Skip to main content

Role of Assisted Reproduction Techniques in the Management of Unexplained Male Infertility

  • Chapter
  • First Online:
Unexplained Infertility

Abstract

The inability of healthcare provider to conclusively identify the cause of infertility in couples leads to the designation of unexplained infertility. It is likely that abnormalities leading to infertility exists in couples but not detected by the current methods and the state of technology. Normal semen parameters in men reduce but do not completely eliminate the probability of male infertility. The wide range in World Health Organization (WHO) reference values of semen parameters, repeated revisions of normal reference range over the years, significant variation in interlaboratory assessment of sperm characteristics, and use of different analytical criteria (WHO versus Krueger’s Strict morphology) further complicates the clinical assessment of normal semen parameters. High incidence of chromosomal aberrations and/or high percentage of DNA damage in sperm, oxidative stress, exposure of men to environmental pollutants/toxins, etc. may be likely factors that can be the suspected cause of unexplained infertility. Abnormal expression of certain sperm proteins may play a role in failure of fertilization resulting in unexplained male infertility at clinical level. Unexplained male infertility is strongly suspected in couples if the female partner presents with the history of successful pregnancy in not too distant past and subsequent comprehensive diagnostic tests fail to lead to a confirmed infertility diagnosis.

In the absence of any apparent treatable condition, the treatment is largely empiric and involves intrauterine insemination (IUI), ovulation induction (OI), and in vitro fertilization (IVF). IVF with intracytoplasmic sperm injection (ICSI) offers couples with unexplained infertility, chance of successful pregnancy while avoiding the probability of fertilization failure. Treatment of men with the suspicion of unexplained male infertility is again empiric and involves prescribing supplements such as L-carnitine, vitamin C, D3, E, folic acid, zinc, selenium, and coenzyme Q10. The efficacy of nutritional supplements in improving male fertility remains to be conclusively documented.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Boivin J, Bunting L, Collins JA, Nygren KG. International estimates of infertility prevalence and treatment seeking: potential need and demand for infertility medical care. Hum Reprod. 2007;22:1506–12.

    PubMed  Google Scholar 

  2. Mallidis C, Howard EJ, Balur HW. Variation of semen quality in normal men. Int J Androl. 1991;14:99–107.

    CAS  PubMed  Google Scholar 

  3. World Health Organization. WHO laboratory manual for examination of human semen and sperm-cervical mucus interaction, 2nd edition. Cambridge: Cambridge University Press; 1987.

    Google Scholar 

  4. Irvine DS. Epidemiology and aetiology of male infertility. Hum Reprod. 1998;13:33–44.

    PubMed  Google Scholar 

  5. Murray KS, McGeady JA, Reed ML, Kuang WW, Nangia AK. The effect of the new 2010 World Health Organization criteria for semen analyses on male infertility. Fertil Steril. 2012;98:1428–31.

    PubMed  Google Scholar 

  6. Lipschultz LI. Office evaluation of the subfertile male. In: Lipschults LI, Niederberger CS, editors. Infertility in the male, 4th edition. Cambridge: Cambridge University Press; 2009. p. 153–76.

    Google Scholar 

  7. Martin RH. Chrosomal abnormalities in human sperm. In: Robaire B, Hales BE, editors. Advances in male-mediated developmental toxicity. New York: Plenum Press; 2003. p. 181–8.

    Google Scholar 

  8. Moosani N, Pattinson HA, Carter MD, Rademaker AW, Martin RH. Chromosomal analysis of sperm from men with idiopathic infertility using sperm karyotyping and fluorescence in situ hybridization. Fert Steril. 1995;64:811–17.

    CAS  Google Scholar 

  9. Carrell DT, Wilcox AL, Lowy L, Peterson CM, Jones KP, Erickson L, Hatasaka HH. Elevated sperm chromosome aneuploidy and apoptosis in patients with unexplained recurrent pregnancy loss. Obstet Gynecol. 2003;101:1229–35.

    PubMed  Google Scholar 

  10. Balkan W, Martin RH. Chromosome segregation into the spermatozoa of two men heterozygous for different reciprocal translocations. Hum Genet. 1983;63:345–48.

    CAS  PubMed  Google Scholar 

  11. Balkan W, Martin RH. Segregation of chromosomes into the spermatozoa of a men heterozygous for a 14; 21 Robertsonian translocation. Am J Med Genet. 1983;16:169–72.

    CAS  PubMed  Google Scholar 

  12. Martin RH. Analysis of human sperm chromosome complements from a male heterozygous for a reciprocal translocation t(11;22)(q23;q11). Clin Genet. 1984;25:357–61.

    CAS  PubMed  Google Scholar 

  13. Martin RH, Rademaker A. The relationship between sperm chromosomal abnormalities and sperm morphology in humans. Mutat Res. 1988;207:159–64.

