Journal of Assisted Reproduction and Genetics

, Volume 29, Issue 9, pp 911–916 | Cite as

Contributing factors for the incidence of aneuploidy in older patients undergoing intracytoplasmic sperm injection cycles

  • Daniela Paes de Almeida Ferreira Braga
  • Amanda S. Setti
  • Rita de Cássia S. Figueira
  • Assumpto IaconelliJr.
  • Edson BorgesJr.



To evaluate different factors that might affect the incidence of embryo aneuploidy in intracytoplasmic sperm injection cycles (ICSI).


One hundred and ninety ICSI cycles in conjunction with preimplantation genetic screening (PGS) were included. The influence of the following variables on the aneuploidy incidence was evaluated: (i) maternal and (ii) paternal ages, (iii) dose of FSH administered, (iv) dose of FSH per number of retrieved matured oocytes (FSH/MII), (v) serum 17β-oestradiol levels on the ovulation trigger day, (vi) aspirated follicles and (vii) retrieved oocytes.


A total of 440 embryos were successfully biopsied, of which 240 were considered euploid and 200 were considered aneuploid. The paternal age (Slope: 0.2, p = 0.372), total dose of FSH (Slope: 0.2, p = 0.218), FSH/MII (Slope: 0.1, p = 0.296) and 17β-oestradiol levels (Slope: 0.2, p = 0.378) were not correlated with the presence of aneuploidy. However, the maternal age (Slope: 1.7, p < 0.01), aspirated follicles (Slope: 1.9, p < 0.01) and retrieved oocytes (Slope: 2.6, p < 0.01) were negatively correlated with the incidence of aneuploidy.


Even in older patients, lower oocyte yields may represent a more appropriate response to ovarian stimulation, allowing the most competent follicles and oocytes to develop and thereby reducing the occurrence of embryo aneuploidy.


