ICSI: a technique too far?1

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Abstract
Even now 10 years after its introduction, there is still debate on the possible adverse effects of intracytoplasmic sperm injection (ICSI). ICSI has raised a lot of concerns because of the mechanical perforation of the oocyte, the possible transmission of foreign genetic material, the use of immature or senescent germ cells and the association between genetic disorders and some forms of male infertility. To date, the data available indicate that ICSI is a safe procedure provided this treatment is performed in clinics with the highest standards of expertise and with a continuous follow-up programme for the offspring. It is becoming increasingly apparent that it is not ICSI itself, but the background risks of the ICSI patients that represent the major risk factor with regard to congenital malformations. More sex-chromosome abnormalities have been reported in ICSI offspring. Again, the risk of aneuploidy in ICSI progeny reflects the higher aneuploidy rate in the sperm of ICSI fathers. Whether ICSI will eventually perpetuate male infertility is far from clear, because at present the inheritance pattern of idiopathic male infertility is unknown. All ICSI candidates should nevertheless be thoroughly screened and counselled. As long as follow-up studies have a limited power to detect small increases in malformations and as long as no information is available on long-term and next-generation cohorts, ICSI must be used with caution and only when no alternative evidence-based therapy is available. All ICSI candidates should be rigorously screened and thoroughly informed of the limitations of current screening methods and our limited knowledge of the genetic background to male infertility. They should be told that there might be a slight increase in congenital malformation rate after ICSI, but that this increase is probably the result of their own 'background risk'. Well-informed patients are in the best position to judge whether the concerns outweigh the benefits of ICSI.