    CAS  PubMed  Google Scholar 

  14. Martin RH, Rademaker A, Barnes M, Arthur K, Ringrose T, Douglas GA. A prospective serial study of the effects of radiotherapy on semen parameters, and hamster egg penetration rates. Clin Invest Med. 1985;8:239–43.

    CAS  PubMed  Google Scholar 

  15. Martin RH, Hildebrand K, Yamamoto J, Rademaker A, Barnes M, Douglas G, Arthur K, Ringrose T, Brown IS. An increased frequency of human sperm chromosomal abnormalities after radiotherapy. Mutat Res. 1986;174:219–25.

    CAS  PubMed  Google Scholar 

  16. Martin RH, Rademaker A, Hildebrand K, Barnes M, Arthur K, Ringrose T, Brown IS, Douglas G. A comparison of chrosomal aberrations induced by in vivo radiotherapy in human sperm and lymphocytes. Mutat Res. 1989;226:21–30.

    CAS  PubMed  Google Scholar 

  17. Devillard F, Metzler-Guillemain C, Pelletier R, DeRobertis C, Bergues U, Hennebicq S, Guichaoua M, Sele B, Rousseaux S. Polyploidy in large-headed sperm: fish study of three cases. Hum Reprod. 2002;17:1292–8.

    CAS  PubMed  Google Scholar 

  18. Bernardini L, Borini A, Preti S, Conte N, Flamigni C, Capitanio GL, et al. Study of aneuploidy in normal and abnormal germ cells from semen of fertile and infertile men. Hum Reprod. 1988;13:3406–13.

    Google Scholar 

  19. Mathieu C, Ecochard R, Bied V, Lornage J, Czyba JC. Andrology: cumulative conception rate following intrauterine artificial insemination with husbandʼs spermatozoa: influence of husbandʼs age. Hum Reprod. 1995;10:1090–97.

    CAS  PubMed  Google Scholar 

  20. Bellver J, Garrido N, Remohí J, Pellicer A, Meseguer M. Influence of paternal age on assisted reproduction outcome. Reprod Biomed Online. 2008;17:595–604.

    PubMed  Google Scholar 

  21. Demir B, Dilbaz B, Cinar O, Karadag B, Tasci Y, Kocak M, Goktolga U. Factors affecting pregnancy outcome of intrauterine insemination cycles in couples with favourable female characteristics. J Obstet Gynaecol. 2011;31:420–3.

    CAS  PubMed  Google Scholar 

  22. Slama R, Bouyer J, Windha G, Fenste L, Werwatz A, Swan SH. Influence of paternal age on the risk of spontaneous abortion. Am J Epidem. 2005;161:816–23.

    Google Scholar 

  23. Green RF, Devine O, Crider KS, Olney RS, Archer N, Olshan AF, Shapira SK. Association of paternal age and risk for major congenital anomalies from the national birth defects prevention study, 1997–2004. Ann Epidemiol. 2010;20:241.

    PubMed Central  PubMed  Google Scholar 

  24. Saha S, Barnett AG, Foldi C, Burne TH, Eyles DW, Buka SL, McGrath JJ. Advanced paternal age is associated with impaired neurocognitive outcomes during infancy and childhood. PLoS Med. 2009;6.3:e1000040.

    Google Scholar 

  25. Hemminki K, Kyyrönen P. Parental age and risk of sporadic and familial cancer in offspring: implications for germ cell mutagenesis. Epidemiology. 1999;10:747–51.

    CAS  PubMed  Google Scholar 

  26. Risch N, Reich EW, Wishnick MM, McCarthy JG. Spontaneous mutation and parental age in humans. Am J Hum Genet. 1987;41:218–48.

    CAS  PubMed Central  PubMed  Google Scholar 

  27. Sartorelli EMP, Mazzucatto LF, de Pina-Neto JM. Effect of paternal age on human sperm chromosomes. Fertil Steril. 2001;76:1119–23.

    CAS  PubMed  Google Scholar 

  28. Kodama H, Yamaguchi R, Fukuda J, Kasai H, Tanaka T. Increased oxidative deoxyribonucleic acid damage in the spermatozoa of infertile male patient. Fertil Steril. 1997;68:519–24.

    CAS  PubMed  Google Scholar 

  29. Spano H, Bonde JP, Hjollund HI, Kolstad HA, Cordelli E, Leter G. The Danish first pregnancy planner study team. Sperm chromatin damage impairs human fertility. Fertil Steril. 2000;73:43–50.

    CAS  PubMed  Google Scholar 

  30. Zini A, Libman J. Sperm DNA damage: clinical significance in the era of assisted reproduction. Can Med Assoc J. 2006;175:495–500.

