Skip to main content
SpringerLink
Log in

The Need for Long-Term Follow-Up of Children Conceived Through ICSI

  • Chapter
  • First Online:
Biennial Review of Infertility

  • 807 Accesses

Abstract

Intracytoplasmic sperm injection (ICSI) has become an important therapeutic intervention in assisted reproduction technologies (ART) since its introduction in 1992, overcoming many of the problems presented by male factor infertility. Although the overwhelming majority of children born following ICSI have been healthy, concerns have been raised about the potential harmful effects of ICSI on the resulting offspring. This chapter reviews the literature to date on the outcomes of children born following ICSI, with emphasis on the incidence of congenital abnormalities, imprinting disorders, chromosomal and karyotypic abnormalities, and neurologic and developmental outcomes. As the oldest children born from ICSI are now 20 years old, little is known about the long-term health of these offspring. Continued follow-up of these children is essential to determine the long-term outcomes of children conceived through ICSI.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
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 169.99
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. Practice Committee of the American Society for Reproductive Medicine. Does intracytoplasmic sperm injection (ICSI) carry inherent genetic risks? Fertil Steril. 2004;82 (Suppl 1):S151–2.

    Google Scholar 

  2. Palermo GD, Neri QV, Monahan D, et al. Development and current applications of assisted fertilization. Fertil Steril. 2012;97(2):248–59.

    Article  PubMed  Google Scholar 

  3. [SART National Data Summary (Internet) Cited 2010 December 5]; Available from: https://http://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?ClinicPKID=0.

  4. Talaulikar VS, Arulkumaran S. Reproductive outcomes after assisted conception. Obstet Gynecol Surv. 2012;67(9):566–83.

    Article  PubMed  Google Scholar 

  5. Palermo GD, Neri QV, Takeuchi T, et al. Genetic and epigenetic characteristics of ICSI children. Reprod Biomed Online. 2008;17(6):820–33.

    Article  PubMed  Google Scholar 

  6. Rimm AA, Katayama AC, Diaz M, et al. A meta-analysis of controlled studies comparing major malformation rates in IVF and ICSI infants with naturally conceived children. J Assist Reprod Genet. 2004; 21(12):437–43.

    Article  PubMed  Google Scholar 

  7. Hansen M, Bower C, Milne E, et al. Assisted reproductive technologies and the risk of birth defects–a systematic review. Hum Reprod. 2005;20(2): 328–38.

    Article  PubMed  Google Scholar 

  8. Schieve LA, Rasmussen SA, Reefhuis J. Risk of birth defects among children conceived with assisted reproductive technology: providing an epidemiologic context to the data. Fertil Steril. 2005;84(5):1320–4. discussion 7.

    Article  PubMed  Google Scholar 

  9. Zhu JL, Basso O, Obel C, et al. Infertility, infertility treatment, and congenital malformations: Danish national birth cohort. BMJ. 2006;333(7570):679.

    Article  PubMed  Google Scholar 

  10. Wen J, Jiang J, Ding C, et al. Birth defects in children conceived by in vitro fertilization and intracytoplasmic sperm injection: a meta-analysis. Fertil Steril. 2012;97(6):1331–7.

    Article  PubMed  Google Scholar 

  11. Woldringh GH, Besselink DE, Tillema AH, et al. Karyotyping, congenital anomalies and follow-up of children after intracytoplasmic sperm injection with non-ejaculated sperm: a systematic review. Hum Reprod Update. 2010;16(1):12–9.

    Article  PubMed  CAS  Google Scholar 

  12. Kallen B, Finnstrom O, Lindam A, et al. Congenital malformations in infants born after in vitro fertilization in Sweden. Birth Defects Res A Clin Mol Teratol. 2010;88(3):137–43.

    PubMed  Google Scholar 

  13. Davies MJ, Moore VM, Willson KJ, et al. Reproductive technologies and the risk of birth defects. N Engl J Med. 2012;366(19):1803–13.

    Article  PubMed  CAS  Google Scholar 

  14. Sutcliffe AG, Taylor B, Saunders K, et al. Outcome in the second year of life after in-vitro fertilisation by intracytoplasmic sperm injection: a UK case–control study. Lancet. 2001;357(9274):2080–4.

    Article  PubMed  CAS  Google Scholar 

  15. Halliday J. Outcomes for offspring of men having ICSI for male factor infertility. Asian J Androl. 2012;14(1):116–20.

