Risk of congenital malformations in live-born singletons conceived after intracytoplasmic sperm injection: a Nordic study from the CoNARTaS group

Abstract:

Objective

To investigate if the risk of major congenital malformations is higher in live- born singletons conceived with ICSI compared with IVF?

Design

Nordic cohort study based on register data from Denmark, Norway and Sweden. Data were included from the year the first child conceived with ICSI was born: Sweden 1992; Denmark 1994 and Norway 1996. Data were included until 2014 for Denmark and 2015 for Norway and Sweden.

Subjects

All live-born singletons conceived with fresh ICSI (n=32 484); fresh IVF (n=47 178); without medical assistance (n=4 804 844); and cryo ICSI (n=7 200) during the study period.

Exposure

Different in-vitro-conception methods; and cryopreservation of embryos. Main Outcome Measures: Risk of major congenital malformations based on ICD-codes (International Classification of Diseases). The European Concerted Action on Congenital Anomalies and Twins (EUROCAT) was used to differentiate between major and minor malformations.

Results

Among singletons conceived with fresh ICSI 6.0 % had a major malformation versus 5.3% of children conceived with fresh IVF; 4.2 % of children conceived without medical assistance; and 4.9% of children conceived with cryo ICSI; adjusted odds ratio (AOR) 1.07; [95% confidence interval (CI) 1.01-1.14] in ICSI versus IVF; and AOR 1.28; [95% CI, 1.23-1.35] in ICSI versus no medical assistance; and AOR 1.11; [95%CI, 0.99-1.26] in ICSI fresh vs cryo ICSI. When malformations were grouped by different organ systems, children conceived with ICSI had a higher risk of respiratory and chromosomal malformations compared with children conceived with IVF, but with very few cases in each group. When categorizing children conceived with ICSI according to treatment indication (male infertility only versus other indications), we found a higher risk of hypospadia, when ICSI was performed due to male infertility only, AOR 1.85; [95%CI 1.03-3.32]. The indications for ICSI changed over time, as male infertility did not remain the primary indication for ICSI throughout the study period.

Conclusion

In this large cohort study, we found the risk of major malformations in live- born singletons to be slightly higher after fresh ICSI compared with fresh IVF. These findings should be considered when choosing ART method in couples without male factor infertility.