Spermogram parameters and genetic abnormalities

The prevalence of genetic abnormalities in men with infertility is 5.8% (n = 9766), of which 4.2% are sex chromosome abnormalities and 1.5% are autosomal abnormalities. In the Russian Federation, this indicator varies from 4.72% (n = 539) (Novosibirsk) to 10.78% (n = 204) (St. Petersburg, the Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott) — the percentage of detectability probably depends on the concentration of patients in specialized institutions. Given the high frequency of genetic abnormalities in infertile men, it is necessary to correctly select diagnostic methods in accordance with the specific clinical situation. When the concentration of spermatozoa decreases to less than 10 million/ml, karyotyping is recommended; at a concentration of less than 5 million/ml, the search for AZF deletions is necessary; in severe disorders of spermatogenesis — the detection of mutations in the cystic fibrosis gene (CFTR). To confirm genetically determined asthenozoospermia, the electron microscopy of spermatozoa is required. Taking into account the development of assisted reproductive technologies, including the active use of intracytoplasmic sperm injection and the relationship of sperm pathology with severe genetically determined diseases, it is necessary to inform potential parents what risks to the health of future children the use of such material carries.

1. European Association of Urology. Guidelines. Sexual and Reproductive Health / A. Salonia (Chair), C. Bettocchi, J. Carvalho et al. Retrieved on March 1, 2021 from https://uroweb.org/guideline/sexual-and-reproductive-health/.

2. Jonson M.D. (1998). Gene tic risk of intracytoplasmic sperm injection in the treatment of male infertility: recommendations for genetic counseling and screening. Fertil. Steril., 70 (3), 397–411.

3. Soukhikh G.T., Bozhedomo v V.A. (2009). Male Infertility. Moscow, 240 p. In Russ.

4. Epanchintseva Е.А., Sely atitskaya V.G., Maksimova Yu.V. et al. (2015). The prevalence of genetic anomalies associated with male infertility in patients of the Novosibirsk region. Medical Genetics, 2, 56–57. In Russ.

5. Shilnikova Е.М. (2015). Gen etic and epigenetic features of the sperm genome and their impact on early embryonic human development: Cand. Sci. (Bio.) Theses. St. Petersburg, 144 p. In Russ.

6. Van Assche E.V., Bonduelle M. , Tournaye H. et al. (1996). Cytogenetics of infertile men. Hum. Reprod., 11 (4), 1–24.

7. Nakamura Y., Kitamura M., Nishimura K. et al. (2001). Chromosomal variants among 1790 infertile men. Int. J. Urol., 8 (2), 49–52.

8. Dul E.C., van Echten-Arends J ., Groen H. et al. (2012). Chromosomal abnormalities in azoospermic and non-azoospermic infertile men: numbers needed to be screened to prevent adverse pregnancy outcomes. Hum. Reprod., 27 (9), 2850–2856.

9. Tovar R.S., Espinosa J.B., García G.G., Romo M.M., Usabiaga R.A. (2009). Prevalence of chromosomal alterations in infertile patients studied in a clinic of assisted reproduction. Ginecol. Obstet. Mex., 77 (3), 128–135.

10. Campanho C. de L., Heinrich J. K., Couto E., Barini R. (2011). Subfertility phenotype, chromosome polymorphism and conception failures. Rev. Bras. Ginecol. Obstet., 33 (5), 246–251.

11. Okay A.C., Isilay O., Fatma D., Munis D. (2010). Cytogenetic results of patients with infertility in Middle Anatolia, Turkey: Do heterochromatin polymorphisms affect fertility? J. Reprod. Infertil., 11 (3), 179–181.

12. Skakkebæk A., Wallentin M., Gr avholt C.H. (2015). Neuropsychology and socioeconomic aspects of Klinefelter syndrome: new developments. Curr. Opin. Endocrinol. Diabetes Obes., 22 (3), 209–216.

13. Pylyp L.Y., Spinenko L.O., Verh oglyad N.V., Kashevarova O.O., Zukin V.D. (2015). Chromosomal abnormalities in patients with infertility. Tsitol. Genet., 49 (3), 33–39.

14. Madon P.F., Althalye A.S., Pari kh F.R. (2005). Polymorphic variants on chromosomes play a significant role in infertility. Reprod. Biomed. Online, 11 (6), 726– 732.

15. Codina-Pascual M., Navarro J., Oliver-Bonet M. et al. (2006). Behaviour of human heterochromatic regions during the synapsis of homologous chromosomes. Hum. Reprod., 21 (6), 1490–1497.

16. Kosyakova N., Grigorian A., Lie hr T. et al. (2013). Heteromorphic variants of chromosome 9. Mol. Cytogenet., 6 (1). Art. number: 14.

17. Sarrate Z., Vidal F., Blanco J. (2014). Meiotic abnormalities in metaphase I human spermatocytes from infertile males: frequencies, chromosomes involved, and the relationships with polymorphic karyotype and seminal parameters. Asian J. Androl., 16 (6), 838–844.

18. Male infertility: Clinical guidelines. Russian Society of Urology (2019). Retrieved on March 1, 2021 from https://www.ooorou.ru/public/uploads/ROU/Files/%D0%9A%D0%A0%20%D0%9C%20%D0%91%D0%B5%D1%81%D0%BF%D0%BB%D0%BE%D0%B4%D0%B8%D0%B5%202019%20(pdf.io).pdf.

