Advertisement

Fathers over 40 and increased failure to conceive: the lessons of in vitro fertilization in France

  • Elise de La Rochebrochard
    Correspondence
    Reprint requests: Elise de La Rochebrochard, Ph.D., INSERM Unit 569, Bicêtre Hospital, 82 rue du Général Leclerc, 94275 Le Kremlin-Bicêtre, France Tel. 33 1 45 21 23 33, (FAX: 33 1 45 21 20 75)
    Affiliations
    INED, Le Kremlin-Bicêtre, F-94276, France

    INSERM, Unit 569, Le Kremlin-Bicêtre, F-94276, France

    Université Paris-Sud 11, Faculté de Médecine Paris-Sud, Bicêtre Hospital, Le Kremlin-Bicêtre, F-94276, France

    AP-HP, Hôpital Bicêtre, Groupement Hospitalier Universitaire Sud, Le Kremlin-Bicêtre, F-94276, France
    Search for articles by this author
  • Jacques de Mouzon
    Affiliations
    INED, Le Kremlin-Bicêtre, F-94276, France

    INSERM, Unit 569, Le Kremlin-Bicêtre, F-94276, France

    Université Paris-Sud 11, Faculté de Médecine Paris-Sud, Bicêtre Hospital, Le Kremlin-Bicêtre, F-94276, France

    AP-HP, Hôpital Bicêtre, Groupement Hospitalier Universitaire Sud, Le Kremlin-Bicêtre, F-94276, France
    Search for articles by this author
  • François Thépot
    Affiliations
    CHU d’Amiens, Laboratoire de Biologie de la Réproduction, Amiens, France
    Search for articles by this author
  • Patrick Thonneau
    Affiliations
    INSERM, Human Fertility Research Group, Hôpital Paule de Viguier, Toulouse, France
    Search for articles by this author
  • French National IVF Registry (FIVNAT) association

      Objective

      To investigate paternal age effect mediated by biological modifications with use of data from assisted reproductive technologies.

      Design

      National IVF registry.

      Setting

      Fifty nine French IVF centers.

      Patient(s)

      A total of 1,938 men whose partners were totally sterile, with bilateral tubal obstruction or absence of both tubes (to avoid bias sampling in analysis of paternal age) and treated by conventional IVF.

      Intervention(s)

      None.

      Main Outcome Measure(s)

      Risk of failure to conceive defined as absence of intrauterine pregnancy.

      Result(s)

      The odds ratio of failure to conceive for paternal age ≥40 years was 2.00 (95% confidence interval [CI]: 1.10–3.61) when the woman was 35–37 years old, 2.03 (95% CI: 1.12–3.68) for age 38–40 years, and 5.74 (95% CI: 2.16, 15.23) for age 41 years and over.

      Conclusion(s)

      As an increasing number of couples choose to postpone childbearing, they should be informed that paternal age over 40 years is an important risk factor for failure to conceive.

      Key Words

      To read this article in full you will need to make a payment

      Subscribe:

