Relationship Between Vitamin D Level and DNA Fragmentation Index of Sperm in Men Referred to Omid Infertility Center in Hamadan-Iran: A Cross-Sectional Study
Abstract
Objective: Unfortunately, the prevalence of infertility in Iran and the world is increasing. There is limited research on the relationship between vitamin D and DNA fragmentation index (DFI). DFI is a measure of DNA damage in sperm cells and is used to evaluate male fertility. Some studies suggest that vitamin D may play a role in sperm health and fertility.
Materials and methods: In this cross-sectional study, 789 eligible men referred to the Omid Infertility Clinic in Hamadan-Iran in 2021-2023. Serum levels of vitamin D, DFI, spermogram indexes and demographic characteristics (occupation, age, and body mass index) were collected by face-to-face interview and records review in case files. Data were analyzed with SPSS version 27 software.
Results: There is no significant relationship between DFI and vitamin D before and after removing the effect of confounding variables. Clearly, increasing age has been associated with increasing (DFI 95%
Cl: 1.06-3.03; p<0.05) odds ratio (OR) = 1.79. The relationship between the increase in DFI and the decrease in normal sperm morphology (95% CI: 1.43-4.20; p<0.01) OR = 2.45 and the decrease in the progressive motility of sperm was seen (95% Cl: 1.66-4.87; p<0.05) OR= 2.85 and also. The relationship between DFI and the decrease in sperm count after removing the effect Confounding variables were observed (95%Cl: 1.06-8.38; p<0.05) OR=2.98.
Conclusion: No correlation between DFI and vitamin D serum level was found. However, a clear association was observed between increased DFI and advanced age, reduced progressive motility, abnormal sperm morphology, and decreased sperm count.
1. Andrabi SW, Ara A, Saharan A, Jaffar M, Gugnani N, Esteves SC. Sperm DNA Fragmentation: causes, evaluation and management in male infertility. JBRA Assist Reprod. 2024;28(2):306-319.
2. Panner Selvam MK, Ambar RF, Agarwal A, Henkel R. Etiologies of sperm DNA damage and its impact on male infertility. Andrologia. 2021;53(1):e13706.
3. Sunder M, Leslie SW. Semen analysis. StatPearls [Internet]: StatPearls Publishing, 2022.
4. Stavros S, Potiris A, Molopodi E, Mavrogianni D, Zikopoulos A, Louis K, et al. Sperm DNA Fragmentation: Unraveling Its Imperative Impact on Male Infertility Based on Recent Evidence. Int J Mol Sci. 2024;25(18):10167.
5. Rilcheva V, Ayvazova N, Ilieva L, Ivanova S, Konova E. Sperm DNA integrity test and assisted reproductive technology (Art) outcome. J Biomed Clin Res. 2016;9(1):21-9.
6. Agarwal A, Maldonado Rosas I, Anagnostopoulou C, Cannarella R, Boitrelle F, Munoz LV, et al. Oxidative stress and assisted reproduction: a comprehensive review of its pathophysiological role and strategies for optimizing embryo culture environment. Antioxidants (Basel). 2022;11(3):477.
7. Stavros S, Potiris A, Molopodi E, Mavrogianni D, Zikopoulos A, Louis K, et al. Sperm DNA fragmentation: Unraveling its imperative impact on male infertility based on recent evidence. Int J Mol Sci. 2024;25(18):10167.
8. Agarwal A, Majzoub A, Baskaran S, Selvam MKP, Cho CL, Henkel R, et al. Sperm DNA fragmentation: A new guideline for clinicians. World J Mens Health. 2020;38(4):412.
9. Shamsi MB, Imam SN, Dada R. Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility. J Assist Reprod Genet. 2011;28:1073-85.
10. Murgia F, Corda V, Serrenti M, Usai V, Santoru ML, Hurt KJ, et al. Seminal fluid metabolomic markers of oligozoospermic infertility in humans. Metabolites. 2020;10(2):64.
11. Marchetti F, Bishop J, Gingerich J, Wyrobek AJ. Meiotic interstrand DNA damage escapes paternal repair and causes chromosomal aberrations in the zygote by maternal misrepair. Sci Rep. 2015;5(1):7689.
12. 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. Fertil Steril. 2014;102(4):998-1005. e8.
13. Cissen M, Wely MV, Scholten I, Mansell S, Bruin JPd, Mol BW, et al. Measuring sperm DNA fragmentation and clinical outcomes of medically assisted reproduction: a systematic review and meta-analysis. PloS One. 2016;11(11):e0165125.
