Skip to main content
Log in

Predictive value of DNA integrity analysis in idiopathic recurrent pregnancy loss following spontaneous conception

  • ASSISTED REPRODUCTION TECHNOLOGIES
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Standard semen parameters are poor predictors of fertility potential. To date, apart from, paternal karyotyping sperm factors are not evaluated in recurrent pregnancy loss (RPL), only recent studies have emphasized the role of sperm factors in early embryonic development as sperm transcribes genes critical for early embryonic development. Sperm DNA integrity is useful diagnostic and prognostic marker and has clinical implications in idiopathic recurrent pregnancy loss (iRPL) following spontaneous conception. The aim of this study was to assess DNA integrity in cases experiencing iRPL following spontaneous conception.

Methods

Semen samples from 45 patients and 20 controls were analyzed as per WHO 1999 guidelines and sperm chromatin structure assay (SCSA) was used to measure DNA fragmentation index (DFI).

Results

By applying receiver operating curve (ROC) analysis, sperm DFI of approximately 26 % was found in male partner of couples experiencing iRPL.

Conclusions

Our data indicate that sperm from men with a history of iRPL have a higher percentage of DNA damage as compared to control group, and this can explain pregnancy loss in these patients. Men with higher DFI are infertile whereas men with lower DFI (26 %) are able to conceive but experience recurrent pregnancy loss. Thus it is important to evaluate sperm DFI in couples experiencing iRPL to understand exact aetiology of RPL and determine prognosis and management.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  1. Badouard C, Menezo Y, Panteix G, Ravanat JL, Douki T, Cadet J, Favier A. Determination of new types of DNA lesions in human sperm. Zygote. 2008;16(1):9–13. doi:10.1017/S0967199407004340.

    Article  PubMed  CAS  Google Scholar 

  2. Barratt CL, Aitken RJ, Bjorndahl L, Carrell DT, de Boer P, Kvist U, Lewis SE, Perreault SD, Perry MJ, Ramos L, Robaire B, Ward S, Zini A. Sperm DNA: organization, protection and vulnerability: from basic science to clinical applications–a position report. Hum Reprod. 2010;25(4):824–38. doi:10.1093/humrep/dep465.

    Article  PubMed  Google Scholar 

  3. Bellver J, Meseguer M, Muriel L, Garcia-Herrero S, Barreto MA, Garda AL, Remohi J, Pellicer A, Garrido N. Y chromosome microdeletions, sperm DNA fragmentation and sperm oxidative stress as causes of recurrent spontaneous abortion of unknown etiology. Hum Reprod. 2010;25(7):1713–21. doi:10.1093/humrep/deq098.

    Article  PubMed  CAS  Google Scholar 

  4. Benchaib M, Braun V, Lornage J, Hadj S, Salle B, Lejeune H, Guerin JF. Sperm DNA fragmentation decreases the pregnancy rate in an assisted reproductive technique. Hum Reprod. 2003;18(5):1023–8.

    Article  PubMed  Google Scholar 

  5. Boe-Hansen GB, Fedder J, Ersboll AK, Christensen P. The sperm chromatin structure assay as a diagnostic tool in the human fertility clinic. Hum Reprod. 2006;21(6):1576–82. doi:10.1093/humrep/del019.

    Article  PubMed  Google Scholar 

  6. Borini A, Tarozzi N, Bizzaro D, Bonu MA, Fava L, Flamigni C, Coticchio G. Sperm DNA fragmentation: paternal effect on early post-implantation embryo development in ART. Hum Reprod. 2006;21(11):2876–81. doi:10.1093/humrep/del251.

    Article  PubMed  CAS  Google Scholar 

  7. Brahem S, Mehdi M, Landolsi H, Mougou S, Elghezal H, Saad A. Semen parameters and sperm DNA fragmentation as causes of recurrent pregnancy loss. Urology. 2011. doi:10.1016/j.urology.2011.05.049.

  8. Bungum M, Bungum L, Giwercman A. Sperm chromatin structure assay (SCSA): a tool in diagnosis and treatment of infertility. Asian J Androl. 2011;13(1):69–75. doi:10.1038/aja.2010.73.

    Article  PubMed  CAS  Google Scholar 

  9. Bungum MP, Humaidan, et al. The predictive value of sperm chromatin structure assay (SCSA) parameters for the outcome of intrauterine insemination, IVF and ICSI. Hum Reprod. 2004;19(6):1401–8.