    Google Scholar 

  31. Evenson DP, Jost LK, Marshall D, Zinaman MJ, Clegg E, Purvis K, de Angelis P, Claussen OP. Utility of sperm chromatin structure assay as a diagnostic and prognostic tool in the human fertility clinics. Hum Reprod. 1999;14:1039–49.

    CAS  PubMed  Google Scholar 

  32. Evenson DP, Larson KL, Jost LK. Sperm chromatin structure assay: its clinical use for detecting sperm DNA fragmentation in male infertility and comparisons with the other techniques. J Androl. 2002;23:25–43.

    PubMed  Google Scholar 

  33. Carrell DT, Liu L, Peterson CM, Jones KP, Hatasaka HH, Erickson L, Campbell B. Sperm DNA fragmentation is increased in couples with unexplained recurrent pregnancy loss. Arch Androl. 2003;49:49–55.

    CAS  PubMed  Google Scholar 

  34. Tesarik J, Greco E, Mendoza C. Late, but not early, paternal effect on human embryo development is related to sperm DNA fragmentation. Hum Reprod. 2004;19:611–15.

    CAS  PubMed  Google Scholar 

  35. Simon L, Proutaski I, Stevenson M, Jennings D, McManus J, Lutton D, Lewis SEM. Sperm DNA damage has a negative association with live-birth rates after IVF. Reprod Biomed Online. 2013;26:68–78.

    CAS  PubMed  Google Scholar 

  36. Twigg J, Irvine DS, Houston P, Fulton N, Michael L, Aitken RJ. Iatrogenic DNA damage induced in human spermatozoa during sperm preparation: protective significance of seminal plasma. Mol Hum Reprod. 1998;4:439–45.

    CAS  PubMed  Google Scholar 

  37. van Overveld FW, Floris WPC, Rhemrev J, Vermeiden JPW, Bast A. Tyrosine as important contributor to the antioxidant capacity of seminal plasma. Chem Biol Interact. 2000;127:151–61.

    CAS  PubMed  Google Scholar 

  38. Jones R, Mann T, Sherins R. Peroxidative breakdown of phospholipids in human spermatozoa, spermicidal properties of fatty acid peroxides, and protective action of seminal plasma. Fertil Steril. 1979;31:531.

    CAS  PubMed  Google Scholar 

  39. Zalata AA, Ahmed AH, Allamanemi SS, Comhaire FH, Agarwal A. Relationship between acrosin activity of human spermatozoa and oxidative stress. Asian J Androl. 2004;6:313–18.

    CAS  PubMed  Google Scholar 

  40. Aitken RJ, Clarkson JS, Fishel S. Generation of reactive oxygen species, lipid peroxidation, and human sperm function. Biol Reprod. 1989;41:183–97.

    CAS  PubMed  Google Scholar 

  41. Ichikawa T, Oeda T, Ohmori H, Schill WB. Reactive oxygen species influence the acrosome reaction but not acrosin activity in human spermatozoa. Int J Androl. 1999;22:37–42.

    CAS  PubMed  Google Scholar 

  42. Jedrzejczak P, Fraczek M, Szumala-Kakol A, Taszarek-Hauke G, Pawelczyk L, Kurpisz M. Consequences of semen inflammation and lipid peroxidation on fertilization capacity of spermatozoa in in vitro conditions. Int J Androl. 2005;28:275–83.

    CAS  PubMed  Google Scholar 

  43. Saleh RA, Agarwal A. Oxidative stress and male infertility: from research bench to clinical practice. J Androl. 2002;23:737–52.

    CAS  PubMed  Google Scholar 

  44. Oger I, Da Cruz C, Panteix G, Menezo Y. Evaluating human sperm DNA integrity: relationship between 8-hydroxydeoxyguanosine quantification and the sperm chromatin structure assay. Zygote. 2003;11:367–71.

    CAS  PubMed  Google Scholar 

  45. Henkel R, Kierspel E, Stalf T, Mehnert C, Menkveld R, Tinneberg HR, Schill WB, Kruger TF. Effect of reactive oxygen species produced by spermatozoa and leukocytes on sperm functions in non-leukocytospermic patients. Fertil Steril. 2005;83:635–42.

    CAS  PubMed  Google Scholar 

  46. Kao SH, Chao HT, Chen HW, Hwang TI, Liao TL, Wei YH. Increase of oxidative stress in human sperm with lower motility. Fertil Steril. 2008;89:1183–90.

