Prospective assessment of Y-chromosome microdeletions and reproductive outcomes among infertile couples of Japanese and African origin

Open Access
Research

Abstract

Background

To compare the frequency of Y-chromosome microdeletions in Japanese and African azoospermic and oligozoospermic men and describe embryo characteristics and reproductive outcome following in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI).

Methods

Our study was performed prospectively at two centers, a private IVF clinic and a university hospital. Japanese and African (Tanzanian) men with nonobstructive azoospermia (NOA) and oligozoospermia (concentration < 5 × 106 /ml) were evaluated for Y-chromosome microdeletions (n = 162). Of the 47 men with NOA, 26 were Japanese and 21 were Africans. Of the 115 men with oligozoospermia, 87 were Japanese and 28 were Africans. Reproductive outcomes of patients with Y-chromosome microdeletions were then compared with those of 19 IVF+ICSI cycles performed on couples with Y-chromosome intact males/tubal factor infertility which served as a control group.

Results

Seven azoospermic and oligozoospermic patients had Y-chromosome deletions; the total number of deletions in the AZFc region was five. There was only one deletion in the AZFa region and one complete deletion involving all three regions (AZFa, b, and c) within AZF. In our study population, microdeletion frequency among Japanese men was 6.2% (95% CI, 4.25% – 14.45%), whereas no deletions were identified in the African group (95% CI, 0.0% – 7.27%). The difference between the two groups was not statistically significant, however. Embryos derived from ICSI utilizing sperm with Y-chromosome microdeletion showed reduced rates of fertilization, blastocyst development, implantation, and pregnancy compared to the Y-chromosome intact group, although these observed differences were not statistically significant.

Conclusion

The observed frequency of Y-chromosome microdeletion was 6.2% among Japanese azoospermic and oligozoospermic males; no microdeletions were identified among our African study patients. In this population of couples undergoing IVF+ICSI, there was no statistically significant difference in embryo characteristics or pregnancy outcome between patients with Y-chromosome microdeletion and those with an intact Y-chromosome.

Notes

Acknowledgements

We wish to thank Dr. Takafumi Utsunomiya, Yoko Kumasako and Keiko Hirotsuri of St. Luke hospital for their advice and technical help ; We also wish to thank Prof. Kensuke Yamamoto, Dr. Kazuo Aoki, Prof. Junichi Misumi and Akira Kono of Oita University school of Medicine for their help in study design and constant examination of our data; Drs. Ramzy E. Kisanga and Godfrey Lema of Muhimbili University of college science, Dar-es-salaam, Tanzania for their technical assistance while in Tanzania and San Francisco Edit http://www.sfedit.net for editing this manuscript.

