The Risk for Four Specific Congenital Heart Defects Associated with Assisted Reproductive Techniques: a Population-based Evaluation

Overview

Journal Hum Reprod

Publisher Oxford University Press

Specialty Reproductive Medicine

Date 2012 Nov 27

PMID 23178272

Citations 32

Authors

Karim Tararbit

Nathalie Lelong

Anne-Claire Thieulin

Lucile Houyel

Damien Bonnet

Francois Goffinet

Babak Khoshnood

Affiliations

Soon will be listed here.

Abstract

Study Question: Are the risks of hypoplastic left heart syndrome, transposition of great arteries, tetralogy of Fallot (TOF) and coarctation of the aorta increased in infants conceived by different assisted reproductive techniques (ARTs)?

Study Answer: ARTs, and particularly intracytoplasmic sperm injection (ICSI), are specifically associated with a higher risk of TOF.

What Is Already Known: ARTs are associated with an increase in the overall risk of birth defects. The risk for congenital heart defects (CHDs) associated with ARTs has been evaluated as a whole but there is limited information on the risks for specific CHDs. STUDY DESIGN, MATERIAL AND METHODS: We conducted a case-control study using population-based data from the Paris registry of congenital malformations for the period 1987-2009 and a cohort study of CHD (EPICARD) on 1583 cases of CHDs and 4104 malformed controls with no known associations with ARTs. ARTs included ovulation induction only, IVF and ICSI.

Results: Exposure to ARTs was significantly higher for TOF than controls (6.6 versus 3.5%, P = 0.002); this was not the case for the other three CHDs. ARTs (all methods combined) were associated with a 2.4-fold higher odds of TOF after adjustment for maternal characteristics, paternal age and year of birth [adjusted odds ratios (OR): 2.4, 95% confidence interval (CI): 1.5-3.7] with the highest risk associated with ICSI (adjusted OR: 3.0, 95% CI: 1.0-8.9). No statistically significant associations were found for the other CHDs.

Limitations: Our study cannot disentangle to what extent the observed associations between the risk of TOF and ARTs are due to causal effects of ARTs and/or the underlying infertility problems of couples who conceive following ART.

Implications: The developmental basis of the specific association between the risk of TOF and ARTs need to be further investigated.

Citing Articles

Congenital heart defects in children born after assisted reproductive technology: a CoNARTaS study.

Sargisian N, Petzold M, Furenas E, Gissler M, Spangmose A, Malchau Lauesgaard S Eur Heart J. 2024; .

PMID: 39326528 PMC: 11638113. DOI: 10.1093/eurheartj/ehae572.

Assisted reproductive technology and the risk of fetal congenital heart disease: insights from a tertiary-care referral center.

Piemonti L, Vettor L, Balducci A, Farina A, Contro E Arch Gynecol Obstet. 2024; 310(4):2073-2080.

PMID: 39085434 PMC: 11393033. DOI: 10.1007/s00404-024-07669-x.

Evolution of intracytoplasmic sperm injection: From initial challenges to wider applications.

Asada Y Reprod Med Biol. 2024; 23(1):e12582.

PMID: 38803410 PMC: 11129627. DOI: 10.1002/rmb2.12582.

Pregnancy by Oocyte Donation: Reviewing Fetal-Maternal Risks and Complications.

Silvestris E, Petracca E, Mongelli M, Arezzo F, Loizzi V, Gaetani M Int J Mol Sci. 2023; 24(18).

PMID: 37762248 PMC: 10530596. DOI: 10.3390/ijms241813945.

Culture conditions in the IVF laboratory: state of the ART and possible new directions.

Sciorio R, Rinaudo P J Assist Reprod Genet. 2023; 40(11):2591-2607.

PMID: 37725178 PMC: 10643723. DOI: 10.1007/s10815-023-02934-5.

References

Tararbit K, Houyel L, Bonnet D, De Vigan C, Lelong N, Goffinet F . Risk of congenital heart defects associated with assisted reproductive technologies: a population-based evaluation. Eur Heart J. 2010; 32(4):500-8. DOI: 10.1093/eurheartj/ehq440. View

Manning N, Archer N . A study to determine the incidence of structural congenital heart disease in monochorionic twins. Prenat Diagn. 2006; 26(11):1062-4. DOI: 10.1002/pd.1556. View

Glinianaia S, Rankin J, Wright C . Congenital anomalies in twins: a register-based study. Hum Reprod. 2008; 23(6):1306-11. DOI: 10.1093/humrep/den104. View