    CAS  PubMed  Google Scholar 

  47. Tremellen K. Oxidative stress and male infertility–a clinical perspective. Hum Reprod Update. 2008;14:243–58.

    CAS  PubMed  Google Scholar 

  48. Fowler JE. Infections of the male reproductive tract and infertility: a selected review. J Androl. 1981;3:121–31.

    Google Scholar 

  49. Berger RE, Alexander ER, Harnisch JP, Paulson CA, Monda GD, Ansel J, Holmes KK. Etiology, manifestations and therapy of acute epiddidymitis: prospective study of 50 cases. J Urol. 1979;121:750–4.

    CAS  PubMed  Google Scholar 

  50. Agarwal A, Ikemoto I, Loughlin KR. Relationship of sperm parameters with levels of reactive oxygen species in semen specimens. J Urol. 1994;152:107–10.

    CAS  PubMed  Google Scholar 

  51. Wolff H, Politch JA, Martinez A, Haimovici F, Hill JA, Anderson DJ. Leukocytospermia is associated with poor semen quality. Fertil Steril. 1990;53:528–36.

    CAS  PubMed  Google Scholar 

  52. Wolff H. The biologic significance of white blood cells in semen. Fertil Steril. 1995;63:1143–57.

    CAS  PubMed  Google Scholar 

  53. Branigan EF, Muller CH. Efficiency of treatment abd recurrence rate of leukocytospermia in infertile men with prostatitis. Fertil Steril. 1994;62:580–4.

    CAS  PubMed  Google Scholar 

  54. Yanushpolsky ET, Politch JA, Hill JA, Anderson DJ. Antibiotic therapy and leukocytospermia: a prospective randomized controlled study. Fertil Steril. 1995;63:142–7.

    CAS  PubMed  Google Scholar 

  55. Branigan EF, Spadoni LR, Muller CH. Identification and treatment of leukocytospermia in couples with unexplained infertility. J Reprod Med. 1995;40:625–9.

    CAS  PubMed  Google Scholar 

  56. Ulstein M, Capell P, Holmes KK, Paulsen CA. Nonsymptomatic genital tract infection and male infertility. In: Hafez ESE, editor. Human semen and fertility regulation in men. Mosby. St. Louis; 1976. p. 355–362.

    Google Scholar 

  57. Gnarpe H, Freiberg J. T mycoplasmas on spermatozoa and infertility. Nature. 1973;245:97–8.

    CAS  PubMed  Google Scholar 

  58. Bartak V. Sperm quality in adult diabetic men. Int J Fertil. 1979;24:226–32.

    CAS  PubMed  Google Scholar 

  59. Glenn DR, McClure N, Lewis SE. The hidden impact of diabetes on male sexual dysfunction and fertility. Hum Fertil. 2003;6:174–9.

    Google Scholar 

  60. Baccetti B, La Marca A, Piomboni P, Capitani S, Bruni E, Petraglia F, DeLeo V. Insulin-dependent diabetes in men is associated with hypothalamo-pituitary derangement and with impairment in semen quality. Hum Reprod. 2002;10:2673–77.

    Google Scholar 

  61. Ballester J, Munoz MC, Dominguez J, Rigau T, Guinovart JJ, Rodriguez-Gil JE. Insulin-dependent diabetes affects testicular function by FSH-and LH-linked mechanisms. J Androl. 2004;25:706–19.

    CAS  PubMed  Google Scholar 

  62. Agbaje IM, Rogers DA, McVicar CM, McClure N, Atkinson AB, Malladis C, Lewis SEM. Insulin-dependent diabetes mellitus: implications for male reproductive function. Hum Reprod. 2007;22:1871–77.

    CAS  PubMed  Google Scholar 

  63. Lestienne P, Reynier P, Chretien MF, Penisson-Besnier I, Malthiery Y, Rohmer V. Oligoasthenospermia associated with multiple mitochondrial DNA arrangements. Mol Hum Reprod. 1997;3:811–14.

    CAS  PubMed  Google Scholar 

  64. Kao SH, Chao HT, Wei YH. Multiple deletions of mitochondrial DNA are associated with the decline of motility and fertility of human spermatozoa. Mol Hum Reprod. 1998;4:657–66.

    CAS  PubMed  Google Scholar 

  65. Spiropoulos J, Turnbull DM, Chinnery PF. Can mitochondrial DNA mutations cause sperm dysfunction. Mol Hum Reprod. 2002;8:719–21.

    CAS  PubMed  Google Scholar 

  66. Green JR, Goble HL, Edwards CR, Dawson AM. Reversible insensitivity to androgens in men with untreated gluten enteropathy. Lancet. 1977;1:1280–2.

    Google Scholar 

  67. Farthing MJ, Edwards CR, Rees LH, Dawson AM. Male gonadal function in celiac disease: 1. Sexual dysfunction, infertility, and semen quality. Gut. 1982;23:608–14.

