Consult the medical resource doctors trust

UpToDate is one of the most respected medical information resources in the world, used by over 360,000 doctors and thousands of patients to find answers to medical questions.

  • Content written by a faculty of over 4,000 physicians from leading medical institutions
  • Unbiased: free of advertising or pharmaceutical funding
  • Evidence-based treatment recommendations
  • Continuously updated to incorporate new medical findings

Related articles included with a subscription

Preview Available
(subscription required for full access)

Effect of advanced paternal age on fertility and pregnancy

INTRODUCTION

Women are generally aware of the reproductive issues related to advanced maternal age, typically defined as 35 years of age or older on the estimated date of confinement. These issues include higher risks of infertility, fetal aneuploidy, gestational diabetes, preeclampsia, and stillbirth [1]. (See "Effect of advanced age on fertility and pregnancy in women".)

Reproductive concerns related to advanced paternal age are less well defined [2]. Analysis of pregnancy outcome in the partners of these men is confounded by the fact that the partners are often of advanced maternal age.

FERTILITY

The probability of conception is primarily dependent upon maternal age, and to a lesser extent, paternal age. In contrast to oogenesis, which appears to be limited to the fetus in humans, spermatogenesis continues even in elderly men. Since the adult male's germ cells have passed through more mitotic replications than the adult female's germ cells, there is a greater opportunity for error. Increasing age has been associated with more breaks in sperm DNA, loss of apoptosis, and a higher frequency of point mutations [3,4]. (See "Male reproductive physiology".)

A literature review on the association between male age and semen quality compared 30-year-old men to 50-year-old men and found decreases in semen volume (3 to 22 percent), sperm motility (3 to 37 percent), and percent of normal sperm (4 to 18 percent), but not sperm concentration, with age [5]. Similar findings were noted in a subsequent series that evaluated men age 22 to 80 years [6]. However, standard sperm parameters do not correlate perfectly with fertilizing capacity and achievement of pregnancy.

A more clinically useful approach to assessing the fertility of older men is to examine pregnancy rates and outcomes after attempting to control for the age of the female partner. These studies have reported conflicting results [7-11] and are limited by relatively small numbers of couples in whom the female partner is young and the male partner is old.
To continue reading this article you need to subscribe.

