Intracytoplasmic Morphologically Selected Sperm Injection (IMSI): Indications and Clinical Results

  • Nino Guy Cassuto
  • André Hazout


High magnification opens different approaches of sperm head morphology examination.

To understand the correlation between sperm normalcy, fertilization, and early embryo development we established, a detailed sperm scoring classification according to strict morphology criteria; permitting to discard the worst spermatozoon, in real time, prior intracytoplasmic sperm injection.

Our consideration of maternal age correlated to sperm score revealed a difference between oocytes from women younger than 30 and oocytes from elderly women.

We showed that high-magnified spermatozoa, in cases of Robertsonian translocation carriers cannot be used to select sperm cells with a balanced chromosomal content.

However, there is a significant correlation between sperm-head morphology assessed by high magnification and sperm chromatin-decondensation rate of specific kind of spermatozoa.

This suggests that this spermatozoon should not be selected for intracytoplasmic sperm injection and must be discarded.

The high magnified spermatozoon observation seems to impact the birth outcome leading to lower risks of major malformation mainly affecting urogenital system and more often boys.


Pregnancy Rate Miscarriage Rate Clinical Pregnancy Rate Sperm Head Sperm Nucleus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



J.R. Kovac is an NIH K12 scholar supported by a Male Reproductive Health Research (MRHR) Career Development Physician-Scientist Award (HD073917-01) from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Program awarded to Dolores J. Lamb (DJL). DJL is supported by NIH grants P01HD36289 from the Eunice Kennedy Shriver NICHD and 1R01DK078121 from the National Institute of Kidney and Digestive Diseases.


