Why? The following hypotheses are put forward based on our knowledge to date.
Firstly, unlike IVF, up to 30% of women (with subfertile partners) have ICSI although they have no detectable problems. Thus, their oocytes have more capacity to repair DNA damage even if the injected sperm is of poor quality. This is supported by the findings of Meseguer et al, 2011 where high quality oocytes from donors offset the negative impact of sperm DNA damage on pregnancy.
Secondly, in ICSI, the gametes are not subjected to prolonged culture in suboptimal conditions so these sperm may have less damage than those exposed to culture media overnight, as in IVF procedures. The recent major study from Dumoulin et al, 2010 shows that even the birth weight of IVF babies can be markedly influenced by minor differences in culture conditions. In contrast to IVF, ICSI sperm are injected into the optimal environment of the ooplasm within a few hours of ejaculation. This may protect them from laboratory induced damage. It also enables the oocyte to begin repairing any damage earlier.
Thirdly, it is well documented that spermatozoa from many infertile men have high levels of reactive oxygen species (Henkel 2011; Aitken et al., 2012) and their antioxidant content is also significant lower than fertile men (Lewis et al., 1995). During the IVF process, oocytes can be exposed to oxidative assault overnight from the 0.5 million spermatozoa releasing ROS around it. This may well impair the oocyte’s functional ability including its capacity to repair sperm DNA fragmentation post fertilization.
Fourthly, evidence is emerging that embryos with high sperm DNA damage are associated with early pregnancy loss (reviewed by Zini et al, 2008 using 11 studies composed of 808 IVF and 741 ICSI cycles) i. e. ICSI success rates are sometimes affected adversely by sperm DNA damage but at a later stage. In fact, high levels of sperm DNA damage are associated with increased risk of pregnancy loss (OR: 2.5; 95% CI: 1.5-4.0), regardless of the in vitro technique applied (reviewed by Robinson et al, 2012).
Up until now, the semen test for choosing ICSI has been a blunt instrument. It has been based on a very pragmatic approach of the gross number of sperm available in the ejaculate. Routinely, semen with <0.5 million motile sperm was unsuitable for IVF so ICSI was the only option. .
At last, we have a scientific rationale for using ICSI. With this knowledge, we should bypass IUI and IVF if we have sperm with poor DNA, and offer affected couples ICSI as a first treatment choice, thereby improving their chances of success.
Using ICSI, we can
· protect sperm DNA by reducing its time in the lab
· inject it into the egg therefore allowing the egg to repair the sperm on the day of ejaculation as Nature intended.