Stem cell-derived gametes: what to expect when expecting their clinical introduction.

Stem cell-derived (SCD)-gametes derived from induced or autologous (i.e. patient-specific) cells may help mitigate human fertility problems caused by physiological or social factors in the (near) future. While this technology is still in its infancy, recent advancements with SCD-gametes generated from mouse pluripotent stem cells have led some researchers to expect-and investors to anticipate-the clinical introduction of human gametes derived from induced pluripotent stem cells (iPSCD-gametes) within two decades. However, it remains to be investigated how realistic these expectations are, and how they would balance against careful consideration of technical, ethical, legal, and societal aspects, including-but not limited to-safety and effectiveness. This mini-review aims to encourage that investigation by providing a brief overview of the state-of-the-art and highlighting the breadth of issues involved in the potential clinical introduction of human iPSCD-gametes. These issues emerge before (Stage 1), during (Stage 2), and after (Stage 3) clinical trials, and are discussed in that order. Issues discussed in the context of Stage 1 suggest that gathering the evidence required to preclinically assess the safety of human iPSCD-gametes will be time-consuming and require parallel experiments with sensitive research materials. Issues discussed in the context of Stage 2 suggest that it might take several years for human iPSCD-gametes to transition through distinct clinical trial phases, and that inevitable (and unforeseeable) variations in the quality of human iPSCD-gametes are likely to further slow this down. Finally, issues discussed in the context of Stage 3 suggest that offering human iPSCD-gametes clinically will require addressing questions of accountability and monitoring, some of which might be difficult to formalize by law. Combined, these findings suggest that a responsible clinical introduction of human iPSCD-gametes may take considerably longer than expected, underscoring the importance of transdisciplinary collaborations with a broad range of stakeholders to make well-informed and well-considered choices about their development and application.