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High prevalence of genetic abnormalities in Middle Eastern patients with idiopathic non-obstructive azoospermia

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

Abstract

Introduction

Our objective is to detect the frequency and types of major genetic abnormalities of idiopathic non-obstructive azoospermia (NOA) to give appropriate genetic counseling before assisted reproductive techniques (ART) in Middle East and to compare the frequencies with other regions of the world.

Material and methods

A total of 880 Middle Eastern patients with NOA were recruited in this multicenter study for genetic evaluation prior to use of ART. Karyotyping was performed on peripheral blood lymphocytes according to standard G-banding methods, polymerase chain reaction (PCR) was performed to screen the microdeletions in the AZF region of the Y chromosome.

Results

The present study shows that the total prevalence of genetic abnormalities is 28.41 %, including 184 patients (20.91 %) with chromosome disorder and 66 patients (7.5 %) with Y chromosome microdeletions. The most prevalent chromosome abnormality is Klinefelter’s syndrome, which includes 161 patients (18.3 %), 7 patients had XX reversal male sex (0.8 %), 2 patients had 47XYY (0.23 %) and 2 patients had 45XO/46XY (0.23 %). Structural abnormalities occurred in 12 patients (1.36 %).

Conclusions

The high prevalence of genetic abnormalities (28.41 %) in our study strongly suggests the need for routine genetic testing and counseling prior to assisted reproduction in such population with idiopathic infertility, as a result may help determine the prognosis, as well as the choice of ART. Moreover it allows specific pre-implantation genetic testing to minimize the risk of transmitting genetic defects to offspring.

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References

  1. Mittal RD et al. Y chromosome micro-deletions in idiopathic infertility from Northern India. Ann Genet. 2004;47(4):331–7.

    Article  PubMed  Google Scholar 

  2. Ferlin A, Arredi B, Foresta C. Genetic causes of male infertility. Reprod Toxicol. 2006;22(2):133–41.

    Article  PubMed  CAS  Google Scholar 

  3. Shefi S, Turek PJ. Definition and current evaluation of subfertile men. Int Braz J Urol. 2006;32(4):385–97.

    Article  PubMed  Google Scholar 

  4. Kleiman SE et al. Genetic evaluation of infertile men. Hum Reprod. 1999;14(1):33–8.

    Article  PubMed  CAS  Google Scholar 

  5. Vutyavanich T et al. Frequency of Y chromosome microdeletions and chromosomal abnormalities in infertile Thai men with oligozoospermia and azoospermia. Asian J Androl. 2007;9(1):68–75.

    Article  PubMed  CAS  Google Scholar 

  6. de Kretser DM. Male infertility. Lancet. 1997;349(9054):787–90.

    Article  PubMed  Google Scholar 

  7. Dohle GR et al. Genetic risk factors in infertile men with severe oligozoospermia and azoospermia. Hum Reprod. 2002;17(1):13–6.

    Article  PubMed  CAS  Google Scholar 

  8. Van Assche E et al. Cytogenetics of infertile men. Hum Reprod. 1996;11 Suppl 4:1–24. discussion 25–6.

    Article  PubMed  Google Scholar 

  9. Koulischer L, Schoysman R. Chromosomes and human infertility. I. Mitotic and meiotic chromosome studies in 202 consecutive male patients. Clin Genet. 1974;5(2):116–26.

    Article  PubMed  CAS  Google Scholar 

  10. Chandley AC. The chromosomal basis of human infertility. Br Med Bull. 1979;35(2):181–6.

    PubMed  CAS  Google Scholar 

  11. Ezeh UI. Beyond the clinical classification of azoospermia: opinion. Hum Reprod. 2000;15(11):2356–9.

    Article  PubMed  CAS  Google Scholar 

  12. Sharif K. Reclassification of azoospermia: the time has come? Hum Reprod. 2000;15(2):237–8.

    Article  PubMed  CAS  Google Scholar 

  13. Ezeh UI et al. Establishment of predictive variables associated with testicular sperm retrieval in men with non-obstructive azoospermia. Hum Reprod. 1999;14(4):1005–12.

    Article  PubMed  CAS  Google Scholar 

  14. McLachlan RI et al. Genetic disorders and spermatogenesis. Reprod Fertil Dev. 1998;10(1):97–104.

    Article  PubMed  CAS  Google Scholar 

  15. Briton-Jones C, Haines CJ. Microdeletions on the long arm of the Y chromosome and their association with male-factor infertility. Hong Kong Med J. 2000;6(2):184–9.

