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Intra-individual changes in sperm DNA fragmentation levels over short and long time periods

  • Gamete Biology
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Abstract

Purpose

We aimed to examine the longitudinal, intra-personal changes in DNA fragmentation index (DFI) over time.

Methods

Men who performed at least two DFI measurements (using sperm chromatin structure assay (SCSA) between 2003 and 2019 were included in this study and allocated to groups by time between DFI tests: < 1 year, 1–3 years, 3–5 years, and > 5 years. An analysis of DFI change over time according to age groups was additionally performed. Regression models were developed to predict changes in DFI with time.

Results

Overall, 225 patients had two or more DFI measurements done at least a month apart (mean of 586.7± 710.0 days). The < 1 year (n = 124) and 1–3 years (n = 68) groups demonstrated decreased DFI levels, while an increase in DFI was shown in 3–5 years (n = 21) and more than 5 years (n = 12) groups − 7.1 ± 14.9%, − 4.5 ± 13.4%, + 3.2 ± 8.4%, and + 10.8 ± 18.0%, respectively, p < 0.001). This trend was similarly shown in age subgroups of under 40 years and 40–50 years at baseline DFI. Linear regression models showed that the factors predictive of DFI increase are baseline DFI and > 3 years between DFI tests.

Conclusion

This study shows that DFI, in men being investigated for infertility, initially decreases in the first 3 years of follow-up, and then increases over time with the highest increase occurring after 5 years interval (an average increase of 10.8%). Testing infertile men’s DFI levels at first evaluation may contribute to personalized consult regarding future reproductive outcomes.

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Data and/or code availability

The datasets and materials used in this study may be available from the corresponding author upon reasonable request.

References

  1. Murray CJL, Callender CSKH, Kulikoff XR, et al. Population and fertility by age and sex for 195 countries and territories, 1950–2017: a systematic analysis for the Global Burden of Disease Study 2017. The Lancet. 2018;392:1995–2051. https://doi.org/10.1016/S0140-6736(18)32278-5.

    Article  Google Scholar 

  2. Thonneau P, Marchand S, Tallec A, et al. Incidence and main causes of infertility in a resident population (1 850 000) of three French regions (1988–1989)*. Hum Reprod. 1991;6:811–6. https://doi.org/10.1093/OXFORDJOURNALS.HUMREP.A137433.

    Article  CAS  PubMed  Google Scholar 

  3. Sharlip ID, Jarow JP, Belker AM, et al. Best practice policies for male infertility. Fertil Steril. 2002;77:873–82. https://doi.org/10.1016/S0015-0282(02)03105-9.

    Article  PubMed  Google Scholar 

  4. Hamilton BE, Martin JA, Osterman MJ, et al. Births: final data for 2014. Natl Vital Stat Rep. 2015;64:1.

    PubMed  Google Scholar 

  5. Khandwala YS, Zhang CA, Lu Y, Eisenberg ML. The age of fathers in the USA is rising: an analysis of 168 867 480 births from 1972 to 2015. Hum Reprod. 2017;32:2110.

    Article  PubMed  Google Scholar 

  6. Brandt JS, Cruz Ithier MA, Rosen T, Ashkinadze E. Advanced paternal age, infertility, and reproductive risks: a review of the literature. Prenat Diagn. 2019;39:81–7. https://doi.org/10.1002/pd.5402.

    Article  PubMed  Google Scholar 

  7. Jimbo M, Kunisaki J, Ghaed M, Yu V, Flores HA, Hotaling JM. Fertility in the aging male: a systematic review. Fertil Steril. 2022;118:1022–34. https://doi.org/10.1016/j.fertnstert.2022.10.035.

    Article  PubMed  Google Scholar 

  8. Johnson SL, Dunleavy J, Gemmell NJ, Nakagawa S. Consistent age-dependent declines in human semen quality: a systematic review and meta-analysis. Ageing Res Rev. 2015;19:22.

    Article  PubMed  Google Scholar 

  9. Kidd SA, Eskenazi B, Wyrobek AJ. Effects of male age on semen quality and fertility: a review of the literature. Fertil Steril. 2001;75:237.

    Article  CAS  PubMed  Google Scholar 

  10. Kühnert B, Nieschlag E. Reproductive functions of the ageing male. Hum Reprod Update. 2004;10:327.

    Article  PubMed  Google Scholar 

  11. Li Y, Lin H, Li Y, Cao J. Association between socio-psycho-behavioral factors and male semen quality: systematic review and meta-analyses. Fertil Steril. 2011;95:116.

    Article  PubMed  Google Scholar 

  12. 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;38:951–60. https://doi.org/10.1016/j.rbmo.2018.12.029.

    Article  CAS  PubMed  Google Scholar 

  13. Bareh GM, Jacoby E, Binkley P, Chang TC, Schenken RS, Robinson RD. Sperm deoxyribonucleic acid fragmentation assessment in normozoospermic male partners of couples with unexplained recurrent pregnancy loss: a prospective study. Fertil Steril. 2016;105:329–36.e1.

