Increased frequency of severe major anomalies in children conceived by intracytoplasmic sperm injection

Abstract

The neurodevelopmental outcome of children born after intracytoplasmic sperm injection (ICSI) is controversial. We compared the medical and developmental outcome of 34 singletons born after ICSI (20 males, 14 females; mean ages of 18mo and 40mo [SD 9mo]; range 2y 10mo–4y 8mo) with 39 case control studies (21 males, 18 females; mean ages of 18mo and 40mo [SD 4mo]; range 3y–4y 1mo). Each child was assessed physically and tested in three development domains (fine motor, gross motor, and language). Five children born after ICSI versus two control children (p=0.2) had major congenital anomalies (MaCAs). Four children born after ICSI versus no control children had severe MaCAs (p=0.04). These were defined as having a significant impact on development or causing chronic disease: Angelman syndrome (n=1), lissencephaly (n=1), Hanhart syndrome (n=1), and persistent hyperinsulinemic hypoglycaemia of infancy (n=1). Karyotyping in 23 children born after ICSI revealed no abnormalities. An imprinting defect was found in the child with Angelman syndrome. Results of developmental assessment were in all cases normal at the age of 18 months except for the three children with Angelman and Hanhart syndromes, and lissencephaly. At the second assessment, five more children born after ICSI and four control children showed abnormalities in one or more developmental domains. We conclude that there seems to be a higher frequency of severe major anomalies in children born after ICSI. An increased risk for imprinting defects cannot be excluded. If we exclude children with severe MaCAs, the incidence of an abnormal somatic or neurodevelopmental outcome in the fourth year of life in children born after ICSI is similar to that of spontaneously conceived children.

Has the Prevalence of Congenital Abnormalities after Intracytoplasmic Sperm Injection Increased? The Leuven Data 1994–2000 and a Review of the Literature

“…In another study involving a small number of patients, there was no significant difference in occurrence of major malformations in the ICSI group (5/34, 14.5%) compared with the natural conception group (2/39, 5%), but the incidence of severe major malformations was significantly increased in the ICSI group (11.8 vs. 0%) [48] .…”

Defects in imprinting and genome-wide DNA methylation are not common in the in vitro fertilization population

“…In addition, there is an apparent increase of Angelman syndrome (OMIM no. 105830) cases presenting with the rare methylation defect at SNRPN (15)(16)(17)(18). It has been suggested that IVF-associated cases of Beckwith-Wiedemann and Angelman syndrome may represent the tip of the iceberg (19), potentially reflecting a larger number of epigenetic changes in the IVF population.…”

A congenital cranial dysinnervation disorder: Möbius’ syndrome

“…However, a mutation in the KIF21A gene, which was identified in congenital fibrosis of extraocular muscles type 1, has been reported in cases of MS accompanied by additional eye movement disorder (3). In the medical literature, a case of MS and a patient with Hanhart syndrome involving Moebius sequence in relation with intracytoplasmic sperm injection (ICSI), which is one of the assisted reproductive techniques, have been reported (4,5). Our patient was born by way of in vitro fertilization and we could no other case reports in relation with in vitro fertilization in the medical literature.…”

“…Studies have shown that some major and/or minor anomalies occur more commonly in babies of mothers who became pregnant by way of assisted reproductive techniques compared with groups that were pregnant through intercourse (2). A case of MS and a case of Hanhart syndrome (MS-associated syndrome) in relation with the intracytoplasmic sperm injection method have been reported previously (4,5). Although studies conducted in recent years have reported that there was no increase in the general risk of congenital anomaly in relation with in vitro fertilization, an increased risk has been reported in under certain conditions (10).…”