Assisted Reproductive Techniques and Risk of Congenital Heart Diseases in Children: a Systematic Review and Meta-analysis

Abstract

Infertility is a growing phenomenon and leads to an increased use of assisted reproductive techniques (ARTs). In recent years, concerns about the safety of these procedures emerged and ARTs were hypothesized to be a risk factor for developing congenital heart diseases (CHDs) in offspring. Our aim is to investigate the association between ART and CHD, specifying results according to various subtypes of defects. We performed a systematic review and random-effects meta-analysis following the PRISMA guidelines. MEDLINE and Google Scholar were searched from January 2011 to May 2022. Data about incidence of CHD in ART were tabulated and extracted from all the studies included. Twenty-four studies were included. Pooled incidence of CHDs after IVF pregnancies was 3% (95% CI 0.3–0.4; I2 = 99%), decreasing to 1% (95% CI 0.00–0.01; I2 = 93%) for major CHDs only. An increased risk of CHDs, especially minor (i.e., not requiring surgical correction), seems to occur in ART compared with non-ART pregnancies [RR 1.71 (95% CI 1.25–2.34; I2 = 99%)]. For major CHDs, not enough evidence is available to assess the real risk. Moreover, some confounding factors (i.e., maternal age and male infertility) seem to play a critical role to determine an increased risk of CHDs. Conflicting results emerged among the studies, setting the need for further research to validate the actual evidence and state the real risk of CHD following ART pregnancies.

Association between lipid profile in early pregnancy and the risk of congenital heart disease in offspring: a prospective cohort study

“…Up to now, the causes of CHD remain mainly unclear, but increasing the environmental factors apart from genetic background 29 . In our study, during the variable selection process, we found that early-pregnancy BMI 30 , gravidity, assisted reproduction 31 , medication history 32 , passive smoking 33 , exposure to air environmental pollution 34 were associated with CHD risk in offspring, which were also proved to play important roles in CHD development in prior study. Thus, we adjusted those factors to explore the independent impact of lipid profile on offspring CHD in early pregnancy.…”

Attitude towards assisted reproductive technology: acceptance of donors eggs, sperms, and embryos as treatment of human infertility: a systematic review and meta-analysis

“…Eight studies with a sample size of 6,108 were included in the final analysis, and the sample sizes of the individual studies ranged from 86 to 2007 [ 19 , 22 ]. The range of positive attitudes toward embryo acceptance was reported from 10% in Japan [ 13 ] to 94% in Spain [ 38 ].…”

“…A study analyzing 24 studies found a 3% pooled incidence of congenital heart disease in ART pregnancies, with a 1% decrease for major CHDs. ART pregnancies have an increased risk of minor CHDs, but insufficient evidence for major CHDs [ 22 ].…”

DI George Syndrome in Newborns Conceived From Assisted Reproductive Techniques: Is Preimplantation Screening Necessary? A Discussion of Two Cases

“…ART is a risk factor for some CHD, in addition to individual risk factors of the pregnant woman. Many women accessing ART have factors such as age and race that proportionally increase the risk of CHD (20,21). Preimplantation diagnosis for congenital anomalies, including CHD and DGS, is conducted individually, taking into account pathological history with Mendelian inheritance patterns, advanced maternal age, family history of genetic syndromes, among others.…”