Human embryo research, stem cell-derived embryo models and in vitro gametogenesis: Considerations leading to the revised ISSCR guidelines

Amander T. Clark
Ali Brivanlou
Jianping Fu
Kazuto Kato
Debra Mathews
Kathy K. Niakan
Nicolas Rivron
Mitinori Saitou
Azim Surani
Fuchou Tang
Janet Rossant
In this perspective, the authors, which include a member of the ISSCR, provide a summary of the recommendations of Working Group 2, the sub-committee in charge of updating the 2021 ISSCR guidelines pertaining to oversight processes and the categories of research. They explain the change to the 2016 guidelines, including the categories of review. The new guidelines divide two of the previous three categories. Former category 1, ‘Exempt from review,’ was split in two. Category 2, ‘Requires review,’ remained unchanged. Category 3, ‘Prohibited research activities,’ was also split in two, and human embryo culture was removed from this third category. The article also provides an overview of reasons to maintain and extend the 14-day rule. Reasons to maintain it include that there remains much to be learned about embryo development between 7 and 14 days post-fertilization; the question remains, what has been the benefit to society of studying the first 14 days of embryo development? Furthermore, the scientific community needs to make the case to publicly revisit the previous compromise. Among the reasons for extending the rule, the authors argue that much remains to be learned about embryo development after 14 days and that this knowledge would provide important cues for developing therapeutic applications, treating pregnancy loss, and understanding diseases that begin to manifest at this stage in embryo development. A second motive for extending the rule is the decrease of experimental use of animals, especially non-human primates.