Congenital heart defects in IVF/ICSI pregnancy: Systematic review and meta-analysis

V. Giorgione, F. Parazzini, V. Fesslova, S. Cipriani, M. Candiani, A. Inversetti, C. Sigismondi, F. Tiberio, P. Cavoretto

Research output: Contribution to journalComment/debatepeer-review


Despite congenital heart disease (CHD) being the most common type of congenital defect, in the majority of cases, the etiology remains unclear. Previous studies analyzing the risk of CHD after in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) show a slightly elevated risk when compared with spontaneously conceived infants. Current literature also shows an elevated risk for all congenital defects in IVF/ICSI conceptions compared with spontaneous conceptions. There is currently no expert consensus on whether fetal echocardiogram is indicated for IVF/ICSI pregnancies. Analysis of potential risk factors for CHD remains an important step in improving screening protocols and clinical outcomes in affected cases. This systematic review and meta-analysis aimed to determine the risk of CHD in pregnancies conceived through IVF or ICSI compared with those conceived spontaneously. A systematic search was conducted using PubMed/MEDLINE, EMBASE, and Scopus databases from inception through September 2017. Cohort and case-control studies presenting data on CHD among infants conceived spontaneously, through IVF, or through ICSI were included. Studies included in the meta-analysis were cohort studies including ICSI and IVF pregnancies; studies excluding other assistive reproductive techniques; studies including intrauterine fetal death, stillbirths, and termination of pregnancies; and studies excluding all chromosomal abnormalities. Diagnosis of birth defects was performed after birth in all studies. The meta-analysis was conducted to estimate the pooled odds ratio (OR) with 95% confidence interval (CI) using the random-effects model and generic inverse variance method. Quality assessment of studies was performed using the Newcastle-Ottawa Scale. A total of 41 studies were included, 35 of which were cohort studies whereas 6 were case-control studies. Of the 41 studies reviewed, 8 were included in the meta-analysis. The analysis included 25,856 fetuses conceived from IVF/ICSI techniques and 287,995 fetuses conceived spontaneously, both in singleton and multiple pregnancies. The total instances of CHD were 337/25,856 (1.30%) and 1952/287,995 (0.68%) in the IVF/ICSI and spontaneous conception populations, respectively. A significantly increased risk of CHD was observed in the IVF/ICSI compared with the spontaneous cohort population (OR, 1.45; 95%CI, 1.20-1.76; P = 0.0001; I2 = 44%; P = 0.08).Among only singleton pregnancies, CHD wasmore prevalent among the IVF/ICSI compared with the spontaneous conception population with less heterogeneity between the 2 groups (OR, 1.55; 95% CI, 1.21-1.99; P = 0.0005; I2 = 36%; P = 0.18). The risk of CHD in IVF/ICSI pregnancies was found to be approximately 50% higher than that in pregnancies conceived spontaneously (1.30%vs 0.68%, respectively). This significant difference in relative risk proved stable in most subgroup analyses adjusting for confounding factors. Based on these results, fetal echocardiography is indicated in all IVF/ICSI pregnancies in accordance with AHA guidelines.

Original languageEnglish
Pages (from-to)331-332
Number of pages2
JournalObstetrical and Gynecological Survey
Issue number6
Publication statusPublished - Jun 1 2018

ASJC Scopus subject areas

  • Obstetrics and Gynaecology


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