    Article  CAS  PubMed  Google Scholar 

  14. Boitrelle F, Shah R, Saleh R, et al. The sixth edition of the WHO manual for human semen analysis: a critical review and SWOT analysis. Life (Basel). 2021;11:1368. https://doi.org/10.3390/life11121368.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Agarwal A, Majzoub A, Baskaran S, et al. Sperm DNA fragmentation: a new guideline for clinicians. World J Mens Health. 2020;38:412–71. https://doi.org/10.5534/wjmh.200128.

    Article  PubMed  PubMed Central  Google Scholar 

  16. Evenson DP, Jost LK, Marshall D, et al. Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic. Hum Reprod. 1999;14:1039–49.

    Article  CAS  PubMed  Google Scholar 

  17. Henkel R, Hajimohammad M, Stalf T, et al. Influence of deoxyribonucleic acid damage on fertilization and pregnancy. Fertil Steril. 2004;81:965–72. https://doi.org/10.1016/j.fertnstert.2003.09.044.

    Article  CAS  PubMed  Google Scholar 

  18. Spano M, Bonde JP, Hjollund HI, et al. Sperm chromatin damage impairs human fertility. Fertil Steril. 2000;73:43–50.

    Article  CAS  PubMed  Google Scholar 

  19. 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;27:2908–17. https://doi.org/10.1093/humrep/des261.

    Article  CAS  PubMed  Google Scholar 

  20. Cissen M, Wely MV, Scholten I, et al. Measuring Sperm DNA Fragmentation and clinical outcomes of medically assisted reproduction: a systematic review and meta-analysis. PLoS One. 2016;11:e0165125. https://doi.org/10.1371/journal.pone.0165125.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Zhang H, Li Y, Wang H, Zhou W, Zheng Y, Ye D. Does sperm DNA fragmentation affect clinical outcomes during vitrified-warmed single-blastocyst transfer cycles? A retrospective analysis of 2034 vitrified-warmed single-blastocyst transfer cycles. J Assist Reprod Genet. 2022;39:1359–66. https://doi.org/10.1007/s10815-022-02484-2.

    Article  PubMed  PubMed Central  Google Scholar 

  22. Repalle D, Saritha KV, Bhandari S. Sperm DNA fragmentation negatively influences the cumulative live birth rate in the intracytoplasmic sperm injection cycles of couples with unexplained infertility. Clin Exp Reprod Med. 2022;49:185–95. https://doi.org/10.5653/cerm.2021.05169.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Hervás I, Pacheco A, Gil Julia M, Rivera-Egea R, Navarro-Gomezlechon A, Garrido N. Sperm deoxyribonucleic acid fragmentation (by terminal deoxynucleotidyl transferase biotin dUTP nick end labeling assay) does not impair reproductive success measured as cumulative live birth rates per donor metaphase II oocyte used. Fertil Steril. 2022;118:79–89. https://doi.org/10.1016/j.fertnstert.2022.04.002.

    Article  CAS  PubMed  Google Scholar 

  24. Gao J, Yuan R, Yang S, et al. Age-related changes in human conventional semen parameters and sperm chromatin structure assay-defined sperm DNA/chromatin integrity. Reprod Biomed Online. 2021;42:973–82. https://doi.org/10.1016/j.rbmo.2021.02.006.

    Article  CAS  PubMed  Google Scholar 

  25. Evenson DP, Djira G, Kasperson K, Christianson J. Relationships between the age of 25,445 men attending infertility clinics and sperm chromatin structure assay (SCSA®) defined sperm DNA and chromatin integrity. Fertil Steril. 2020;114:311–20. https://doi.org/10.1016/j.fertnstert.2020.03.028.

    Article  CAS  PubMed  Google Scholar 

  26. Luo Y, Wu S, Zhang M, et al. Sperm DNA integrity is critically impacted by male age but does not influence outcomes of artificial insemination by husband in the Chinese infertile couples. Aging (Albany NY). 2022;14:4326–35. https://doi.org/10.18632/aging.204058.

    Article  PubMed  PubMed Central  Google Scholar 

  27. Deenadayal Mettler A, Govindarajan M, Srinivas S, Mithraprabhu S, Evenson D, Mahendran T. Male age is associated with sperm DNA/chromatin integrity. Aging Male. 2020;23:822–9. https://doi.org/10.1080/13685538.2019.1600496.

    Article  CAS  PubMed  Google Scholar 

  28. Cooper TG, Noonan E, von Eckardstein S, et al. World Health Organization reference values for human semen characteristics. Hum Reprod Update. 2010;16:231–45. https://doi.org/10.1093/humupd/dmp048.

    Article  PubMed  Google Scholar 

  29. Moskovtsev SI, Librach CL. Methods of sperm vitality assessment. Methods Mol Biol. 2013;927:13–9. https://doi.org/10.1007/978-1-62703-038-0_2.

    Article  CAS  PubMed  Google Scholar 

  30. Zini A, Kamal K, Phang D, Willis J, Jarvi K. Biologic variability of sperm DNA denaturation in infertile men. Urology. 2001;58:258–61.