19. Bragina Ye.Ye., Bocharova Ye.N. (20 14). Quantitative electron microscopic examination of sperm for male infertility diagnosis. Andrology and Genital Surgery, 15 (1), 41–50.

20. Blouin J.L., Meeks M., Radhakrishna U. et al. (2000). Primary ciliary dyskinesia: a genome-wide linkage analysis reveals extensive locus heterogeneity. Eur. J. Hum. Genet., 8, 109–118.

21. Chemes H.E., Olmedo S.B., Carrere C . et al. (1998). Ultrastructural pathology of the sperm flagellum: association between flagellar pathology and fertility prognosis in severely asthenozoospermic men. Hum. Reprod., 13 (9), 2521–2526.

22. Kennedy M.P., Omran H., Leigh M.W. et al. (2007). Congenital heart disease and other heterotaxic defects in a large cohort of patients with primary ciliary dyskinesia. Circulation, 115 (22), 2814–2821.

23. Dávila Garza S.A., Patrizio P. (201 3). Reproductive outcomes in patients with male infertility because of Klinefelter’s syndrome, Kartagener’s syndrome, roundhead sperm, dysplasia fibrous sheath, and “stump” tail sperm: an updated literature review. Curr. Opin. Obstet. Gynecol., 25 (3), 229–246.

24. Amiri-Yekta A., Coutton C., Kherraf Z.E. et al. (2016). Whole-exome sequencing of familial cases of multiple morphological abnormalities of the sperm flagella (MMAF) reveals new DNAH1 mutations. Hum. Reprod., 31 (12), 2872–2880.

25. Liu X., Han R., Ma J. et al. (2017). Mutation analysis and treatment of a case with globozoospermia. Zhonghua Yi Xue Yi Chuan Xue Za Zhi, 34 (5), 764–766.

26. Ghédir H., Ibala-Romdhane S., Okutma n O. et al. (2016). Identification of a new DPY19L2 mutation and a better definition of DPY19L2 deletion breakpoints leading to globozoospermia. Mol. Hum. Reprod., 22 (1), 35–45.

27. ElInati E., Fossard C., Okutman O. et al. (2016). A new mutation identified in SPATA16 in two globozoospermic patients. J. Assist. Reprod. Genet., 33 (6), 815– 820.

28. Bragina Е.Е., Sorokina Т.М., Arifulin Е.А., Kurilo L.F. (2015). Genetically determined patozoospermia. Literature review and research results. Andrology and Genital Surgery, 16(3), 29–39.

29. De Braekeleer M., Nguyen M.H., Morel F., Perrin A. (2015). Genetic aspects of monomorphic teratozoospermia: a review. J. Assist. Reprod. Genet., 32 (4), 615–623.

30. Zhu F., Wang F., Yang X. et al. (2016). Biallelic SUN5 mutations cause autosomal-recessive acephalic spermatozoa syndrome. Am. J. Hum. Genet., 99 (4), 942– 949.

31. Gambera L., Falcone P., Mencaglia L. et al. (2010). Intracytoplasmic sperm injection and pregnancy with decapitated sperm. Fertil. Steril., 93 (4), 1347.e7–1347. e12.

32. Epanchintseva Е.А., Selyatitskaya V.G., Bozh edomov V.A. (2020). Sperm DNA fragmentation is a necessity for modern clinical practice. Andrology and Genital Surgery, 21 (1), 14–21.

33. Agarwal А., Said T.М. (2003). Role of sperm chromatin abnormalities and DNA damage in male infertility. Hum. Reprod., 9 (4), 331–345.

34. Seli Е., Sakkas D. (2005). Spermatozoal nuclear determinants of reproductive outcome: implications for ART. Hum. Reprod. Update, 11 (4), 337–349.

35. Simon L., Castillo J., Oliva R., Lewis S.E.M. (2011). Relationships between human sperm protamines, DNA damage and assisted reproduction outcomes. Reprod. Biomed. Online, 23 (6), 724–734.

36. Dada R., Mahfouz R.Z, Kumar R. et al. (2011). А comprehensive work up for an asthenozoospermic man with repeated intracytoplasmic sperm injection (ICSI) failure. Andrologia, 43 (5), 368–372.

37. Santi D., Spaggiari G., Simoni M. (2018). Sperm DNA fragmentation index as a promising predictive tool for male infertility diagnosis and treatment management — meta-analyses. Reprod. Biomed. Online, 37 (3), 315–326.

38. Epanchintseva Е.А., Selyatitskaya V.G., Mitrofanov I.M. et al. (2017). Quantitative and qualitative abnormalities in spermogram and other semen tests in men from infertile couples. Russian Journal of Human Reproduction, 23 (6), 90–96. In Russ.

39. Pastuszek E., Kiewisz J., Kulwikowska P.M., Lukaszuk M., L ukaszuk K. (2015). Sperm parameters and DNA fragmentation of balanced chromosomal rearrangements carriers. Folia Histochem. Cytobiol., 53 (4), 314–321.

40. Olszewska M., Wiland E., Huleyuk N. et al. (2019). Chromos ome (re)positioning in spermatozoa of fathers and sons — carriers of reciprocal chromosome translocation (RCT). BMC Med. Genom., 12 (1), 30.