Gynäkologische Endokrinologie

, Volume 12, Issue 1, pp 16–20 | Cite as

Fertilität bei Männern über 40 Jahren

Leitthema
  • 98 Downloads

Zusammenfassung

Hintergrund

Eine Elternschaft im späteren Lebensalter wird von vielen Menschen als vorteilhaft wahrgenommen, da oft in vielerlei Hinsicht stabilere Lebensbedingungen gegeben sind. Auch gibt es Männer, für die eine zweite Familie eine Lebensoption darstellt. Daher rücken auch biologische Aspekte der älteren Vaterschaft in den wissenschaftlichen und klinischen Fokus.

Altersabhängige Faktoren mit Einfluss auf die männliche Fertilität

Das Alter beeinflusst die männliche Fertilität durch eine Reihe von Faktoren, die in ihrer Gänze nicht komplett verstanden sind. Die Spermienproduktion und -motilität nimmt aufgrund der verfallenden testikulären Feinarchitektur mit zunehmendem Alter ab. Auch nimmt mit dem Alter des Mannes die Fekundität durch weitere Faktoren ab: Ein gestörter Schwangerschaftsverlauf wird oft beobachtet. Einige sehr seltene autosomal-dominante Erkrankungen sind deutlich mit dem väterlichen Alter assoziiert.

Epigenetische Effekte

Hinzu kommen epigenetische Effekte, die mit neurokognitiven Störungen und möglicherweise sogar metabolischen Dysbalancen vergesellschaftet sind. Solche Effekte können sich, einmal ausgelöst, offensichtlich über mehrere Generationen erstrecken. Dabei wird ein Alter des Mannes über 40 Jahre bereits als biologischer Einflussfaktor angesehen, der möglicherweise jedoch durch ein jüngeres Alter der Partnerin ausgeglichen werden kann – zumindest in Teilaspekten. Eine entsprechende Beratung sollte auf jeden Fall patientenorientiert sein. Statistische Wahrscheinlichkeiten sind gegen individuelle Wünsche abzuwägen.

Schlüsselwörter

Väterliches Alter Epigenetik Mutation Alter Spermien 

Fertility in men aged 40 and over

Abstract

Background

Parenting in later life is perceived by many as advantageous because more stable living conditions are often possible. In addition, this gives men the option to have a second family. Therefore, biological aspects of becoming a father later in life have become the focus of scientific and clinical research.

Age-dependent factors influencing male fertility

Age affects male fertility by a number of factors that are not yet completely understood. Generally, the amount of produced spermatozoa as well as their motility decrease with advancing age, and testicular histological architecture deteriorates. This results in decreased fecundity and also an increased risk for difficult pregnancies with advancing paternal age. Some rare autosomal dominant diseases are associated with paternal age.

Epigenetic effects

Dysbalanced patterns of epigenetics and gene expression in aging sperm seem to affect a range of neurocognitive disorders across generations. A man’s age older than 40 years is viewed as a biological factor which may, however, be —at least partially—compensated by a younger female partner. Nevertheless, counseling of older fathers-to-be must be patient-oriented and statistical probabilities must be weighed against individual wishes and life-planning.

