Follow-up of children born after ICSI.

The comparison of outcome of assisted reproductive technology (ART) children and naturally conceived children may be hampered by the difference in characteristics of the infertile patients such as age and genetic risks. Follow-up studies are further hampered by the type of neonatal surveillance protocol, the number of individuals lost to follow-up, the size of the cohort study, and the lack of standardization, for example to define major anomalies. The limited available data on ICSI fetal karyotypes reveal that, in comparison with a general neonatal population, there is: (i) a slight but significant increase in de-novo sex chromosomal aneuploidy (0.6% instead of 0.2%) and structural autosomal abnormalities (0.4% instead of 0.07%); and (ii) an increased number of inherited (mostly from the infertile father) structural aberrations. Available data indicate that in 8319 liveborn ICSI children, the mean percentage who do not originate from singleton pregnancies was 40% (range 32.6-60.8% according to centre). Most multiples are twins, but there are also 4.4% triplets (in one survey 13.2%). This substantial increase in multiple pregnancies must be considered the most important complication of ART. The different percentages of major and minor congenital malformations cannot be compared, but overall the data in large and reliable surveys does not indicate a higher rate of malformations in ICSI children than in naturally conceived children. To date, only three studies have examined the medical and developmental outcome of ICSI children at 1 and 2 years. These do not reveal obvious problems, but in future further comparison of matched cohorts of children and case-control studies are needed before final conclusions can be drawn.