Türk popülasyonunda oligozoospermi ve azospermi hastalarında infertilitenin genetik nedenleri

Year 2021, Volume: 16 Issue: 2, 159 - 164, 29.06.2021

Yavuz Onur Danacioglu , Mustafa Yenice , Fatih Akkaş , Mustafa Soytaş , Serhat Seyhan Ali İhsan Taşçı

https://doi.org/10.33719/yud.2021;16-2-834672

Abstract

Amaç: Genetik bilimindeki ilerlemeler ve yardımcı üreme tekniklerindeki gelişmeler, infertilitenin genetik nedenlerine odaklanmamızı sağlamaktadır. Bu çalışmada, sex kromozomu anöploidisi ve Y kromozom mikrodelesyonları açısından genetik anormallikleriaraştırmayı amaçladık.

Gereç ve Yöntemler: Azospermi veya şiddetli oligozoospermi (≤ 5 milyon spermatozoa/ml) olan toplam 350 hasta analiz edildi. Hastalar genel muayene ve laboratuvar değerlendirmesi sonrası, karyotip ve Y kromozom mikrodelesyonu açısından değerlendirildi.

Bulgular: Non-obstrüktif azospermi (NOA) olan toplam 225 infertil erkek ve oligozoospermi olan 125 infertil erkek çalışmaya dahil edildi. Genel sitogenetik anomali oranı% 16 idi. Üç yüz elli vakanın 32’sinde (% 9,1) kromozom değişiklikleri tespit edildi. En sık görülen genetik anomali 47, XXY (Klinefelter sendromu KS) idi ve insidansı NOA grubunda % 11.5 ve oligozoospermi grubunda % 3,2 idi. Y kromozom mikrodelesyonu 24 (% 6.8) hastada tespit edildi ve benzer şekilde NOA grubunda oligozoospermi grubuna göre daha sık görüldü (% 9.3 vs % 2.4, sırasıyla).

Sonuç: İnfertilitenin şiddeti ile birlikte genetik nedenlerin görülme sıklığı artmaktadır. Sonuç olarak, yardımcı üreme tekniklerinin kullanılmasından önce genetik tarama ve uygun genetik danışmanlığa ihtiyaç duyulmaktadır.

Keywords

azospermi , kromozom , infertilite , mikrodelesyon , oligoozospermi

The genetic causes of infertility in patients with oligozoospermia and azoospermia in Turkish population

Abstract

Objective: Advances in the science of genetics and the development of assisted reproductive techniques focus on the genetic causes of infertility. The aim of this research is to reveal genetic abnormalities in terms of sex chromosome aneuploidy and Y chromosome microdeletions.

Material and Methods: A total of 350 patients with azoospermia or severe oligozoospermia were selected. After general examination of the patients and laboratory investigations were performed, cartoypes and Y chromosome microdeletions were examined.

Results: A total of 225 infertile men with non-obstructive azoospermia (NOA) and 125 infertile men with oligozoospermia were enrolled into the study. The overall cytogenetic anomaly rate was 16%. Chromosomal changes were detected in 32 of 350 (9.1%) cases. The most common genetic anomaly was 47, XXY (Klinefelter syndrome) and the incidence was 11.5% in NOA group. This rate was 3.2% in oligozoospermia group. Y chromosome microdeletions were detected in 24 (6.8%) patients and similarly, it was observed more frequently in the NOA group than in the oligozoospermia group.

Conclusion: The incidence of genetic causes have been increasing with the severity of infertility. As a result, genetic screening and appropriate genetic counseling are needed before the use of assisted reproductive techniques.

Keywords

azospermia , chromosome , infertility , microdeletion , oligozoospermia

Thanks

Dear Editor; The study entitled “The prevelance of Y chromosome microdeletions and chromosomal abnormalities in infertile men with oligozoospermia and azoospermia in Turkish population” was submitted to The New Journal of Urology. We state that all authors have read and approved submission of the manuscript and the manuscript has not been published and is not being considered for publication elsewhere in whole or part in any language. There is no conflict of interest. All authors have agreed to be so listed and have seen and approved the manuscript, its consent and its submission to to The New Journal of Urology. We think that the readership of the journal would be interested in this study. Best regards,

