Skip to main content
Log in

Chromatin Packaging as an Indicator of Human Sperm Dysfunction

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

Abstract

Purpose: Understanding the causes of fertilization failure is an important research field in assisted reproductive programs. The present study aimed to evaluated the possible relationship between chromatin packaging quality (CMA3 staining) and (i) normal morphology and (ii) its ability to predict the functional integrity of spermatozoa in both in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) treatment programs.

Methods: Semen of 140 men from IVF and ICSI couples were analyzed for sperm concentration, motility, morphology, and chromatin packaging (CMA3). For CMA3 classification, two cutoff values were used, namely, 44.5%±13 and 1 SD above the mean, i.e., 57.5% (rounded off to 60%). IVF and ICSI data were stratified using three basic cutoff values for CMA3 staining, namely, <44%, >44–60%, and >60%.

Results: Based on CMA3 results patients were divided into four groups, namely, group A, <44% CMA3 (n = 15, IVF); group B, ≥44% and <60% CMA3 (n = 39, IVF); group C, ≥60% CMA3 (n = 45 IVF); and group D, ≥60% CMA3(n = 41 ICSI). During receiver operator characteristic analyses the estimated cutoff value for CMA3 staining, to distinguish between <4% and ≥4% morphology groups, was 60%. The area under the curve was 0.89, sensitivity of 75%, and specificity of 100%. When IVF rates of >60% and <60% were used, the optimal CMA3 value for prediction of fertilization success again was recorded at 60%. The area under the curve was 0.76, sensitivity of 81.5%, and specificity of 63.6%.

Conclusions: Chromatin packaging assessments should be included as a complementary assay to the sequential diagnostic approach of the male-factor patients.

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.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Van Steirteghem AC, Nagy Z, Joris H, Liu J, Staessen C, Smitz J, Wisanto A, Devroey P: High fertilization and implantation rates after intracytoplasmic sperm injection. Hum Reprod 1993;8:1061-1066

    Google Scholar 

  2. Kruger TF, Menkveld R, Stander FSH, Lombard CJ, van der Merwe JP, van Zyl JA, Smith K: Sperm morphologic features as a prognostic factor in in vitro fertilization. Fertil Steril 1986;46:1118-1123

    Google Scholar 

  3. Nagy ZP, Lui J, Cecile J, Silber S, Devroey P, Van Steirteghem A: Using ejaculated, fresh, and frozen-thawed epdidymal and testicular spermatozoa gives rise to comparable results after intracytoplasmic sperm injection. Fertil Steril 1995;808-815

  4. Silber SJ, Van Steirteghem AC, Liu J, Nagy Z, Tournaye H, Devroey P: High fertilization and pregnancy rate after intracytoplasmic sperm injection with spermatozoa obtained from testicle biopsy. Hum Reprod 1995;10:148-152

    Google Scholar 

  5. Silber SJ, Nagy Z, Liu J, Tournaye H, Lissens W, Ferec C, Liebaers I, Devroey P, Van Steirteghem AC: The use of epididymal and testicular spermatozoa for intracytoplasmic sperm injection: The genetic implications for male infertility. Hum Reprod 1995;10:2031-2043

    Google Scholar 

  6. Kent-First M, Kol S, Muallem, A Blazer S, Itskovitz-Eldor J: Infertility in intracytoplasmic sperm injection derived sons. Lancet 1997;348:332-

    Google Scholar 

  7. De Jonge C. Attributes of fertile spermatozoa: An update. J Androl 1999;20:463-473

    Google Scholar 

  8. Consensus Workshop on Advanced Diagnostic Andrology Techniques: ESHRE Andrology Special Interest Group. Hum Reprod 1996;11:1463-1479

    Google Scholar 

  9. Pandiyan N, Jequier A: Mitotic chromosomal anomalies among 1210 infertile men. Hum Reprod 1996;11:2604-2608

    Google Scholar 

  10. Manicardi GC, Bianchi PG, Pantano S, Azzoni P, Bizzaro D, Bianchi U, Sakkas D: Presence of endogenous nicks in DNA of ejaculated human spermatozoa and its relationship to chromomycin A3 accessibility. Biol Reprod 1995;52:864-867

    Google Scholar 

  11. Sakkas D: The use of blastocyst culture to avoid inheritance of an abnormal paternal genome after ICSI. Hum Reprod 1999;14:4-5

    Google Scholar 

  12. Bianchi PG, Manicardi GC, Urner F, Campana A, Sakkas D: Chromatin packaging and morphology in ejaculated human spermatozoa: evidence of hidden anomalies in normal spermatozoa. Mol Hum Reprod 1996;2:139-144

    Google Scholar 

  13. Balhorn R: Mammalian protamine: Structures and molecular interactions. In Molecular Biology of Chromosome Function, KW Adolph (ed). New York, Springer Verlag pp 366-395

  14. Franken DR, Franken CJ, de la Guerre H, de Villiers A: Normal sperm morphology and chromatin packaging: Comparison between analine blue and chromomycin A3 staining. Andrologia 1999;31:361-366

    Google Scholar 

  15. Granberg, M: Manual of Recommended Use of Scandinavian IVF Science Products, 2nd ed. 1999

  16. World Health Organization. WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interaction, 3rd ed. Cambridge, England, Cambridge University Press, 1992, p 23

    Google Scholar 

  17. Geigy scientific tables. In Physical Chemistry Composition of Blood Hematology, Somatometric Data, Vol 3, C Lentner (ed). Ciba Geigy, pp 58-59

  18. Altman DG, Bland JM: Diagnostic tests, 3: Receiver operating characteristic plots. Br Med J 1994;309:188-

    Google Scholar 

  19. Schatten G, Hewittson L, Simerly C, Sutovsky P, Huszar G: Cell and molecular biological challenges of ICSI. ART before science? L Law Med Nas Ethics 1998;26:29-37

    Google Scholar 

  20. Sakkas D. Bianchi PG, Manicardi G, Bizzaro D, Bianchi U: Chromatin packaging anomalies and DNA damage in human sperm: Their possible implications in the treatment of male factor infertility. In Genetics of Human Male Fertility. C Barratt, C De Jonge, D Mortimer, J Parinaud (eds). EDK, 1997, pp 205-221

  21. Corczyca W, Traganos F, Jesionowska H, Darzynkiewicz Z: Presence of DNA strand breaks and increased sensitivity of DNA in situ to denaturation in abnormal human sperm cells. Analogy to apoptosis of somatic cells. Exp Cell Res 1993;207:202-205

    Google Scholar 

  22. Bianchi PG, Manicardi GC, Bizzaro D, Bianchi U Sakkas D: Effect of DNA protamination on fluorochrome staining and in situ nick-translation of murine and human mature spermatozoa. Biol Reprod 1993;49:1038-1043

    Google Scholar 

  23. Evenson D, Jost L, Marshall D, et al.: Utility of sperm chromatin structure assay (SCSA) as adiagnostic and prognostic tool in the human fertility clinic. Hum Reprod 1999;14:1039-1049

    Google Scholar 

  24. Oehninger S, Acosta A, Veeck L, Brzyski R, Kruger TF, Muasher SJ, Hodgen GD: Recurrent failure of in vitro fertilization: Role of the hemizona assay in the sequential diagnosis of specific sperm-oocyte defects. Am J Obstet Gynecol 1991;164:1210-1215

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Esterhuizen, A.D., Franken, D.R., Lourens, J.G.H. et al. Chromatin Packaging as an Indicator of Human Sperm Dysfunction. J Assist Reprod Genet 17, 508–514 (2000). https://doi.org/10.1023/A:1009493824953

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1009493824953

Navigation