Read the rest of this article and others like it

The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use (click here) ©2009 UpToDate, Inc.
References Top
  1. Leuzzi, RA, Scoles, KS. Preconception counseling for the primary care physician. Med Clin North Am 1996; 80:337.
  2. Thacker, PD. Biological clock ticks for men, too: genetic defects linked to sperm of older fathers. JAMA 2004; 291:1683.
  3. Singh, NP, Muller, CH, Berger, RE. Effects of age on DNA double-strand breaks and apoptosis in human sperm. Fertil Steril 2003; 80:1420.
  4. Glaser, RL, Broman, KW, Schulman, RL, et al. The paternal-age effect in Apert syndrome is due, in part, to the increased frequency of mutations in sperm. Am J Hum Genet 2003; 73:939.
  5. Kidd, SA, Eskenazi, B, Wyrobek, AJ. Effects of male age on semen quality and fertility: a review of the literature. Fertil Steril 2001; 75:237.
  6. Eskenazi, B, Wyrobek, AJ, Sloter, E, et al. The association of age and semen quality in healthy men. Hum Reprod 2003; 18:447.
  7. Dunson, DB, Colombo, B, Baird, DD. Changes with age in the level and duration of fertility in the menstrual cycle. Hum Reprod 2002; 17:1399.
  8. Hassan, MA, Killick, SR. Effect of male age on fertility: evidence for the decline in male fertility with increasing age. Fertil Steril 2003; 79 Suppl 3:2.
  9. Klonoff-Cohen, HS, Natarajan, L. The effect of advancing paternal age on pregnancy and live birth rates in couples undergoing in vitro fertilization or gamete intrafallopian transfer. Am J Obstet Gynecol 2004; 191:507.
  10. de La, Rochebrochard E, Thonneau, P. Paternal age >or=40 years: an important risk factor for infertility. Am J Obstet Gynecol 2003; 189:901.
  11. de La, Rochebrochard E, de Mouzon, J, Thepot, F, Thonneau, P. Fathers over 40 and increased failure to conceive: the lessons of in vitro fertilization in France. Fertil Steril 2006; 85:1420.
  12. Paulson, RJ, Milligan, RC, Sokol, RZ. The lack of influence of age on male fertility. Am J Obstet Gynecol 2001; 184:818.
  13. Frattarelli, JL, Miller, KA, Miller, BT, et al. Male age negatively impacts embryo development and reproductive outcome in donor oocyte assisted reproductive technology cycles. Fertil Steril 2008; 90:97.
  14. Gallardo, E, Simon, C, Levy, M, et al. Effect of age on sperm fertility potential: oocyte donation as a model. Fertil Steril 1996; 66:260.
  15. Auroux, M. [Age of the father and development]. Contracept Fertil Sex 1993; 21:382.
  16. Tarin, JJ, Brines, J, Cano, A. Long-term effects of delayed parenthood. Hum Reprod 1998; 13:2371.
  17. Martin, RH, Rademaker, AW. The effect of age on the frequency of sperm chromosomal abnormalities in normal men. Am J Hum Genet 1987; 41:484.
  18. Sartorelli, EM, Mazzucatto, LF, de Pina-Neto, JM. Effect of paternal age on human sperm chromosomes. Fertil Steril 2001; 76:1119.
  19. Friedman, JM. Genetic disease in the offspring of older fathers. Obstet Gynecol 1981; 57:745.
  20. McIntosh, GC, Olshan, AF, Baird, PA. Paternal age and the risk of birth defects in offspring. Epidemiology 1995; 6:282.
  21. Olshan, AF, Schnitzer, PG, Baird, PA. Paternal age and the risk of congenital heart defects. Teratology 1994; 50:80.
  22. Olson, JM, Breslow, NE, Beckwith, JB. Wilms' tumour and parental age: a report from the National Wilms' Tumour Study. Br J Cancer 1993; 67:813.
  23. Zhu, JL, Madsen, KM, Vestergaard, M, et al. Paternal age and congenital malformations. Hum Reprod 2005; 20:3173.
  24. Lian, ZH, Zack, MM, Erickson, JD. Paternal age and the occurrence of birth defects. Am J Hum Genet 1986; 39:648.
  25. Yang, Q, Wen, SW, Leader, A, et al. Paternal age and birth defects: how strong is the association?. Hum Reprod 2007; 22:696.
  26. Malaspina, D, Harlap, S, Fennig, S, et al. Advancing paternal age and the risk of schizophrenia. Arch Gen Psychiatry 2001; 58:361.
  27. Sipos, A, Rasmussen, F, Harrison, G, et al. Paternal age and schizophrenia: a population based cohort study. BMJ 2004; 329:1070.