14. Mostafa RM, Nasrallah YS, Hassan MM, Farrag AF, Majzoub A, Agarwal A. The effect of cigarette smoking on human seminal parameters, sperm chromatin structure and condensation. Andrologia. 2018;50(3).
15. Gill K, Rosiak-Gill A, Jakubik J, Patorski L, Lukaszuk M, Piasecka M. The higher risk for sperm DNA damage in infertile men. Ginekol Pol. 2019;90(12):684-91.
16. Ruvolo G, Fattouh R, Bosco L, Brucculeri A, Cittadini E. New molecular markers for the evaluation of gamete quality. J Assist Reprod Genet. 2013;30:207-12.
17. Sharbatoghli M, Valojerdi MR, Amanlou M, Khosravi F, Jafar-Abadi MA. Relationship of sperm DNA fragmentation, apoptosis and dysfunction of mitochondrial membrane potential with semen parameters and ART outcome after intracytoplasmic sperm injection. Arch Gynecol Obstet. 2012;286:1315-22.
18. Blaseg E, Von Wald T, Hansen KA. Vitamin D levels and human sperm DNA fragmentation: a prospective, cohort study. Basic Clin Androl. 2022;32(1):14.
19. Bøllehuus Hansen L, Lorenzen M, Bentin-Ley U, Nielsen JE, Krog H, Berg AH, et al. Presence of the vitamin D inactivating enzyme CYP24A1 in human sperm and prediction of the success of intrauterine insemination: A prospective study. J Steroid Biochem Mol Biol. 2019;191:105353.
20. Almujaydil MS. The role of dietary nutrients in male infertility: a review. Life (Basel). 2023;13(2):519.
21. Hussein TM, Eldabah N, Zayed HA, Genedy RM. Assessment of serum vitamin D level and seminal vitamin D receptor gene methylation in a sample of Egyptian men with idiopathic infertility. Andrologia. 2021;53(9):e14172.
22. Catanzariti F, Cantoro U, Lacetera V, Muzzonigro G, Polito M. Comparison between WHO (World Health Organization) 2010 and WHO 1999 parameters for semen analysis–interpretation of 529 consecutive samples. Arch Ital Urol Androl. 2013;85(3):125-9.
23. Maghsoumi-Norouzabad L, Zare Javid A, Aiiashi S, Hosseini SA, Dadfar M, Bazyar H, et al. The impact of obesity on various semen parameters and sex hormones in Iranian men with infertility: a cross-sectional study. Res Rep Urol. 2020;12:357-65.
24. Hоlick МF. Vitamin D deficiency. N Еngl J Med. 2007;357:266-81.
25. Sadeghi S, García-Molina A, Celma F, Valverde A, Fereidounfar S, Soler C. Morphometric comparison by the ISAS® CASA-DNAf system of two techniques for the evaluation of DNA fragmentation in human spermatozoa. Asian J Androl. 2016;18(6):835-9.
26. Fernández JL, Muriel L, Goyanes V, Segrelles E, Gosálvez J, Enciso M, et al. Simple determination of human sperm DNA fragmentation with an improved sperm chromatin dispersion test. Fertil Steril. 2005;84(4):833-42.
27. Maghsoumi-Norouzabad L, Zare Javid A, Mansoori A, Dadfar M, Serajian A. Vitamin D3 supplementation effects on spermatogram and oxidative stress biomarkers in asthenozoospermia infertile men: a randomized, triple-blind, placebo-controlled clinical trial. Reprod Sci. 2022;29(3):823-835.
28. Humaidan P, Haahr T, Povlsen BB, Kofod L,
Laursen RJ, Alsbjerg B, et al. The combined effect of lifestyle intervention and antioxidant therapy on sperm DNA fragmentation and seminal oxidative stress in IVF patients: a pilot study. Int Braz J Urol. 2022;48(1):131-156.
29. Blomberg Jensen M, Lawaetz JG, Petersen JH, Juul A, Jørgensen N. Effects of vitamin D supplementation on semen quality, reproductive hormones, and live birth rate: a randomized clinical trial. J Clin Endocrinol
Metab. 2018;103(3):870-881.
30. Adamczewska D, Słowikowska-Hilczer J, Walczak-Jędrzejowska R. The association between vitamin D and the components of male fertility: a systematic review. Biomedicines. 2022;11(1):90.
31. Ciccone IM, Costa EM, Pariz JR, Teixeira TA, Drevet JR, Gharagozloo P, et al. Serum vitamin D content is associated with semen parameters and serum testosterone levels in men. Asian J Androl. 2021;23(1):52-58.