    Article  PubMed  Google Scholar 

  16. Fedder J, Gabrielsen A, Humaidan P, et al. Malformation rate and sex ratio in 412 children conceived with epididymal or testicular sperm. Hum Reprod. 2007;22(4):1080–5.

    Article  PubMed  Google Scholar 

  17. Fedder J, Loft A, Parner ET, et al. Neonatal outcome and congenital malformations in children born after ICSI with testicular or epididymal sperm: a controlled national cohort study. Hum Reprod. 2012;28: 230–40.

    Article  PubMed  Google Scholar 

  18. Belva F, De Schrijver F, Tournaye H, et al. Neonatal outcome of 724 children born after ICSI using non-ejaculated sperm. Hum Reprod. 2011;26(7):1752–8.

    Article  PubMed  CAS  Google Scholar 

  19. Manipalviratn S, DeCherney A, Segars J. Imprinting disorders and assisted reproductive technology. Fertil Steril. 2009;91(2):305–15.

    Article  PubMed  CAS  Google Scholar 

  20. Morison IM, Ramsay JP, Spencer HG. A census of mammalian imprinting. Trends in Genetics: TIG. 2005;21(8):457–65.

    Article  PubMed  CAS  Google Scholar 

  21. Hartmann S, Bergmann M, Bohle RM, et al. Genetic imprinting during impaired spermatogenesis. Mol Hum Reprod. 2006;12(6):407–11.

    Article  PubMed  CAS  Google Scholar 

  22. Marques CJ, Carvalho F, Sousa M, et al. Genomic imprinting in disruptive spermatogenesis. Lancet. 2004;363(9422):1700–2.

    Article  PubMed  CAS  Google Scholar 

  23. Kobayashi H, Sato A, Otsu E, et al. Aberrant DNA methylation of imprinted loci in sperm from oligospermic patients. Hum Mol Genet. 2007;16(21): 2542–51.

    Article  PubMed  CAS  Google Scholar 

  24. Dasoula A, Georgiou I, Kontogianni E, et al. Methylation status of the SNRPN and HUMARA genes in testicular biopsy samples. Fertil Steril. 2007;87(4):805–9.

    Article  PubMed  CAS  Google Scholar 

  25. Marques CJ, Costa P, Vaz B, et al. Abnormal methylation of imprinted genes in human sperm is associated with oligozoospermia. Mol Hum Reprod. 2008; 14(2):67–74.

    Article  PubMed  CAS  Google Scholar 

  26. Maher ER. Imprinting and assisted reproductive technology. Hum Mol Genet. 2005;14(Spec No 1):133–8.

    Article  Google Scholar 

  27. Eroglu A, Layman LC. Role of ART in imprinting disorders. Semin Reprod Med. 2012;30(2):92–104.

    Article  PubMed  CAS  Google Scholar 

  28. Lim D, Bowdin SC, Tee L, et al. Clinical and molecular genetic features of Beckwith–Wiedemann syndrome associated with assisted reproductive technologies. Hum Reprod. 2009;24(3):741–7.

    Article  PubMed  Google Scholar 

  29. Mann MR, Bartolomei MS. Towards a molecular understanding of Prader-Willi and Angelman syndromes. Hum Mol Genet. 1999;8(10):1867–73.

    Article  PubMed  CAS  Google Scholar 

  30. Cox GF, Burger J, Lip V, et al. Intracytoplasmic sperm injection may increase the risk of imprinting defects. Am J Hum Genet. 2002;71(1):162–4.

    Article  PubMed  CAS  Google Scholar 

  31. Moll AC, Imhof SM, Cruysberg JR, et al. Incidence of retinoblastoma in children born after in-vitro fertilisation. Lancet. 2003;361(9354):309–10.

    Article  PubMed  Google Scholar 

  32. Thompson JR, Williams CJ. Genomic imprinting and assisted reproductive technology: connections and potential risks. Semin Reprod Med. 2005;23(3): 285–95.

    Article  PubMed  CAS  Google Scholar 

  33. Zeschnigk M, Bohringer S, Price EA, et al. A novel real-time PCR assay for quantitative analysis of methylated alleles (QAMA): analysis of the retinoblastoma locus. Nucleic Acids Res. 2004;32(16):e125.