  1. 1.
    Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992;340(8810):17–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Bartoov B, Berkovitz A, Eltes F. Selection of spermatozoa with normal nuclei to improve the pregnancy rate with intracytoplasmic sperm injection. N Engl J Med. 2001;345(14):1067–8.PubMedCrossRefGoogle Scholar
  3. 3.
    Bartoov B, Berkovitz A, Eltes F, Kogosowski A, Menezo Y, Barak Y. Real-time fine morphology of motile human sperm cells is associated with IVF-ICSI outcome. J Androl. 2002;23(1):1–8.PubMedGoogle Scholar
  4. 4.
    Bartoov B, Berkovitz A, Eltes F, et al. Pregnancy rates are higher with intracytoplasmic morphologically selected sperm injection than with conventional intracytoplasmic injection. Fertility and Sterility. 2003;80: 1413–9.PubMedCrossRefGoogle Scholar
  5. 5.
    Vanderzwalmen P, Hiemer A, Rubner P, Bach M, Neyer A, Stecher A, Uher P, Zintz M, Lejeune B, Vanderzwalmen S, Cassuto G, Zech NH. Blastocyst development after sperm selection at high magnification is associated with size and number of nuclear vacuoles. Reprod Biomed Online. 2008;17:617–27.PubMedCrossRefGoogle Scholar
  6. 6.
    Berkovitz A, Eltes F, Ellenbogen E, et al. Does the presence of nuclear vacuoles in human sperm selected for ICSI affect pregnancy outcome? Human Reproduction. 2006;21:1787–90.PubMedCrossRefGoogle Scholar
  7. 7.
    Greco E, Scarselli F, Fabozzi G, Colasante A, Zavaglia D, Alviggi E, Litwicka K, Varricchio MT, Minasi MG, Tesarik J. Sperm vacuoles negatively affect outcomes in intracytoplasmic morphologically selected sperm injection in terms of pregnancy, implantation, and live-birth rates. Fertil Steril. 2013;100(2):379–85.PubMedCrossRefGoogle Scholar
  8. 8.
    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;24:211–8.PubMedCrossRefGoogle Scholar
  9. 9.
    Tanaka A, Nagayoshi M, Tanaka I, Kusunoki H. Human sperm head vacuoles are physiological structures formed during the sperm development and maturation process. Fertil Steril. 2012;98(2):315–20.PubMedCrossRefGoogle Scholar
  10. 10.
    Cassuto NG, Bouret D, Plouchart JM, Jellad S, Vanderzwalmen P, Balet R, Larue L, Barak Y. A new real-time morphology classification for human spermatozoa: a link for fertilization and improved embryo quality. Fertil Steril. 2009;92:1616–25.PubMedCrossRefGoogle Scholar
  11. 11.
    Cassuto N, Le Foll N, Chantot-Bastaraud S, Balet R, Bouret D, Rouen A, Bhouri R, Hyon C, Siffroi JP. Sperm fluorescence in situ hybridization study in nine men carrying a Robertsonian or a reciprocal translocation: relationship between segregation modes and high-magnification sperm morphology examination. Fertil Steril. 2011;96(4):826–32.PubMedCrossRefGoogle Scholar
  12. 12.
    De Vos A, Van De Velde H, Joris H, Verheyen G, Devroey P, Van Steirteghem A. Influence of individual sperm morphology on fertilization, embryo morphology, and pregnancy outcome of intracytoplasmic sperm injection. Fertil Steril. 2003;79:42–8.PubMedCrossRefGoogle Scholar
  13. 13.
    Antinori M, Licata E, Dani G, Cerusico F, Versaci C, d’Angelo D, Antinori S. Intracytoplasmic morphologically selected sperm injection: a prospective randomized trial. Reprod Biomed online. 2008;16:835–41.PubMedCrossRefGoogle Scholar
  14. 14.
    Wilding M, Coppola G, di Matteo L, Palagiano A, Fusco E, Dale B. Intracytoplasmic injection of morphologically selected spermatozoa (IMSI) improves outcome after assisted reproduction by deselecting physiologically poor quality spermatozoa. J Assist Reprod Genet. 2011;28(3):253–62.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Setti AS, Figueira RC, Braga DP, Aoki T, Iaconelli Jr A, Borges Jr E. Intracytoplasmic morphologically selected sperm injection is beneficial in cases of advanced maternal age: a prospective randomized study. Eur J Obstet Gynecol Reprod Biol. 2013;171(2):286–90.PubMedCrossRefGoogle Scholar
  16. 16.
    Cassuto NG, Hazout A, Bouret D, Balet R, Larue L, Benifla JL, Viot G. Low birth defects by deselecting abnormal spermatozoa before ICSI. Reprod BioMed Online. 2014;28(1):47–53.PubMedCrossRefGoogle Scholar
  17. 17.
    Simon L, Proutski I, Stevenson M, Jennings D, McManus J, Lutton D, Lewis SE. Sperm DNA damage has a negative association with live-birth rates after IVF. Reprod Biomed Online. 2013;26:68–78.PubMedCrossRefGoogle Scholar
  18. 18.
    Aitken RJ, Nixon B. Sperm capacitation: a distant landscape glimpsed but unexplored. Mol Hum Reprod. 2013;19(12):785–93.PubMedCrossRefGoogle Scholar
  19. 19.
    Avendano C, Oehninger S. DNA fragmentation in morphologically normal spermatozoa: how much should we be concerned in the ICSI era? J Androl. 2011;32:356–63.PubMedCrossRefGoogle Scholar
  20. 20.
    Teixeira DM, Barbosa MA, Ferriani RA, Navarro PA, Raine-Fenning N, Nastri CO, Martins WP. Regular (ICSI) versus ultra-high magnification (IMSI) sperm selection for assisted reproduction. Cochrane Database Syst Rev. 2013; 7: CD010167Google Scholar
  21. 21.
    Klement AH, Koren-Morag N, Itsykson P, Berkovitz A. Intracytoplasmic morphologically selected sperm injection versus intracytoplasmic sperm injection: a step toward a clinical algorithm. Fertil Steril. 2013;99(5):1290–3.PubMedCrossRefGoogle Scholar
  22. 22.
    Marci R, Murisier F, Lo Monte G, Soave I, Chanson A, Urner F, Germond M. Clinical outcome after IMSI procedure in an unselected infertile population: a pilot study. Reprod Health. 2013;10:16.PubMedCentralPubMedCrossRefGoogle Scholar
