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Original research article
Cyanotic congenital heart disease following fertility treatments in the United States from 2011 to 2014
  1. Alireza A Shamshirsaz1,
  2. Zhoobin H Bateni1,
  3. Haleh Sangi-haghpeykar1,
  4. Sara E Arian2,
  5. Hadi Erfani1,
  6. Amir A Shamshirsaz1,
  7. Alfred Abuhamad3,
  8. Karin A Fox1,
  9. Susan M Ramin1,
  10. Amirhossein Moaddab1,
  11. Shiraz A Maskatia4,
  12. Bahram Salmanian1,
  13. Keila N Lopez2,
  14. Pardis Hosseinzadeh1,
  15. Amy K Schutt2,
  16. Ahmed A Nassr1,5,
  17. Jimmy Espinoza1,
  18. Gary A Dildy1,
  19. Michael A Belfort1,
  20. Steven L Clark1
  1. 1 Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas, USA
  2. 2 Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology and Infertility, Baylor College of Medicine and Texas Children’s Hospital, Houston, Texas, USA
  3. 3 Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Eastern Virginia Medical School, Norfolk, Virginia, USA
  4. 4 Department of Pediatrics, Section of Pediatric Cardiology, Stanford University School of Medicine, Palo Alto, California, USA
  5. 5 Women’s Health Hospital, Assiut University Hospitals, Assiut, Egypt
  1. Correspondence to Dr Alireza A Shamshirsaz, Division of Maternal Fetal Medicine, Baylor College of Medicine, Texas Children’s Fetal Center, Texas Children’s Hospital Pavilion for Women, Suite F1020, Houston, Texas; alirezashamshirsaz{at}


Objective To examine the risk for cyanotic congenital heart diseases (CCHDs) among live births in the USA, resulting from various forms of infertility treatments.

Methods This study is a cross-sectional analysis of live births in the USA from 2011 to 2014. Infertility treatments are categorised into two of the following groups on birth certificates: assisted reproductive technology (ART) fertility treatment (surgical egg removal; eg, in vitro fertilisation and gamete intrafallopian transfer) and non-ART fertility treatment (eg, medical treatment and intrauterine insemination). We compared the risk for CCHD in ART and non-ART fertility treatment groups with those infants whose mothers received no documented fertility treatment and were naturally conceived (NC).

Results Among 14 242 267 live births from 2011 to 2014, a total of 101 494 live births were in the ART and 81 242 resulted from non-ART fertility treatments. CCHD prevalence in ART, non-ART and NC groups were 393/100 892 (0.39%), 210/80 884 (0.26%) and 10 749/14 020 749 (0.08%), respectively. As compared with naturally conceiving infants, risk for CCHD was significantly higher among infants born in ART (adjusted relative risk (aRR) 2.4, 95% CI 2.1 to 2.7) and non-ART fertility treatment groups (aRR 1.9, 95% CI 1.6 to 2.2). Absolute risk increase in CCHD due to ART and non-ART treatments were 0.03% and 0.02%, respectively. A similar pattern was observed when the analysis was restricted to twins, newborns with birth weights under 1500 g and gestational age of less than 32 weeks.

Conclusions Our findings suggest an increased risk for CCHD in infants conceived after all types of infertility treatment.

  • congenital heart disease
  • epidemiology
  • echocardiography

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  • Contributors AlAS contributed in study design, execution, manuscript drafting, reviewing and critical discussion. ZHB, SEA, HE, AmAS, AM, AAN, BS and PH contributed in manuscript drafting. HS contributed in data analysis and interpretation. AA, KAF, SMR, SAM, KNL, AKS, JE and GAD supervised and reviewed the article. MAB and SLC advised throughout the study. All authors read and approved the final manuscript.

  • Funding This study was funded by Baylor College of Medicine internal funding.

  • Competing interests None declared.

  • Ethics approval The Institutional Review Board at Baylor College of Medicine (Houston, Texas, USA) determined that this epidemiological study using the Vital Statistics database does not constitute human subjects research.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Presented at This study has been presented in part as an oral presentation at the 63rd Annual Scientific Meeting of the Society of Reproductive Investigation (SRI), March 16–21, 2016—Montreal, Canada. This study has also been presented in part as a poster at the 37th Annual Meeting of the Society for Maternal–Fetal Medicine (SMFM2017) (Pregnancy Meeting), Las Vegas, Nevada, USA.