    Article  CAS  PubMed  Google Scholar 

  31. Evenson DP. Sperm Chromatin Structure Assay (SCSA®) for Fertility Assessment. Curr Protoc. 2022;2:e508. https://doi.org/10.1002/cpz1.508.

    Article  CAS  PubMed  Google Scholar 

  32. Keel BA. Within- and between-subject variation in semen parameters in infertile men and normal semen donors. Fertil Steril. 2006;85:128–34. https://doi.org/10.1016/j.fertnstert.2005.06.048.

    Article  PubMed  Google Scholar 

  33. Erenpreiss J, Bungum M, Spano M, Elzanaty S, Orbidans J, Giwercman A. Intra-individual variation in sperm chromatin structure assay parameters in men from infertile couples: clinical implications. Hum Reprod. 2006;21:2061–4. https://doi.org/10.1093/humrep/del134.

    Article  CAS  PubMed  Google Scholar 

  34. Smit M, Dohle GR, Hop WC, Wildhagen MF, Weber RF, Romijn JC. Clinical correlates of the biological variation of sperm DNA fragmentation in infertile men attending an andrology outpatient clinic. Int J Androl. 2007;30:48–55. https://doi.org/10.1111/j.1365-2605.2006.00710.x.

    Article  CAS  PubMed  Google Scholar 

  35. Evenson DP, Jost LK, Baer RK, Turner TW, Schrader SM. Individuality of DNA denaturation patterns in human sperm as measured by the sperm chromatin structure assay. Reprod Toxicol. 1991;5:115–25. https://doi.org/10.1016/0890-6238(91)90039-i.

    Article  CAS  PubMed  Google Scholar 

  36. Punjabi U, Roelant E, Peeters K, Goovaerts I, Van Mulders H, De Neubourg D. Variability in sperm dna fragmentation in men with mild/unexplained subfertility in a prospective longitudinal intrauterine insemination trial. Life (Basel). 2022;12:1826. https://doi.org/10.3390/life12111826.

    Article  PubMed  PubMed Central  Google Scholar 

  37. Moskovtsev SI, Lecker I, Mullen JB, et al. Cause-specific treatment in patients with high sperm DNA damage resulted in significant DNA improvement. Syst Biol Reprod Med. 2009;55:109–15. https://doi.org/10.1080/19396360902787944.

    Article  CAS  PubMed  Google Scholar 

  38. Moskovtsev SI, Willis J, Mullen JB. Age-related decline in sperm deoxyribonucleic acid integrity in patients evaluated for male infertility. Fertil Steril. 2006;85:496–9. https://doi.org/10.1016/j.fertnstert.2005.05.075.

    Article  CAS  PubMed  Google Scholar 

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

    Article  PubMed  Google Scholar 

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Author notes

  1. Gilad Karavani and Mohamed S. Kattan have equal contributions as first authors.

Authors and Affiliations

  1. Division of Urology, Department of Surgery, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada

    Gilad Karavani, Mohamed S. Kattan, Susan Lau, Kirk C. Lo, Ethan D. Grober, Bader Akroof, Katherine Lajkosz & Keith Jarvi

  2. Department of biostatistics, Princess Margaret Cancer Centre, Toronto, Ontario, Canada

    Katherine Lajkosz

  3. Department of Pathology, Mount Sinai Hospital and New Women’s College Hospital, University of Toronto, Toronto, Ontario, Canada

    Brendan Mullen

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Contributions

G. K. and M. S. K. contributed substantially to the conception and design of the study, the analysis and interpretation of data, and the drafting of the article. S. L. contributed to the conception and design of the study, the acquisition and interpretation of data, and the drafting. K. C. L. and E. D. G. contributed to the analysis and interpretation of data and the revision of the article. B. A. contributed to the conception and design of the study and interpretation of data. K. L. contributed to the design of the study, analysis, and interpretation of the data. B. M. contributed to the acquisition, analysis, and interpretation of the data. K. J. contributed substantially to the conception and design of the study, the acquisition, analysis, and interpretation of the data, and the drafting and revision of the article. All authors approved the final version of the study.

Corresponding author

Correspondence to Gilad Karavani.

Ethics declarations

Ethical approval

All participants have signed the IRB-approved informed consent form. The Research Ethics Board of the Mount Sinai Hospital approved data collection (reference number 05-0161-E) and analysis (reference number 07-0032-E). The dates of approval were October 18, 2005, and October 30, 2007, respectively.

Informed consent

The IRB-approved informed consent was provided by all participants prior to filling out the computer-based survey after upon first visit to the clinic.

Competing interests

The authors declare no competing interests.

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Supplementary information

ESM 1

Suppl. Figure 1. Scatterplot visualizing relationship between age at first DNA fragmentation index (DFI) and change in DFI (final – baseline DFI) with loess curve. (PNG 96 kb)

High Resolution Image (TIF 33 kb)

ESM 2

(DOCX 24 kb)

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Karavani, G., Kattan, M.S., Lau, S. et al. Intra-individual changes in sperm DNA fragmentation levels over short and long time periods. J Assist Reprod Genet 40, 2267–2274 (2023). https://doi.org/10.1007/s10815-023-02891-z

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