THE FREQUENCY OF Y CHROMOSOME MICRODELETIONS AND CYTOGENETIC ABNORMALITIES IN CASES WITH MALE INFERTILITY FROM THRACE REGION: SINGLE CENTER EXPERIENCE

Abstract

Objective: Genetic factors, including Y chromosome microdeletions, are responsible for about 10% of male infertility cases and are particularly associated with azoospermia or severe oligozoospermia. In our study, it was aimed to determine the frequency of Y chromosome microdeletions in the Thrace region and to provide information about the heterogeneous phenotype in infertile male patients with AZF microdeletion. Material and Method: Chromosome analysis and Y chromosome microdeletion analysis were performed on 446 male patients with non-obstructive azoospermia or oligozoospermia, who applied to the Trakya University Hospital Medical Genetics Department Genetic Diseases Diagnosis Center clinic between the years 2011-2019. Results: Y chromosome microdeletion was detected in 19 (4.26%) of 446 cases. Structural chromosomal anomalies were accompanied in 5 of 19 cases with Y chromosome microdeletions. Three hundred fifty-two cases had no Y chromosome microdeletion, 35 (9.94%) of these cases had Klinefelter syndrome, 1 (0.28%) case had Klinefelter syndrome low grade mosaicism, 3 (0.85%) cases had Robertsonian translocation carriage, and 1 (0.28%) had Reciprocal translocation carriage. Conclusion: Y chromosome microdeletion screening in non-obstructive azoospermic or oligosoospermic infertile male patients has prognostic value and affects clinical prognosis. The results of our study support the proposal to perform Y chromosome microdeletion analysis before microTESE in azoospermic or oligosoospermic infertile male patients as reported in the literature.

Keywords

• Y microdeletion
• male infertility
• chromosome anomaly
• azoospermia
• oligospermia

TRAKYA BÖLGESİ ERKEK İNFERTİLİTE OLGULARINDA Y KROMOZOM MİKRODELESYONLARI VE SİTOGENETİK ANOMALİLERİN SIKLIĞI: TEK MERKEZ DENEYİMİ

Abstract

Amaç: Y kromozom mikrodelesyonları dahil olmak üzere genetik faktörler erkek infertilitesi olgularının yaklaşık %10’undan sorumludur ve özellikle azoospermi veya ciddi oligozoospermi ile ilişkilidir. Çalışmamızda Trakya bölgesi’nde Y kromozom mikrodelesyon sıklığını saptamak ve AZF mikrodelesyonu olan infertil erkek olgularda heterojen fenotip hakkında bilgi sunmak amaçlanmıştır. Gereç ve Yöntem: Trakya Üniversitesi Hastanesi Tıbbi Genetik Anabilim Dalı Genetik Hastalıklar Değerlendirme Merkezi Polikliniği’ne 2011-2019 yılları arasında infertilite nedeni ile müracaat eden, non-obstruktif azoospermik veya oligozoospermik 446 erkek olguda konvansiyonel sitogenetik yöntemle karyotip analizi ve Y kromozom mikrodelesyon analizi yapıldı. Bulgular: Dört yüz kırk altı olgunun 19’unda (%4,26) Y kromozom mikrodelesyonu saptandı. Y kromozom mikrodelesyonu saptanan 19 olgunun 5’inde yapısal kromozom anomalileri eşlik etmekteydi. Y kromozomunda mikrodelesyon saptanmayan 352 olgunun 35’inde (%9,94) Klinefelter sendromu, 1’inde (%0,28) düşük oranlı Klinefelter sendromu mozaikliği, 3’ünde (%0,85) Robertsonian translokasyon taşıyıcılığı, 1’inde (%0,28) resiprokal translokasyon taşıyıcılığı saptandı. Sonuç: Non-obstruktif azoospermik veya oligozoospermik infertil erkek olgularda Y kromozom mikrodelesyon taraması prognostik değere sahiptir ve klinik prognozu etkilemektedir. Çalışmamızın sonuçları literatürde bildirilmiş olan azoospermik veya oligozoospermik infertil erkek olgularda mikroTESE öncesinde Y kromozom mikrodelesyon analizi yapılması önerisini desteklemektedir.

Keywords

• Y mikrodelesyon
• erkek infertilitesi
• kromozom anomalisi
• azospermi
• oligospermi

References

1. 1. Vander Borght M, Wyns C. Fertility and infertility: Definition and epidemiology. Clin Biochem 2018;62:2-10. [CrossRef]
2. 2. Heidary Z, Saliminejad K, Zaki-Dizaji M, Khorram Khorshid HR. Genetic aspects of idiopathic asthenozoospermia as a cause of male infertility. Hum Fertil (Camb) 2018;1-10. doi: 10.1080/14647273.2018.1504325. [Epub ahead of print] [CrossRef]
3. 3. Hwang K, Yatsenko AN, Jorgez CJ, Mukherjee S, Nalam RL, Matzuk MM, et al. Mendelian genetics of male infertility. Ann N Y Acad Sci 2010;1214:E1-E17. [CrossRef]
4. 4. Koh E, Sin HS, Fukushima M, Namiki M. Azoospermia factor and male infertility. Reprod Med Biol 2010;9(3):129-37. [CrossRef]
5. 5. Lee HD , Lee HS, Park SH, Jo DG, Choe JH, Lee JS, et al. Causes and classification of male infertility in Korea. Clin Exp Reprod Med 2012;39(4):172-5. [CrossRef]
6. 6. 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):890-4. doi.org/10.1111/and.12527 Epub 2016 Jan 14. [CrossRef]
7. 7. Mokánszki A, Ujfalusi A, Gombos É, Balogh I. Examination of Y-Chromosomal Microdeletions and Partial Microdeletions in Idiopathic Infertility in East Hungarian Patients. J Hum Reprod Sci 2018;11(4):329-36. [CrossRef]
8. 8. Kent-First M, Muallem A, Shultz J, Pryor J, Roberts K, Nolten W, et al. Defining regions of the Y-chromosome responsible for male infertility and identification of a fourth AZF region (AZFd) by Y-chromosome microdeletion detection. Mol Reprod Dev 1999;53(1):27-41. [CrossRef]