References

  1. 1.
    Thonneau P, Marchand S, Tallec A: Incidence of main causes of infertility in a resident population (1 850 000 inhabitants) of three French regions (1988–1989). Hum Reprod. 1991, 6: 811-81.CrossRefGoogle Scholar
  2. 2.
    Abma JC, Chandra A, Mosher WD, Peterson LS: Fertility, Family Planning and Women's Health: New data from the 1995 national Survey of Family Growth. Vital heath statistics. 1997, 23: 1-114.Google Scholar
  3. 3.
    Tiepolo L, Zuffardi O: Localization of factors controlling spermatogenesis in nonfluorescent portion of the human chromosome Y long arm. Hum Genet. 1976, 34: 119-124. 10.1007/BF00278879.CrossRefGoogle Scholar
  4. 4.
    Van Assche E, Bonduelle M, Tournaye H, Joris H, Verheyen G, Devroey P, Van Steirteghem A, Liebaers I: Cytogenetics of infertile men. Hum Reprod. 1996, 11: 1-24.CrossRefGoogle Scholar
  5. 5.
    Bonduelle M, Aytoz A, Van Assche E: Incidence of chromosomal aberrations in children born after assisted reproduction through intracytoplasmic sperm injection. Hum Reprod. 1998, 13: 781-2. 10.1093/humrep/13.4.781.CrossRefPubMedGoogle Scholar
  6. 6.
    Bonduelle M, Camus M, De Vos A, Staessen C, Tournaye H, Van Assche E: Seven Years of Intracytoplasmic Sperm injection and follow up of 1987 subsequent children. Hum Reprod. 1999, 14: 243-264.CrossRefGoogle Scholar
  7. 7.
    Egozcue S, Blanco J, Vendrell JM, García F, Veiga A, Aran B, Barri PN, Vidal F, Egozcue J: Human male infertility: chromosome anomalies, meiotic disorders, abnormal spermatozoa and recurrent abortion. Hum Reprod Update. 2000, 6: 93-105. 10.1093/humupd/6.1.93.CrossRefPubMedGoogle Scholar
  8. 8.
    Devroey P, Vandervorst M, Nagy P, Van Steirteghem AC: Do we treat the male or his gamete? In "Current Theory and Practice of ICSI". Hum Reprod. Edited by: Devroey P, Tarlatzis B, Van Steirteghem A. 1998, Oxford, UK, Oxford University Press, 13: 178-185. 10.1093/humrep/13.1.178.Google Scholar
  9. 9.
    Silber SJ, Van Sterteghem AC, Liu J, Nagy Z, Tournaye H, Devroey P: High fertilization and pregnacy rates after ICSI with spermatozoa obtained from testicle biopsy. Hum Reprod. 1999, 10: 148-152.CrossRefGoogle Scholar
  10. 10.
    Obrien SJ, Wildt DE, Bush M: The Cheetah in genetic peril. Sci Am. 1986, 254: 84-92.CrossRefGoogle Scholar
  11. 11.
    Ma K, Sharkey A, Kirsch S: Towards the molecular localisation of the AZF locus: mapping of microdeletions in azoospermic men within 14 subintervals of interval 6 of the human Y-chromosome. Hum Mol Genet. 1992, 1: 29-33.CrossRefGoogle Scholar
  12. 12.
    Ma K, Inglis JD, Sharkey A, Bickmore WA, Hill RE, Prosser EJ: A Y chromosome gene family with RNA binding protein homology; candidate for the azoospermia factor AZF controlling human spermatogenesis. Cell. 1993, 75: 1287-1295. 10.1016/0092-8674(93)90616-X.CrossRefPubMedGoogle Scholar
  13. 13.
    Eberhart CG, Maines JZ, Wasserman SA: Meiotic cell requirement for a fly homologue of human deleted in azoospermia. Nature. 1996, 381: 783-5. 10.1038/381783a0.CrossRefPubMedGoogle Scholar
  14. 14.
    Simoni M, Bakker E, Eurlings MC: Laboratory guidelines for molecular diagnosis of Y-chromosomal microdeletions. Int J Androl. 1999, 22: 292-299. 10.1046/j.1365-2605.1999.00193.x.CrossRefPubMedGoogle Scholar
  15. 15.
    Tsujimura A, Matsumiya K, Takao T, Miyagawa Y, Koga M, Takeyama M, Fujioka H, Okuyama A: Clinical analysis of patients with azoospermia factor deletions by microdissection testicular sperm extraction. Int J Androl. 2004, 27: 76-81. 10.1046/j.0105-6263.2003.00450.x.CrossRefPubMedGoogle Scholar
  16. 16.
    Carvalho CM, Fujisawa M, Shirakawa T, Kamidono GA, Freitas S, Paulo T, Santos SE, Rocha J, Pena SD, Santos F: Lack of association between Y chromosome haplogroups and male infertility in Japanese men. American J Med Genet. 2003, 116A (2): 152-8. 10.1002/ajmg.a.10827.CrossRefGoogle Scholar
  17. 17.
    Ewis AA, Lee J, Shinka T, Nakahori Y: Microdeletions of a Y-specific marker, Yfm1, and implications for a role in spermatogenesis. Journal of Hum Genet. 2002, 47 (5): 257-61. 10.1007/s100380200035.CrossRefGoogle Scholar
