Page 28 - ASPIRE JANUARY 2023 Volume 8 / Issue 1

MALE INFERTILITY SIG
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Gwo-Jang Wu (Taiwan)
How to improve clinical outcome of round spermatid injection into the oocyte
By Professors Gwo-Jang Wu and Atsushi Tanaka
Tesarik et al. reported the birth of normal babies following round spermatid injection (ROSI) into human oocytes in 1996. Eight pregnancies were reported after that and seven deliveries were reported.
Doctors gradually became sceptical about its clinical usefulness and ROSI disappeared from clinical application. However, in 2015 our clinic reported in Proceedings of the National Academy of Sciences (PNAS) the birth of 14 healthy babies following ROSI from azoospermic patients.
Previously, Micro-TESE conducted by urologists at other institutions had not found any spermatozoa in these patients, but a second Micro-TESE at our clinic found round spermatids.
Fertility and Sterility in 2018 reported on clinical data of 90 babies born after ROSI whose physical and cognitive abilities proved to be not significantly different in comparison with normal conception.
Atsushi Tanaka (Japan)
However, clinical outcomes following ROSI are still low. Our studies have elucidated the main cause of this poor clinical outcome as derived from epigenetic abnormalities by differences of nuclear protein in round spermatid (histone) and mature spermatozoa (protamine).
Since histone-protamine replacement is incomplete in RS, it is thought that reprogramming of the paternal genome does not occur in the usual manner after ROSI. The other factor is active DNA demethylation.
These epigenetic errors affect gene expression, and we are now experimenting to solve epigenetic errors using Histone deacetylase inhibitor (HDAC) which presents the possibility of correcting epigenetically abnormal genetic expression.
However, HDAC is subject of regulation in Japan. It is our hope that the clinical application of Scriptaid will be soon allowed.