    Article  PubMed  Google Scholar 

  34. Marees T, Dommering CJ, Imhof SM, et al. Incidence of retinoblastoma in Dutch children conceived by IVF: an expanded study. Hum Reprod. 2009;24(12): 3220–4.

    Article  PubMed  CAS  Google Scholar 

  35. Dommering CJ, van der Hout AH, Meijers-Heijboer H, et al. IVF and retinoblastoma revisited. Fertil Steril. 2012;97(1):79–81.

    Article  PubMed  Google Scholar 

  36. Draper ES, Kurinczuk JJ, Abrams KR, et al. Assessment of separate contributions to perinatal mortality of infertility history and treatment: a case–control analysis. Lancet. 1999;353(9166):1746–9.

    Article  PubMed  CAS  Google Scholar 

  37. Neelanjana M, Sabaratnam A. Malignant conditions in children born after assisted reproductive technology. Obstet Gynecol Surv. 2008;63(10):669–76.

    Article  PubMed  Google Scholar 

  38. Doornbos ME, Maas SM, McDonnell J, et al. Infertility, assisted reproduction technologies and imprinting disturbances: a Dutch study. Hum Reprod. 2007;22(9):2476–80.

    Article  PubMed  Google Scholar 

  39. Lidegaard O, Pinborg A, Andersen AN. Imprinting diseases and IVF: Danish National IVF cohort study. Hum Reprod. 2005;20(4):950–4.

    Article  PubMed  Google Scholar 

  40. Kallen B, Finnstrom O, Nygren KG, et al. In vitro fertilization (IVF) in Sweden: risk for congenital malformations after different IVF methods. Birth Defects Res A Clin Mol Teratol. 2005;73(3):162–9.

    Article  PubMed  Google Scholar 

  41. Klip H, Burger CW, de Kraker J, et al. Risk of cancer in the offspring of women who underwent ovarian stimulation for IVF. Hum Reprod. 2001;16(11): 2451–8.

    PubMed  CAS  Google Scholar 

  42. Bruinsma F, Venn A, Lancaster P, et al. Incidence of cancer in children born after in-vitro fertilization. Hum Reprod. 2000;15(3):604–7.

    Article  PubMed  CAS  Google Scholar 

  43. Lim DH, Maher ER. Genomic imprinting syndromes and cancer. Adv Genet. 2010;70:145–75.

    Article  PubMed  CAS  Google Scholar 

  44. Jozwiak EA, Ulug U, Mesut A, et al. Prenatal karyotypes of fetuses conceived by intracytoplasmic sperm injection. Fertil Steril. 2004;82(3):628–33.

    Article  PubMed  Google Scholar 

  45. Aboulghar H, Aboulghar M, Mansour R, et al. A prospective controlled study of karyotyping for 430 consecutive babies conceived through intracytoplasmic sperm injection. Fertil Steril. 2001;76(2):249–53.

    Article  PubMed  CAS  Google Scholar 

  46. Bonduelle M, Camus M, De Vos A, et al. Seven years of intracytoplasmic sperm injection and follow-up of 1987 subsequent children. Hum Reprod. 1999;14 Suppl 1:243–64.

    Article  PubMed  Google Scholar 

  47. Jacobs PA, Browne C, Gregson N, et al. Estimates of the frequency of chromosome abnormalities detectable in unselected newborns using moderate levels of banding. J Med Genet. 1992;29(2):103–8.

    Article  PubMed  CAS  Google Scholar 

  48. Bonduelle M, Liebaers I, Deketelaere V, et al. Neonatal data on a cohort of 2889 infants born after ICSI (1991–1999) and of 2995 infants born after IVF (1983–1999). Hum Reprod. 2002;17(3):671–94.

    Article  PubMed  Google Scholar 

  49. Bonduelle M, Ponjaert I, Steirteghem AV, et al. Developmental outcome at 2 years of age for children born after ICSI compared with children born after IVF. Hum Reprod. 2003;18(2):342–50.

    Article  PubMed  CAS  Google Scholar 

  50. Leslie GI, Gibson FL, McMahon C, et al. Children conceived using ICSI do not have an increased risk of delayed mental development at 5 years of age. Hum Reprod. 2003;18(10):2067–72.

    Article  PubMed  CAS  Google Scholar 

  51. Sutcliffe AG, Saunders K, McLachlan R, et al. A retrospective case–control study of developmental and other outcomes in a cohort of Australian children conceived by intracytoplasmic sperm injection compared with a similar group in the United Kingdom. Fertil Steril. 2003;79(3):512–6.

