Major malformation risk after assisted reproductive treatment higher with ICSI vs IVF

Children conceived via fresh intracytoplasmic sperm injection (ICSI) are at higher risk of major malformations compared with those conceived via fresh in vitro fertilization (IVF), according to a study.

Researchers used register data from Denmark, Norway, and Sweden, identifying all live-born singletons conceived via different in-vitro-conception methods and cryopreservation of embryos. In total, 32,484 singletons were conceived with fresh ICSI, 47,178 with fresh IVF, 7,200 with cryo ICSI, and 4,804,844 without medical assistance.

The main outcome was the risk of major congenital malformations, which were distinguished from minor malformations using the European Concerted Action on Congenital Anomalies and Twins (EUROCAT). Major malformations occurred in 6.0 percent of children conceived with fresh ICSI, 5.3 percent of those conceived with fresh IVF, 4.9 percent of those conceived with cryo ICSI, and 4.2 percent of those conceived without medical assistance.

ICSI was associated with a higher risk of major malformations compared with IVF (adjusted odds ratio [AOR], 1.07, 95 percent confidence interval [CI], 1.01–1.14), no medical assistance (AOR, 1.28, 95 percent CI, 1.23–1.35), and cryo ICSI (AOR, 1.11, 95 percent CI, 0.99–1.26).

When malformations were categorized according to different organ systems, children conceived with ICSI were at higher risk of respiratory and chromosomal malformations compared with those conceived with IVF, but with very few cases in each group.

When children conceived with ICSI were grouped according to treatment indication, a higher risk of hypospadias was seen when ICSI was performed due to male infertility only (vs other indications: AOR, 1.85, 95 percent CI, 1.03–3.32). The indications for ICSI changed over time, with male infertility losing its status as the primary indication for ICSI throughout the study period.

The present data should be considered when choosing a specific assisted reproductive treatment method in couples without male factor infertility.