Journal of Assisted Reproduction and Genetics

, Volume 30, Issue 11, pp 1471–1475 | Cite as

A prospective randomized study to evaluate the effect of hyaluronic acid sperm selection on the intracytoplasmic sperm injection outcome of patients with unexplained infertility having normal semen parameters

Assisted Reproduction Technologies



Sperm quality plays an important role in determining embryo development and intracytoplasmic sperm injection (ICSI) outcome. Selection of competent sperm based on its ability to bind to hyaluronic acid (HA) has been suggested as one of the methods to assess sperm quality. The aim of the present study was to examine whether injection of HA bound sperm helps in improving outcome in patients undergoing ICSI with unexplained infertility having normal semen parameters.


Patients with unexplained infertility having normal semen parameters in accordance with WHO 2010 criterion, undergoing their first IVF-ICSI cycle were enrolled during the course of the study.156 patients were prospectively randomized after oocyte retrieval and were assigned to either the ICSI group, where sperm selection for injection was based on visual assessment, or the PICSI group, where sperm were selected based on their ability to bind to HA. Only fresh embryo transfers were included in the analysis.


There was no difference in the fertilization rates, number of top quality embryos and clinical pregnancy rates between the ICSI and PICSI groups (65.7 % vs 64.7 %; 45.8 % vs 43.6 % and 35 % vs 35.2 % respectively). However, a higher pregnancy loss rate was observed in the ICSI group (25 % vs 12 %; P = 0.227) as compared to the PICSI group, but the difference was not statistically significant. Implantation rates were 22.03 % and 18.84 % in the PICSI and ICSI groups respectively. There were 22 (31 %) live births in the PICSI group and 21(26.3 %) live births in the ICSI group.


Patients with unexplained infertility having normal semen parameters may constitute a patient group which does not benefit from this sperm selection method. A larger study may be necessary to establish a relationship between PICSI and pregnancy loss rate in patients undergoing IVF with unexplained infertility.


Hyaluronic acid binding Sperm selection PICSI Unexplained infertility Pregnancy loss rate 



The authors would like to express their gratitude to Shweta Gupta and Ruma Satwik for giving valuable inputs in the study, the team of embryologists working in the IVF laboratory and all patients who participated in the study.

Conflict of interest

The authors declare they have no conflict of interest.