References

• 1. Hopps C, Mielnik A, Goldstein M, Palermo G, Rosenwaks Z, Schlegel P. Detection of sperm in men with Y chromosome microdeletions of the AZFa, AZFb and AZFc regions. Human reproduction 2003;18:1660-5.
• 2. De Kretser D, Baker H. Infertility in men: recent advances and continuing controversies. The Journal of Clinical Endocrinology & Metabolism 1999;84:3443-50.
• 3. Krausz C, Riera-Escamilla A. Genetics of male infertility. Nature Reviews Urology 2018;15:369-84.
• 4. Balkan M, Tekes S, Gedik A. Cytogenetic and Y chromosome microdeletion screening studies in infertile males with Oligozoospermia and Azoospermia in Southeast Turkey. Journal of assisted reproduction and genetics 2008;25:559-65.
• 5. Özdemir TR, Özyılmaz B, Çakmak Ö, Kaya ÖÖ, Köse C, Kırbıyık Ö, et al. Evaluation of chromosomal abnormalities and Y-chromosome microdeletions in 1696 Turkish cases with primary male infertility: A single-center study. Turkish journal of urology 2020;46:95.
• 6. Organisation WH. WHO laboratory manual for the examination of human semen and sperm-cervical mucus interaction: Cambridge university press; 1999.
• 7. Palermo GD, Colombero LT, Hariprashad JJ, Schlegel PN, Rosenwaks Z. Chromosome analysis of epididymal and testicular sperm in azoospermic patients undergoing ICSI. Human Reproduction 2002;17:570-5.
• 8. Barch MJ, Barch, Knutsen, Spurbeck. AGT Cytogenetics Laboratory Manual: Lippincott Williams & Wilkins Philadelphia NY; 1997.
• 9. Dada R, Gupta N, Kucheria K. Cytogenetic and molecular analysis of male infertility. Cell biochemistry and biophysics 2006;44:171-7.
• 10. Quilter CR, Svennevik EC, Serhal P, Ralph D, Bahadur G, Stanhope R, et al. Cytogenetic and Y chromosome microdeletion screening of a random group of infertile males. Fertility and sterility 2003;79:301-7.
• 11. Nakamura Y, Kitamura M, Nishimura K, Koga M, Kondoh N, Takeyama M, et al. Chromosomal variants among 1790 infertile men. International Journal of Urology 2001;8:49-52.
• 12. Yoshida A, Miura K, Shirai M. Cytogenetic survey of 1,007 infertile males. Urologia internationalis 1997;58:166-76.
• 13. Elghezal H, Hidar S, Braham R, Denguezli W, Ajina M, Saâd A. Chromosome abnormalities in one thousand infertile males with nonobstructive sperm disorders. Fertility and sterility 2006;86:1792-5.
• 14. Aksglaede L, Juul A. Testicular function and fertility in men with Klinefelter syndrome: a review. Eur J Endocrinol 2013;168:R67-76.
• 15. Lin YM, Huang WJ, Lin JSN, Kuo PL. Progressive depletion of germ cells in a man with nonmosaic Klinefelter's syndrome: optimal time for sperm recovery. Urology 2004;63:380-1.
• 16. Peters O, King WA. The detection of female cell activity in male sex chromosome chimeric Rideau Arcott sheep, using the Xist gene product as a marker. SURG Journal 2008;1:20-5.
• 17. Bojesen A, Juul S, Gravholt CH. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. The Journal of Clinical Endocrinology & Metabolism 2003;88:622-6.
• 18. Swerdlow AJ, Higgins CD, Schoemaker MJ, Wright AF, Jacobs PA, Group UKCC. Mortality in patients with Klinefelter syndrome in Britain: a cohort study. The Journal of Clinical Endocrinology & Metabolism 2005;90:6516-22.
• 19. Fainberg J, Hayden RP, Schlegel PN. Fertility management of Klinefelter syndrome. Expert Review of Endocrinology & Metabolism 2019;14:369-80.
• 20. Massart A, Lissens W, Tournaye H, Stouffs K. Genetic causes of spermatogenic failure. Asian journal of andrology 2012;14:40.
• 21. Colaco S, Modi D. Genetics of the human Y chromosome and its association with male infertility. Reproductive biology and endocrinology 2018;16:14.
• 22. Sargın CF, Berker-Karaüzüm S, Manguoğlu E, Erdoğru T, Karaveli Ş, Gülkesen KH, et al., editors. AZF microdeletions on the Y chromosome of infertile men from Turkey. Annales de genetique; 2004: Elsevier.
• 23. Akin H, Onay H, Turker E, Ozkinay F. Primary male infertility in Izmir/Turkey: a cytogenetic and molecular study of 187 infertile Turkish patients. Journal of assisted reproduction and genetics 2011;28:419-23.
• 24. Küçükaslan AŞ, Çetintaş VB, Altıntaş R, Vardarlı AT, Mutlu Z, Ulukuş M, et al. Identification of Y chromosome microdeletions in infertile Turkish men. Turkish journal of urology 2013;39:170.
• 25. Akbarzadeh Khiavi M, Jalili A, Safary A, Gharedaghchi Z, Mirinezhad SK, Mehdizadeh A, et al. Karyotypic abnormalities and molecular analysis of Y chromosome microdeletion in Iranian Azeri Turkish population infertile men. Systems Biology in Reproductive Medicine 2020;66:140-6.
• 26. Reijo R, Lee T-Y, Salo P, Alagappan R, Brown LG, Rosenberg M, et al. Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA–binding protein gene. Nature genetics 1995;10:383-93.