How to improve the clinical outcome of round spermatid injection (ROSI) into the oocyte: Correction of epigenetic abnormalities

BACKGROUND: First successful human round spermatid injection (ROSI) was conducted by Tesarik et al. in 1996 for the sole treatment of nonobstructive azoospermic men whose most advanced spermatogenic cells were elongating round spermatids. Nine offsprings from ROSI were reported between 1996 and 2000. No successful deliveries were reported for 15 years after that. Tanaka et al. reported 90 babies born after ROSI and their follow‐up studies in 2015 and 2018 showed no significant differences in comparison with those born after natural conception in terms of physical and cognitive abilities. However, clinical outcomes remain low. METHOD: Clinical and laboratory data of successful cases in the precursor ROSI groups and those of Tanaka et al. were reviewed. RESULTS: Differences were found between the two groups in terms of identification of characteristics of round spermatid and oocyte activation. Additionally, epigenetic abnormalities were identified as underlying causes for poor ROSI results, besides correct identification of round spermatid and adequate oocyte activation. Correction of epigenetic errors could lead to optimal embryonic development. CONCLUSION: Correction of epigenetic abnormalities has a probability to improve the clinical outcome of ROSI.