Aneuploidy Ovarian stimulation FSH PGS FISH 


  1. 1.
    Aboulghar M, Mansour R, Al-Inany H, Abou-Setta AM, Aboulghar M, Mourad L, et al. Paternal age and outcome of intracytoplasmic sperm injection. Reprod Biomed Online. 2007;14(5):588–92.PubMedCrossRefGoogle Scholar
  2. 2.
    Al-Azemi M, Bernal AL, Steele J, Gramsbergen I, Barlow D, Kennedy S. Ovarian response to repeated controlled stimulation in in-vitro fertilization cycles in patients with ovarian endometriosis. Hum Reprod. 2000;15(1):72–5.PubMedCrossRefGoogle Scholar
  3. 3.
    Baart EB, Martini E, Eijkemans MJ, Van Opstal D, Beckers NG, Verhoeff A, et al. Milder ovarian stimulation for in-vitro fertilization reduces aneuploidy in the human preimplantation embryo: a randomized controlled trial. Hum Reprod. 2007;22(4):980–8.PubMedCrossRefGoogle Scholar
  4. 4.
    Dursun P, Gultekin M, Yuce K, Ayhan A. What is the underlying cause of aneuploidy associated with increasing maternal age? Is it associated with elevated levels of gonadotropins? Med Hypotheses. 2006;66(1):143–7.PubMedCrossRefGoogle Scholar
  5. 5.
    Edgar DH, Whalley KM, Mills JA. Effects of high-dose and multiple-dose gonadotropin stimulation on mouse oocyte quality as assessed by preimplantation development following in vitro fertilization. J In Vitro Fert Embryo Transf. 1987;4(5):273–6.PubMedCrossRefGoogle Scholar
  6. 6.
    Elbling L, Colot M. Abnormal development and transport and increased sister-chromatid exchange in preimplantation embryos following superovulation in mice. Mutat Res. 1985;147(4):189–95.PubMedCrossRefGoogle Scholar
  7. 7.
    Emery BR, Wilcox AL, Aoki VW, Peterson CM, Carrell DT. In vitro oocyte maturation and subsequent delayed fertilization is associated with increased embryo aneuploidy. Fertil Steril. 2005;84(4):1027–9.PubMedCrossRefGoogle Scholar
  8. 8.
    Ferreira RC, Braga DP, Bonetti TC, Pasqualotto FF, Iaconelli Jr A, Borges Jr E. Negative influence of paternal age on clinical intracytoplasmic sperm injection cycle outcomes in oligozoospermic patients. Fertil Steril. 2010;93(6):1870–4.PubMedCrossRefGoogle Scholar
  9. 9.
    Fragouli E, Bianchi V, Patrizio P, Obradors A, Huang Z, Borini A, et al. Transcriptomic profiling of human oocytes: association of meiotic aneuploidy and altered oocyte gene expression. Mol Hum Reprod. 2011;16(8):570–82.CrossRefGoogle Scholar
  10. 10.
    Fragouli E, Katz-Jaffe M, Alfarawati S, Stevens J, Colls P, Goodall NN, et al. Comprehensive chromosome screening of polar bodies and blastocysts from couples experiencing repeated implantation failure. Fertil Steril. 2011;94(3):875–87.CrossRefGoogle Scholar
  11. 11.
    Gianaroli L, Magli MC, Ferraretti AP, Munne S. Preimplantation diagnosis for aneuploidies in patients undergoing in vitro fertilization with a poor prognosis: identification of the categories for which it should be proposed. Fertil Steril. 1999;72(5):837–44.PubMedCrossRefGoogle Scholar
  12. 12.
    Gianaroli L, Magli MC, Fiorentino F, Baldi M, Ferraretti AP. Clinical value of preimplantation genetic diagnosis. Placenta. 2003;24(Suppl B):S77–83.PubMedCrossRefGoogle Scholar
  13. 13.
    Haaf T, Hahn A, Lambrecht A, Grossmann B, Schwaab E, Khanaga O, et al. A high oocyte yield for intracytoplasmic sperm injection treatment is associated with an increased chromosome error rate. Fertil Steril. 2009;91(3):733–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Hansen M, Kurinczuk JJ, Bower C, Webb S. The risk of major birth defects after intracytoplasmic sperm injection and in vitro fertilization. N Engl J Med. 2002;346(10):725–30.PubMedCrossRefGoogle Scholar
  15. 15.
    Harper JC, Sengupta SB. Preimplantation genetic diagnosis: state of the art 2011. Hum Genet. 2012;131(2):175–86.PubMedCrossRefGoogle Scholar
  16. 16.
    Hassold T, Hunt P. To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet. 2001;2(4):280–91.PubMedCrossRefGoogle Scholar
  17. 17.
    Hohmann FP, Macklon NS, Fauser BC. A randomized comparison of two ovarian stimulation protocols with gonadotropin-releasing hormone (GnRH) antagonist cotreatment for in vitro fertilization commencing recombinant follicle-stimulating hormone on cycle day 2 or 5 with the standard long GnRH agonist protocol. J Clin Endocrinol Metab. 2003;88(1):166–73.PubMedCrossRefGoogle Scholar
  18. 18.
    Katz-Jaffe MG, Trounson AO, Cram DS. Chromosome 21 mosaic human preimplantation embryos predominantly arise from diploid conceptions. Fertil Steril. 2005;84(3):634–43.PubMedCrossRefGoogle Scholar
  19. 19.
    Kuhnert B, Nieschlag E. Reproductive functions of the ageing male. Hum Reprod Update. 2004;10(4):327–39.PubMedCrossRefGoogle Scholar
  20. 20.
