In order to evaluate the safety of the intracytoplasmic sperm injection (ICSI) procedure, a prospective follow-up study of 423 children born after ICSI was carried out. The aim of this study was to compile data on karyotypes, congenital malformations, growth parameters and developmental milestones. Before starting the infertility treatment, couples were asked to participate in a follow-up study including genetic counselling and prenatal diagnosis. The follow-up study of the child was based on a visit to the paediatrician-geneticist at birth or at 2 months of age, at 1 year and at 2 years of age when a physical examination for major and minor malformations and a psychomotoric evaluation were done. Between April 1991 and September 1994, 320 pregnancies obtained after ICSI led to the birth of 423 children (222 singletons, 186 twins and 15 triplets). Prenatal diagnosis determined a total of 293 karyotypes, one of which was abnormal (0.3%), and four were benign familial structural aberrations, all inherited from the paternal side. A total of 14 (3.3%) major malformations were observed, defined as those causing functional impairment or requiring surgical correlation. Neurological or developmental problems at the age of 2 months were found in 14 children, four of whom were multiples. Compared to most registers of children born after assisted reproduction and to registers of malformations in the general population, the figure of 3.3% major malformations is within the expected range. Before drawing any firm conclusion, further careful evaluations of the available data are necessary.

A prospective follow-up study of 877 children born after ICSI was carried out. The aim of this study was to compile data on karyotypes, congenital malformations, growth parameters and developmental milestones so as to evaluate the safety of this new technique. The follow-up study included agreement to genetic counselling and prenatal diagnosis and was based on a physical examination at the Centre for Medical Genetics (Dutch-speaking Brussels Free University, Brussels, Belgium) at 2 months, 1 year and 2 years, when major and minor malformations and a psychomotor evolution were recorded. Between April 1991 and July 1995, 904 pregnancies obtained after intracytoplasmic sperm injection (ICSI) led to the birth of 877 children (465 singletons, 379 twins and 33 triplets). Prenatal diagnosis determined a total of 486 karyotypes, of which six were abnormal (1.2%) and six (1.2%) were familial structural aberrations, all transmitted from the father. This slight increase in de-novo chromosomal aberrations and the higher frequency of transmitted chromosomal aberrations are probably linked directly to the characteristics of the infertile men treated rather than to the ICSI procedure itself. In all, 23 (2.6%) major malformations were observed in the children born, defined as those causing functional impairment or requiring surgical correction. No particular malformation was disproportionately frequent. Compared with most registers of children born after assisted reproduction and with registers of malformation in the general population, the figure of 2.6% was within the expected range. These observations should be further completed by others and by collaborative efforts. In the meantime, patiens should be counselled about the available data before any treatment: the risk of transmitted chromosomal aberrations, the risk of de-novo, mainly sex chromosomal, aberrations and the risk of transmitting fertility problems to the offspring. Patients should also be reassured that there seems to be no higher incidence of congenital malformations in children born after ICSI.

The aim of this prospective follow-up study of children born after intracytoplasmic sperm injection (ICSI) was to compile data on karyotypes, congenital malformations, growth parameters and developmental milestones in order to evaluate the safety of this new technique. The study design included karyotyping of the parents and their agreement to genetic counselling and prenatal diagnosis and it was based on a physical examination of the child at the Centre for Medical Genetics at the ages of 2 months, 1 year and at 2 years, where major and minor malformations and psychomotor evolution are recorded. Here we describe the first 57 children born from 40 ICSI pregnancies with epididymal spermatozoa (group 1), the first 50 children born from 34 ICSI pregnancies with testicular spermatozoa (group 2) and the first 58 children born from 48 pregnancies after replacement of cryopreserved ICSI embryos (group 3). Parental karyotypes were obtained from only 72/246 (29%) parents and were all normal. Prenatal karyotypes were determined for a total of 70 samples (40%): 21 in group 1, 15 in group 2 and 34 in group 3. In this last group 2 abnormal 47,XXY karyotypes (5.8%) and no structural aberrations were found. This increase in de-novo sex-chromosomal aberrations has already been described with regard to the first 877 children born after ICSI carried out at our Centre and is probably linked directly to the characteristics of the infertile men treated rather than to the ICSI procedure itself. Major malformations, defined as those causing functional impairment or requiring surgical correction, were observed in four children: two born after ICSI with epididymal spermatozoa, one after ICSI with testicular spermatozoa and one after ICSI and cryopreservation. No particular malformation was disproportionally frequent. In the follow-up examinations at 2 months (107/161 or 66.5%) and at 1 year (37/161 or 22.9%), no additional anomalies were observed. Lost for follow-up rate at 2 months was 33.5%. These observations on a limited number of children do not suggest a higher incidence of diseases linked to imprinting, nor do they suggest a higher incidence of congenital malformations. These observations are still limited in number and should be further completed by others and by collaborative efforts. In the meanwhile patients should be told about the available data before any treatment: there appears to be some risk of transmitted chromosomal aberrations, of de-novo, mainly sex-chromosomal aberrations and of transmitting fertility problems to the offspring. Patients should also be reassured that until now there seems to be no higher incidence of congenital malformations in children born after ICSI with epididymal or testicular spermatozoa or after replacement of ICSI embryos.

In 163 couples referred for assisted fertilization, pregnancy was established by subzonal insemination (SUZI), intracytoplasmic sperm injection (ICSI) or a combination of both techniques. These couples agreed to participate in a prospective study that included a prenatal diagnosis and clinical follow-up of the children. No cytogenetic aberrations were observed in 43 children tested. In 23 pregnancies occurring after SUZI, 15 women gave birth to 21 children. After replacement of combined SUZI and ICSI embryos, 10 pregnancies resulted in 8 deliveries with 10 children. Transfer of ICSI embryos led to 130 pregnancies ending in 20 deliveries with 24 children, with many others still ongoing successfully. In total, 55 children have been examined: 29 boys and 26 girls. One child from a singleton pregnancy presented multiple congenital malformations; one twin child presented a quadriparesis. In this observational study on a limited number of children, the incidence of major malformations was not different from the incidence in the general population.

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