32. Blomberg Jensen M. Vitamin D and male reproduction. Nat Rev Endocrinol. 2014;10(3):175-86.
33. Boisen IM, Nielsen JE, Verlinden L, Lorenzen M, Holt R, Pinborg A, et al. Calcium transport in male reproduction is possibly influenced by vitamin D and CaSR. J Endocrinol. 2021;251(3):207-222.
34. Calagna G, Catinella V, Polito S, Schiattarella A, De Franciscis P, D’Antonio F, et al. Vitamin D and male reproduction: updated evidence based on literature review. Nutrients. 2022;14(16):3278.
35. Della Nera G, Sabatino L, Gaggini M, Gorini F, Vassalle C. Vitamin D determinants, status, and antioxidant/anti-inflammatory-related effects in cardiovascular risk and disease: not the last word in the controversy. Antioxidants (Basel). 2023;12(4):948.
36. Abed HH, Ali AM, Mahdi ZS. Effect of vitamin D3 supplement on the semen quality in human patients with vitamin D deficiency. HAYATI Journal of Biosciences. 2022;29(5):562-9.
37. Gu XL, Li HG, Xiong CL. [Correlation of sperm
DNA fragmentation index with age and semen parameters in infertile men]. Zhonghua Nan Ke Xue. 2018;24(7):608-612.
38. Kaarouch I, Bouamoud N, Madkour A, Louanjli N, Saadani B, Assou S, et al. Paternal age: Negative impact on sperm genome decays and IVF outcomes after 40 years. Mol Reprod Dev. 2018;85(3):271-80.
39. Evenson DP. Sperm chromatin structure assay (SCSA®) for fertility assessment. Curr Protoc. 2022;2(8):e508.
40. Vladimirov IK. IVF Technologies and Infertility: Current Practices and New Perspectives. IntechOpen. 2023.
41. 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(2):311-320.
42. Oleszczuk K, Giwercman A, Bungum M. Sperm chromatin structure assay in prediction of in vitro fertilization outcome. Andrology. 2016;4(2):290-6.
43. Chua SC, Yovich SJ, Hinchliffe PM, Yovich JL. How
well do semen analysis parameters correlate with sperm DNA fragmentation? a retrospective study from 2567 semen samples analyzed by the Halosperm test. J Pers Med. 2023;13(3):518.
44. Le MT, Nguyen TAT, Nguyen HTT, Nguyen TTT, Nguyen VT, Le DD, et al. Does sperm DNA fragmentation correlate with semen parameters? Reprod Med Biol. 2019;18(4):390-396.
45. Hasanzadeh Keshteli S, Farsi MM, Khafri S. Should We Perform Semen Analysis, DNA Fragmentation, and Hypo-osmotic Swelling Tests together? Int J Mol Cell
Med. 2016;5(4):246-254.
2. Panner Selvam MK, Ambar RF, Agarwal A, Henkel R. Etiologies of sperm DNA damage and its impact on male infertility. Andrologia. 2021;53(1):e13706.
3. Sunder M, Leslie SW. Semen analysis. StatPearls [Internet]: StatPearls Publishing, 2022.
4. Stavros S, Potiris A, Molopodi E, Mavrogianni D, Zikopoulos A, Louis K, et al. Sperm DNA Fragmentation: Unraveling Its Imperative Impact on Male Infertility Based on Recent Evidence. Int J Mol Sci. 2024;25(18):10167.
5. Rilcheva V, Ayvazova N, Ilieva L, Ivanova S, Konova E. Sperm DNA integrity test and assisted reproductive technology (Art) outcome. J Biomed Clin Res. 2016;9(1):21-9.
6. Agarwal A, Maldonado Rosas I, Anagnostopoulou C, Cannarella R, Boitrelle F, Munoz LV, et al. Oxidative stress and assisted reproduction: a comprehensive review of its pathophysiological role and strategies for optimizing embryo culture environment. Antioxidants (Basel). 2022;11(3):477.
7. Stavros S, Potiris A, Molopodi E, Mavrogianni D, Zikopoulos A, Louis K, et al. Sperm DNA fragmentation: Unraveling its imperative impact on male infertility based on recent evidence. Int J Mol Sci. 2024;25(18):10167.
8. Agarwal A, Majzoub A, Baskaran S, Selvam MKP, Cho CL, Henkel R, et al. Sperm DNA fragmentation: A new guideline for clinicians. World J Mens Health. 2020;38(4):412.