    Lamberts SWJ. Endocrinology and aging. In: Kronenberg HM, Polonsky KS, Larsen PR, editors. Williams’ textbook of endocrinology. Philadelphia: Saunders Elsevier; 2008.Google Scholar
  21. 21.
    Massie JA, Burney RO, Milki AA, Westphal LM, Lathi RB. Basal follicle-stimulating hormone as a predictor of fetal aneuploidy. Fertil Steril. 2008;90(6):2351–5.PubMedCrossRefGoogle Scholar
  22. 22.
    Massie JA, Shahine LK, Milki AA, Westphal LM, Lathi RB. Ovarian stimulation and the risk of aneuploid conceptions. Fertil Steril. 2011;95(3):970–2.PubMedCrossRefGoogle Scholar
  23. 23.
    Mastenbroek S, Twisk M, van der Veen F, Repping S. Preimplantation genetic screening: a systematic review and meta-analysis of RCTs. Hum Reprod Update. 2011;17(4):454–66. doi: 454.PubMedCrossRefGoogle Scholar
  24. 24.
    Mastenbroek S, Twisk M, van der Veen F, Repping S. Preimplantation genetic screening: a systematic review and meta-analysis of RCTs. Hum Reprod Update. 2012;17(4):454–66.CrossRefGoogle Scholar
  25. 25.
    Mizunuma H, Takagi T, Yamada K, Andoh K, Ibuki Y, Igarashi M. Ovulation induction by step-down administration of purified urinary follicle-stimulating hormone in patients with polycystic ovarian syndrome. Fertil Steril. 1991;55(6):1195–6.PubMedGoogle Scholar
  26. 26.
    Munne S. Chromosome abnormalities and their relationship to morphology and development of human embryos. Reprod Biomed Online. 2006;12(2):234–53.PubMedCrossRefGoogle Scholar
  27. 27.
    Munne S, Magli C, Adler A, Wright G, de Boer K, Mortimer D, et al. Treatment-related chromosome abnormalities in human embryos. Hum Reprod. 1997;12(4):780–4.PubMedCrossRefGoogle Scholar
  28. 28.
    Munne S, Sandalinas M, Escudero T, Velilla E, Walmsley R, Sadowy S, et al. Improved implantation after preimplantation genetic diagnosis of aneuploidy. Reprod Biomed Online. 2003;7(1):91–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Palermo G, Joris H, Devroey P, Van Steirteghem AC. Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet. 1992;340(8810):17–8.PubMedCrossRefGoogle Scholar
  30. 30.
    Paulson RJ, Milligan RC, Sokol RZ. The lack of influence of age on male fertility. Am J Obstet Gynecol. 2001;184(5):818–22. discussion 822–4.PubMedCrossRefGoogle Scholar
  31. 31.
    Philipp T, Philipp K, Reiner A, Beer F, Kalousek DK. Embryoscopic and cytogenetic analysis of 233 missed abortions: factors involved in the pathogenesis of developmental defects of early failed pregnancies. Hum Reprod. 2003;18(8):1724–32.PubMedCrossRefGoogle Scholar
  32. 32.
    Platteau P, Staessen C, Michiels A, Van Steirteghem A, Liebaers I, Devroey P. Preimplantation genetic diagnosis for aneuploidy screening in patients with unexplained recurrent miscarriages. Fertil Steril. 2005;83(2):393–7. quiz 525–6.PubMedCrossRefGoogle Scholar
  33. 33.
    Roberts R, Iatropoulou A, Ciantar D, Stark J, Becker DL, Franks S, et al. Follicle-stimulating hormone affects metaphase I chromosome alignment and increases aneuploidy in mouse oocytes matured in vitro. Biol Reprod. 2005;72(1):107–18.PubMedCrossRefGoogle Scholar
  34. 34.
    Sato F, Marrs RP. The effect of pregnant mare serum gonadotropin on mouse embryos fertilized in vivo or in vitro. J In Vitro Fert Embryo Transf. 1986;3(6):353–7.PubMedCrossRefGoogle Scholar
  35. 35.
    Staessen C, Platteau P, Van Assche E, Michiels A, Tournaye H, Camus M, et al. Comparison of blastocyst transfer with or without preimplantation genetic diagnosis for aneuploidy screening in couples with advanced maternal age: a prospective randomized controlled trial. Hum Reprod. 2004;19(12):2849–58.PubMedCrossRefGoogle Scholar
  36. 36.
    Verberg MF, Eijkemans MJ, Macklon NS, Heijnen EM, Baart EB, Hohmann FP, et al. The clinical significance of the retrieval of a low number of oocytes following mild ovarian stimulation for IVF: a meta-analysis. Hum Reprod Update. 2009;15(1):5–12.PubMedCrossRefGoogle Scholar
  37. 37.
    Verpoest W, Fauser BC, Papanikolaou E, Staessen C, Van Landuyt L, Donoso P, et al. Chromosomal aneuploidy in embryos conceived with unstimulated cycle IVF. Hum Reprod. 2008;23(10):2369–71.PubMedCrossRefGoogle Scholar
  38. 38.
    Wells D. Embryo aneuploidy and the role of morphological and genetic screening. Reprod Biomed Online. 2010;21(3):274–7.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Daniela Paes de Almeida Ferreira Braga
    • 1
    • 2
  • Amanda S. Setti
    • 2
  • Rita de Cássia S. Figueira
    • 1
  • Assumpto IaconelliJr.
    • 1
    • 2
  • Edson BorgesJr.
    • 1
    • 2
  1. 1.Fertility – Assisted Fertilization CentreSão PauloBrazil
  2. 2.Sapientiae Institute – Educational and Research Centre in Assisted ReproductionSão PauloBrazil

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