    PubMed  CAS  Google Scholar 

  16. Vicdan A et al. Genetic aspects of human male infertility: the frequency of chromosomal abnormalities and Y chromosome microdeletions in severe male factor infertility. Eur J Obstet Gynecol Reprod Biol. 2004;117(1):49–54.

    Article  PubMed  CAS  Google Scholar 

  17. Hucklenbroich K et al. Partial deletions in the AZFc region of the Y chromosome occur in men with impaired as well as normal spermatogenesis. Hum Reprod. 2005;20(1):191–7.

    Article  PubMed  CAS  Google Scholar 

  18. Bache I et al. An excess of chromosome 1 breakpoints in male infertility. Eur J Hum Genet. 2004;12(12):993–1000.

    Article  PubMed  CAS  Google Scholar 

  19. Hellani A et al. Y chromosome microdeletions in infertile men with idiopathic oligo- or azoospermia. J Exp Clin Assist Reprod. 2006;3:1.

    Article  PubMed  Google Scholar 

  20. Reijo R et al. Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene. Nat Genet. 1995;10(4):383–93.

    Article  PubMed  CAS  Google Scholar 

  21. Foresta C, Moro E, Ferlin A. Y chromosome microdeletions and alterations of spermatogenesis. Endocr Rev. 2001;22(2):226–39.

    Article  PubMed  CAS  Google Scholar 

  22. De Palma A et al. Patients with abnormal sperm parameters have an increased sex chromosome aneuploidy rate in peripheral leukocytes. Hum Reprod. 2005;20(8):2153–6.

    Article  PubMed  Google Scholar 

  23. Lissitsina J, Mikelsaar R, Punab M. Cytogenetic analyses in infertile men. Arch Androl. 2006;52(2):91–5.

    Article  PubMed  CAS  Google Scholar 

  24. Lee YS et al. Genital anomalies in Klinefelter’s syndrome. Horm Res. 2007;68(3):150–5.

    Article  PubMed  CAS  Google Scholar 

  25. Ferlin A et al. Human male infertility and Y chromosome deletions: role of the AZF-candidate genes DAZ, RBM and DFFRY. Hum Reprod. 1999;14(7):1710–6.

    Article  PubMed  CAS  Google Scholar 

  26. Rucker GB et al. Preoperative screening for genetic abnormalities in men with nonobstructive azoospermia before testicular sperm extraction. J Urol. 1998;160(6 Pt 1):2068–71.

    PubMed  CAS  Google Scholar 

  27. Tuerlings JH et al. Chromosome studies in 1792 males prior to intra-cytoplasmic sperm injection: the Dutch experience. Eur J Hum Genet. 1998;6(3):194–200.

    Article  PubMed  CAS  Google Scholar 

  28. Gunduz G, Luleci G, Baykara M. Cytogenetic study in 102 infertile men. Urol Int. 1998;61(1):32–4.

    Article  PubMed  CAS  Google Scholar 

  29. Rao L et al. Chromosomal abnormalities and y chromosome microdeletions in infertile men with varicocele and idiopathic infertility of South Indian origin. J Androl. 2004;25(1):147–53.

    PubMed  Google Scholar 

  30. Nagvenkar P et al. Chromosomal studies in infertile men with oligozoospermia & non-obstructive azoospermia. Indian J Med Res. 2005;122(1):34–42.

    PubMed  Google Scholar 

  31. Zhou-Cun A et al. Chromosomal abnormality and Y chromosome microdeletion in Chinese patients with azoospermia or severe oligozoospermia. Yi Chuan Xue Bao. 2006;33(2):111–6.

    PubMed  CAS  Google Scholar 

  32. Pina-Neto JM et al. Somatic cytogenetic and azoospermia factor gene microdeletion studies in infertile men. Braz J Med Biol Res. 2006;39(4):555–61.

    Article  PubMed  CAS  Google Scholar 

  33. Meza-Espinoza JP et al. Chromosomal abnormalities in patients with azoospermia in Western Mexico. Arch Androl. 2006;52(2):87–90.

    Article  PubMed  CAS  Google Scholar 

  34. Samli H et al. Genetic anomalies detected in patients with non-obstructive azoospermia and oligozoospermia. Arch Androl. 2006;52(4):263–7.

    Article  PubMed  CAS  Google Scholar 

  35. Martinez-Garza SG et al. Genetic screening in infertile Mexican men: chromosomal abnormalities, Y chromosome deletions, and androgen receptor CAG repeat length. J Androl. 2008;29(6):654–60.

