Genetic effects of intracytoplasmic sperm injection

Intracytoplasmic sperm injection (ICSI) must be proved safe as well as efficacious. In this communication we first review available data following ICSI pregnancies concerning frequency of spontaneous abortion, malformations, and chromosomal abnormalities. In ICSI the spontaneous abortion rate is slightly increased, just as it is in in vitro fertilization (IVF) without ICSI. Among 6077 ICSI cycles begun in 1997 in the United States, there were 17.5% pregnancy losses. The same cohort showed a malformation rate of 1.7% in live-born infants. Malformations in live-born infants are not increased: 1.7% in the United States and 2.3% in Brussels. However, the Swedish IVF Registry encompassing 1139 ICSI infants found hypospadias to be increased (relative risk 2.9, 95% C.I. 1.4 to 5.4). Birth weight and prematurity rate in ICSI pregnancies seem similar to that following conventional IVF without ICSI. The category of genetic defects for which concerns have most often been raised is chromosomal abnormalities. A cohort of 1987 pregnancies in Brussels yielded a frequency of de novo autosomal rearrangements of 0.36% and a de novo sex chromosomal abnormalities of 0.83%. Both rates are higher than expected in the general population. Various explanations for these increased cytogenetic autosomal abnormalities are explored in this communication. In addition to arising from the procedure per se, a genetic or cytogenetic abnormality in offspring of an ICSI pregnancy could arise as result of offspring inheriting the mutant gene or chromosomal abnormality conferring paternal infertility: Y deletions (DAZ) in oligospermia males, cystic fibrosis in offspring of males with congenital bilateral absence vas deferens (CBAVD), and sex chromosomal abnormalities in offspring of Klinefelter syndrome (47,XXY) males.