9. Shamsi MB, Imam SN, Dada R. Sperm DNA integrity assays: diagnostic and prognostic challenges and implications in management of infertility. J Assist Reprod Genet. 2011;28:1073-85.
10. Murgia F, Corda V, Serrenti M, Usai V, Santoru ML, Hurt KJ, et al. Seminal fluid metabolomic markers of oligozoospermic infertility in humans. Metabolites. 2020;10(2):64.
11. Marchetti F, Bishop J, Gingerich J, Wyrobek AJ. Meiotic interstrand DNA damage escapes paternal repair and causes chromosomal aberrations in the zygote by maternal misrepair. Sci Rep. 2015;5(1):7689.
12. 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. Fertil Steril. 2014;102(4):998-1005. e8.
13. Cissen M, Wely MV, Scholten I, Mansell S, Bruin JPd, Mol BW, et al. Measuring sperm DNA fragmentation and clinical outcomes of medically assisted reproduction: a systematic review and meta-analysis. PloS One. 2016;11(11):e0165125.
14. Mostafa RM, Nasrallah YS, Hassan MM, Farrag AF, Majzoub A, Agarwal A. The effect of cigarette smoking on human seminal parameters, sperm chromatin structure and condensation. Andrologia. 2018;50(3).
15. Gill K, Rosiak-Gill A, Jakubik J, Patorski L, Lukaszuk M, Piasecka M. The higher risk for sperm DNA damage in infertile men. Ginekol Pol. 2019;90(12):684-91.
16. Ruvolo G, Fattouh R, Bosco L, Brucculeri A, Cittadini E. New molecular markers for the evaluation of gamete quality. J Assist Reprod Genet. 2013;30:207-12.
17. Sharbatoghli M, Valojerdi MR, Amanlou M, Khosravi F, Jafar-Abadi MA. Relationship of sperm DNA fragmentation, apoptosis and dysfunction of mitochondrial membrane potential with semen parameters and ART outcome after intracytoplasmic sperm injection. Arch Gynecol Obstet. 2012;286:1315-22.
18. Blaseg E, Von Wald T, Hansen KA. Vitamin D levels and human sperm DNA fragmentation: a prospective, cohort study. Basic Clin Androl. 2022;32(1):14.
19. Bøllehuus Hansen L, Lorenzen M, Bentin-Ley U, Nielsen JE, Krog H, Berg AH, et al. Presence of the vitamin D inactivating enzyme CYP24A1 in human sperm and prediction of the success of intrauterine insemination: A prospective study. J Steroid Biochem Mol Biol. 2019;191:105353.
20. Almujaydil MS. The role of dietary nutrients in male infertility: a review. Life (Basel). 2023;13(2):519.
21. Hussein TM, Eldabah N, Zayed HA, Genedy RM. Assessment of serum vitamin D level and seminal vitamin D receptor gene methylation in a sample of Egyptian men with idiopathic infertility. Andrologia. 2021;53(9):e14172.
22. Catanzariti F, Cantoro U, Lacetera V, Muzzonigro G, Polito M. Comparison between WHO (World Health Organization) 2010 and WHO 1999 parameters for semen analysis–interpretation of 529 consecutive samples. Arch Ital Urol Androl. 2013;85(3):125-9.
23. Maghsoumi-Norouzabad L, Zare Javid A, Aiiashi S, Hosseini SA, Dadfar M, Bazyar H, et al. The impact of obesity on various semen parameters and sex hormones in Iranian men with infertility: a cross-sectional study. Res Rep Urol. 2020;12:357-65.
24. Hоlick МF. Vitamin D deficiency. N Еngl J Med. 2007;357:266-81.
25. Sadeghi S, García-Molina A, Celma F, Valverde A, Fereidounfar S, Soler C. Morphometric comparison by the ISAS® CASA-DNAf system of two techniques for the evaluation of DNA fragmentation in human spermatozoa. Asian J Androl. 2016;18(6):835-9.
26. Fernández JL, Muriel L, Goyanes V, Segrelles E, Gosálvez J, Enciso M, et al. Simple determination of human sperm DNA fragmentation with an improved sperm chromatin dispersion test. Fertil Steril. 2005;84(4):833-42.
27. Maghsoumi-Norouzabad L, Zare Javid A, Mansoori A, Dadfar M, Serajian A. Vitamin D3 supplementation effects on spermatogram and oxidative stress biomarkers in asthenozoospermia infertile men: a randomized, triple-blind, placebo-controlled clinical trial. Reprod Sci. 2022;29(3):823-835.
