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Y chromosome microdeletions as a cause for male infertility

Mariya Levkova, Trifon Chervenkov, Lyudmila Angelova


Male infertility represents around half of all cases of infertility. The microdeletions of the azoospermia factor (AZF) region, located in the long arm of Y chromosome, are the second most common reason for reproductive problems among men. This genetic mutation results in low sperm count and fertility rate. The presence of Y microdeletions can lower the success rate of in vitro procedures and would be transmitted to the next generation. We have analyzed 30 articles about the connection between the deletions of the Y chromosome and the decreased sperm count. 25 of them confirm the role of this genetic mutation, while the rest do not, but they investigate only some AZF loci. The negative results could also be due to the different ethnic origin of the participants, difference between the research method and etc. Testing infertile men for Y chromosome deletions could lead to a major improvement in the options for treating infertility. Also, if such mutation is diagnosed, this is an indication for genetic counseling in order to avoid future fertility issues in the next generation. The review of the included articles proves the role of the Y chromosome microdeletions as a reason for male infertility and outlines the main principles when performing the genetic test for this mutation.


molecular genetics, infertility, azoospermia factor (AZF), chromosome deletions

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Rowe PJ, Comhaire FH, Organization WH, Hargreave TB, Mahmoud AMA. WHO Manual for the Standardized Investigation and Diagnosis of the Infertile Male. Cambridge University Press. 2000.

Okabe M, Ikawa M, Ashkenas J. Male infertility and the genetics of spermatogenesis. Am J Hum Genet 1998;62(6):1274-1281. doi:10.1086/301895

Krausz C, Hoefsloot L, Simoni M, Tuttelmann F, European Academy of A, European Molecular Genetics Quality N. EAA/EMQN best practice guidelines for molecular diagnosis of Y-chromosomal microdeletions: state-of-the-art 2013. Andrology 2014;2(1):5-19. doi:10.1111/j.2047- 2927.2013.00173.x

Tiepolo L, Zuffardi O. Localization of factors controlling spermatogenesis in the nonfluorescent portion of the human Y chromosome long arm. Hum Genet 1976;34(2):119-124.

Vogt PH, Edelmann A, Kirsch S, Henegariu O, Hirschmann P, Kiesewetter F, et al. Human Y chromosome azoospermia factors (AZF) mapped to different subregions in Yq11. Hum Mol Genet 1996;5(7):933-943.

Skaletsky H, Kuroda-Kawaguchi T, Minx PJ, Cordum HS, Hillier L, Brown LG, et al. The male-specific region of the human Y chromosome is a mosaic of discrete sequence classes. Nature 2003;423(6942):825-837. doi:10.1038/nature01722

Kuroda-Kawaguchi T, Skaletsky H, Brown LG, Minx PJ, Cordum HS, Waterston RH, et al. The AZFc region of the Y chromosome features massive palindromes and uniform recurrent deletions in infertile men. Nat Genet 2001;29(3):279-286. doi:10.1038/ng757

Vogt PH. Genomic heterogeneity and instability of the AZF locus on the human Y chromosome. Mol Cell Endocrinol 2004;224(1-2):1-9. doi:10.1016/j.mce.2004.06.008

Repping S, Skaletsky H, Lange J, Silber S, Van Der Veen F, Oates RD, et al. Recombination between palindromes P5 and P1 on the human Y chromosome causes massive deletions and spermatogenic failure. Am J Hum Genet 2002;71(4):906-922. doi:10.1086/342928

Sargent CA, Boucher CA, Kirsch S, Brown G, Weiss B, Trundley A, et al. The critical region of overlap defining the AZFa male infertility interval of proximal Yq contains three transcribed sequences. J Med Genet 1999;36(9):670-677.

