This RCT provides no arguments in favour of PGD-AS for improving clinical outcome per initiated cycle in patients with AMA when there are no restrictions in the number of embryos to be transferred.

A significantly higher rate of de-novo chromosomal anomalies (1.6 versus 0.5% in amniocentesis for a mean maternal age of 33.5 years; P < 0.007) was observed in ICSI offspring, relating mainly to a higher number of sex chromosomal anomalies and partly to a higher number of autosomal structural anomalies. This finding was related to sperm concentration and motility. The significantly higher rate of observed inherited anomalies (1.4 versus 0.3-0.4% in prenatal tests in the general population; P < 0.001) was related to a higher rate of constitutional chromosomal anomalies, mainly in the fathers. The hypothesis of a higher risk of post-zygotic events as a consequence of the ICSI procedure leading to a higher proportion of chromosomal mosaicism was not confirmed in this study. Couples should be informed of the risks of an abnormal result related to sperm quality, and of the risk linked to a prenatal procedure as well as about the relatively benign character of some chromosomal anomalies such as de-novo structural anomalies or sex chromosomal anomalies in order to be able to make a choice for prenatal testing, or not.

No abstract

Intracytoplasmic sperm injection (ICSI) with ejaculated, epididymal or testicular spermatozoa was first successful in 1992 and has since become the widely accepted treatment for couples with severe male-factor infertility. The outcome of several thousands of ICSI cycles in terms of fertilization, embryo cleavage and implantation is similar to that for conventional in-vitro fertilization in couples with tubal or idiopathic infertility. To evaluate the important issue of safety of the new technique of ICSI, a prospective follow-up study of 1987 children born after ICSI was carried out. The aim was to compile data on karyotypes, congenital malformations, growth parameters and developmental milestones. Parents' agreement to genetic counselling was obtained as well as prenatal diagnosis, followed by a physical examination of the children at 2 months, 1 year and 2 years. Between April 1991 and August 1997, 1699, 91 and 118 children were born after ICSI with ejaculated, epididymal and testicular spermatozoa respectively; 79 children were born from cryopreserved ICSI embryos. In all, 1082 karyotypes were determined by prenatal diagnosis, 18 of which were abnormal and de novo (1.66%) (nine each of autosomal and sex chromosomal aberrations), and 10 karyotypes (0.92%) were inherited structural aberrations. Of these, nine (eight balanced structural aberrations and one unbalanced trisomy 21) were transmitted from the father. Ten pregnancies were terminated after prenatal karyotyping or DNA testing. Forty-six major malformations (2.3%) were observed at birth. Seven malformations, observed by prenatal ultrasound, were terminated. Twenty-one (1.1 %) stillbirths, including four with major malformations, occurred later than 20 weeks of pregnancy. Mean gestational age at birth was 38.7 weeks for singletons, 36.0 weeks for twins and 32.0 weeks for triplets. No specifically higher incidence of malformations was found in any given subgroup.

The use of ICSI has been a major breakthrough in the treatment of male infertility. Even azoospermic patients with focal spermatogenesis in the testis, may benefit from the ICSI technique in order to father a child. As ICSI use has become more common, centres have introduced infertility treatment for Klinefelter patients. To date, 34 healthy children have been born using ICSI without PGD, and the conception of one 47,XXY fetus has been reported. In view of the possible risk of an increased gonosome number in the spermatozoa of Klinefelter patients, a safer approach--offering these couples ICSI combined with PGD--has been used, and has resulted in the birth of three healthy children. Couples in which the male suffered from Klinefelter's syndrome were first treated in 1995; these patients were offered ICSI + PGD using FISH technology, notably to enumerate the X and Y chromosomes. ICSI + PGD was performed in 32 cycles of 20 couples with spermatozoa originating from a fresh ejaculate (n = 1), testicular biopsy (n = 21) or frozen-thawed testicular biopsy (n = 10). Normal fertilization occurred in 56.0 +/- 22.4% of the successfully injected oocytes. On day 3 of development, 119 embryos from 29 cycles were of sufficient quality to undergo biopsy and subsequent PGD; a positive result was obtained in 113 embryos. Embryos were available for transfer in 26 cycles, with a mean of 1.6 +/- 0.6 embryos per transfer. Eight pregnancies were obtained, and five resulted in a delivery. A total of 113 embryos from couples with Klinefelter's syndrome was compared with 578 embryos from control couples with X-linked disease where PGD was used to determine gender. A significant fall occurred in the rate of normal embryos for couples with Klinefelter's syndrome (54.0%) compared with controls (77.2%). Moreover, a significantly increased risk of abnormalities was observed for sex chromosomes and autosomes; for each autosome separately, this reached significance level for chromosomes 18 and 21 only. Hence, a cautious approach is warranted in advising couples with non-mosaic Klinefelter's syndrome. Moreover, the use of ICSI + PGD or prenatal diagnosis should be carefully considered.