  1. 1.
    Huszar G. Hyaluronic acid binding-mediated sperm selection for ICSI. In: Gardner DK, Weissman A, Howles CM, Shoham Z, editors. Textbook of assisted reproductive techniques. London; 2011. pp.122–34.Google Scholar
  2. 2.
    Huszar G, Ozenci CC, Cayli S, Zavaczki Z, Hansch E, Vigue L. Hyaluronic acid binding by human sperm indicates cellular maturity, viability, and unreacted acrosomal status. Fertil Steril. 2003;79 Suppl 3:1616–24.PubMedCrossRefGoogle Scholar
  3. 3.
    Huszar G, Jakab A, Sakkas D, Ozenci CC, Cayli S, Delpiano E, et al. Fertility testing and ICSI sperm selection by hyaluronic acid binding: Clinical and genetic aspects. Reprod Biomed Online. 2007;14:650–63.PubMedCrossRefGoogle Scholar
  4. 4.
    Cayli S, Jakab A, Ovari L, Delpiano E, Celik-Ozenci C, Sakkas D, et al. Biochemical markers of sperm function: Male fertility and sperm selection for ICSI. Reprod Biomed Online. 2003;7:462–8.PubMedCrossRefGoogle Scholar
  5. 5.
    Prinosilova P, Kruger T, Sati L, Ozkavukcu S, Vigue L, Kovanci E, et al. Selectivity of hyaluronic acid binding for spermatozoa with normal Tygerberg strict morphology. Reprod Biomed Online. 2009;18:177–83.PubMedCrossRefGoogle Scholar
  6. 6.
    Jakab A, Sakkas D, Delpiano E, Cayli S, Kovanci E, Ward D, et al. Intracytoplasmic sperm injection: A novel selection method for sperm with normal frequency of chromosomal aneuploidies. Fertil Steril. 2005;84:1665–73.PubMedCrossRefGoogle Scholar
  7. 7.
    Parmegiani L, Cognigni GE, Bernardi S, Troilo E, Ciampaglia W, Filicori M. “Physiologic ICSI”: Hyaluronic acid (HA) favors selection of spermatozoa without DNA fragmentation and with normal nucleus, resulting in improvement of embryo quality. Fertil Steril. 2010 Feb;93(2):598–604.Google Scholar
  8. 8.
    Nasr-Esfahani MH, Razavi S, Vahdati AA, Fathi F, Tavalaee M. Evaluation of sperm selection procedure based on hyaluronic acid binding ability on ICSI outcome. J Assist Reprod Genet. 2008;25:197–203.PubMedCrossRefGoogle Scholar
  9. 9.
    Parmegiani L, Cognigni GE, Ciampaglia W, Pocognoli P, Marchi F, Filicori M. Efficiency of hyaluronic acid (HA) sperm selection. J Assist Reprod Genet. 2010;27:13–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Ménézo Y, Nicollet B. Replacement of PVP by hyaluronate (SpermSlow™) in ICSI—Impact on outcome. 2004 Abstract of 18th World Congress on Fertility and Sterility IFFS.Google Scholar
  11. 11.
    Worrilow KC, Huynh T, Bower JB, Anderson AR, Schillings W, Crain JL. PICSI VS ICSI: statistically significant improvement in clinical outcomes in 240 in vitro fertilization (IVF) patients. Fertil Steril 2007; 88 Supp 1: s37.Google Scholar
  12. 12.
    Menezo Y, Junca AM, Dumont M, De Mouzon J, Cohen-Bacrie P, Ben KM. "Physiologic" (hyaluronic acid-carried) ICSI results in the same embryo quality and pregnancy rates as with the use of potentially toxic polyvinylpyrrolidone (PVP). Fertil Steril. 2010;94:S232.CrossRefGoogle Scholar
  13. 13.
    Castillo-Baso J, Garcia-Villafaña G, Santos-Haliscak R, Diaz P, Sepluveda-Gonzalez J, Hernandez-Ayup S. Embryo quality and reproductive outcomes of spermatozoa selected by physiologic-icsi or conventional icsi in patients with kruger <4% and >4% normo-morphology. Fertil Steril. 2011;96:S159.CrossRefGoogle Scholar
  14. 14.
    Worrilow KC, Eid S, Woodhouse D, Witmyer J, Khoury C, Liebermann J. Increased clinical pregnancy rates (CPR) and statistically significant decrease in loss rates using hyaluronan in sperm selection: prospective, multi-center, double-blind, randomized clinical trial. Fertil Steril. 2011;96:S179.CrossRefGoogle Scholar
  15. 15.
    Worrilow KC, Eid S, Woodhouse D, Perloe M, Smith S, Witmyer J, et al. Use of hyaluronan in the selection of sperm for intracytoplasmic sperm injection (ICSI): Significant improvement in clinical outcomes–multicenter, double-blinded and randomized controlled trial. Hum Reprod. 2013;28(2):306–14.PubMedCrossRefGoogle Scholar
  16. 16.
    WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: World Health Organization; 2010.Google Scholar
  17. 17.
    Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group of Embryology. The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting. Hum Reprod. 2011;26:1270–1283Google Scholar
  18. 18.
    Choe SA, Tae JC, Shin MY, Kim HJ, Kim CH, Lee JY, et al. Application of sperm selection using hyaluronic acid binding in intracytoplasmic sperm injection cycles: A sibling oocyte study. J Korean Med Sci. 2012 December;27(12):1569–73.Google Scholar
  19. 19.
    Yagci A, Murk W, Stronk J, Huszar G. Spermatozoa bound to solid state hyaluronic acid show chromatin structure and high DNA chain intergrity: An acridine orange fluorescence study. J Androl. 2010;31(6):566–72.PubMedCrossRefGoogle Scholar
  20. 20.
    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;19:611.PubMedCrossRefGoogle Scholar
  21. 21.
    Tesarik J. The paternal effects on cell division in the human preimplantation embryo. Reprod Biomed Online. 2005;10:370.PubMedCrossRefGoogle Scholar
  22. 22.
    Pfeifer S, Fritz M, Goldberg J, McClure RD, Lobo R, Thomas M, et al. Intracytoplasmic sperm injection (ICSI) for non male factor infertility: A committee opinion. Fertil Steril. 2012;98(6):1395–9.Google Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Center of IVF and Human Reproduction, Institute of Obstetrics and GynaecologySir Ganga Ram HospitalNew DelhiIndia

Personalised recommendations