Soto-Rifo R, Ohlmann T. The role of the DEAD-box RNA helicase DDX3 in mRNA metabolism. Wiley Interdiscip Rev RNA. 2013;4(4):369-385. doi:10.1002/wrna.1165

Ferras C, Fernandes S, Marques CJ, Carvalho F, Alves C, Silva J, et al. AZF and DAZ gene copy-specific deletion analysis in maturation arrest and Sertoli cell-only syndrome. Mol Hum Reprod 2004;10(10):755-761. doi:10.1093/molehr/gah104

Kleiman SE, Almog R, Yogev L, Hauser R, Lehavi O, Paz G, et al. Screening for partial AZFa microdeletions in the Y chromosome of infertile men: is it of clinical relevance? Fertil Steril 2012;98(1):43-47. doi:10.1016/j. fertnstert.2012.03.034

Choi JM, Chung P, Veeck L, Mielnik A, Palermo GD, Schlegel PN. AZF microdeletions of the Y chromosome and in vitro fertilization outcome. Fertil Steril 2004;81(2):337-341. doi:10.1016/j.fertnstert.2003.06.030

Luddi A, Margollicci M, Gambera L, Serafini F, Cioni M, De Leo V, et al. Spermatogenesis in a man with complete deletion of USP9Y. N Engl J Med 2009;360(9):881-885. doi:10.1056/NEJMoa0806218

Ferlin A, Moro E, Rossi A, Dallapiccola B, Foresta C. The human Y chromosome`s azoospermia factor b (AZFb) region: sequence, structure, and deletion analysis in infertile men. J Med Genet 2003;40(1):18-24.

Soares AR, Costa P, Silva J, Sousa M, Barros A, Fernandes S. AZFb microdeletions and oligozoospermia - which mechanisms? Fertil Steril 2012;97(4):858-863. doi:10.1016/j.fertnstert.2012.01.099

Yang Y, Ma MY, Xiao CY, Li L, Li SW, Zhang SZ. Massive deletion in AZFb/b+c and azoospermia with Sertoli cell only and/or maturation arrest. Int J Androl 2008;31(6):573- 578. doi:10.1111/j.1365-2605.2007.00808.x

Vogt PH. AZF deletions and Y chromosomal haplogroups: history and update based on sequence. Hum Reprod Update. 2005;11(4):319-336. doi:10.1093/humupd/ dmi017

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(8):1660-1665.

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):1431-1434.

Foresta C, Moro E, Ferlin A. Y chromosome microdeletions and alterations of spermatogenesis. Endocr Rev 2001;22(2):226-239. doi:10.1210/edrv.22.2.0425

Mau Kai C, Juul A, McElreavey K, Ottesen AM, Garn ID, Main KM, et al. Sons conceived by assisted reproduction techniques inherit deletions in the azoospermia factor (AZF) region of the Y chromosome and the DAZ gene copy number. Hum Reprod 2008;23(7):1669-1678. doi:10.1093/humrep/den124

Zhang F, Lu C, Li Z, Xie P, Xia Y, Zhu X, et al. Partial deletions are associated with an increased risk of complete deletion in AZFc: a new insight into the role of partial AZFc deletions in male infertility. J Med Genet. 2007;44(7):437-444. doi:10.1136/jmg.2007.049056

Kim SY, Kim HJ, Lee BY, Park SY, Lee HS, Seo JT. Y Chromosome microdeletions in infertile men with non-obstructive azoospermia and severe oligozoospermia. J Reprod Infertil 2017;18(3):307-315.

Fu L, Xiong DK, Ding XP, Li C, Zhang LY, Ding M, et al. Genetic screening for chromosomal abnormalities and Y chromosome microdeletions in Chinese infertile men. J Assist Reprod Genet 2012;29(6):521-527. doi:10.1007/ s10815-012-9741-y

Behulova R, Varga I, Strhakova L, Bozikova A, Gabrikova D, Boronova I, 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):33-38.