    CAS  PubMed Central  PubMed  Google Scholar 

  68. Zugna D, Richiardi L, Akre O, Stephansson O, Ludvigsson JF. Celiac disease is not a risk factor for infertility in men. Fertil Steril. 2011;95:1709–11.

    PubMed  Google Scholar 

  69. Kruger TF, Acosta AA, Simmons KF, Swanson RJ, Matta JF, Veeck LL, Morshedi M, Brugo S. New method of evaluating sperm morphology with predictive value for human in vitro fertilization. Urology. 1987;30:248–51.

    CAS  PubMed  Google Scholar 

  70. Kruger TF, Acosta AA, Simmons KF, Swanson RJ, Matta JF, Oehninger S. Predictive values of abnormal sperm morphology in in vitro fertilization. Fertil Steril. 1998;49:112–17.

    Google Scholar 

  71. Check JH, Adelson HG, Schubert BR, Bollendorf A. Evaluation of sperm morphology using Krugerʼs strict criteria. Arch Androl. 1992;28:15–7.

    CAS  PubMed  Google Scholar 

  72. Eggert-Kruse W, Schwarz H, Rohr G, Demirakca T, Tilgen W, Runnebaum B. Sperm morphology assessment using strict criteria and male fertility under in-vivo conditions of conception. Hum Reprod. 1996;11:139–46.

    CAS  PubMed  Google Scholar 

  73. Ghirelli-Filio M, Mizrahi FE, Pompeo ACL, Glina S. Influence of strict morphology on the results of classic in vitro fertilization. Int Braz J Urol. 2012;38:519–28.

    Google Scholar 

  74. Benoff S, Cooper GW, Hurley I, Mandel FS, Rosenfeld DL, Scholl GM, Gilbert BR, Hershlag A. The effect of calcium ion channel blockers on sperm fertilization potential. Fertil Steril. 1994;62:606–17.

    CAS  PubMed  Google Scholar 

  75. Hull MG, Williams JA, Ray B, McLaughlin EA, Akande VA, Ford WC. The contribution of subtle oocyte or sperm dysfunction affecting fertilization in endometriosis-associated or unexplained infertility: a controlled comparison with tubal infertility and use of donor spermatozoa. Hum Reprod. 1998;7:1825–30.

    Google Scholar 

  76. Wolf JP, Bulwa S, Ducot B, Rodrigues D, Jouannet P. Fertilizing ability of sperm with unexplained in vitro fertilization failures, as assessed by the zona-free hamster egg penetration assay: its prognostic value for sperm-oolema interaction. Fertil Steril. 1996;65:1196–201.

    CAS  PubMed  Google Scholar 

  77. Frapsauce C, Pionneau C, Booley J, de Larouziere V, Berthaut I, Ravel C, Antoine JM, Soubrier F, Madelbaum J. Unexpected in vitro fertilization failure in patients with normal sperm: a proteomic analysis. Gynecol Obstet Fertil. 2009;37:796–802.

    CAS  PubMed  Google Scholar 

  78. Tollner TL, Venners SA, Hollox EJ, Yudin Al, Liu X, Tang G, Xing H, Kays RJ, Lau T, Overstreet JW, Xu X, Bevins CL, Cherr GN. A common mutation in the defensin DEFB126 causes impaired sperm function and subfertility. Sci Trans Med. 2011;3:92.

    Google Scholar 

  79. Barratt CL, Dunphy BC, McLeod I, Cooke ID. The poor prognostic value of low to moderate levels of sperm surface-bound antibodies. Hum Reprod. 1992;7:95–8.

    CAS  PubMed  Google Scholar 

  80. Jarow JP, Sanzone JJ. Risk factors for male partner antisperm antibodies. J Urol. 1992;148:1805–7.

    CAS  PubMed  Google Scholar 

  81. Rajah SV, Parslow JM, Howell RJ, Hendry WF. The effects of in-vitro fertilization of autoandibodies to spermatozoa in subfertile men. Hum Reprod. 1993;8:1079–82.

    CAS  PubMed  Google Scholar 

  82. Hjort T, Hansen KB. Seminal antigens in man with particular regard to possible immunological contraception. In: Shulman S, Dondero F, editors. Immunological factors in human contraception. Rome: Acta Medica; 1983. p. 47–56.

    Google Scholar 

  83. Hammitt DG, Muench MM, Williamson RA. Antibody binding to greater than 50 % of the tail tip does not impair male fertility. Fertil Steril. 1988;49:1.

    Google Scholar 

  84. Acosta AA, van der Merwe JP, Doncel G, Kruger TF, Sayilgan A, Franken DR, Kolm P. Fertilization efficiency of morphologically abnormal spermatozoa in assisted reproduction is further impaired by antisperm antibodies on the male partnerʼs sperm. Fertil Steril. 1994;62:826–33.

