Y chromosome microdeletions: implications for assisted conception

Cram, David S; Osborne, Elissa; McLachlan, Robert I

doi:10.5694/j.1326-5377.2006.tb00641.x

Topics

Some boys conceived through artificial techniques may inherit their fathers’ subfertility

Clinical assessment of couples unable to conceive naturally often identifies causative or contributory factors associated with the male partner. Male infertility affects one in 20 men, accounts for a third of all infertility, and is a cofactor in over half of assisted reproductive technology (ART) treatments worldwide.1 Primary spermatogenic failure (SgF, also termed idiopathic infertility) accounts for more than half the cases, yet, in most of these cases, its cause is unknown.1 In clinical practice, classification of SgF is based on semen parameters (describing combinations of poor sperm number, motility or function) and reflects an ignorance of the pathogenesis.2 However, recent research has determined that up to 15% of SgF is related to at least six known Y chromosomal deletions, with implications for genetic testing, counselling, assisted reproduction and even subsequent male offspring conceived by ART.

1 Monash IVF Business Centre, Epworth Hospital, Melbourne, VIC.
2 Monash Immunology and Stem Cell Laboratories, Faculty of Medicine, Monash University, Melbourne, VIC.
3 Department of Obstetrics and Gynaecology, Faculty of Medicine, Nursing and Health Sciences, Prince Henry’s Institute of Medical Research, Melbourne, VIC.

Correspondence: david.cram@med.monash.edu.au

1. Baker HWG. Clinical evaluation and management of testicular disorders in the adult. In: Burger H, de Kretser D, editors. The testis. 2nd ed. New York: Raven Press, 1989.
2. Jequier AM. Clinical andrology — still a major problem in the treatment of infertility. Hum Reprod 2004; 19: 1245-1249.
3. Foresta C, Moro E, Ferkin A. Y chromosome microdeletions and alterations of spermatogenesis. Endocr Rev 2001; 22: 226-239.
4. Skaletsky H, Kuroda-Kawaguchi T, Minx PJ, et al. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature 2003; 423: 825-837.
5. Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet 1992; 340: 17-18.
6. Sousa M, Cremades N, Siva J, et al. Predictive value of testicular histology in secretory azoospermic subgroups and clinical outcome after microinjection of fresh and frozen-thawed sperm and spermatids. Hum Reprod 2002; 17: 1800-1810.
7. Tiepolo L, Zuffardi O. Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm. Hum Genet 1976; 34: 119-124.
8. Vogt PH. Human chromosome deletions in Yq11, AZF candidate genes and male infertility: history and update. Mol Hum Reprod 1998; 4: 739-744.
9. Repping S, Skaletsky H, Brown L, et al. Polymorphism for a 1.6-Mb deletion of the human Y chromosome persists through balance between recurrent mutation and haploid selection. Nat Genet 2003; 35: 247-251.
10. McLachlan R, Rajpert-De Meyts E, Hoei-Hansen CE, et al. Histological evaluation of the human testis: approaches to optimizing the clinical value of the assessment. Hum Reprod 2006 Aug 3; Epub ahead of print.
11. Giachini C, Guarducci E, Longepied G, et al. The gr/gr deletion(s): a new genetic test in male infertility? J Med Genet 2005; 42: 497-502.
12. Lynch M, Cram DS, Reilly A, et al. The Y chromosome gr/gr subdeletion is associated with male infertility. Mol Hum Reprod 2005; 11: 507-512.
13. McElreavey K, Ravel C, Chantot-Bastaraud S, Siffroi JP. Y chromosome variants and male reproductive function. Int J Androl 2006; 29: 298-303.
14. Cram DS, Ma K, Bhasin S, et al. Y chromosome analysis of infertile men and their sons conceived through intracytoplasmic sperm injection: vertical transmission of deletions and rarity of de novo deletions. Fertil Steril 2000; 74: 909-915.
15. 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: 240-249.
16. 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: 1431-1434.
17. Andersson AM, Jorgensen N, Frydelund-Larsen L, et al. Impaired Leydig cell function in infertile men: a study of 357 idiopatic infertile men and 318 proven fertile controls. J Clin Endocrinol Metab 2004; 89: 3158-3160.
18. Jacobsen R, Bostofte E, Engholm G, et al. Risk of testicular cancer in men with abnormal semen characteristics: cohort study. BMJ 2000; 321: 789-792.
19. Stouffs K, Lissens W, Tournaye H, et al. The choice and outcome of the fertility treatment of 38 couples in whom the male partner has a Yq microdeletion. Hum Reprod 2005; 20: 1887-1896.

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