Risk of chromosomal aberration in spermatozoa during intracytoplasmic sperm injection

Abstract

Intracytoplasmic sperm injection (ICSI) has become critical for the treatment of severe male infertility. The principal feature of ICSI is the direct injection of spermatozoon into an oocyte, which facilitates the production of fertilized embryos regardless of semen characteristics, such as sperm concentration and motility. However, the chromosomal integrity of ICSI zygotes is degraded compared to that of zygotes obtained via in vitro fertilization. This chromosomal damage may occur due to the injection of non-capacitated, acrosome-intact spermatozoa, which never enter the oocytes under natural fertilization. Furthermore, it is possible that the in vitro incubation and pre-treatment of spermatozoa during ICSI results in DNA damage. Chromosomal aberrations in embryos induce early pregnancy losses. However, these issues may be overcome by embryo production using gametes with guaranteed chromosomal integrity. Because conventional chromosome analysis requires fixing cells to obtain the chromosome spreads, embryos cannot be produced using the nucleus that has been analyzed. On the other hand, genome cloning using androgenic or gynogenic embryos provides an additional nucleus for chromosome analysis following embryo production. Thus, this review aims to highlight the hazardous nature of chromosomal aberrations in sperm during ICSI and to introduce a method for the prezygotic examination for chromosomal aberrations.

Use of intracytoplasmic sperm injection (ICSI) in normospermic men may result in lower clinical pregnancy and live birth rates

“…In addition to efficacy there are safety concerns. Despite its widespread application, ICSI has not been subjected to ethical review, animal studies or rigorous testing in humans to assess biological impact and overall safety 20 . The procedure bypasses natural selection safeguards, which may affect offspring and future generations [21][22][23] .…”

“…Chromosomal damage may occur due to the injection of non-capacitated, acrosome intact spermatozoa, which with natural fertilization would never enter the oocytes. Furthermore, it is possible that incubation and pre-treatment of spermatozoa during ICSI results in DNA damage 20 . Some studies have demonstrated an increase in genetic abnormalities, birth defects and developmental delay with the use of ICSI [22][23][24][25][26] .…”

Co-existence of Goldenhar and Klinefelter Syndromes in a Patient Born Following ICSI

“…Several studies found that there was an increased incidence of aneuploidies, mainly sex chromosome aberrations, among children conceived by ICSI (2). Subfertile men are considered to have higher rates of aneuploid offsprings, secondary to gametes with higher rates of chromosomal segregation errors (3). The invasive nature of the ICSI procedure may also lead to embryonic aneuploidy by disruption of the oocyte meiotic spindle or nuclear decondensation of spermatozoa (4).…”

Aneuploidy Rates Inversely Correlate with Implantation during In Vitro Fertilization Procedures: In Favor of PGT

“…Studies on mouse models revealed that the chromosomal integrity of zygotes derived from ICSI without any pretreatment of spermatozoa was impaired in comparison with zygotes derived from conventional IVF [83]; even the culture sperm conditions may affect the chromosomal stability of the embryo [84]. Chromosomal damage may occur due to the injection of non-capacitated, acrosomeintact spermatozoa, so to reduce the risk of chromosomal aberrations during the ICSI procedure, it is crucial that sperm capacitation and the acrosome reaction be appropriately artificially induced in the proper medium before use [85].…”