Are Offspring of IVF/ICSI Pregnancies at Higher Risk for Congenital Heart Defects?

BACKGROUND AND PURPOSE:

There have been studies that suggest an increased risk for cardiac defects in IVF/ICSI pregnancies
There are no meta-analyses that specifically look at the incidence of CHD in the IVF/ICSI
Giorgione et al. (Ultrasound in Obstetrics & Gynecology, 2018) examined whether there was a higher risk of congenital heart defects (CHD) in offspring conceived through IVF/ICSI

Systematic review and meta-analysis
Literature search of studies comparing neonatal incidence of CHD in pregnancies conceived after IVF/ICSI and those conceived spontaneously
For the meta-analysis, the authors selected cohort studies to estimate the pooled odds ratio (OR) with 95% CI

Data was pooled from 8 cohort studies for meta-analysis
- 25,856 children were conceived using IVF/ICSI techniques and 287,995 children conceived spontaneously
- Both singleton and multiple gestations were included
1.30% of patients in the IVF/ICSI group and 0.68% in the spontaneous conception group had CHD events
The risk of CHD was significantly increased in the IVF/ICSI group
- Pooled OR, 1.45; 95% CI, 1.20–1.76 (P = 0.0001)
In the subgroup of singleton pregnancies, a significant difference was also evident
- Pooled OR, 1.29; 95% CI, 1.03–1.60; P = 0.02
CHD subtypes
- VSD was more frequent in IVF/ICSI
- TOF (tetralogy of Fallot) and TGA (transposition of great arteries) were more common in pregnancies conceived spontaneously

The risk of CHD in IVF/ICSI pregnancies is significantly increased by approximately 50%
CHD subtypes
- VSD was more frequent in IVF/ICSI
- TOF and TGA were more common in pregnancies conceived spontaneously
These results held in subgroup analyses even after adjusting for confounding factors, including maternal age
The authors cite results of this paper as evidence to support fetal echocardiography in IVF/ICSI pregnancies

There have been reports of an association between assisted reproductive techniques (ART) and imprinting disorders, for example (clinical findings and management for syndromes can be found in ‘Learn More – Primary Sources below)
- Beckwith-Wiedemann syndrome (BWS)
- Russell-Silver syndrome
- Angelman syndrome
Mussa et al. (Pediatrics, 2017) examined the prevalence of Beckwith-Wiedemann syndrome (BWS) in children born through ART to further refine relative risk

BWS patients were identified and matched with general demographic data and corresponding regional ART registry
BWS criteria included at least 2 of the following
- Abdominal wall defect, macroglossia, macrosomia, embryonal tumor, ear malformations, organ enlargement, nevus flammeus, hemihyperplasia, nephron/urological malformations, hypoglycemia, or family history of BWS

Out of a total population of 379,872 live births, 7884 ART live births were studied
Within the total population, there were 38 patients with BWS (7 from ART and 31 naturally)
BWS birth prevalence was significantly higher in the ART group
In the ART group the relative risk was higher in BWS compared to non-ART at 10.7 (887.9 per 1,000,000 vs 83.3 per 1,000,000 risk)