28. Humaidan P, Haahr T, Povlsen BB, Kofod L,
Laursen RJ, Alsbjerg B, et al. The combined effect of lifestyle intervention and antioxidant therapy on sperm DNA fragmentation and seminal oxidative stress in IVF patients: a pilot study. Int Braz J Urol. 2022;48(1):131-156.
29. Blomberg Jensen M, Lawaetz JG, Petersen JH, Juul A, Jørgensen N. Effects of vitamin D supplementation on semen quality, reproductive hormones, and live birth rate: a randomized clinical trial. J Clin Endocrinol
Metab. 2018;103(3):870-881.
30. Adamczewska D, Słowikowska-Hilczer J, Walczak-Jędrzejowska R. The association between vitamin D and the components of male fertility: a systematic review. Biomedicines. 2022;11(1):90.
31. Ciccone IM, Costa EM, Pariz JR, Teixeira TA, Drevet JR, Gharagozloo P, et al. Serum vitamin D content is associated with semen parameters and serum testosterone levels in men. Asian J Androl. 2021;23(1):52-58.
32. Blomberg Jensen M. Vitamin D and male reproduction. Nat Rev Endocrinol. 2014;10(3):175-86.
33. Boisen IM, Nielsen JE, Verlinden L, Lorenzen M, Holt R, Pinborg A, et al. Calcium transport in male reproduction is possibly influenced by vitamin D and CaSR. J Endocrinol. 2021;251(3):207-222.
34. Calagna G, Catinella V, Polito S, Schiattarella A, De Franciscis P, D’Antonio F, et al. Vitamin D and male reproduction: updated evidence based on literature review. Nutrients. 2022;14(16):3278.
35. Della Nera G, Sabatino L, Gaggini M, Gorini F, Vassalle C. Vitamin D determinants, status, and antioxidant/anti-inflammatory-related effects in cardiovascular risk and disease: not the last word in the controversy. Antioxidants (Basel). 2023;12(4):948.
36. Abed HH, Ali AM, Mahdi ZS. Effect of vitamin D3 supplement on the semen quality in human patients with vitamin D deficiency. HAYATI Journal of Biosciences. 2022;29(5):562-9.
37. Gu XL, Li HG, Xiong CL. [Correlation of sperm
DNA fragmentation index with age and semen parameters in infertile men]. Zhonghua Nan Ke Xue. 2018;24(7):608-612.
38. Kaarouch I, Bouamoud N, Madkour A, Louanjli N, Saadani B, Assou S, et al. Paternal age: Negative impact on sperm genome decays and IVF outcomes after 40 years. Mol Reprod Dev. 2018;85(3):271-80.
39. Evenson DP. Sperm chromatin structure assay (SCSA®) for fertility assessment. Curr Protoc. 2022;2(8):e508.
40. Vladimirov IK. IVF Technologies and Infertility: Current Practices and New Perspectives. IntechOpen. 2023.
41. 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(2):311-320.
42. Oleszczuk K, Giwercman A, Bungum M. Sperm chromatin structure assay in prediction of in vitro fertilization outcome. Andrology. 2016;4(2):290-6.
43. Chua SC, Yovich SJ, Hinchliffe PM, Yovich JL. How
well do semen analysis parameters correlate with sperm DNA fragmentation? a retrospective study from 2567 semen samples analyzed by the Halosperm test. J Pers Med. 2023;13(3):518.
44. Le MT, Nguyen TAT, Nguyen HTT, Nguyen TTT, Nguyen VT, Le DD, et al. Does sperm DNA fragmentation correlate with semen parameters? Reprod Med Biol. 2019;18(4):390-396.
45. Hasanzadeh Keshteli S, Farsi MM, Khafri S. Should We Perform Semen Analysis, DNA Fragmentation, and Hypo-osmotic Swelling Tests together? Int J Mol Cell
Med. 2016;5(4):246-254.
| Files | ||
| Issue | Vol 19, No 2 (June 2025) | |
| Section | Original Articles | |
| DOI | https://doi.org/10.18502/jfrh.v19i2.19304 | |
| Keywords | ||
| DNA Fragmentation Index Vitamin D Spermogram | ||
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How to Cite
1.
Holakouie Naini M, Talebi Ghane E, Pilehvari S. Relationship Between Vitamin D Level and DNA Fragmentation Index of Sperm in Men Referred to Omid Infertility Center in Hamadan-Iran: A Cross-Sectional Study. J Family Reprod Health. 2025;19(2):152-160.