    Article  PubMed  CAS  Google Scholar 

  10. Bungum MP, Humaidan, et al. Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. Hum Reprod. 2007;22(1):174–9.

    Article  PubMed  CAS  Google Scholar 

  11. Carrell DT, Wilcox AL, Lowy L, Peterson CM, Jones KP, Erickson L, Campbell B, Branch DW, Hatasaka HH. Elevated sperm chromosome aneuploidy and apoptosis in patients with unexplained recurrent pregnancy loss. Obstet Gynecol. 2003;101(6):1229–35.

    Article  PubMed  Google Scholar 

  12. Cassuto NG, Hazout A, Hammoud I, Balet R, Bouret D, Barak Y, Jellad S, Plouchart JM, Selva J, Yazbeck C. Correlation between DNA defect and sperm-head morphology. Reprod Biomed Online. 2012;24(2):211–8. doi:10.1016/j.rbmo.2011.10.006.

    Article  PubMed  Google Scholar 

  13. Cho C, Jung-Ha H, Willis WD, Goulding EH, Stein P, Xu Z, Schultz RM, Hecht NB, Eddy EM. Protamine 2 deficiency leads to sperm DNA damage and embryo death in mice. Biol Reprod. 2003;69(1):211–7. doi:10.1095/biolreprod.102.015115.

    Article  PubMed  CAS  Google Scholar 

  14. Cho C, Willis WD, Goulding EH, Jung-Ha H, Choi YC, Hecht NB, Eddy EM. Haploinsufficiency of protamine-1 or −2 causes infertility in mice. Nat Genet. 2001;28(1):82–6. doi:10.1038/88313.

    PubMed  CAS  Google Scholar 

  15. Erenpreiss J, Elzanaty S, Giwercman A. Sperm DNA damage in men from infertile couples. Asian J Androl. 2008;10(5):786–90. doi:10.1111/j.1745-7262.2008.00417.x.

    Article  PubMed  Google Scholar 

  16. Evenson D, Jost L. Sperm chromatin structure assay is useful for fertility assessment. Methods Cell Sci. 2000;22(2–3):169–89.

    Article  PubMed  CAS  Google Scholar 

  17. Evenson DP, Jost LK, Marshall D, Zinaman MJ, Clegg E, Purvis K, de Angelis P, Claussen OP. Utility of the sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinic. Hum Reprod. 1999;14(4):1039–49.

    Article  PubMed  CAS  Google Scholar 

  18. Evenson DP, Larson KL, Jost LK. Sperm chromatin structure assay: its clinical use for detecting sperm DNA fragmentation in male infertility and comparisons with other techniques. J Androl. 2002;23(1):25–43.

    PubMed  Google Scholar 

  19. Feng Z, Hu W, Tang MS. Trans-4-hydroxy-2-nonenal inhibits nucleotide excision repair in human cells: a possible mechanism for lipid peroxidation-induced carcinogenesis. Proc Natl Acad Sci U S A. 2004;101(23):8598–602. doi:10.1073/pnas.0402794101.

    Article  PubMed  CAS  Google Scholar 

  20. Gil-Villa AM, Cardona-Maya W, Agarwal A, Sharma R, Cadavid A. Assessment of sperm factors possibly involved in early recurrent pregnancy loss. Fertil Steril. 2010;94(4):1465–72. doi:10.1016/j.fertnstert.2009.05.042.

    Article  PubMed  Google Scholar 

  21. Gil-Villa AM, Cardona-Maya W, Agarwal A, Sharma R, Cadavid Á. Assessment of sperm factors possibly involved in early recurrent pregnancy loss. Fertil Steril. 2010;94(4):1465–72.

    Article  PubMed  Google Scholar 

  22. Gupta S, Agarwal A, Banerjee J, Alvarez JG (2007) The role of oxidative stress in spontaneous abortion and recurrent pregnancy loss: a systematic review. Obstet Gynecol Surv 62 (5):335–347; quiz 353–334. doi:10.1097/01.ogx.0000261644.89300.df

  23. Hamatani T, Falco G, Carter MG, Akutsu H, Stagg CA, Sharov AA, Dudekula DB, VanBuren V, Ko MS. Age-associated alteration of gene expression patterns in mouse oocytes. Hum Mol Genet. 2004;13(19):2263–78. doi:10.1093/hmg/ddh241.

    Article  PubMed  CAS  Google Scholar 

  24. Henkel R, Hajimohammad M, Stalf T, Hoogendijk C, Mehnert C, Menkveld R, Gips H, Schill WB, Kruger TF. Influence of deoxyribonucleic acid damage on fertilization and pregnancy. Fertil Steril. 2004;81(4):965–72. doi:10.1016/j.fertnstert.2003.09.044.

    Article  PubMed  CAS  Google Scholar 

  25. Janny L, Menezo YJ. Evidence for a strong paternal effect on human preimplantation embryo development and blastocyst formation. Mol Reprod Dev. 1994;38(1):36–42. doi:10.1002/mrd.1080380107.

    Article  PubMed  CAS  Google Scholar 

  26. Jaroudi S, Kakourou G, Cawood S, Doshi A, Ranieri DM, Serhal P, Harper JC, SenGupta SB. Expression profiling of DNA repair genes in human oocytes and blastocysts using microarrays. Hum Reprod. 2009;24(10):2649–55. doi:10.1093/humrep/dep224.

    Article  PubMed  CAS  Google Scholar 

  27. Larson-Cook KL, Brannian JD, Hansen KA, Kasperson KM, Aamold ET, Evenson DP. Relationship between the outcomes of assisted reproductive techniques and sperm DNA fragmentation as measured by the sperm chromatin structure assay. Fertil Steril. 2003;80(4):895–902.

    Article  PubMed  Google Scholar 

  28. Larson KL, DeJonge CJ, Barnes AM, Jost LK, Evenson DP. Sperm chromatin structure assay parameters as predictors of failed pregnancy following assisted reproductive techniques. Hum Reprod. 2000;15(8):1717–22.

    Article  PubMed  CAS  Google Scholar 

  29. Lewis SE, Aitken RJ. DNA damage to spermatozoa has impacts on fertilization and pregnancy. Cell Tissue Res. 2005;322(1):33–41. doi:10.1007/s00441-005-1097-5.

    Article  PubMed  CAS  Google Scholar 

  30. Marchesi DE, Feng HL. Sperm DNA integrity from sperm to egg. J Androl. 2007;28(4):481–9. doi:10.2164/jandrol.106.002105.

    Article  PubMed  CAS  Google Scholar 

  31. Menezo Y, Dale B, Cohen M. DNA damage and repair in human oocytes and embryos: a review. Zygote. 2010;18(4):357–65. doi:10.1017/S0967199410000286.

    Article  PubMed  CAS  Google Scholar 

  32. Oger I, Da Cruz C, Panteix G, Menezo Y. Evaluating human sperm DNA integrity: relationship between 8-hydroxydeoxyguanosine quantification and the sperm chromatin structure assay. Zygote. 2003;11(4):367–71.

    Article  PubMed  CAS  Google Scholar 

  33. Olsen AK, Duale N, Bjoras M, Larsen CT, Wiger R, Holme JA, Seeberg EC, Brunborg G. Limited repair of 8-hydroxy-7,8-dihydroguanine residues in human testicular cells. Nucleic Acids Res. 2003;31(4):1351–63.

    Article  PubMed  CAS  Google Scholar 

  34. Rai R, Regan L. Recurrent miscarriage. Lancet. 2006;368(9535):601–11.

    Article  PubMed  Google Scholar 

  35. Rubes J, Rybar R, Prinosilova P, Veznik Z, Chvatalova I, Solansky I, Sram RJ. Genetic polymorphisms influence the susceptibility of men to sperm DNA damage associated with exposure to air pollution. Mutat Res. 2010;683(1–2):9–15. doi:10.1016/j.mrfmmm.2009.09.010.

    PubMed  CAS  Google Scholar 

  36. Saleh RA, Agarwal A, Nada EA, El-Tonsy MH, Sharma RK, Meyer A, Nelson DR, Thomas AJ. Negative effects of increased sperm DNA damage in relation to seminal oxidative stress in men with idiopathic and male factor infertility. Fertil Steril. 2003;79 Suppl 3:1597–605.

    Article  PubMed  Google Scholar 

  37. Seli E, Gardner DK, Schoolcraft WB, Moffatt O, Sakkas D. Extent of nuclear DNA damage in ejaculated spermatozoa impacts on blastocyst development after in vitro fertilization. Fertil Steril. 2004;82(2):378–83. doi:10.1016/j.fertnstert.2003.12.039.