  18. 18.
    Nagafuchi S, Namiki M, Nakahori Y, Kondoh N, Okuyama A, Nakagome Y: A minute deletion of the Y chromosome in men with azoospermia. J Urol. 1993, 150 (4): 1155-7.CrossRefGoogle Scholar
  19. 19.
    Takao T, Akira T, Sada M, Goto R, Koga M, Miyagawa Y: Susceptibility gene for non azoospermia in the HLA 11 region ; Correlations with Y chromosome microdeletions and spermatogenesis. Inter J Androl. 2004, 27: 37-41. 10.1046/j.0105-6263.2003.00445.x.CrossRefGoogle Scholar
  20. 20.
    Kobayashi K, Mizuno K, Hida A, Komaki R, Tomita K, Matsushita I, Namiki M, Iwamoto T, Tamura S, Minowada S: PCR analysis of the Y chromosome long arm in azoospermic patients: evidence for a second locus required for spermatogenesis published erratum appears in. Hum Mol Genet. 1995, 4 (5): 974-PubMedGoogle Scholar
  21. 21.
    Kato H, Komori S, Nakata Y, Sakata K, Kanazawa R, Handa M, Kobayashi S, Koyama K, Isojima S: Screening for deletions in interval D16-22 of the Y chromosome in azoospermic and oligozoospermic Japanese men. J Hum Genet. 2001, 46 (3): 110-4. 10.1007/s100380170097.CrossRefPubMedGoogle Scholar
  22. 22.
    Nakahori Y, Kuroki Y, Komaki R, Kondoh N, Namiki M, Iwamoto T, Toda T, Kobayashi K: The Y chromosome region essential for spermatogenesis. Hormone Research. 1996, 46 (Suppl 1): 20-3.CrossRefGoogle Scholar
  23. 23.
    Reijo R, Alagappan RK, Patrizio P, Page DC: Severe oligozoospermia resulting from deletions of azoospermia factor gene on Y chromosome. Lancet. 1996, 347: 1290-1293. 10.1016/S0140-6736(96)90938-1.CrossRefPubMedGoogle Scholar
  24. 24.
    Silber SJ, Alagappan R, Brown LG, Page DC: Y chromosome deletions in azoospermic and severely oligozoospermic men undergoing intracytoplasmic sperm injection after testicular sperm extraction. Hum Reprod. 13: 3332-3337. 10.1093/humrep/13.12.3332.CrossRefGoogle Scholar
  25. 25.
    Hopps CV, Mielnik A, Goldstein M, Palermo GD, Rosenwaks Z, Schlegel PN: Detection of sperm in men with Y chromosome microdeletions of the AZFa, AZFb and AZFc regions. Hum Reprod. 2003, 18: 1660-1665. 10.1093/humrep/deg348.CrossRefGoogle Scholar
  26. 26.
    Mulhall JP, Reijo R, Alagappan : Azoospermic men with deletion of the DAZ gene cluster are capable of completing spermatogenesis: fertilization, normal embryonic development and pregnancy occur when retrieved testicular spermatozoa are used for intracytoplasmic sperm injection. Hum Reprod. 1997, 12: 503-508. 10.1093/humrep/12.3.503.CrossRefPubMedGoogle Scholar
  27. 27.
    Oates RD, Silber S, Brown L, Page DC: Clinical characterization of 42 oligospermic or azoospermic men with microdeletion of the AZFc region of the Y chromosome, and of 18 children conceived via ICSI. Hum Reprod. 2002, 17: 2813-2824. 10.1093/humrep/17.11.2813.CrossRefPubMedGoogle Scholar
  28. 28.
    Choi JM, Chung P, Veeck LA, Mielnik LA, Palermo GD, Schlegel PN: AZF microdeletions of the Y chromosome and in vitro fertilization outcome. Fertil Steril. 2004, 81: 337-341. 10.1016/j.fertnstert.2003.06.030.CrossRefPubMedGoogle Scholar
  29. 29.
    Van Golde RJT, Wetzels AMM, de Graaf R: Decreased fertilization rate and embryo quality after ICSI in oligozoospermic men with microdeletions in the azoospermia factor c region of the Y chromosome. Hum Reprod. 2001, 16: 289-292. 10.1093/humrep/16.2.289.CrossRefPubMedGoogle Scholar
  30. 30.
    Silber SJ: pontaneous pregnancy in couples with very severe oligospermia (<0.5 × 10.6 sperm): implications for transmission of Y chromosome deletions. Fertil Steril. 2001, 76: S10-10.1016/S0015-0282(01)02044-1.CrossRefGoogle Scholar
  31. 31.
    Kihaile PE, Kisanga RE, Aoki K, Kumasako Y, Misumi J, Utsunomiya T: Embryo Outcome in Y-chromosome Microdeleted Infertile Males after ICSI:. Mo Reprod Dev. 2004, 68: 176-181. 10.1002/mrd.20074.CrossRefGoogle Scholar
  32. 32.
    Page DC, Silber S, Brown LG: Men with infertility caused by AZFc deletion can produce sons by intracytoplasmic sperm injection but are likely to transmit the deletion and infertility. Hum Reprod. 1999, 14: 1722-1726. 10.1093/humrep/14.7.1722.CrossRefPubMedGoogle Scholar
