Archives of Gynecology and Obstetrics

, Volume 297, Issue 6, pp 1397–1403 | Cite as

The effect of assisted reproductive technology on the incidence of birth defects among livebirths

  • Gil Shechter-Maor
  • Nicholas Czuzoj-Shulman
  • Andrea R. Spence
  • Haim Arie Abenhaim
Maternal-Fetal Medicine



Our study objective is to examine the association between births conceived with assisted reproductive technology (ART) and birth defects using a large database from the United States.


Using the Centers for Disease Control and Prevention’s Period-linked birth–infant death data files and fetal death database for 2011–2013, we conducted a retrospective cohort study comprised of live births that occurred in the USA during that time. Multivariate logistic regression was used to estimate the association between ART and birth defects, both overall and by specific defects.


There were 11,862,780 live births between 2011 and 2013. Of these births, 11,791,730 were spontaneous pregnancies and 71,050 were conceived by ART, with an increasing trend in incidence of ART during the study period and an overall increasing trend of birth defects. Overall, infants conceived by ART had a greater risk of having birth defects than did infants conceived spontaneously (77/10,000 vs 25/10,000, respectively, OR 2.14, 95% CI 1.94–2.35). The malformations most commonly associated with ART were cyanotic heart defects (OR 2.74, 95% CI 2.42–3.09), cleft lip and/or palate (OR 1.47, 95% CI 1.14–1.89), and hypospadias (OR 1.77, 95% CI 1.42–2.19). There were no differences in risk of omphalocele or neural tube defects between the two groups.


There is an overall and type-specific increased risk of birth defects in the ART population. Appropriate counseling and specialized ultrasound evaluations should be considered in pregnancies conceived by ART.


Assisted reproductive technology Birth defects Morbidity Pregnancy 


Author contributions

GSM: contributed to study design; interpretation of data; drafting of manuscript. NC-S: data management; data analysis; revision of manuscript. AS: contributed to study design; interpretation of data; critical revision of manuscript for important intellectual content. HAA: conception and design; acquisition of data; supervision; interpretation of data; critical revision of manuscript for important intellectual content.


No funding was received for this study.

Compliance with ethical standards

Conflict of interest

The authors report no conflict of interest. We had full control of all primary data and we agree to allow the Journal to review these data, if requested.

Ethical approval

This study involved humans. These data files are available to the public; therefore, the institutional review board deemed this study to be exempt from ethics approval in accordance with the Tri-Council Policy statement (2010).

Informed consent

This study used exclusively publicly available data; hence, we did not personally obtain informed consent from study subjects. This would be the responsibility of the Agency for Healthcare Research and Quality (AHRQ), who sponsors the National Inpatient Sample.