    CAS  PubMed  Google Scholar 

  85. Shushan A, Schenker JG. Immunological factors in infertility. Am J Reprod Immunol. 1992;28:285–7.

    CAS  PubMed  Google Scholar 

  86. Robbins WA, Vine MF, Trung KY, Everson RB. Use of fluorescence in situ hybridization (FISH) to assess effects of smoking, caffeine and alcohol on aneuploidy load in sperm of healthy men. Environ Mol Mutagen. 1997;30:175–83.

    CAS  PubMed  Google Scholar 

  87. Rubes J, Lowe X, Moore D, Perrault S, Slott V, Evenson D, Selevan SG, Wyrobek AJ. Smoking cigarettes is associated with increased sperm disomy in teenage men. Fertil Steril. 1998;70:715–23.

    CAS  PubMed  Google Scholar 

  88. Hughes EG, Brennan BG. Does cigarette smoking impair natural or assisted fecundity? Fertil Steril. 1996;66:679–89.

    CAS  PubMed  Google Scholar 

  89. Richthoff J, Elzanaty S, Rylander L, Hagmer L, Giwercman A. Association between tobacco exposure and reproductive parameters in adolescent males. Int J Androl. 2007;31:31–9.

    PubMed  Google Scholar 

  90. Vine MF, Margolin BH, Morrison HI, Hulka BS. Cigarette smoking and sperm density: a meta-analysis. Fertil Steril. 1994;61:35–43.

    CAS  PubMed  Google Scholar 

  91. Vine MF, Tse CK, Hu P, Truong KY. Cigarette smoking and semen quality. Fertil Steril. 1996;65:835–42.

    CAS  PubMed  Google Scholar 

  92. Practice Committee of the American Society for Reproductive Medicine. Smoking and infertility: a committee opinion. Fertil Steril. 2012;98(6):1400–6.

    Google Scholar 

  93. Zenzes MT, Bielecki R, Reed TE. Detection of benzo(a)pyrene diol epoxide-DNA adducts in sperm of men exposed to cigarette smoke. Fertil Steril. 1999;72:330–35.

    CAS  PubMed  Google Scholar 

  94. Fraga CG, Motchnik PA, Wyrobek AJ, Rempel DM, Ames BN. Smoking and low antioxidant levels increase oxidative damage to sperm DNA. Mutat Res. 1996;351:199–203.

    PubMed  Google Scholar 

  95. Hauser R. The environment and male fertility: recent research on emerging chemicals and semen quality. Sem Reprod Med. 2006;24:156–67.

    CAS  Google Scholar 

  96. McAuliffe ME, Williams PL, Korrick SA, Altshul LM, Perry MJ. Environmental exposure to polychlorinated biphenyls and p, pʹ-DDE and sperm sex-chromosome disomy. Environ Health Persp. 2012;120:535–40.

    CAS  Google Scholar 

  97. Duty SM, Silva MJ, Barr DB, Brock JW, Ryan L, Chen Z, Herrick RF, Christani DL, Hauser R. Phthalate exposure and human semen parameters. Epidemiology. 2003;14:269–77.

    PubMed  Google Scholar 

  98. Hauser R, Meeker JD, Singh NP, Silva MJ, Ryan L, Duty S, Calafat AM. DNA damage in human sperm is related to urinary levels of phthalate monoester and oxidative metabolites. Hum Reprod. 2007;22:688–95.

    CAS  PubMed  Google Scholar 

  99. Xu DX, Shen HM, Zhu QX, Chua L, Wang QN, Chia SE, Ong CN. The association among semen quality, oxidative DNA damage in human spermatozoa and concentrations of cadmium, lead and selenium in seminal plasma. Mutat Res. 2003;534:155–63.

    CAS  PubMed  Google Scholar 

  100. Gennart JP, Buchet JP, Roels H, Ghyselen P, Ceulemans E, Lauwerys R. Fertility of male workers exposed to cadmium, lead, or manganese. Am J Epidemiol. 1992;135:1208–19.

    CAS  PubMed  Google Scholar 

  101. Thonneau P, Marchand S, Tallec A, ferial ML, Ducot B, Lansac J, Lopes P, Tabaste JM, Spira M. Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988–1989). Hum Reprod. 1991;6:811–6.

    CAS  PubMed  Google Scholar 

  102. Patel ZP, Niederberger CS. Male factor assessment in infertility. Med Clin North Am. 2011;95:223–34.

    PubMed  Google Scholar 

  103. World Health Organization. WHO laboratory manual for examination and processing of semen, 5th ed., 2010.

    Google Scholar 

  104. Barratt CL, Aitken RJ, Bjorndahl DT, Carrell DT, de Boer U, Kvist SE, Perrault SD, Perry MJ, Ramos L, Robaire B, Ward S, Zini A. Sperm DNA: organisation, protection, and vulnerability: from basic science to clinical applications–a position report. Hum Reprod. 2010;25:824–38.