9. 9. Sciarra F, Pelloni M, Faja F, Pallotti F, Martino G, Radicioni AF, et al. Incidence of Y chromosome microdeletions in patients with Klinefelter syndrome. J Endocrinol Invest 2019;42(7):833-42. [CrossRef]
10. 10. Kim SY, Kim HJ, Lee BY, Park SY, Lee HS, Seo JT. Y Chromosome Microdeletions in Infertile Men with Nonobstructive Azoospermia and Severe Oligozoospermia. J Reprod Infertil 2017;18(3):307-15.
11. 11. 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. [CrossRef]
12. 12. Samli H, Samli MM, Solak M, Imirzalioglu N. Genetic anomalies detected in patients with non-obstructive azoospermia and oligozoospermia. Arch Androl 2006;52(4):263-7. [CrossRef]
13. 13. Colaco S, Modi D. Genetics of the human Y chromosome and its association with male infertility. Reprod Biol Endocrinol 2018;16(1):14. [CrossRef]
14. 14. Sabbaghian M, Mohseni Meybodi A, Rafaee A, Saba S, Zamanian M, Sadighi Gilani MA. Sperm retrieval rate and reproductive outcome of infertile men with azoospermia factor c deletion. Andrologia 2018;50(7):e13052. doi: 10.1111/and.13052. Epub 2018 Jun 19. [CrossRef]
15. 15. Gürkan H. Y kromozomu mikrodelesyonu ve fertiliteyi etkileyen Y kromozomu genleri. Çefle K, Öztürk Ş, editörler. İnfertilite ve Genetik Yönü. 1. Baskı. Ankara: Türkiye Klinikleri 2019;25-31.
16. 16. Cetinkaya M, Onem K, Zorba OU, Ozkara H, Alici B. Evaluation of Microdissection Testicular Sperm Extraction Results in Patients with Non-Obstructive Azoospermia: Independent Predictive Factors and Best Cut off Values for Sperm Retrieval. Urol J 2015;12(6):2436-43.
17. 17. Kamp C, Huellen K, Fernandes S, Sousa M, Schlegel PN, Mielnik A, et al. High deletion frequency of the complete AZFa sequence in men with Sertoli-cell only syndrome. Mol Hum Reprod 2001;7:987-94. [CrossRef]
18. 18. Perrin J, Metzler-Guillemain C, Karsenty G, Grillo JM, Mitchell MJ, Guichaoua MR. Meiotic arrest at the midpachytene stage in a patient with complete azoospermia factor b deletion of the Y chromosome. Fertil Steril 2006;85(2):494. e5-8. [CrossRef]
19. 19. Longepied G, Saut N, Aknin-Seifer I, Levy R, Frances AM, Metzler-Guillemain C, et al. Complete deletion of the AZFb interval from the Y chromosome in an oligozoospermic man. Hum Reprod. 2010;25(10):2655-63. [CrossRef]
20. 20. Totonchi M, Meybodi AM, Boroujeni PB, Gilani MS, Almadani N, Gourabi H. Clinical data for 185 infertile Iranian men with Y-chromosome microdeletion. J Assist Reprod Genet 2012; 29(8):847-853. [CrossRef]
21. 21. Kumtepe Y, Beyazyurek C, Cinar C, Ozbey I, Ozkan S, Cetinkaya K, et al. A genetic survey of 1935 Turkish men with severe male factor infertility. Reprod Biomed Online 2009;18(4):465-74. [CrossRef]
22. 22. 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;18:1660-5. [CrossRef]
23. 23. 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;93:822-32. [CrossRef]
24. 24. Alves C, Carvalho F, Cremades N, Sousa M, Barros A. Unique (Y;13) translocation in a male with oligozoospermia: cytogenetic and molecular studies. Eur J Hum Genet 2002;10(8):467-74. [CrossRef]
25. 25. Brisset S, Izard V, Misrahi M, Aboura A, Masoux S, Ferlicot S, et al. Cytogenetic, molecular and testicular tissue studies in an infertile 45,X male carrying an unbalanced (Y;22) translocation: case report. Hum Reprod 2005;20(8):2168-72. [CrossRef]
26. 26. Gao M, Pang H, Zhao YH, Hua J, Tong D, Zhao H, et al. Karyotype analysis in large sample cases from Shenyang Women’s and Children’s hospital: a study of 16,294 male infertility patients. Andrologia 2017;49(4). [CrossRef]
27. 27. Wu QY, Li N, Li WW, Li TF, Zhang C, Cui YX, et al. Clinical, molecular and cytogenetic analysis of 46, xx testicular disorder of sex development with sry-positive. BMC Urology 2014;14:70 [CrossRef]
28. 28. Anik A, Catli G, Abaci A, Bober E. 46,xx male disorder of sexual development: A case report. Journal of Clinical Research in Pediatric Endocrinology 2013;5:258-260. [CrossRef]
29. 29. Andrade JG, Guerra-Júnior G, Maciel-Guerra AT. 46, XY and 45, X/46, XY testicular dysgenesis: similar gonadal and genital phenotype, different prognosis. Arq Bras Endocrinol Metabol 2010;54:331-4. [CrossRef]