  1. 1.
    Sunderam S et al (2017) Assisted reproductive technology surveillance—United States, 2014. MMWR Surveill Summ 66(6):1–24CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Bonduelle M et al (2002) Neonatal data on a cohort of 2889 infants born after ICSI (1991–1999) and of 2995 infants born after IVF (1983–1999). Hum Reprod 17(3):671–694CrossRefPubMedGoogle Scholar
  3. 3.
    Donnez J, Dolmans MM (2015) Ovarian tissue freezing: current status. Curr Opin Obstet Gynecol 27(3):222–230CrossRefPubMedGoogle Scholar
  4. 4.
    Hosseini SM, Nasr-Esfahani MH (2016) What does the cryopreserved oocyte look like? A fresh look at the characteristic oocyte features following cryopreservation. Reprod Biomed Online 32(4):377–387CrossRefPubMedGoogle Scholar
  5. 5.
    Reefhuis J et al (2009) Assisted reproductive technology and major structural birth defects in the United States. Hum Reprod 24(2):360–366CrossRefPubMedGoogle Scholar
  6. 6.
    Pinborg A et al (2010) Infant outcome of 957 singletons born after frozen embryo replacement: the Danish National Cohort Study 1995–2006. Fertil Steril 94(4):1320–1327CrossRefPubMedGoogle Scholar
  7. 7.
    Davies MJ et al (2012) Reproductive technologies and the risk of birth defects. N Engl J Med 366(19):1803–1813CrossRefPubMedGoogle Scholar
  8. 8.
    Hansen M et al (2012) Assisted reproductive technology and major birth defects in Western Australia. Obstet Gynecol 120(4):852–863CrossRefPubMedGoogle Scholar
  9. 9.
    Seggers J et al (2015) Congenital anomalies in offspring of subfertile couples: a registry-based study in the northern Netherlands. Fertil Steril 103(4):1001.e3–1010.e3CrossRefGoogle Scholar
  10. 10.
    Adler-Levy Y, Lunenfeld E, Levy A (2007) Obstetric outcome of twin pregnancies conceived by in vitro fertilization and ovulation induction compared with those conceived spontaneously. Eur J Obstet Gynecol Reprod Biol 133(2):173–178CrossRefPubMedGoogle Scholar
  11. 11.
    Apantaku O, Chandrasekaran I, Bentick B (2008) Obstetric outcome of singleton pregnancies achieved with in vitro fertilisation and intracytoplasmic sperm injection: experience from a district general hospital. J Obstet Gynaecol 28(4):398–402CrossRefPubMedGoogle Scholar
  12. 12.
    Bowen JR et al (1998) Medical and developmental outcome at 1 year for children conceived by intracytoplasmic sperm injection. Lancet 351(9115):1529–1534CrossRefPubMedGoogle Scholar
  13. 13.
    Smithers PR et al (2003) High frequency of cesarean section, antepartum hemorrhage, placenta previa, and preterm delivery in in vitro fertilization twin pregnancies. Fertil Steril 80(3):666–668CrossRefPubMedGoogle Scholar
  14. 14.
    Shevell T et al (2005) Assisted reproductive technology and pregnancy outcome. Obstet Gynecol 106(5 Pt 1):1039–1045CrossRefPubMedGoogle Scholar
  15. 15.
    Hansen M et al (2013) Assisted reproductive technology and birth defects: a systematic review and meta-analysis. Hum Reprod Update 19(4):330–353CrossRefPubMedGoogle Scholar
  16. 16.
    Wen J et al (2012) Birth defects in children conceived by in vitro fertilization and intracytoplasmic sperm injection: a meta-analysis. Fertil Steril 97(6):1331–1337CrossRefPubMedGoogle Scholar
  17. 17.
    Qin J et al (2015) Assisted reproductive technology and risk of congenital malformations: a meta-analysis based on cohort studies. Arch Gynecol Obstet 292(4):777–798CrossRefPubMedGoogle Scholar
  18. 18.
    National Centre for Health Statistics. National vital statistics system. linked birth and infant death data. Accessed 15 March
  19. 19.
    Kallen B et al (2010) Congenital malformations in infants born after in vitro fertilization in Sweden. Birth Defects Res A Clin Mol Teratol 88(3):137–143PubMedGoogle Scholar
  20. 20.
    Silver RI et al (1999) In vitro fertilization is associated with an increased risk of hypospadias. J Urol 161(6):1954–1957CrossRefPubMedGoogle Scholar
  21. 21.
    Wennerholm UB et al (2000) Incidence of congenital malformations in children born after ICSI. Hum Reprod 15(4):944–948CrossRefPubMedGoogle Scholar
  22. 22.
    Ericson A, Kallen B (2001) Congenital malformations in infants born after IVF: a population-based study. Hum Reprod 16(3):504–509CrossRefPubMedGoogle Scholar
  23. 23.
    Simpson JL (2014) Birth defects and assisted reproductive technologies. Semin Fetal Neonatal Med 19(3):177–182CrossRefPubMedGoogle Scholar
  24. 24.
    Parker SE et al (2010) Updated National Birth Prevalence estimates for selected birth defects in the United States, 2004–2006. Birth Defects Res A Clin Mol Teratol 88(12):1008–1016CrossRefPubMedGoogle Scholar
  25. 25.
    Adzick NS (2013) Fetal surgery for spina bifida: past, present, future. Semin Pediatr Surg 22(1):10–17CrossRefPubMedGoogle Scholar
  26. 26.
    Adzick NS, Walsh DS (2003) Myelomeningocele: prenatal diagnosis, pathophysiology and management. Semin Pediatr Surg 12(3):168–174CrossRefPubMedGoogle Scholar
  27. 27.
    Jin L et al (2017) Prevalence of neural tube defects and the impact of prenatal diagnosis in three districts of Beijing, China. Paediatr Perinat Epidemiol 31(4):293–300CrossRefPubMedGoogle Scholar
  28. 28.
    Matthews TJ, MacDorman MF, Thoma ME (2015) Infant mortality statistics from the 2013 period linked birth/infant death data set. Natl Vital Stat Rep 64(9):1–30Google Scholar
  29. 29.
    Broussard CS et al (2012) Racial/ethnic differences in infant mortality attributable to birth defects by gestational age. Pediatrics 130(3):e518–e527CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Zhu JL et al (2006) Infertility, infertility treatment, and congenital malformations: danish national birth cohort. BMJ 333(7570):679CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Manipalviratn S, DeCherney A, Segars J (2009) Imprinting disorders and assisted reproductive technology. Fertil Steril 91(2):305–315CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Uyar A, Seli E (2014) The impact of assisted reproductive technologies on genomic imprinting and imprinting disorders. Curr Opin Obstet Gynecol 26(3):210–221CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    ESHRE Capri Workshop Group (2014) Birth defects and congenital health risks in children conceived through assisted reproduction technology (ART): a meeting report. J Assist Reprod Genet 31(8):947–958Google Scholar
  34. 34.
    Hutt KJ et al (2008) The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin disrupts morphogenesis of the rat pre-implantation embryo. BMC Dev Biol 8:1CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Hutt KJ et al (2010) The environmental toxicant 2,3,7,8-tetrachlorodibenzo-p-dioxin disturbs the establishment and maintenance of cell polarity in preimplantation rat embryos. Biol Reprod 82(5):914–920CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Feng C et al (2008) Assisted reproductive technology may increase clinical mutation detection in male offspring. Fertil Steril 90(1):92–96CrossRefPubMedGoogle Scholar
  37. 37.
    Fortunato A, Tosti E (2011) The impact of in vitro fertilization on health of the children: an update. Eur J Obstet Gynecol Reprod Biol 154(2):125–129CrossRefPubMedGoogle Scholar
  38. 38.
    Maheshwari A et al (2012) Obstetric and perinatal outcomes in singleton pregnancies resulting from the transfer of frozen thawed versus fresh embryos generated through in vitro fertilization treatment: a systematic review and meta-analysis. Fertil Steril 98(2):368–377CrossRefPubMedGoogle Scholar
  39. 39.
    Jaques AM et al (2010) Adverse obstetric and perinatal outcomes in subfertile women conceiving without assisted reproductive technologies. Fertil Steril 94(7):2674–2679CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Gil Shechter-Maor
    • 1
  • Nicholas Czuzoj-Shulman
    • 2
  • Andrea R. Spence
    • 2
  • Haim Arie Abenhaim
    • 1
    • 2
  1. 1.Department of Obstetrics and Gynecology, Jewish General HospitalMcGill UniversityMontrealCanada
  2. 2.Centre for Clinical Epidemiology and Community Studies, Jewish General HospitalMontrealCanada

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