    PubMed  Google Scholar 

  105. Larson KL, DeJonge CJ, Barnes AM, Jost LK, Evenson DP. Sperm chromatin structure assay parameters as predictors of failed pregnancy following assisted reproductive techniques. Hum Reprod. 2000;15:1717–22.

    CAS  PubMed  Google Scholar 

  106. Saleh RA, Agarwal A, Nelson DR, Nada EA, El-Tonsy MH, Alvarez JG, Thomas AJ, Sharma RK. Increased sperm nuclear DNA damage in normozoospermic infertile men: a prospective study. Fertil Steril. 2002;78:313–18.

    PubMed  Google Scholar 

  107. Practice Committee of the American Society for Reproductive Medicine. The clinical utility of sperm DNA integrity testing. Fertil Steril. 2008;90:S178–80.

    Google Scholar 

  108. Aktan G, Dogru-Abbasoglu S, Kucukgergin C, Kadioglu A, Ozdemirler-Erata G, Kocak-Toker N. Mystery of idiopathic male infertility: is oxidative stress an actual risk? Fertil Steril. 2013;99:1211–15.

    CAS  PubMed  Google Scholar 

  109. Erenpreiss J, Hlevica S, Zalkalns J, Erenpreisa J. Effect of leukocytospermia on sperm DNA integrity: a negative effect in abnormal semen samples. J Androl. 2002;23:717–23.

    PubMed  Google Scholar 

  110. Greco E, Romano S, Iacobelli M, Ferrero S, Baroni E, Minasi MG, Ubaldi F, Rienzi L, Tesarik J. ICSI in cases of sperm DNA damage: beneficial effect of oral antioxidant treatment. Hum Reprod. 2005;20:2590–4.

    CAS  PubMed  Google Scholar 

  111. Safarinejad MR. Efficacy of coenzyme Q10 on semen parameters, sperm function, and reproductive hormones in infertile men. J Urol. 2009;182:237–48.

    CAS  PubMed  Google Scholar 

  112. Safarinejad MR, Safarinejad S, Shafiei N, Safarinejad S. Effects of the reduced form of coenzyme Q10 (ubiquinol) on semen parameters in men with idiopathic infertility: a double-blind, placebo controlled, randomized study. J Urol. 2012;188:526–31.

    CAS  PubMed  Google Scholar 

  113. Li X, Pan J, Liu Q, Xiong E, Chen Z, Zhou Z, Su Y, Lu G. Glutathione S-transferases gene polymorphisms and risk of male idiopathic infertility: a systematic review and meta-analysis. Mol Biol Rep. 2013;40:2431–8.

    CAS  PubMed  Google Scholar 

  114. Salvolini E, Buldreghini E, Lucarini G, Vignini A, Lenzi A, Di Primio R, Balercia G. Involvement of sperm plasma membrane and cytoskeletal proteins in human male infertility. Fertil Steril. 2013;99:697–704.

    CAS  PubMed  Google Scholar 

  115. Hamada A, Esteves SC, Agarwal A. Unexplained male infertility: potential causes and management. Hum Androl. 2011;1:2–16.

    Google Scholar 

  116. Practice Committee of the American Society for Reproductive Medicine. Effectiveness and treatment of unexplained infertility. Fertil Steril. 2006;86 (Suppl 4):S111–4.

    Google Scholar 

  117. Guzick DS, Grefenstette I, Baffone K, Berga SL, Krasnow JS, Stovall DW. Infertility evaluation in fertile women: a model for assessing the efficacy of infertility testing. Hum Reprod. 1994;9:2306–10.

    CAS  PubMed  Google Scholar 

  118. Guzick DS, Sullivan MW, Adamson GD, Cedars MI, Falk RJ, Peterson EP, Steinkampf MP. Efficacy of treatment for unexplained infertility. Fertil Steril. 1998;70:207–13.

    CAS  PubMed  Google Scholar 

  119. Hull MG, Glazener CM, Kelly NJ, Conway DI, Foster PA, Hinton RA Coulson C, Lambert PA, Watt EM, Desai KM. Population study of causes, treatment, and outcome of infertility. Br Med J. 1985;291:1693–7.

    CAS  Google Scholar 

  120. Van Waart J, Ktuger F, Lombard CJ, Ombelet W. Predictive value of normal sperm morphology in intrauterine insemination (IUI): a structured literature review. Hum Reprod Update. 2001;7:495–500.