Klemetti R, Gissler M, Sevon T, Koivurova S, Ritvanen A, Hemminki E . Children born after assisted fertilization have an increased rate of major congenital anomalies. Fertil Steril. 2005; 84(5):1300-7. DOI: 10.1016/j.fertnstert.2005.03.085. View

Khoshnood B, Lelong N, Houyel L, Thieulin A, Jouannic J, Magnier S . Prevalence, timing of diagnosis and mortality of newborns with congenital heart defects: a population-based study. Heart. 2012; 98(22):1667-73. DOI: 10.1136/heartjnl-2012-302543. View

Swan S, Shaw G, Schulman J . Reporting and selection bias in case-control studies of congenital malformations. Epidemiology. 1992; 3(4):356-63. DOI: 10.1097/00001648-199207000-00011. View

Olson C, Keppler-Noreuil K, Romitti P, Budelier W, Ryan G, Sparks A . In vitro fertilization is associated with an increase in major birth defects. Fertil Steril. 2005; 84(5):1308-15. DOI: 10.1016/j.fertnstert.2005.03.086. View

Reefhuis J, Honein M, Schieve L, Correa A, Hobbs C, Rasmussen S . Assisted reproductive technology and major structural birth defects in the United States. Hum Reprod. 2008; 24(2):360-6. DOI: 10.1093/humrep/den387. View

Mastroiacovo P, Castilla E, Arpino C, Botting B, Cocchi G, Goujard J . Congenital malformations in twins: an international study. Am J Med Genet. 1999; 83(2):117-24. DOI: 10.1002/(sici)1096-8628(19990312)83:2<117::aid-ajmg7>3.0.co;2-4. View

10.

Lieff S, Olshan A, Werler M, Savitz D, Mitchell A . Selection bias and the use of controls with malformations in case-control studies of birth defects. Epidemiology. 1999; 10(3):238-41. View

11.

Zhu J, Basso O, Obel C, Bille C, Olsen J . Infertility, infertility treatment, and congenital malformations: Danish national birth cohort. BMJ. 2006; 333(7570):679. PMC: 1584372. DOI: 10.1136/bmj.38919.495718.AE. View

12.

Vrijheid M, Dolk H, Stone D, Abramsky L, Alberman E, Scott J . Socioeconomic inequalities in risk of congenital anomaly. Arch Dis Child. 2000; 82(5):349-52. PMC: 1718336. DOI: 10.1136/adc.82.5.349. View

13.

Bahtiyar M, Dulay A, Weeks B, Friedman A, Copel J . Prevalence of congenital heart defects in monochorionic/diamniotic twin gestations: a systematic literature review. J Ultrasound Med. 2007; 26(11):1491-8. DOI: 10.7863/jum.2007.26.11.1491. View

14.

Khoshnood B, Greenlees R, Loane M, Dolk H . Paper 2: EUROCAT public health indicators for congenital anomalies in Europe. Birth Defects Res A Clin Mol Teratol. 2011; 91 Suppl 1:S16-22. PMC: 3320858. DOI: 10.1002/bdra.20776. View

15.

Bajolle F, Zaffran S, Kelly R, Hadchouel J, Bonnet D, Brown N . Rotation of the myocardial wall of the outflow tract is implicated in the normal positioning of the great arteries. Circ Res. 2006; 98(3):421-8. DOI: 10.1161/01.RES.0000202800.85341.6e. View

16.

Houyel L, Khoshnood B, Anderson R, Lelong N, Thieulin A, Goffinet F . Population-based evaluation of a suggested anatomic and clinical classification of congenital heart defects based on the International Paediatric and Congenital Cardiac Code. Orphanet J Rare Dis. 2011; 6:64. PMC: 3198675. DOI: 10.1186/1750-1172-6-64. View

17.

Hook E . Normal or affected controls in case-control studies of congenital malformations and other birth defects: reporting bias issues. Epidemiology. 1993; 4(2):182-4. DOI: 10.1097/00001648-199303000-00017. View

18.

Greenlees R, Neville A, Addor M, Amar E, Arriola L, Bakker M . Paper 6: EUROCAT member registries: organization and activities. Birth Defects Res A Clin Mol Teratol. 2011; 91 Suppl 1:S51-S100. DOI: 10.1002/bdra.20775. View

19.

Hansen M, Kurinczuk J, 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. DOI: 10.1056/NEJMoa010035. View

20.

Wennerholm U, Bergh C, Hamberger L, Lundin K, Nilsson L, Wikland M . Incidence of congenital malformations in children born after ICSI. Hum Reprod. 2000; 15(4):944-8. DOI: 10.1093/humrep/15.4.944. View