  33. 33.
    Rolf C, Gromoll J, Simoni M, Nieschlag1 E: Natural transmission of a partial AZFb deletion of the Y chromosome over three generations: Case report. Hum Reprod. 2002, 17 (9): 2267-2271. 10.1093/humrep/17.9.2267.CrossRefPubMedGoogle Scholar
  34. 34.
    Henegariu O, Hirschmann P, Kilian K: Rapid screening of the Y chromosome in idiopathic sterile men, diagnostic for deletions in AZF, a genetic Y factor expressed during spermatogenesis. Andrologia. 1994, 26: 97-106.CrossRefGoogle Scholar
  35. 35.
    Utsunomiya T, Naitou T, Nagaki M: A prospective trial of blastocyst culture and transfer. Hum Reprod. 2002, 17 (7): 1846-1851. 10.1093/humrep/17.7.1846.CrossRefPubMedGoogle Scholar
  36. 36.
    Peterlin B, Kunej T, Sinkovec J, Gligorievska N, Zorn B: Screening for Y chromosome microdeletions in 226 Slovenian subfertile men. Hum Reprod. 2000, 17 (1): 17-24. 10.1093/humrep/17.1.17.CrossRefGoogle Scholar
  37. 37.
    Foresta C, Moro E, Ferlin A: Y chromosome microdeletions and alterations of spermatogenesis. Endocrine Reviews. 2001, 22: 226-239. 10.1210/er.22.2.226.CrossRefPubMedGoogle Scholar
  38. 38.
    Reijo R, Lee TY, Salo P, Alagappan R, Brown LG, Rosenberg M: Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene. Nature Genetics. 1995, 10: 383-393. 10.1038/ng0895-383.CrossRefPubMedGoogle Scholar
  39. 39.
    Foresta C, Ferlin A, Garolla A, Moro E, Pistorello M, Barbaux S, Rossato M: High frequency of well-defined Y-chromosome deletions in idiopathic Sertoli cell-only syndrome. Human Reproduction. 1998, 13: 302-307. 10.1093/humrep/13.2.302.CrossRefPubMedGoogle Scholar
  40. 40.
    Yeboah ED, Wadhwani JM, Wilson JB: Etiological factors of male infertility in Africa. International Journal of Fertility. 1992, 37 (5): 300-7.PubMedGoogle Scholar
  41. 41.
    Cates W, Farley TM, Rowe PJ: Worldwide patterns of infertility: is Africa different?. Lancet. 1985, 2 (8455): 596-8. 10.1016/S0140-6736(85)90594-X.CrossRefPubMedGoogle Scholar
  42. 42.
    Imade GE, Towobola OA, Sagay AS, Otubu JA: Sexually transmitted diseases and medico-social factors associated with male infertility in Nigeria. Archives of AIDS Research. 1993, 7 (3–4): 245-52.PubMedGoogle Scholar
  43. 43.
    Bornman MS, Crewe-brown HH, Reif S, Mahomed MF, Broomker D, Schulenburg GW: Sexually transmitted diseases (STD) in infertile males attending the andrology clinic at Ga-Rankuwa Hospital. Archives of AIDS Research. 1993, 145-150.Google Scholar
  44. 44.
    Collet M, Reniers J, Frost E, Gass R, Yvert F, Leclerc A, Roth-Meyer C, Ivanoff B, Meheus A: Infertility in Central Africa: infection is the cause. International Journal of Gynaecol & Obstet. 1988, 26: 423-8. 10.1016/0020-7292(88)90340-2.CrossRefGoogle Scholar
  45. 45.
    Vigil P, Morales P, Tapia A, Riquelme R, Salgado AM: Chlamydia trachomatis infection in male partners of infertile couples: incidence and sperm function. Andrologia. 2002, 34: 155-61. 10.1046/j.1439-0272.2002.00472.x.CrossRefPubMedGoogle Scholar
  46. 46.
    Ness R, Markovic N, Carlson CL, Coughlin MT: Do men become infertile after having sexually transmitted urethritis? An epidemiologic examination. Fertil & Steril. 1997, 68: 205-13. 10.1016/S0015-0282(97)81502-6.CrossRefGoogle Scholar
  47. 47.
    Bambra CS: Current status of reproductive behaviour in Africa. Human Reproduction Update. 1999, 5: 1-20. 10.1093/humupd/5.1.1.CrossRefPubMedGoogle Scholar
  48. 48.
    Gausset Q: AIDS and cultural practices in Africa: the case of the Tonga (Zambia). Social Science & Medicine. 2001, 52: 509-18. 10.1016/S0277-9536(00)00156-8.CrossRefGoogle Scholar

Copyright information

© Kihaile et al; licensee BioMed Central Ltd. 2005

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Authors and Affiliations

  • Paul E Kihaile
    • 1
    • 2
    • 3
  • Atsushi Yasui
    • 1
  • Yoshihiro Shuto
    • 1
  1. 1.Oita Medical UniversityOita CityJapan
  2. 2.St. Luke IVF CenterOita CityJapan
  3. 3.Muhimbili University College of Health ScienceDar Es SalaamTanzania

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