Keywords

Paternal age Epigenetics Mutation Aging Sperm 

Literatur

  1. 1.
    Tatone C (2008) Oocyte senescence: a firm link to age-related female subfertility. Gynecol Endocrinol 24:59–63PubMedCrossRefGoogle Scholar
  2. 2.
    Balasch J (2010) Ageing and infertility: an overview. Gynecol Endocrinol 26:855–860PubMedCrossRefGoogle Scholar
  3. 3.
    Sartorius GA, Nieschlag E (2010) Paternal age and reproduction. Hum Reprod Update 16:65–79PubMedCrossRefGoogle Scholar
  4. 4.
    Bray I, Gunnell D, Davey Smith G (2006) Advanced paternal age: how old is too old? J Epidemiol Community Health 60:851–853Google Scholar
  5. 5.
    Wiener-Megnazi Z, Auslender R, Dirnfeld M (2012) Advanced paternal age and reproductive outcome. Asian J Androl 14:69–76PubMedCrossRefGoogle Scholar
  6. 6.
    Shindel AW, Nelson CJ, Naughton CK et al (2008) Sexual function and quality of life in the male partner of infertile couples: prevalence and correlates of dysfunction. J Urol 179:1056–1059Google Scholar
  7. 7.
    Wu FC, Tajar A, Beynon JM et al (2010) Identification of late-onset hypogonadism in middle-aged and elderly men. N Engl J Med 363:123–135Google Scholar
  8. 8.
    Corona G, Lee DM, Forti G et al (2010) Age-related changes in general and sexual health in middle-aged and older men: results from the European Male Ageing Study (EMAS). J Sex Med 7:1362–1380Google Scholar
  9. 9.
    Han TS, Tajar A, O’Neill TW et al (2011) Impaired quality of life and sexual function in overweight and obese men: the European Male Ageing Study. Eur J Endocrinol 164:1003–1011PubMedCrossRefGoogle Scholar
  10. 10.
    Lindau ST, Schumm LP, Laumann EO et al (2007) A study of sexuality and health among older adults in the United States. N Engl J Med 357:762–774Google Scholar
  11. 11.
    Lee DM, Tajar A, Ravindrarajah R et al (2013) Frailty and sexual health in older European men. J Gerontol A Biol Sci Med Sci 68:837–844Google Scholar
  12. 12.
    Nicolosi A, Buvat J, Glasser DB et al (2006) Sexual behaviour, sexual dysfunctions and related help seeking patterns in middle-aged and elderly Europeans: the global study of sexual attitudes and behaviors. World J Urol 24:423–428PubMedCrossRefGoogle Scholar
  13. 13.
    McVary KT (2007) Clinical practice. Erectile dysfunction. N Engl J Med 357:2472–2481Google Scholar
  14. 14.
    Luo YH, Hou Q, Zheng SB (2012) Meta-analysis of dapoxetine on demand in the treatment of premature ejaculation. Zhonghua Nan Ke Xue 18:930–935PubMedGoogle Scholar
  15. 15.
    Rago R, Salacone P, Caponecchia L et al (2012) Effect of vardenafil on semen parameters in infertile men: a pilot study evaluating short-term treatment. J Endocrinol Invest 35:897–900Google Scholar
  16. 16.
    Traish AM, Hassani J, Guay AT et al (2011) Adverse side effects of 5α-reductase inhibitors therapy: persistent diminished libido and erectile dysfunction and depression in a subset of patients. J Sex Med 8:872–884Google Scholar
  17. 17.
    Amory JK, Wang C, Swerdloff RS et al (2007) The effect of 5alpha-reductase inhibition with dutasteride and finasteride on semen parameters and serum hormones in healthy men. J Clin Endocrinol Metab 92:1659–1665Google Scholar
  18. 18.
    Dakouane Giudicelli M, Serazin V, Le Sciellour CR et al (2008) Increased achondroplasia mutation frequency with advanced age and evidence for G1138A mosaicism in human testis biopsies. Fertil Steril 89:1651–1656CrossRefGoogle Scholar
  19. 19.
    Handelsman DJ, Staraj S (1985) Testicular size: the effects of aging, malnutrition, and illness. J Androl 6:144–151Google Scholar
  20. 20.
    Kidd SA, Eskenazi B, Wyrobek AJ (2001) Effects of male age on semen quality and fertility: a review of the literature. Fertil Steril 75:237–248PubMedCrossRefGoogle Scholar
  21. 21.
    Hellstrom WJ, Overstreet JW, Sikka SC et al (2006) Semen and sperm reference ranges for men 45 years of age and older. J Androl 27:421–428Google Scholar
  22. 22.
    Sloter E, Schmid TE, Marchetti F et al (2006) Quantitative effects of male age on sperm motion. Hum Reprod 21:2868–2875PubMedCrossRefGoogle Scholar
  23. 23.