Krausz C, Rajpert-De Meyts E, Frydelund-Larsen L, Quintana-Murci L, McElreavey K, Skakkebaek NE. 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):2638-2642. doi:10.1210/jcem.86.6.7527

Fernandes S, Huellen K, Goncalves J, Dukal H, Zeisler J, Rajpert De Meyts E, et al. High frequency of DAZ1/DAZ2 gene deletions in patients with severe oligozoospermia. Mol Hum Reprod 2002;8(3):286-298.

Ferlin A, Arredi B, Speltra E, Cazzadore C, Selice R, Garolla A, et al. Molecular and clinical characterization of Y chromosome microdeletions in infertile men: a 10-year experience in Italy. J Clin Endocrinol Metab 2007;92(3):762-770. doi:10.1210/jc.2006-1981

Vutyavanich T, Piromlertamorn W, Sirirungsi W, Sirisukkasem S. Frequency of Y chromosome micro-deletions and chromosomal abnormalities in infertile Thai men with oligozoospermia and azoospermia. Asian J Androl 2007;9(1):68-75. doi:10.1111/j.1745- 7262.2007.00239.x

Imken L, El Houate B, Chafik A, Nahili H, Boulouiz R, Abidi O, et al. AZF microdeletions and partial deletions of AZFc region on the Y chromosome in Moroccan men. Asian J Androl 2007;9(5):674-678. doi:10.1111/j.1745- 7262.2007.00290.x

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):559-565. doi:10.1007/s10815-008-9272-8

Simoni M, Tuttelmann F, Gromoll J, Nieschlag E. Clinical consequences of microdeletions of the Y chromosome: the extended Munster experience. Reprod Biomed Online 2008;16(2):289-303.

Patrat C, Bienvenu T, Janny L, Faure AK, Fauque P, Aknin- Seifer I, et al. Clinical data and parenthood of 63 infertile and Y-microdeleted men. Fertil Steril 2010;93(3):822- 832. doi:10.1016/j.fertnstert.2008.10.033

Wang RX, Fu C, Yang YP, Han RR, Dong Y, Dai RL, 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):391-396. doi:10.1007/s10815-010- 9420-9

Stahl PJ, Masson P, Mielnik A, Marean MB, Schlegel PN, Paduch DA. 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):1753-1756. doi:10.1016/j.fertnstert.2009.09.006

Rozen SG, Marszalek JD, Irenze K, Skaletsky H, Brown LG, Oates RD, et al. AZFc deletions and sper-matogenic failure: a population-based survey of 20,000 Y chromosomes. Am J Hum Genet 2012;91(5):890-896. doi:10.1016/j.ajhg.2012.09.003

Kim MJ, Choi HW, Park SY, Song IO, Seo JT, Lee HS. Molecular and cytogenetic studies of 101 infertile men with microdeletions of Y chromosome in 1,306 infertile Korean men. J Assist Reprod Genet 2012;29(6):539-546. doi:10.1007/s10815-012-9748-4

Motovali-Bashi M, Rezaei Z, Dehghanian F, Rezaei H. Multiplex PCR based screening for micro/partial deletions in the AZF region of Y-chromosome in severe oligozoospermic and azoospermic infertile men in Iran. Iran J Reprod Med 2015;13(9):563-570.

Naasse Y, Charoute H, El Houate B, Elbekkay C, Razoki L, Malki A, et al. Chromosomal abnormalities and Y chromosome microdeletions in infertile men from Morocco. BMC Urol 2015;15:95. doi:10.1186/s12894- 015-0089-3

Atia T, Abbas M, Ahmed AF. Azoospermia factor microdeletion in infertile men with idiopathic severe oligozoospermia or non-obstructive azoospermia. African J Urol 2015;21(4):246-253. doi:10.1016/j.afju.2015.02.004

Bansal SK, Jaiswal D, Gupta N, Singh K, Dada R, Sankhwar SN, et al. Gr/gr deletions on Y-chromosome correlate with male infertility: an original study, meta-analyses, and trial sequential analyses. Sci Rep 2016;6:19798. doi:10.1038/srep19798