    PubMed  Google Scholar 

  121. Ombelet W, Vandeput H, Van de Potte G, Cox A, Janssen M, Jacobs P, Bosmans E, Steeno O, Kruger T. Intrauterine insemination after ovarian stimulation with clomiphene citrate: predictive potential of inseminating motile count and sperm morphology. Hum Reprod. 1997;12:1458–63.

    CAS  PubMed  Google Scholar 

  122. Kirby CA, Flaherty SP, Godfrey BM, Warnes GM, Matthews CD. A prospective trial of intrauterine insemination of motile spermatozoa versus timed intercourse. Fertil Steril. 1991;56:102–7.

    CAS  PubMed  Google Scholar 

  123. Guzick DS, Carson SA, Coutifaris C, Overstreet JW, Factor-Litvak P, Steinkampf MP, et al. Efficacy of superovulation and intrauterine insemination in the treatment of infertility. National Cooperative Reproductive Medicine Network. N Engl J Med. 1999;340:177–83.

    CAS  PubMed  Google Scholar 

  124. Aboulghar M, Mansour R, Serour G, Abdrazek A, Amin Y, Rhodes C. Controlled ovarian hyperstimulation and intrauterine insemination should be limited to three trials. Fertil Steril. 2001;75:88–91.

    CAS  PubMed  Google Scholar 

  125. Horvath PM, Beck M, Bohrer MK, Shelden RM, Kemmann E. A prospective study on the lack of development of antisperm antibodies in women undergoing intrauterine insemination. Am J Obstet Gynecol. 1989;160:631–7.

    CAS  PubMed  Google Scholar 

  126. Stanford J, Mikolajczyk R, Lynch C, Simonsen S. Cumulative pregnancy rate probability among couples with subfertility: effects of varying treatments. Fertil Steril. 2010;93:2175–81.

    PubMed  Google Scholar 

  127. Saleh RA, Agarwal A, Kandirali E, Sharma RK, Thomas AJ, Nada EA, Evenson DP, Alvarez JG. Leukocytospermia is associated with increased reactive oxygen species production by human spermatozoa. Fertil Steril. 2002;78:1215–24.

    PubMed  Google Scholar 

  128. Nagy ZP, Verheyen G, Liu J, Joris H, Janssenswillen C, Wisanto A, Van Steirteghem AC. Andrology: results of 55 intracytoplasmic sperm injection cycles in the treatment of male-immunological infertility. Hum Reprod. 1995;10:1775–80.

    CAS  PubMed  Google Scholar 

  129. Check ML, Check JH, Katsoff D, Summers-Chase D. ICSI as an effective therapy for male factor with antisperm antibodies. Syst Biol Reprod Med. 2000;45:125–30.

    CAS  Google Scholar 

  130. Kastrop PMM, Weima SM, van Kooij RJ, Velde ER. Comparison between intracytoplasmic sperm injection and in vitro fertilization (IVF) with high insemination concentration after total fertilization failure in a previous IVF attempt. Hum Reprod. 1998;14:65–9.

    Google Scholar 

  131. Hershlag A, Paine T, Kupail G, Feng H, Napolitano B. In vitro fertilization- intracytoplasmic sperm injection split: an insemination method to prevent fertilization failure. Fertil Steril. 2002;77:229–32.

    PubMed  Google Scholar 

  132. Jaroudi K, Al-Hassan S, Al-Sufayan H, Al-Mayman H, Qeba M, Coskun S. Intracytoplasmic sperm injection and conventional in vitro fertilization are complementary techniques for management of unexplained infertility. J Assist Reprod Genet. 2003;20:377–81.

    PubMed Central  PubMed  Google Scholar 

  133. Bartoov B, Berkovitz A, Eltes F, Kogosowski A, Menezo Y, Barak Y. Real time fine morphology of motile human sperm cells is associated with IVF-ICSI outcome. J Androl. 2002;23:1–8.

    PubMed  Google Scholar 

  134. Hazout A, Dumont-Hassan M, Junca AM, Cohen BP, Tesarik J. High magnification ICSI overcomes paternal effect resistant to conventional ICSI. Reprod Biomed Online. 2006;12:19–25.

    PubMed  Google Scholar 

  135. Antinori M, Licata E, Dani G, Cerusico F, Versaci C, d’Angelo D, Antinori S. Intracytoplasmic morphologically selected sperm injection: a prospective randomized trial. Reprod Biomed Online. 2008;6:835–41.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Bhushan K. Gangrade PhD .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Science+Business Media, LLC

About this chapter

Cite this chapter

Gangrade, B., Patel, Z., Patel, S. (2015). Role of Assisted Reproduction Techniques in the Management of Unexplained Male Infertility. In: Schattman, G., Esteves, S., Agarwal, A. (eds) Unexplained Infertility. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-2140-9_31

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2140-9_31

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4939-2139-3

  • Online ISBN: 978-1-4939-2140-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics