study. Fengbin Zhang and Jinggen Wu collected the retrospective clinical data; Jingping Li and Zhongyan Liang analyzed data and conducted the statistical analysis. Fengbin Zhang and Chong Chen wrote the manuscript. Yonghong Tian and Lejun Li reviewed and assessed the manuscript.

Corresponding author

Correspondence to Yonghong Tian.

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This study received ethical approval from the Institutional Review Boards of our facility (IRB-20200152-R).

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The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

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Zhang, F., Li, J., Liang, Z. et al. Sperm DNA fragmentation and male fertility: a retrospective study of 5114 men attending a reproductive center. J Assist Reprod Genet 38, 1133–1141 (2021). https://doi.org/10.1007/s10815-021-02120-5

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