Ghorbel M, Gargouri Baklouti S, Ben Abdallah F, Zribi N, Cherif M, Keskes R, et al. Chromosomal defects in infertile men with poor semen quality. J Assist Reprod Genet 2012;29(5):451-456. doi:10.1007/s10815-012-9737-7

Liu XG, Hu HY, Guo YH, Sun YP. Correlation between Y chromosome microdeletion and male infertility. Genet Mol Res 2016;15(2). doi:10.4238/gmr.15028426

Birowo P, Putra DE, Dewi M, Rasyid N, Taher A. Y-chromosomal microdeletion in idiopathic azoospermic and severe sligozoospermic Indonesian men. Acta Med Indones 2017;49(1):17-23.

Ambulkar PS, Pande SS. Male infertility: screening of azoospermia factor (AZF) microdeletion in idiopathic infertile men. J Exp Biol Agricultl Sci 2017;5(1):7-13. doi:10.18006/2017.5(1).007.013

Nailwal M, Chauhan JB. Gene scanning for microdeletions in the azoospermia factor region of Y-chromosome in infertile men of Gujarat, India. J Clin Diagn Res 2017;11(8):GC01-GC06. doi:10.7860/ JCDR/2017/26750.10350

Akinsal EC, Baydilli N, Dundar M, Ekmekcioglu O. The frequencies of Y chromosome microdeletions in infertile males. Turk J Urol 2018;44(5):389-392. doi:10.5152/ tud.2018.73669

Johnson M, Raheem A, De Luca F, Hallerstrom M, Zainal Y, Poselay S, et al. An analysis of the frequency of Y-chromosome microdeletions and the determination of a threshold sperm concentration for genetic testing in infertile men. BJU Int 2018. doi:10.1111/bju.14521

Stouffs K, Lissens W, Tournaye H, Haentjens P. What about gr/gr deletions and male infertility? Systematic review and meta-analysis. Hum Reprod Update 2011;17(2):197-209. doi:10.1093/humupd/dmq046

Liu XY, Zhang HY, Pang DX, Xue LT, Yang X, Li YS, et al. AZFa microdeletions: occurrence in Chinese infertile men and novel deletions revealed by semiconductor sequencing. Urology 2017;107:76-81. doi:10.1016/j. urology.2017.04.024

Hucklenbroich K, Gromoll J, Heinrich M, Hohoff C, Nieschlag E, Simoni M. 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- 197. doi:10.1093/humrep/deh558

Mierla D, Jardan D, Stoian V. Chromosomal abnormality in men with impaired spermatogenesis. Int J Fertil Steril 2014;8(1):35-42.

Dos Santos Godoy GC, Galera BB, Araujo C, Barbosa JS, de Pinho MF, Galera MF, et al. The low prevalence of Y chromosomal microdeletions is observed in the oligozoospermic men in the area of Mato Grosso State and Amazonian region of Brazilian patients. Clin Med Insights Reprod Health 2014;8:51-57. doi:10.4137/CMRH.S15475

Alimardanian L, Saliminejad K, Razi S, Ahani A. Analysis of partial azoospermia factor c deletion and DAZ copy number in azoospermia and severe oligozoospermia. Andrologia 2016;48(9):890-894. doi:10.1111/and.12527

Miraghazadeh A, Sadighi Gilani MA, Reihani-Sabet F, Ghaheri A, Borjian Boroujeni P, Zamanian M. Detection of partial AZFc microdeletions in azoospermic infertile men is not pnformative of microTESE outcome. Int J Fertil Steril 2019;12(4):298-302. doi:10.22074/ijfs.2019.5397



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About The Authors

Mariya Levkova
Medical University of Varna

Department of Medical Genetics

Trifon Chervenkov
Medical University of Varna

Department of Medical Genetics

Laboratory of Clinical Immunology, St Marina University Hospital, Varna, Bulgaria

Lyudmila Angelova
Medical University of Varna

Department of Medical Genetics

Laboratory of Medical Genetics, St Marina University Hospital, Varna, Bulgaria

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