  23. 23.
    De Vos A, Van de Velde H, Bocken G, Eylenbosch G, Franceus N, Meersdom G, Tistaert S, Vankelecom A, Tournaye H, Verheyen G. Does intracytoplasmic morphologically selected sperm injection improve embryo development? A randomized sibling-oocyte study. Hum Reprod. 2013;28:617–26.PubMedCrossRefGoogle Scholar
  24. 24.
    Balaban B, Yakin K, Alatas C, Oktem O, Isiklar A, Urman B. Clinical outcome of intracytoplasmic injection of spermatozoa morphologically selected under high magnification: a prospective randomized study. Reprod Biomed Online. 2011;22:472–6.CrossRefGoogle Scholar
  25. 25.
    Souza Setti A, Ferreira RC, de Almeida P, Ferreira Braga D, de Cassia Savio Figueira R, Iaconelli Jr A, Borges Jr E. Intracytoplasmic sperm injection outcome versus intracytoplasmic morphologically selected sperm injection outcome: a meta-analysis. Reprod Biomed Online. 2010;21:450–5.PubMedCrossRefGoogle Scholar
  26. 26.
    Hazout A, Dumont-Hassan M, Junca AM, et al. High-magnification ICSI overcomes paternal effect resistant to conventional ICSI. Reprod Biomed Online. 2006;12:19–25.PubMedCrossRefGoogle Scholar
  27. 27.
    Pedersen H. Ultrastructure of the ejaculated human sperm. Z Zellforsch Mikrosk Anat. 1969;94:542–54.PubMedCrossRefGoogle Scholar
  28. 28.
    Garolla A, Fortini D, Menegazzo M, De Toni L, Nicoletti V, Moretti A, Selice R, Engl B, Foresta C. High-power microscopy for selecting spermatozoa for ICSI by physiological status. Reprod Biomed Online. 2008;17:610–6.PubMedCrossRefGoogle Scholar
  29. 29.
    Perdrix A, Travers A, Chelli MH, Escalier D, Do Rego JL, Milazzo JP, Mousset-Simeon N, Mace B, Rives N. Assessment of acrosome and nuclear abnormalities in human spermatozoa with large vacuoles. Hum Reprod. 2011;26:47–58.PubMedCrossRefGoogle Scholar
  30. 30.
    Berkovitz A, Eltes F, Lederman H, et al. How to improve IVF-ICSI outcome by sperm selection. Reprod Biomed Online. 2006;12:634–8.PubMedCrossRefGoogle Scholar
  31. 31.
    Boitrelle F, Ferfouri F, Petit JM, Segretain D, Tourain C, Bergere M, Bailly M, Vialard F, Albert M, Selva J. Large human sperm vacuoles observed in motile spermatozoa under high magnification: nuclear thumbprints linked to failure of chromatin condensation. Hum Reprod. 2011;26:1650–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Franco Jr JG, Baruffi RL, Mauri AL, Petersen CG, Oliveira JB, Vagnini L. Significance of large nuclear vacuoles in human spermatozoa: implications for ICSI. Reprod Biomed Online. 2008;17:42–5.PubMedCrossRefGoogle Scholar
  33. 33.
    Franco Jr JG, Mauri AL, Petersen CG, Massaro FC, Silva LF, Felipe V, Cavagna M, Pontes A, Baruffi RL, Oliveira JB, Vagnini LD. Large nuclear vacuoles are indicative of abnormal chromatin packaging in human spermatozoa. Int J Androl. 2012;35:46–51.PubMedCrossRefGoogle Scholar
  34. 34.
    Oliveira JB, Massaro FC, Baruffi RL, Mauri AL, Petersen CG, Silva LF, Vagnini LD, Franco Jr JG. Correlation between semen analysis by motile sperm organelle morphology examination and sperm DNA damage. Fertil Steril. 2010;94:1937–40.PubMedCrossRefGoogle Scholar
  35. 35.
    Watanabe S, Tanaka A, Fujii S, Mizunuma H, Fukui A, Fukuhara R, Nakamura R, Yamada K, Tanaka I, Awata S, Nagayoshi M. An investigation of the potential effect of vacuoles in human sperm on DNA damage using a chromosome assay and the TUNEL assay. Hum Reprod. 2011;26:978–86.PubMedCrossRefGoogle Scholar
  36. 36.
    Montjean D, Belloc S, Benkhalifa M, Dalleac A, Menezo Y. Sperm vacuoles are linked to capacitation and acrosomal status. Hum Reprod. 2012;27:2927–32.PubMedCrossRefGoogle Scholar
  37. 37.
    Kacem O, Sifer C, Barraud-Lange V, Ducot B, De Ziegler D, Poirot C, Wolf J. Sperm nuclear vacuoles, as assessed by motile sperm organellar morphological examination, are mostly of acrosomal origin. Reprod Biomed Online. 2011;20:132–7.CrossRefGoogle Scholar
  38. 38.
    Hammoud I, Boitrelle F, Ferfouri F, Vialard F, Bergere M, Wainer B, Bailly M, Albert M, Selva J. Selection of normal spermatozoa with a vacuole-free head (·6300) improves selection of spermatozoa with intact DNA in patients with High sperm DNA fragmentation rates. Andrologia. 2013;45:163–70.PubMedCrossRefGoogle Scholar
  39. 39.
    Tesarik J, Greco E, Mendoza C. Late, but not early, paternal effect on human embryo development is related to sperm DNA fragmentation. Human Reproduction. 2004;19:611–5.PubMedCrossRefGoogle Scholar
  40. 40.
    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;21:2876–81.PubMedCrossRefGoogle Scholar
  41. 41.
    Miller D, Brinkworth M, Iles D. Paternal DNA packaging in spermatozoa: more than the sum of its parts? DNA, histones, protamines and epigenetics. Reproduction. 2010;139:287–301.PubMedCrossRefGoogle Scholar
  42. 42.
    Palermo GD, Neri QV, Takeuchi T, Squires J, Moy F, Rosenwaks Z. Genetic and epigenetic characteristics of ICSI children. Reprod Biomed Online. 2008;17: 820–33.PubMedCrossRefGoogle Scholar
  43. 43.
    Setti AS, Ferreira Braga DP, Iaconelli A, Aoki T, Borges E. Twelve years of MSOME and IMSI: a review. Reproductive BioMedicine Online. 2013;27:338–52.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  1. 1.Art UnitDrouot LaboratoryParisFrance

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