Current status and clinical and biological prospects of research on the creation of viable gametes from induced pluripotent stem cells

This article examines the current state and clinical and biological prospects of research aimed at creating viable gametes from induced pluripotent stem cells (iPSCs). The relevance of the work is justified by the increasing frequency of infertility and clinical situations where standard assisted reproductive technologies (ART) prove ineffective, while in vitro gametogenesis (IVG) technology potentially offers sources of autologous gametes to restore reproductive function, particularly in the context of oncofertility. The goal of the study is clearly formulated as a systematic analysis of current protocols, clinical and biological barriers, and translational prospects for generating human gametes from iPSCs. Methodologically, the paper relies on critical typology of sources and comparison of two fundamentally different strategies for germline reconstruction: bio-reconstitution in 3D organoids and molecular engineering (direct induction of meiosis). The scientific novelty of the study lies in its integrative authorial synthesis, which not only summarizes recent methodological advances (such as 3D organoids, two-phase IVM protocols, direct induction of meiosis), but also focuses on the inextricable connection between progress in culture protocols and growing uncertainties concerning epigenetic safety. Key findings of the study can be summarized as follows. Firstly, despite convincing proof-of-concept results in rodent models, translation of IVG to humans remains limited. Secondly, a dual-layered and interconnected pair of biological barriers (failure to fully reconstruct somatic niche leading to asynchronous development and meiotic failures) and safety-oriented barriers (high risks of genetic and specially epigenetic instability, including defects in genomic imprinting) have been identified. Thirdly, there exists a profound gap between tactical solutions (pharmacological crutches, two-phase IVM) and strategic goals (authentic gametogenesis with multiomic equivalence to natural gametes). The article will be useful for researchers in the field of reproductive biology and stem cell science, reproductive clinicians, experts in oncofertility, as well as specialists in bioethics and regulatory policy.