Journal of Reproduction & Infertility

Journal of Reproduction & Infertility

Prevalence of Cytomegalovirus in Semen of Male Partners of Infertile Couples and the Virus Impact on Sperm Parameters

Authors
1 Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Obstetrics and Gynecology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran; Maternal-Fetal Medicine Research C
2 Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
3 IVF Section, Ghadir Mother and Child Hospital of Shiraz, Shiraz, Iran
4 Department of Obstetrics and Gynecology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
5 Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Obstetrics and Gynecology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
6 Infertility Research Center, Shiraz University of Medical Sciences, Shiraz, Iran; Department of Biostatistics, Shiraz University of Medical Sciences, Shiraz, Iran
7 Department of Pediatrics, Shiraz University of Medical Sciences, Shiraz, Iran
8 Molecular Medicine Department, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
Abstract
Background: Genital tract infection is one of the causes of male infertility. Several studies have shown a role for human cytomegalovirus (CMV) in this context. In the present study, the prevalence of CMV in a population of male partners of infertile couples was estimated and the impact of CMV on sperm parameters was determined. Methods: In this cross sectional study, CMV DNA and virus copy number were examined in the semen of 150 participants including 80 with normal semen analysis (SA) and 70 with abnormal SA, by quantitative Real-Time PCR. Sperm parameters were compared between CMV positive and negative groups. Comparisons with p-values under 0.05 were considered significant. Logistic regression was performed to control the effect of some variables with p<0.25 on sperm parameters. Results: CMV DNA was detected in the semen of 28 (18.6%) individuals. 21 men (30%) with abnormal SA and 7 (8.8%) with normal SA were positive for CMV DNA (p=0.001). The mean virus copy number was 883.1±4662.01 for the men with abnormal SA and 2525.7±12680.9 for those with normal SA (p=0.001). Sperm count was (32.1±23.5) x10 6 in CMV positive and (44.2±24.1) x10 6 in CMV negative groups (p=0.022). Normal sperm morphology was 2.73±2.83% and 5.99±5.44% in CMV positive and negative groups, respectively (p<0.001). After controlling some variables, the sperm morphology remains the only statistically significant sperm parameter that was reduced by CMV. Conclusion: The higher CMV prevalence in the semen of males with abnormal SA compared to normal SA and significant reduction of sperm morphology in the presence of CMV, are in favor of the negative impact of CMV on male fertility.
Keywords

  1. Habibi M, Bahrami A, Morteza A, Sadighi Gilani MA, Hassanzadeh G, Ghadami M, et al. Study of cytomegalovirus infection in idiopathic infertility men referred to Shariati hospital, Tehran, Iran. Iran J Reprod Med. 2014;12(2):151-4.
  2. Malm G, Engman ML. Congenital cytomegalovirus infections. Semin Fetal Neonatal Med. 2007;12(3):154-9.
  3. Mack I, Burckhardt MA, Heininger U, Prufer F, Schulzka S, Wellmann S. Symptomatic congenital cytomegalovirus infection in children of seropositive women. Front Pediatr. 2017;5:134.
  4. Buxmann H, Hamprecht K, Meyer-Wittkopf M, Friese K. Primary human cytomegalovirus (CMV) infection in pregnancy. Dtsch Artztebl Int. 2017;114(4):45-52.
  5. Stadler LP, Bernstein DI, Callahan ST, Turley CB, Munoz FM, Ferreira J, et al. Seroprevalence and risk factors for cytomegalovirus infections in adolescent females. J Pediatric Infect Dis Soc. 2013;2(1):7-14.
  6. Jung JH, Kim MH, Kim J, Baik SK, Koh SB, Park HJ, et al. Treatment of leukocytospermia in male infertility: a systematic review. World J Mens Health. 2016;34(3):165-72.
  7. Nasri F, Gharesi-Fard B, Namavar Jahromi B, Farazi-Fard MA, Banaei M, Davari M, et al. Sperm DNA methylation of H19 imprinted gene and male infertility. Andrologia. 2017;49(10).
  8. Berek JS. Berek & Novak's gynecology. 14th ed. Philadelphia: Lippincott Williams & Wilkins; 2007. 1671 p.
  9. Parsanezhad ME, Namavar Jahromi B, Zare N, Keramati P, Khalili A, Parsa-Nezhad M. Epidemiology and etiology of infertility in Iran, systematic review and meta-analysis. J Womens Health Issues Care. 2014;2(6):1-6.
  10. Gimenes F, Souza RP, Bento JC, Teixeira JJ, Maria-Engler SS, Bonini MG, et al. Male infertility: a public health issue caused by sexually transmitted pathogens. Nat Rev Urol. 2014;11(12):672-87.
  11. Naumenko VA, Tyulenev YA, Yakovenko SA, Kurilo LF, Shileyko LV, Segal AS, et al. Detection of human cytomegalovirus in motile spermatozoa and spermatogenic cells in testis organotypic culture. Herpesviridae. 2011;2(1):7.
  12. Eggert-Kruse W, Reuland M, Johannsen W, Strowitzki T, Schlehofer JR. Cytomegalovirus (CMV) infection--related to male and/or female infertility factors? Fertil Steril. 2009;91(1):67-82.
  13. Naumenko V, Tyulenev Y, Kurilo L, Shileiko L, Sorokina T, Evdokimov V, et al. Detection and quantification of human herpes virus types 4-6 in sperm samples of patients with fertility disorders and chronic inflammatory urogenital tract disease. Andrology. 2014;2(5):687-94.
  14. Neofytou E, Sourvinos G, Asmarianaki M, Spandidos DA, Makrigiannakis A. Prevalence of human herpes virus types 1-7 in the semen of men attending an infertility clinic and correlation with semen parameters. Fertil Steril. 2009;91(6):2487-94.
  15. Bezold G, Politch JA, Kiviat NB, Kuypers JM, Wolff H, Anderson DJ. Prevalence of sexually transmissible pathogens in semen from asymptomatic male infertility patients with and without leukocytospermia. Fertil Steril. 2007;87(5):1087-97.
  16. Behboudi E, Mokhtari-Azad T, Yavarian J, Ghavami N, Seyed Khorrami SM, Rezaei F, et al. Molecular detection of HHV1-5, AAV and HPV in semen specimens and their impact on male fertility. Hum Fertil (Camb). 2018;22(2):133-8.
  17. World health organization, department of reproductive health and research. WHO laboratory manual for the examination and processing of human semen. 5th ed. Geneva: World health organization; 2010. 287 p.
  18. Shaiegan M, Rasouli M, Zadsar M, Zolfaghari S. Meta-analysis of cytomegalovirus seroprevalence in volunteer blood donors and healthy subjects in Iran from 1992 to 2013. Iran J Basic Med Sci. 2015;18(7):627-34.
  19. Eivazi-Ziaei J, Movassagpour A, Asgharzadeh M, Dastgiri S. Seroprevalence of cytomegalovirus in blood donors in the northwest of Iran. J Analyt Res Clin Med. 2013;1(2):96-100.
  20. Dejucq N, Jégou B. Viruses in the mammalian male genital tract and their effects on the reproductive system. Microbiol Mol Biol Rev. 2001;65(2):208-31.
  21. Kapranos N, Petrakou E, Anastasiadou C, Kotronias D. Detection of herpes simplex virus, cytomegalovirus, and Epstein-Barr virus in the semen of men attending an infertility clinic. Fertil Steril. 2003;79 Suppl 3:1566-70.
  22. Mohseni M, Mollaei H, Arabzadeh SA, Mirshekari TR, Ghorbani P. Frequency of cytomegalovirus in fertile and infertile men, referring to Afzalipour hospital IVF research center, Kerman, Iran: a case-control study. Int J Reprod Biomed (Yazd). 2018;16(7):443-6.
  23. Tafvizi F, Baghdadi K, Hayati Roodbari N. Lack of relatedness between human cytomegalovirus in semen and male infertility. Iran J Med Microbiol. 2016;10(3):39-46.
  24. Klimova RR, Chichev EV, Naumenko VA, Gadzhieva ZS, Tsibisov AS, Adieva AA, et al. [Herpes simplex virus and cytomegalovirus in male ejaculate: herpes simplex virus is more frequently encountered in idiopathic infertility and correlates with the reduction in sperm parameters. Vopr Virusol. 2010;55(1):27-31.
  25. Kanduc D. Describing the potential crossreactome between mumps virus and spermatogenesis-associated proteins. Endocr Metab Immune Disord Drug Targets. 2014:14(3):218-25.
  26. Swanson EC, Schleiss MR. Congenital cytomegalovirus infection: new prospects for prevention and therapy. Pediatr Clin North Am. 2013;60(2):335-49.
  27. Suganuma E, Oka A, Sakata H, Adachi N, Asanuma S, Oguma E, et al. 10-year follow-up of congenital cytomegalovirus infection complicated with severe neurological findings in infancy: a case report. BMC Pediatr. 2018;18(1):369.
  28. Gantt S, Bitnun A, Renaud C, Kakkar F, Vaudry W. Diagnosis and management of infants with congenital cytomegalovirus infection. Pediatr Child Health. 2017;22(2):72-4.
  29. Lanzieri TM, Dollard SC, Josephson CD, Schmid DS, Bialek SR. Breast milk-acquired cytomegalovirus infection and disease in very low birth weight and premature infants. Pediatrics. 2013;131(6):e1937-e45.
  30. Gang MH, Chang MY. Breast milk-transmitted cytomegalovirus infection in preterm infants. Neonatal Med. 2018;25(2):58-65.
  31. Ronchi A, Shimamura M, Malhotra PS, Sánchez PJ. Encouraging postnatal cytomegalovirus (CMV) screening: the time is NOW for universal screening! Expert Rev Anti Infect Ther. 2017;15(5):417-9.
  32. Cunningham FG, Leveno KJ, Bloom SL, Hauth JC, Rouse DJ, Spong CY. Williams Obstetrics. 25 th ed. New York: McGraw-Hill; 2001. 1404 p.