    Rolf C, Behre HM, Nieschlag E (1996) Reproductive parameters of older compared to younger men of infertile couples. Int J Androl 19:135–142PubMedCrossRefGoogle Scholar
  24. 24.
    Jensen TK, Andersson AM, Jorgensen N et al (2004) Body mass index in relation to semen quality and reproductive hormones among 1,558 Danish men. Fertil Steril 82:863–870PubMedCrossRefGoogle Scholar
  25. 25.
    Hammoud AO, Wilde N, Gibson M et al (2008) Male obesity and alteration in sperm parameters. Fertil Steril 90:2222–2225PubMedCrossRefGoogle Scholar
  26. 26.
    Rolf C, Kenkel S, Nieschlag E (2002) Age-related disease pattern in infertile men: increasing incidence of infections in older patients. Andrologia 34:209–217PubMedCrossRefGoogle Scholar
  27. 27.
    Gagnon C, Lamirande E de (2006) Controls of sperm motility. In: De Jonge CC, Barratt CLR (Hrsg) The sperm cell: production, maturation, fertilization, regeneration. Cambridge University Press, Cambridge, S 108–133Google Scholar
  28. 28.
    Aitken RJ, Nixon B, Lin M et al (2007) Proteomic changes in mammalian spermatozoa during epididymal maturation. Asian J Androl 9:554–564PubMedCrossRefGoogle Scholar
  29. 29.
    Amann RP (2008) The cycle of the seminiferous epithelium in humans: a need to revisit? J Androl 29:469–487Google Scholar
  30. 30.
    Mahmoud AM, Goemaere S, El-Garem Y et al (2003) Testicular volume in relation to hormonal indices of gonadal function in community-dwelling elderly men. J Clin Endocrinol Metab 88:179–184Google Scholar
  31. 31.
    Nieschlag E, Lammers U, Freischem CW et al (1982) Reproductive functions in young fathers and grandfathers. J Clin Endocrinol Metab 55:676–681Google Scholar
  32. 32.
    Baccarelli A, Morpurgo PS, Corsi A et al (2001) Activin A serum levels and aging of the pituitary-gonadal axis: a cross-sectional study in middle-aged and elderly healthy subjects. Exp Gerontol 36:1403–1412PubMedCrossRefGoogle Scholar
  33. 33.
    Zitzmann M (2009) Testosterone deficiency, insulin resistance and the metabolic syndrome. Nat Rev Endocrinol 12:673–681CrossRefGoogle Scholar
  34. 34.
    Kelly DM, Jones TH (2013) Testosterone: a metabolic hormone in health and disease. J Endocrinol 217:R25–R45Google Scholar
  35. 35.
    Ford WC, North K, Taylor H et al (2000) Increasing paternal age is associated with delayed conception in a large population of fertile couples: evidence for declining fecundity in older men. The ALSPAC Study Team (Avon Longitudinal Study of Pregnancy and Childhood). Hum Reprod 15:1703–1708PubMedCrossRefGoogle Scholar
  36. 36.
    La Rochebrochard E de, Mouzon J de, Thepot F, Thonneau P (2006) Fathers over 40 and increased failure to conceive: the lessons of in vitro fertilization in France. Fertil Steril 85:1420–1424CrossRefGoogle Scholar
  37. 37.
    La Rochebrochard E de, McElreavey K, Thonneau P (2003) Paternal age over 40 years: the ‚amber light‘ in the reproductive life of men? J Androl 24:459–465Google Scholar
  38. 38.
    Hassan MA, Killick SR (2003) Effect of male age on fertility: evidence for the decline in male fertility with increasing age. Fertil Steril 79:1520–1527PubMedCrossRefGoogle Scholar
  39. 39.
    Dain L, Auslander R, Dirnfeld M (2011) The effect of paternal age on assisted reproduction outcome. Fertil Steril 95:1–8PubMedCrossRefGoogle Scholar
  40. 40.
    Alio AP, Salihu HM, McIntosh C et al (2012) The effect of paternal age on fetal birth outcomes. Am J Mens Health 6:427–435PubMedCrossRefGoogle Scholar
  41. 41.
    Martin RH (2006) Meiotic chromosome abnormalities in human spermatogenesis. Reprod Toxicol 22:142–147PubMedCrossRefGoogle Scholar
  42. 42.
    Griffin DK, Abruzzo MA, Millie EA et al (1995) Non-disjunction in human sperm: evidence for an effect of increasing paternal age. Hum Mol Genet 4:2227–2232PubMedCrossRefGoogle Scholar
  43. 43.
    Buwe A, Guttenbach M, Schmid M (2005) Effect of paternal age on the frequency of cytogenetic abnormalities in human spermatozoa. Cytogenet Genome Res 111:213–228PubMedCrossRefGoogle Scholar
  44. 44.
