The Risk of Major Birth Defects After Intracytoplasmic Sperm Injection and in Vitro Fertilization

Abstract

Although most studies have failed to demonstrate an elevated risk of major birth defects in children conceived by intracytoplasmic sperm injection (ICSI) or standard in vitro fertilization (IVF), most past work is methodologically problematic and definitions of major defects may differ from those applied to naturally conceived infants. This study examined the prevalence of major birth defects diagnosed within 12 months after birth in infants conceived either naturally or using ICSI or IVF. All births took place in Western Australia in the years 1993 to 1997. Data from a reproductive technology registry identified all pregnancies of at least 20 weeks' gestation. The study population included 301 infants conceived by ICSI; 837 conceived by standard IVF; and 4000 conceived naturally. Infants conceived with assisted methods were likelier than those conceived naturally to be delivered by cesarean section, to be born before term, and to have low birth weight. Major birth defects were identified by age 1 year in 8.6% of infants conceived with ICSI, 9.0% of the IVF group, and 4.2% of naturally conceived infants. In all, infants conceived using assisted reproductive technology were more than twice as likely as those conceived naturally to have a major defect. The difference remained significant when only singleton infants, or only singletons born at term, were analyzed, and after adjusting for maternal age and parity and infant gender. Approximately two thirds of major defects were diagnosed in the first week of life, and more than 90% by age 6 months. Excluding defects that may have been diagnosed early because of close surveillance, the odds ratio for a major defect was 1.8 in the ICSI group and 2.2 in the IVF group. Major defects remained about twice as frequent in these groups as with natural conception after excluding infants known to have inherited conditions and those with metabolic disorders. Musculoskeletal and chromosomal defects were significantly more prevalent with assisted reproductive technology. The IVF group (but not ICSI infants) had significantly more cardiovascular, urogenital, and other defects. Multiple major defects were significantly more frequent in the IVF and ICSI groups. Minor birth defects were diagnosed by age 12 months in less than 1% of all groups. These findings support the possibility of an excessive risk of major birth defects in infants born with the benefit of assisted reproductive technology. Nevertheless caution is in order when establishing associations with particular birth defects.