    Article  PubMed  Google Scholar 

  36. Balkan M, Tekes S, Gedik A. Cytogenetic and Y chromosome microdeletion screening studies in infertile males with Oligozoospermia and Azoospermia in Southeast Turkey. J Assist Reprod Genet. 2008;25(11–12):559–65.

    Article  PubMed  CAS  Google Scholar 

  37. Ceylan GG, Ceylan C, Elyas H. Genetic anomalies in patients with severe oligozoospermia and azoospermia in eastern Turkey: a prospective study. Genet Mol Res. 2009;8(3):915–22.

    Article  PubMed  CAS  Google Scholar 

  38. Akgul M et al. Cytogenetic abnormalities in 179 cases with male infertility in Western Region of Turkey: report and review. J Assist Reprod Genet. 2009;26(2–3):119–22.

    Article  PubMed  CAS  Google Scholar 

  39. Ng PP et al. Chromosomal anomalies and Y-microdeletions among Chinese subfertile men in Hong Kong. Hong Kong Med J. 2009;15(1):31–8.

    PubMed  Google Scholar 

  40. Kumtepe Y et al. A genetic survey of 1935 Turkish men with severe male factor infertility. Reprod Biomed Online. 2009;18(4):465–74.

    Article  PubMed  Google Scholar 

  41. Kosar PA, Ozcelik N, Kosar A. Cytogenetic abnormalities detected in patients with non-obstructive azoospermia and severe oligozoospermia. J Assist Reprod Genet. 2010;27(1):17–21.

    Article  PubMed  Google Scholar 

  42. Mafra FA et al. Chromosomal and molecular abnormalities in a group of Brazilian infertile men with severe oligozoospermia or non-obstructive azoospermia attending an infertility service. Int Braz J Urol. 2011;37(2):244–50. discussion 250-1.

    Article  PubMed  Google Scholar 

  43. Akbari MT et al. Cytogenetic abnormalities in 222 infertile men with azoospermia and oligospermia in Iran: report and review. Indian J Hum Genet. 2012;18(2):198–203.

    Article  PubMed  Google Scholar 

  44. Kremer JA et al. Microdeletions of the Y chromosome and intracytoplasmic sperm injection: from gene to clinic. Hum Reprod. 1997;12(4):687–91.

    Article  PubMed  CAS  Google Scholar 

  45. Foresta C et al. High frequency of well-defined Y-chromosome deletions in idiopathic Sertoli cell-only syndrome. Hum Reprod. 1998;13(2):302–7.

    Article  PubMed  CAS  Google Scholar 

  46. Tse JY et al. A comparative study of Y chromosome microdeletions in infertile males from two Chinese populations. J Assist Reprod Genet. 2002;19(8):376–83.

    Article  PubMed  CAS  Google Scholar 

  47. SaoPedro SL et al. Prevalence of Y chromosome deletions in a Brazilian population of nonobstructive azoospermic and severely oligozoospermic men. Braz J Med Biol Res. 2003;36(6):787–93.

    Article  PubMed  CAS  Google Scholar 

  48. Omrani MD et al. Y chromosome microdeletions in idiopathic infertile men from West Azarbaijan. Urol J. 2006;3(1):38–43.

    PubMed  Google Scholar 

  49. Arruda JT et al. Y chromosome microdeletions in Brazilian fertility clinic patients. Genet Mol Res. 2007;6(2):461–9.

    PubMed  CAS  Google Scholar 

  50. Imken L et al. AZF microdeletions and partial deletions of AZFc region on the Y chromosome in Moroccan men. Asian J Androl. 2007;9(5):674–8.

    Article  PubMed  Google Scholar 

  51. Malekasgar AM, Mombaini H. Screening of ‘Y’ chromosome microdeletions in Iranian infertile males. J Hum Reprod Sci. 2008;1(1):2–9.

    Article  PubMed  Google Scholar 

  52. Stahl PJ et al. A decade of experience emphasizes that testing for Y microdeletions is essential in American men with azoospermia and severe oligozoospermia. Fertil Steril. 2010;94(5):1753–6.

    Article  PubMed  CAS  Google Scholar 

  53. Wang RX et al. Male infertility in China: laboratory finding for AZF microdeletions and chromosomal abnormalities in infertile men from Northeastern China. J Assist Reprod Genet. 2010;27(7):391–6.

    Article  PubMed  CAS  Google Scholar 

  54. Mirfakhraie R et al. High prevalence of AZFb microdeletion in Iranian patients with idiopathic non-obstructive azoospermia. Indian J Med Res. 2010;132:265–70.

    PubMed  CAS  Google Scholar 

  55. Behulova R et al. Incidence of microdeletions in the AZF region of the Y chromosome in Slovak patients with azoospermia. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2011;155(1):33–8.

    Article  PubMed  Google Scholar 

  56. Krausz C et al. Double-blind Y chromosome microdeletion analysis in men with known sperm parameters and reproductive hormone profiles: microdeletions are specific for spermatogenic failure. J Clin Endocrinol Metab. 2001;86(6):2638–42.

    Article  PubMed  CAS  Google Scholar 

  57. Sadeghi-Nejad H, Farrokhi F. Genetics of azoospermia: current knowledge, clinical implications, and future directions. Part II: Y chromosome microdeletions. Urol J. 2007;4(4):192–206.

    PubMed  Google Scholar 

  58. Simoni M, Bakker E, Krausz C. EAA/EMQN best practice guidelines for molecular diagnosis of y-chromosomal microdeletions. State of the art 2004. Int J Androl. 2004;27(4):240–9.

    Article  PubMed  CAS  Google Scholar 

  59. Vogt PH et al. Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum Mol Genet. 1996;5(7):933–43.

    Article  PubMed  CAS  Google Scholar 

  60. Krausz C, Quintana-Murci L, McElreavey K. Prognostic value of Y deletion analysis: what is the clinical prognostic value of Y chromosome microdeletion analysis? Hum Reprod. 2000;15(7):1431–4.

    Article  PubMed  CAS  Google Scholar 

  61. Cram DS, Osborne E, McLachlan RI. Y chromosome microdeletions: implications for assisted conception. Med J Aust. 2006;185(8):433–4.

    PubMed  Google Scholar 

  62. Poongothai J, Gopenath TS, Manonayaki S. Genetics of human male infertility. Singapore Med J. 2009;50(4):336–47.

    PubMed  CAS  Google Scholar 

  63. Scriven PN et al. Robertsonian translocations–reproductive risks and indications for preimplantation genetic diagnosis. Hum Reprod. 2001;16(11):2267–73.

    Article  PubMed  CAS  Google Scholar 

  64. Moradkhani K et al. Rare Robertsonian translocations and meiotic behaviour: sperm FISH analysis of t(13;15) and t(14;15) translocations: a case report. Hum Reprod. 2006;21(12):3193–8.

    Article  PubMed  CAS  Google Scholar 

  65. Aittomaki K et al. Safety issues in assisted reproduction technology: should ICSI patients have genetic testing before treatment? A practical proposition to help patient information. Hum Reprod. 2004;19(3):472–6.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

We appreciate the collaboration of the patients and express gratitude to Dr. Sawsan Alsamawi, Dr. Adnan Alkhatib, Dr. Jamal Alsharif, Dr. Ahmad Taha and Professor Ahmad Othman for their kind Collaboration. We also acknowledge the scientific research committee of the faculty of medicine and the research deputy of Orient Hospital for providing grant to carry out this study

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Authors and Affiliations

  1. Assisted reproduction unit, Orient Hospital, Damascus, Syria

    Marwan Alhalabi & Mazen Kenj

  2. Division of Reproductive Medicine and Embryology, Faculty of Medicine, Damascus, Syria

    Marwan Alhalabi

  3. Department of Reproductive Medicine and Embryology, Damascus University, Damascus, Syria

    Ghalia Abou Alchamat

  4. Al Assad University Hospital, Damascus University, Damascus, Syria

    Fawza Monem & Zaina Mahayri

  5. Department of Radiation Medicine, Atomic Energy Commission of Syria, Damascus, Syria

    Ammar Madania

Authors
  1. Marwan Alhalabi
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  2. Mazen Kenj
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  3. Fawza Monem
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  4. Zaina Mahayri
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  5. Ghalia Abou Alchamat
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  6. Ammar Madania
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Correspondence to Marwan Alhalabi.

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Capsule

Men with Non-obstructive azoospermia need genetic testing and counseling prior to assisted reproduction.

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Alhalabi, M., Kenj, M., Monem, F. et al. High prevalence of genetic abnormalities in Middle Eastern patients with idiopathic non-obstructive azoospermia. J Assist Reprod Genet 30, 799–805 (2013). https://doi.org/10.1007/s10815-013-9995-z

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  • DOI: https://doi.org/10.1007/s10815-013-9995-z

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