    Fonseka KG, Griffin DK (2011) Is there a paternal age effect for aneuploidy? Cytogenet Genome Res 33:280–291CrossRefGoogle Scholar
  45. 45.
    Oeseburg H, Boer RA de, Gilst WH van, Harst P van der (2010) Telomere biology in healthy aging and disease. Pflugers Arch 459:259–268PubMedCentralPubMedCrossRefGoogle Scholar
  46. 46.
    Martinez P, Blasco MA (2011) Telomeric and extra-telomeric roles for telomerase and the telomere-binding proteins. Nat Rev Cancer 11:161–176PubMedCrossRefGoogle Scholar
  47. 47.
    Eisenberg DT (2011) An evolutionary review of human telomere biology: the thrifty telomere hypothesis and notes on potential adaptive paternal effects. Am J Hum Biol 23:149–167PubMedCrossRefGoogle Scholar
  48. 48.
    Unryn BM, Cook LS, Riabowol KT (2005) Paternal age is positively linked to telomere length of children. Aging Cell 4:97–101PubMedCrossRefGoogle Scholar
  49. 49.
    Meyer T de, Rietzschel ER, Buyzere ML de et al (2007) Asklepios investigators. Paternal age at birth is an important determinant of offspring telomere length. Hum Mol Genet 16:3097–3102PubMedCrossRefGoogle Scholar
  50. 50.
    Nordfjäll K, Larefalk A, Lindgren P et al (2005) Telomere length and heredity: indications of paternal inheritance. Proc Natl Acad Sci U S A 102:16374–16378CrossRefGoogle Scholar
  51. 51.
    Njajou OT, Cawthon RM, Damcott CM et al (2007) Telomere length is paternally inherited and is associated with parental lifespan. Proc Natl Acad Sci U S A 104:12135–12139CrossRefGoogle Scholar
  52. 52.
    Kimura M, Cherkas LF, Kato BS et al (2008) Offspring’s leukocyte telomere length, paternal age, and telomere elongation in sperm. PLoS Genet 4:e37PubMedCentralPubMedCrossRefGoogle Scholar
  53. 53.
    Aston KI, Hunt SC, Susser E et al (2012) Divergence of sperm and leukocyte age-dependent telomere dynamics: implications for male-driven evolution of telomere length in humans. Mol Hum Reprod 18:517–522PubMedCrossRefGoogle Scholar
  54. 54.
    Singh NP, Muller CH, Berger RE (2003) Effects of age on DNA double-strand breaks and apoptosis in human sperm. Fertil Steril 80:1420–1430PubMedCrossRefGoogle Scholar
  55. 55.
    Hemminki K, Kyyronen P, Vaittinen P (1999) Parental age as a risk factor of childhood leukemia and brain cancer in offspring. Epidemiology 10:271–275PubMedCrossRefGoogle Scholar
  56. 56.
    Spano M, Bonde JP, Hjollund HI et al (2000) Sperm chromatin damage impairs human fertility. The Danish first pregnancy planner study team. Fertil Steril 73:43–50PubMedCrossRefGoogle Scholar
  57. 57.
    Lopes S, Sun JG, Jurisicova A et al (1998) Sperm deoxyribonucleic acid fragmentation is increased in poor-quality semen samples and correlates with failed fertilization in intracytoplasmic sperm injection. Fertil Steril 69:528–532PubMedCrossRefGoogle Scholar
  58. 58.
    Zini A, Libman J (2006) Sperm DNA damage: clinical significance in the era of assisted reproduction. CMAJ 175:495–500PubMedCentralPubMedCrossRefGoogle Scholar
  59. 59.
    Smith TB, De Iuliis G, Lord T, Aitken RJ (2013) The senescence-accelerated mouse prone 8 as a model for oxidative stress and impaired DNA repair in the male germ line. Reproduction 146:253–262PubMedCrossRefGoogle Scholar
  60. 60.
    Vagnini L, Baruffi RL, Mauri AL et al (2007) The effects of male age on sperm DNA damage in an infertile population. Reprod Biomed Online 15:514–519PubMedCrossRefGoogle Scholar
  61. 61.
    Katz-Jaffe MG, Parks J, McCallie B, Schoolcraft WB (2013) Aging sperm negatively impacts in vivo and in vitro reproduction: a longitudinal murine study. Fertil Steril 100:262–268PubMedCrossRefGoogle Scholar
  62. 62.
    Penrose LS (1955) Parental age and mutation. Lancet 269:312–313PubMedCrossRefGoogle Scholar
  63. 63.
    Jones KL, Smith DW, Harvey MA et al (1975) Older paternal age and fresh gene mutation: data on additional disorders. J Pediatr 86:84–88Google Scholar
  64. 64.
    Crow JF (2000) The origins, patterns and implications of human spontaneous mutation. Nat Rev Genet 1:40–47PubMedCrossRefGoogle Scholar
  65. 65.