  28. Tsuchiya, KJ, Takagai, S, Kawai, M, et al. Advanced paternal age associated with an elevated risk for schizophrenia in offspring in a Japanese population. Schizophr Res 2005; 76:337.
  29. Perrin, MC, Brown, AS, Malaspina, D. Aberrant epigenetic regulation could explain the relationship of paternal age to schizophrenia. Schizophr Bull 2007; 33:1270.
  30. Reichenberg, A, Gross, R, Weiser, M, et al. Advancing paternal age and autism. Arch Gen Psychiatry 2006; 63:1026.
  31. Tsuchiya, KJ, Matsumoto, K, Miyachi, T, et al. Paternal age at birth and high-functioning autistic-spectrum disorder in offspring. Br J Psychiatry 2008; 193:316.
  32. Durkin, MS, Maenner, MJ, Newschaffer, CJ, et al. Advanced parental age and the risk of autism spectrum disorder. Am J Epidemiol 2008; 168:1268.
  33. Croen, LA, Najjar, DV, Fireman, B, Grether, JK. Maternal and paternal age and risk of autism spectrum disorders. Arch Pediatr Adolesc Med 2007; 161:334.
  34. Lauritsen, MB, Pedersen, CB, Mortensen, PB. Effects of familial risk factors and place of birth on the risk of autism: a nationwide register-based study. J Child Psychol Psychiatry 2005; 46:963.
  35. American College of Obstetricians and Gynecologists. Advanced paternal age. ACOG Committee Opinion #189, American College of Obstetricians and Gynecologists, Washington, DC 1997.
  36. Erickson, JD. Paternal age and Down syndrome. Am J Hum Genet 1979; 31:489.
  37. Stene, J, Fischer, G, Stene, E, et al. Paternal age effect in Down's syndrome. Ann Hum Genet 1977; 40:299.
  38. Roth, MP, Feingold, J, Baumgarten, A, et al. Reexamination of paternal age effect in Down's syndrome. Hum Genet 1983; 63:149.
  39. Hook, EB, Regal, RR. A search for a paternal-age effect upon cases of 47, +21 in which the extra chromosome is of paternal origin. Am J Hum Genet 1984; 36:413.
  40. Sloter, E, Nath, J, Eskenazi, B, Wyrobek, AJ. Effects of male age on the frequencies of germinal and heritable chromosomal abnormalities in humans and rodents. Fertil Steril 2004; 81:925.
  41. Yip, BH, Pawitan, Y, Czene, K. Parental age and risk of childhood cancers: a population-based cohort study from Sweden. Int J Epidemiol 2006; 35:1495.
  42. Hatch, M, Kline, J, Levin, B, et al. Paternal age and trisomy among spontaneous abortions. Hum Genet 1990; 85:355.
  43. de la, Rochebrochard E, Thonneau, P. Paternal age and maternal age are risk factors for miscarriage; results of a multicentre European study. Hum Reprod 2002; 17:1649.
  44. Slama, R, Werwatz, A, Boutou, O, Ducot, B. Does male age affect the risk of spontaneous abortion? An approach using semiparametric regression. Am J Epidemiol 2003; 157:815.
  45. Slama, R, Bouyer, J, Windham, G, et al. Influence of paternal age on the risk. Am J Epidemiol 2005; 161:816.
  46. Nybo Andersen, AM, Hansen, KD, Andersen, PK, Davey Smith, G. Advanced paternal age and risk of fetal death: a cohort study. Am J Epidemiol 2004; 160:1214.
  47. Aging and infertility in women: a committee opinion. Fertil Steril 2002; 78:215.
  48. Olshan, AF, Ananth, CV, Savitz, DA. Intrauterine growth retardation as an endpoint in mutation epidemiology: an evaluation based on paternal age. Mutat Res 1995; 344:89.
  49. Chen, XK, Wen, SW, Krewski, D, et al. Paternal age and adverse birth outcomes: teenager or 40+, who is at risk?. Hum Reprod 2008; 23:1290.
  50. Resseguie, LJ. Paternal age, stillbirths and mutation. Ann Hum Genet 1976; 40:213.
  51. Yerushalmy, J. Age of father and survival of offspring. Hum Biol 1939; 11:342.
  52. Woolf, CM. Stillbirths and paternal age. Obstet Gynecol 1965; 26:1.
  53. Selvin, S, Garfinkel, J. Paternal age, maternal age and birth order and the risk of a fetal loss. Hum Biol 1976; 48:223.
  54. Astolfi, P, De Pasquale, A, Zonta, LA. Late paternity and stillbirth risk. Hum Reprod 2004; 19:2497.
  55. www.asrm.org/.
white circle LOG IN
white circle DEMO