Limits to the clinical Application of ICSI.

Abstract

Microinsemination is a revolutionary and promising technique for the treatment of severe male infertility, such as severe oligozoospermia, asthenozoospermia, and the case of unexplained unfertilization in which the conventional IVF is ineffective even if semen parameters are normal. Several different microinsemination techniques, such as zona opening [1][2][3], subzona sperm injection [4, 5], and intracytoplasmic sperm injection (ICSI) [6], have been introduced. ICSI is considered the most effective technique, because ICSI has the highest fertilization rate and can be performed with the smallest number of spermatozoa. In addition, this technique is effective for functional disorders, such as disorders of capacitation, acrosome reaction, and spermegg fusion. ICSI was first reported in 1992 [6], and for the above reasons became a powerful fertilization tool in only three or four years [7, 8].At first, ICSI was indicated for the treatment of severe infertility in which the probability of pregnancy was nonexistent or very law. Its indications were then expanded to include azoospermia, and it has been fairly effective [9][10][11], but in such cases chromosomal and genetic abnormalities may be passed on to children [12][13][14]. In addition, it has been clarified that ICSI is not effective in some cases, such as necrozoospermia [15], in which there are no viable spermatozoa; immotile spermatozoa [16], in which viable spermatozoa cannot always be picked up; cases in which spermatozoa have the disorder of oocyte activation factor; and azoospermia, in which mature spermatozoa cannot be found in the testes. The present paper concerns issues that must be considered in the performance of ICSI, as well as limitations to the effectiveness of ICSI. -ReviewNecrozoospermiaIn necrozoospermia, every spermatozoa on in semen is found to be dead when analyzed by vital staining (eosin stain [17], FertiLight stain (Molecular Probes, Eugene, OR) [18]). Sperm-injected oocytes are less likely to develop when injected with dead spermatozoa than with motile spermatozoa. The rate of fertilization for ICSI ranges from 0 to 11% [15]. Since 1992, 659 patients have been treated for infertility, a total of 1,317 treatment cycles at our hospital, and there had been six treatment cycles for necrozoospermia (3 patients). Among these cases, the rate of fertilization was 33.3% (5/15 oocytes), but there were no pregnancies. Since the fertilization rate was very low, dead (nonviable) spermatozoa may reduce the oocyte activating factor or have fragmented nuclear DNA or have chromosome disintegration [19]. Even when the sperm factor is injured and nuclear DNA is damaged, fertilization is possible with ICSI, but we cannot get well developed embryos from these spermatozoa, so that there is no hope of pregnancy. In humans, the development of fertilized oocytes to 4-cell stage embryos is controlled by the maternal genes rather than the paternal ones [20], so that fertilized oocytes can develop to this stage regardless of the state of the paternal DNA. The res...