The risk for four specific congenital heart defects associated with assisted reproductive techniques: a population-based evaluation

Tararbit K; Lelong N; Thieulin AC; Houyel L; Bonnet D; Goffinet F; Khoshnood B

doi:10.1093/humrep/des400

Assisted Reproduction · Safety and Risks

The risk for four specific congenital heart defects associated with assisted reproductive techniques: a population-based evaluation

Tararbit K, Lelong N, Thieulin AC, Houyel L, Bonnet D, Goffinet F, Khoshnood B

Published February 2013 Human Reproduction, 28(2), 367-374

DOI 10.1093/humrep/des400 PMC PMC3874677

RRM Academy Synopsis

Pregnancies conceived with ART had higher odds of tetralogy of Fallot

Pregnancies conceived with assisted reproduction (ART) had higher odds of tetralogy of Fallot. A Paris case-control study compared 1583 cases of four heart defects with 4104 controls who had other malformations. About 7 out of 100 tetralogy cases followed ART, against about 4 out of 100 controls. Three other defects showed no statistically significant link.

Key Findings

Exposure to ART was 6.6% among 395 tetralogy of Fallot cases and 3.5% among 4104 controls with other malformations (P = 0.002).
With all ART methods combined, the adjusted odds ratio for tetralogy of Fallot was 2.4 (95% CI 1.5-3.7), adjusting for the mother's characteristics, the father's age and the birth year.
Adjusted odds ratios for tetralogy of Fallot were 3.0 (95% CI 1.0-8.9) after intracytoplasmic sperm injection (ICSI), 2.0 (1.0-4.2) after IVF and 2.5 (1.3-4.8) after ovulation induction only.
No statistically significant associations were found for hypoplastic left heart syndrome (adjusted OR 0.8, 95% CI 0.4-1.8), transposition of the great arteries (0.7, 0.4-1.4) or coarctation (1.1, 0.6-2.0).
Excluding cases with chromosomal anomalies gave essentially the same estimates; for tetralogy of Fallot the adjusted odds ratio with all methods combined was 2.6 (95% CI 1.6-4.2).

Interpretation

This case-control study compared ART exposure in pregnancies with each heart defect against pregnancies with other malformations that the literature had not linked to ART. The data come from the Greater Paris area, 1987 to 2009. The design shows association only. The authors state that the study cannot separate how much of the tetralogy association reflects causal effects of ART and how much reflects the underlying infertility of the couples. Power was limited for odds ratios below 2, so the null results for the other three defects may reflect small numbers. The authors imputed paternal age, which was missing for 20.6% of the study population.

RRM Context

Restorative reproductive medicine starts with the cause of infertility in both partners. The authors name the couple's own infertility as one possible explanation for the heart defect link. The procedures are the other. IVF and ICSI go around the underlying condition and leave it in place.

Our editorial summary of this paper, not the article's abstract.

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)?

Summary Answer

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

What Is Known Already

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, Materials 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.

Topics

Assisted Reproduction Safety and Risks Birth Defects

Assisted Reproduction › Safety and Risks › Birth Defects

Francois Goffinet, Babak Khoshnood

F Goffinet, B Khoshnood

DOI 10.1093/humrep/des400 10.1093/humrep/des400 Tararbit et al. 2013, Tararbit 2013

The risk for four specific congenital heart defects associated with assisted reproductive techniques: a population-based evaluation

Pregnancies conceived with ART had higher odds of tetralogy of Fallot

Key Findings

Interpretation

RRM Context

Abstract

Topics

By this author

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