A Review of Microfluidic Technologies in Fertility Preservation with a Focus on Ovarian Tissue: Clinical Evidence and Research Perspectives

Abstract

Background Microfluidic technologies have emerged as transformative tools in reproductive medicine. By enabling precise control of fluid dynamics at the microscale, they make it possible to recreate physiological conditions for gamete handling, embryo culture, and ovarian tissue modeling. Methods: This review draws on highly cited literature published between 2015 and 2025 to map the current landscape of microfluidic platforms. It examines droplet-based, continuous-flow, 3D-printed, and porous-media systems, with particular attention to material selection, device architecture, and functional integration with a deep focus on ovarian tissue in assisted reproductive Techniques. Findings: In assisted reproductive Techniques, microfluidic sperm sorting has been shown to select motile spermatozoa with intact DNA and to improve embryo morphology. However, consistent gains in fertilization rate, clinical pregnancy, and live birth remain unproven in unselected populations. Lab-on-a-chip systems that combine oocyte denudation, fertilization, and embryo culture have proven feasible in animal models but lack robust human data. In ovarian biology, follicle-on-a-chip platforms support the growth of human follicles under perfusion, and chips such as EVATAR have reproduced the hormonal profiles of a 28-day cycle. Core-shell encapsulation has advanced in vitro folliculogenesis in mice through to the metaphase II oocyte stage, pointing toward transplantation-independent fertility-preservation strategies. Conclusion: Key barriers to clinical investigations include manufacturing scalability, regulatory standardization, limited human endpoints, and the challenges of vascularization and long-term culture. Future priorities are multicenter randomized trials with live birth as the primary endpoint, standardized reporting frameworks, and early engagement with regulatory bodies. © 2026, Isfahan University of Medical Sciences(IUMS). All rights reserved.