Intracytoplasmic sperm injection (ICSI) can be applied to treat male infertility patients of oligospermia, asthenospermia, teratospermia, azoospermia and failure of the common in-vitro fertilization (IVF), which may overcome the sperm deficiency and even obtain sperms directly from percutaneous epididymal sperm aspiration (PESA) and testicular sperm extraction (TESE). As for direct injection of a single sperm into an egg, the ICSI disobeys the biological laws of natural insemination, thus leading to high genetic and epigenetic risk for patients owing to genetic and epigenetic defect of sperm. By reviewing the genetic and epigenetic defects of ICSI sperm, as well as related diseases, this article aims at understanding of the risks resulting from the genetic and epigenetic defects of ICSI sperm at a molecular mechanism level. The results show that the quality control of ICSI sperm via detecting its epigenetic factors, such as methylated DNA and acetylated histone, is essential for reducing the genetic and epigenetic risk from ICSI.
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