      Subscribe to Fertility and Sterility
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Menken J.
        • Trussell J.
        • Larsen U.
        Age and infertility.
        Science. 1986; 233: 1389-1394
        • Nybo Andersen A.M.
        • Wohlfahrt J.
        • Christens P.
        • Olsen J.
        • Melbye M.
        Maternal age and fetal loss.
        BMJ. 2000; 320: 1708-1712
        • Leridon H.
        Can assisted reproduction technology compensate for the natural decline in fertility with age? A model assessment.
        Hum Reprod. 2004; 19: 1548-1553
        • Gosden R.
        • Rutherford A.
        Delayed childbearing.
        BMJ. 1995; 311: 1585-1586
        • Nybo Andersen A.M.
        • Hansen K.D.
        • Andersen P.K.
        • Davey Smith G.
        Advanced paternal age and risk of fetal death.
        Am J Epidemiol. 2004; 160: 1214-1222
        • 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: 1649-1656
        • de La Rochebrochard E.
        • Thonneau P.
        Paternal age over 40 years.
        Am J Obstet Gynecol. 2003; 189: 901-905
        • Dunson D.B.
        • Colombo B.
        • Baird D.D.
        Changes with age in the level and duration of fertility in the menstrual cycle.
        Hum Reprod. 2002; 17: 1399-1403
        • de La Rochebrochard E.
        • McElreavey K.
        • Thonneau P.
        Paternal age over 40 years.
        J Androl. 2003; 24: 459-465
        • Schwartz D.
        • Mayaux M.J.
        Female fecundity as a function of age: results of artificial insemination in 2193 nulliparous women with azoospermic husbands. Federation CECOS.
        N Engl J Med. 1982; 306: 404-406
        • de Mouzon J.
        • Bachelot A.
        • Spira A.
        Establishing a national in vitro fertilization registry.
        Stat Med. 1993; 12: 39-50
        • Piette C.
        • de Mouzon J.
        • Bachelot A.
        • Spira A.
        • FIVNAT (French In Vitro National)
        In-vitro fertilization.
        Hum Reprod. 1990; 5: 56-59
        • Practice Committee of the American Society for Reproductive Medicine (ASRM)
        Aging and infertility in women.
        Fertil Steril. 2004; 82: 102-106
        • Faddy M.J.
        • Gosden R.G.
        • Gougeon A.
        • Richardson S.J.
        • Nelson J.F.
        Accelerated disappearance of ovarian follicles in mid-life.
        Hum Reprod. 1992; 7: 1342-1346
        • Heffner L.J.
        Advanced maternal age—how old is too old?.
        N Engl J Med. 2004; 351: 1927-1929
        • Wang X.
        • Dai W.
        Shugoshin, a guardian for sister chromatid segregation.
        Exp Cell Res. 2005; 310: 1-9
        • Michaelis C.
        • Ciosk R.
        • Nasmyth K.
        Cohesins.
        Cell. 1997; 91: 35-45
        • Haering C.H.
        • Nasmyth K.
        Building and breaking bridges between sister chromatids.
        Bioessays. 2003; 25: 1178-1191
        • Gray R.H.
        • Wu L.Y.
        Subfertility and risk of spontaneous abortion.
        Am J Public Health. 2000; 90: 1452-1454
        • Slama R.
        • Bouyer J.
        • Windham G.
        • Fenster L.
        • Werwatz A.
        • Swan S.H.
        Influence of paternal age on the risk of spontaneous abortion.
        Am J Epidemiol. 2005; 161: 816-823
        • American College of Obstetricians and Gynecologists (ACOG) Committee
        ACOG committee opinion. Advanced paternal age: risks to the fetus. No. 189, October 1997. Committee on Genetics.
        Int J Gynaecol Obstet. 1997; 59: 271-272
        • Kuhnert B.
        • Nieschlag E.
        Reproductive functions of the ageing male.
        Hum Reprod Update. 2004; 10: 327-339
        • Thépot F.
        • Mayaux M.J.
        • Czyglick F.
        • Wack T.
        • Selva J.
        • Jalbert P.
        Incidence of birth defects after artificial insemination with frozen donor spermatozoa.
        Hum Reprod. 1996; 11: 2319-2323
        • Luetjens C.M.
        • Rolf C.
        • Gassner P.
        • Werny J.E.
        • Nieschlag E.
        Sperm aneuploidy rates in younger and older men.
        Hum Reprod. 2002; 17: 1826-1832
        • Martin R.H.
        Mechanisms of nondisjunction in human spermatogenesis.
        Cytogenet Genome Res. 2005; 111: 245-249
        • Sartorelli E.M.
        • Mazzucatto L.F.
        • de Pina-Neto J.M.
        Effect of paternal age on human sperm chromosomes.
        Fertil Steril. 2001; 76: 1119-1123
        • Sloter E.
        • Nath J.
        • Eskenazi B.
        • Wyrobek A.J.
        Effects of male age on the frequencies of germinal and heritable chromosomal abnormalities in humans and rodents.
        Fertil Steril. 2004; 81: 925-943
        • Friedman J.M.
        Genetic disease in the offspring of older fathers.
        Obstet Gynecol. 1981; 57: 745-749
        • Morris I.D.
        • Ilott S.
        • Dixon L.
        • Brison D.R.
        The spectrum of DNA damage in human sperm assessed by single cell gel electrophoresis (Comet assay) and its relationship to fertilization and embryo development.
        Hum Reprod. 2002; 17: 990-998
        • Singh N.P.
        • Muller C.H.
        • Berger R.E.
        Effects of age on DNA double-strand breaks and apoptosis in human sperm.
        Fertil Steril. 2003; 80: 1420-1430
        • Crow J.F.
        The origins, patterns and implications of human spontaneous mutation.
        Nat Rev Genet. 2000; 1: 40-47
        • Rolf C.
        • Nieschlag E.
        Reproductive functions, fertility and genetic risks of ageing men.
        Exp Clin Endocrinol Diabetes. 2001; 109: 68-74
        • Plas E.
        • Berger P.
        • Hermann M.
        • Pfluger H.
        Effects of aging on male fertility?.
        Exp Gerontol. 2000; 35: 543-551
        • Kidd S.A.
        • Eskenazi B.
        • Wyrobek A.J.
        Effects of male age on semen quality and fertility.
        Fertil Steril. 2001; 75: 237-248