    Goriely A, McVean GA, Rojmyr M et al (2003) Evidence for selective advantage of pathogenic FGFR2 mutations in the male germ line. Science 301:643–646PubMedCrossRefGoogle Scholar
  66. 66.
    Tiemann-Boege I, Navidi W, Grewal R et al (2002) The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect. Proc Natl Acad Sci U S A 99:14952–14957CrossRefGoogle Scholar
  67. 67.
    Tarin JJ, Brines J, Cano A (1998) Long-term effects of delayed parenthood. Hum Reprod 13:2371–2376PubMedCrossRefGoogle Scholar
  68. 68.
    Crow JF (1997) The high spontaneous mutation rate: is it a health risk? Proc Natl Acad Sci U S A 94:8380–8386CrossRefGoogle Scholar
  69. 69.
    Inoue M, Kurihara T, Yamashita M, Tatsumi K (1993) Effects of treatment with methyl methanesulfonate during meiotic and postmeiotic stages and maturation of spermatozoa in mice. Mutat Res 294:179–186PubMedCrossRefGoogle Scholar
  70. 70.
    Kelso KA, Redpath A, Noble RC, Speake BK (1997) Lipid and antioxidant changes in spermatozoa and seminal plasma throughout the reproductive period of bulls. J Reprod Fertil 109:1–6Google Scholar
  71. 71.
    Matsuda Y, Tobari I, Maemori M, Seki N (1989) Mechanism of chromosome aberration induction in the mouse egg fertilized with sperm recovered from postmeiotic germ cells treated with methyl methanesulfonate. Mutat Res 214:165–180PubMedCrossRefGoogle Scholar
  72. 72.
    Curley JP, Mashoodh R, Champagne FA (2011) Epigenetics and the origins of paternal effects. Horm Behav 59:306–314PubMedCentralPubMedCrossRefGoogle Scholar
  73. 73.
    Jenkins TG, Aston KI, Cairns BR, Carrell DT (2013) Paternal aging and associated intraindividual alterations of global sperm 5-methylcytosine and 5-hydroxymethylcytosine levels. Fertil Steril 100:945–951PubMedCrossRefGoogle Scholar
  74. 74.
    Gosden R, Trasler J, Lucifero D, Faddy M (2003) Rare congenital disorders, imprinted genes, and assisted reproductive technology. Lancet 361:1975–1977PubMedCrossRefGoogle Scholar
  75. 75.
    Marques CJ, Carvalho F, Sousa M, Barros A (2004) Genomic imprinting in disruptive spermatogenesis. Lancet 363:1700–1702PubMedCrossRefGoogle Scholar
  76. 76.
    Jenkins TG, Carrell DT (2012) The sperm epigenome and potential implications for the developing embryo. Reproduction 143:727–734PubMedCrossRefGoogle Scholar
  77. 77.
    La Salle S, Trasler JM (2006) Epigenetic patterning in male germ cells: importance of DNA methylation to progeny outcome. In: De Jonge CC, Barratt CLR (Hrsg) The sperm cell: production, maturation, fertilization, regeneration. Cambridge University Press, CambridgeGoogle Scholar
  78. 78.
    Oakes CC, Smiraglia DJ, Plass C et al (2003) Aging results in hypermethylation of ribosomal DNA in sperm and liver of male rats. Proc Natl Acad Sci U S A 100:1775–1780CrossRefGoogle Scholar
  79. 79.
    Perrin MC, Brown AS, Malaspina D (2007) Aberrant epigenetic regulation could explain the relationship of paternal age to schizophrenia. Schizophr Bull 33:1270–1273PubMedCrossRefGoogle Scholar
  80. 80.
    Anagnostou E, Taylor MJ (2011) Review of neuroimaging in autism spectrum disorders: what have we learned and where we go from here. Mol Autism 2:4PubMedCentralPubMedCrossRefGoogle Scholar
  81. 81.
    Reichenberg A, Gross R, Weiser M et al (2006) Advancing paternal age and autism. Arch Gen Psychiatry 63:1026–1032PubMedCrossRefGoogle Scholar
  82. 82.
    Buizer-Voskamp JE, Laan W, Staal WG et al (2011) Paternal age and psychiatric disorders: findings from a Dutch population registry. Schizophr Res 129:128–132PubMedCentralPubMedCrossRefGoogle Scholar
  83. 83.
    Alter MD, Kharkar R, Ramsey KE et al (2011) Autism and increased paternal age related changes in global levels of gene expression regulation. PLoS One 6:e16715PubMedCentralPubMedCrossRefGoogle Scholar
  84. 84.
    Frans EM, Sandin S, Reichenberg A et al (2013) Autism risk across generations: a population-based study of advancing grandpaternal and paternal age. JAMA Psychiatry 70:516–521PubMedCentralPubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  1. 1.Centrum für Reproduktionsmedizin und AndrologieUniversitätsklinikum MünsterMünsterDeutschland

Personalised recommendations