    Article  PubMed  Google Scholar 

  38. Shen H, Ong C. Detection of oxidative DNA damage in human sperm and its association with sperm function and male infertility. Free Radic Biol Med. 2000;28(4):529–36.

    Article  PubMed  CAS  Google Scholar 

  39. Spano M, Bonde JP, Hjollund HI, Kolstad HA, Cordelli E, Leter G. Sperm chromatin damage impairs human fertility. The Danish first pregnancy planner study team. Fertil Steril. 2000;73(1):43–50.

    Article  PubMed  CAS  Google Scholar 

  40. Stephenson M, Kutteh W. Evaluation and management of recurrent early pregnancy loss. Clin Obstet Gynecol. 2007;50(1):132–45. doi:10.1097/GRF.0b013e31802f1c28.

    Article  PubMed  Google Scholar 

  41. Tanaka H, Iguchi N, Isotani A, Kitamura K, Toyama Y, Matsuoka Y, Onishi M, Masai K, Maekawa M, Toshimori K, Okabe M, Nishimune Y. HANP1/H1T2, A novel histone H1-like protein involved in nuclear formation and sperm fertility. Mol Cell Biol. 2005;25(16):7107–19. doi:10.1128/MCB.25.16.7107-7119.2005.

    Article  PubMed  CAS  Google Scholar 

  42. 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. doi:10.1093/humrep/deh127.

    Article  PubMed  CAS  Google Scholar 

  43. Trisini AT, Singh NP, Duty SM, Hauser R. Relationship between human semen parameters and deoxyribonucleic acid damage assessed by the neutral comet assay. Fertil Steril. 2004;82(6):1623–32. doi:10.1016/j.fertnstert.2004.05.087.

    Article  PubMed  Google Scholar 

  44. Venkatesh S, Singh A, Shamsi MB, Thilagavathi J, Kumar R, Mitra DK, Dada R. Clinical significance of sperm DNA damage threshold value in the assessment of male infertility. Reprod Sci. 2011;18(10):1005–13. doi:10.1177/1933719111401662.

    Article  PubMed  CAS  Google Scholar 

  45. Virro MR, Larson-Cook KL, Evenson DP. Sperm chromatin structure assay (SCSA) parameters are related to fertilization, blastocyst development, and ongoing pregnancy in in vitro fertilization and intracytoplasmic sperm injection cycles. Fertil Steril. 2004;81(5):1289–95. doi:10.1016/j.fertnstert.2003.09.063.

    Article  PubMed  Google Scholar 

  46. WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. Cambridge: Cambridge University Press; 1999.

    Google Scholar 

  47. 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. doi:10.1093/humrep/den321.

    Article  PubMed  CAS  Google Scholar 

  48. Zini A, Meriano J, Kader K, Jarvi K, Laskin CA, Cadesky K. Potential adverse effect of sperm DNA damage on embryo quality after ICSI. Hum Reprod. 2005;20(12):3476–80. doi:10.1093/humrep/dei266.

    Article  PubMed  CAS  Google Scholar 

  49. Zini A, Phillips S, Courchesne A, Boman JM, Baazeem A, Bissonnette F, Kadoch IJ, San Gabriel M. Sperm head morphology is related to high deoxyribonucleic acid stainability assessed by sperm chromatin structure assay. Fertil Steril. 2009;91(6):2495–500. doi:10.1016/j.fertnstert.2008.03.032.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgment

The grant and support from Department of Biotechnology (BT/PR13558/MED/30/282/2010) is highly acknowledged.

Declaration of conflicting interests

The author(s) declared no potential conflicts of interests with respect to the authorship and/or publication of this article.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rima Dada.

Additional information

Capsule

Recurrent pregnancy loss affects 3-5% of couples and the aetiology is not known in about 40% of cases. Despite comprehensive analysis of all female factors leading to this condition, the male factor is ignored especially in cases conceived spontaneously. In this article we emphasized role of sperm DNA integrity in etiology of this condition and how it can impact management.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kumar, K., Deka, D., Singh, A. et al. Predictive value of DNA integrity analysis in idiopathic recurrent pregnancy loss following spontaneous conception. J Assist Reprod Genet 29, 861–867 (2012). https://doi.org/10.1007/s10815-012-9801-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10815-012-9801-3

Keywords

Navigation