    Article  PubMed  Google Scholar 

  52. Bowen JR, Gibson FL, Leslie GI, et al. Medical and developmental outcome at 1 year for children conceived by intracytoplasmic sperm injection. Lancet. 1998;351(9115):1529–34.

    Article  PubMed  CAS  Google Scholar 

  53. Knoester M, Helmerhorst FM, Vandenbroucke JP, et al. Cognitive development of singletons born after intracytoplasmic sperm injection compared with in vitro fertilization and natural conception. Fertil Steril. 2008;90(2):289–96.

    Article  PubMed  Google Scholar 

  54. Woldringh GH, Horvers M, Janssen AJ, et al. Follow-up of children born after ICSI with epididymal spermatozoa. Hum Reprod. 2011;26(7):1759–67.

    Article  PubMed  CAS  Google Scholar 

  55. Sanchez-Albisua I, Lidzba K, Borell-Kost S, et al. Medical, psychological and intellectual development of 5-year-old children born after intracytoplasmic sperm injection. Neuropediatrics. 2011;42(3):104–9.

    Article  PubMed  CAS  Google Scholar 

  56. Middelburg KJ, Heineman MJ, Bos AF, et al. Neuromotor, cognitive, language and behavioural outcome in children born following IVF or ICSI-a systematic review. Hum Reprod Update. 2008;14(3): 219–31.

    Article  PubMed  CAS  Google Scholar 

  57. Hvidtjorn D, Schieve L, Schendel D, et al. Cerebral palsy, autism spectrum disorders, and developmental delay in children born after assisted conception: a systematic review and meta-analysis. Arch Pediatr Adolesc Med. 2009;163(1):72–83.

    Article  PubMed  Google Scholar 

  58. Autism, Developmental Disabilities Monitoring Network Surveillance Year Principal I, Centers for Disease C et al. Prevalence of autism spectrum disorders—Autism and Developmental Disabilities Monitoring Network, 14 sites, United States, 2008. MMWR Surveill Summ. 2008;61(3):1–19.

    Google Scholar 

  59. Nangia AK, Luke B, Abdel Megid W, et al. National study of factors influencing assisted reproductive technology (ART) outcomes with male factor infertility. Fertil Steril. 2010;94(4):S33.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Penn Fertility Care, Department of Obstetrics and Gynecology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Rachel Weinerman M.D., Kurt T. Barnhart M.D., M.S.C.E. & Suleena Kansal Kalra M.D., M.S.C.E.

  2. Women’s Health Clinical Research Center, Department of Obstetrics and Gynecology, University of Pennsylvania, Philadelphia, PA, USA

    Kurt T. Barnhart M.D., M.S.C.E.

Authors
  1. Rachel Weinerman M.D.
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kurt T. Barnhart M.D., M.S.C.E.
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Suleena Kansal Kalra M.D., M.S.C.E.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kurt T. Barnhart M.D., M.S.C.E. .

Editor information

Editors and Affiliations

  1. Weill Cornell Medical Center, Dept. Urology, New York Presbyterian Hospital, East 68th St. 525, New York, 10021, New York, USA

    Peter N. Schlegel

  2. , Department of Reproductive Medicine, University Medical Center Utrecht, PO Box 85500, Utrecht, 3508 GA, Netherlands

    Bart C. Fauser

  3. S. Arapeen Drive 675, Salt Lake, 84108, Utah, USA

    Douglas T. Carrell

  4. and Infertility, Department of Obstetrics and Gynecology, Division of Reproductive Endocrinlogy, Francis St. 75, Boston, 02115, Massachusetts, USA

    Catherine Racowsky

Rights and permissions

Reprints and permissions

Copyright information

© 2013 Springer Science+Business Media New York

About this chapter

Cite this chapter

Weinerman, R., Barnhart, K.T., Kalra, S.K. (2013). The Need for Long-Term Follow-Up of Children Conceived Through ICSI. In: Schlegel, P., Fauser, B., Carrell, D., Racowsky, C. (eds) Biennial Review of Infertility. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7187-5_18

Download citation

  • DOI: https://doi.org/10.1007/978-1-4614-7187-5_18

  • Published:

  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-7186-8

  • Online ISBN: 978-1-4614-7187-5

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation