Oocyte activation during round spermatid injection: state of the art.

Spermatozoa can be recovered in half of patients with non-obstructive azoospermia (NOA) via testicular sperm extraction (TESE) or microTESE. Intracytoplasmic sperm injection (ICSI) with the recovered spermatozoa has been established at IVF clinics to help these patients. Those who fail to achieve spermatozoa in testicular samples usually turn to donor spermatozoa or adoption. Instead of spermatozoa, only round spermatids are present in testicular biopsy in some NOA patients, a form of globozoospermia. Of these men, those who are unwilling to use donor spermatozoa still have the option to have their own biological child. In recent years, round spermatid injection (ROSI) has been developed as a potential option, with about 100 healthy babies born. However, the outcomes have so far been poor, with low pregnancy rates. One reason for this could be oocyte activation deficiency (OAD). Different from regular ICSI, round spermatids after ROSI do not induce calcium oscillation, which is critical for later oocyte activation and embryo development. Therefore, optimal assisted oocyte activation (AOA) stimulation is needed to mimic the physiological events. So far, a number of methods have been examined, including vigorous cytoplasm aspiration, calcium chloride injection, calcium ionophore treatment and electroporation. Over 100 healthy babies have been born, with no developmental or physiological abnormalities compared with regular children or those born from IVF and ICSI procedures, although some studies have found epigenetic modification. More recent studies have shown that electroporation for AOA has more credits than those tested so far. The overall positive outcome of ROSI is still poor and unstable, so it has not become a routine procedure in IVF clinics. Success rates would be improved with further optimization of AOA to enable patients to have their own genetic offspring.