Advertisement

Journal of Assisted Reproduction and Genetics

, Volume 29, Issue 9, pp 861–867 | Cite as

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

  • Kishlay Kumar
  • Deepika Deka
  • Amar Singh
  • D. K. Mitra
  • B. R. Vanitha
  • Rima DadaEmail author
ASSISTED REPRODUCTION TECHNOLOGIES

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.

Keywords

Idiopathic recurrent pregnancy loss SCSA DFI Sperm 

Notes

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.

References

  1. 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.PubMedCrossRefGoogle Scholar
  2. 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.PubMedCrossRefGoogle Scholar
  3. 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.PubMedCrossRefGoogle Scholar
  4. 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.PubMedCrossRefGoogle Scholar
  5. 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.PubMedCrossRefGoogle Scholar
  6. 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.PubMedCrossRefGoogle Scholar
  7. 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. 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.PubMedCrossRefGoogle Scholar
  9. 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.PubMedCrossRefGoogle Scholar
  10. 10.
    Bungum MP, Humaidan, et al. Sperm DNA integrity assessment in prediction of assisted reproduction technology outcome. Hum Reprod. 2007;22(1):174–9.PubMedCrossRefGoogle Scholar
  11. 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.PubMedCrossRefGoogle Scholar
  12. 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.PubMedCrossRefGoogle Scholar
  13. 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.PubMedCrossRefGoogle Scholar
  14. 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.PubMedGoogle Scholar
  15. 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.PubMedCrossRefGoogle Scholar
  16. 16.
    Evenson D, Jost L. Sperm chromatin structure assay is useful for fertility assessment. Methods Cell Sci. 2000;22(2–3):169–89.PubMedCrossRefGoogle Scholar
  17. 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.PubMedCrossRefGoogle Scholar
  18. 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.PubMedGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. 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.PubMedCrossRefGoogle Scholar
  22. 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. 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.PubMedCrossRefGoogle Scholar
  24. 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.PubMedCrossRefGoogle Scholar
  25. 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.PubMedCrossRefGoogle Scholar
  26. 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.PubMedCrossRefGoogle Scholar
  27. 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.PubMedCrossRefGoogle Scholar
  28. 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.PubMedCrossRefGoogle Scholar
  29. 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.PubMedCrossRefGoogle Scholar
  30. 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.PubMedCrossRefGoogle Scholar
  31. 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.PubMedCrossRefGoogle Scholar
  32. 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.PubMedCrossRefGoogle Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 34.
    Rai R, Regan L. Recurrent miscarriage. Lancet. 2006;368(9535):601–11.PubMedCrossRefGoogle Scholar
  35. 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.PubMedGoogle Scholar
  36. 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.PubMedCrossRefGoogle Scholar
  37. 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.PubMedCrossRefGoogle Scholar
  38. 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.PubMedCrossRefGoogle Scholar
  39. 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.PubMedCrossRefGoogle Scholar
  40. 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.PubMedCrossRefGoogle Scholar
  41. 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.PubMedCrossRefGoogle Scholar
  42. 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.PubMedCrossRefGoogle Scholar
  43. 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.PubMedCrossRefGoogle Scholar
  44. 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.PubMedCrossRefGoogle Scholar
  45. 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.PubMedCrossRefGoogle Scholar
  46. 46.
    WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction. Cambridge: Cambridge University Press; 1999.Google Scholar
  47. 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.PubMedCrossRefGoogle Scholar
  48. 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.PubMedCrossRefGoogle Scholar
  49. 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.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Kishlay Kumar
    • 1
  • Deepika Deka
    • 2
  • Amar Singh
    • 3
  • D. K. Mitra
    • 3
  • B. R. Vanitha
    • 2
  • Rima Dada
    • 1
    Email author
  1. 1.Laboratory for Molecular Reproduction and Genetics, Department of AnatomyAll India Institute of Medical SciencesNew Delhi 29India
  2. 2.Department of Obstetrics and GynaecologyAll India Institute of Medical SciencesNew DelhiIndia
  3. 3.Department of Transplant ImmunologyAll India Institute of Medical SciencesNew DelhiIndia

Personalised recommendations