Abstract
Endometriosis is a prevalent inflammatory disease affecting approximately one in ten women, characterized by endometrial tissue outside the uterus. Despite its high incidence, treatment options are limited, and the underlying pathology remains poorly understood. Reliable models are essential for investigating the mechanisms of endometriosis, necessitating an updated review of 3D in vitro models that better mimic the disease environment. This review aims to provide a comprehensive overview of existing 3D in vitro models of endometriosis, focusing on their evolution, refinement, and application in understanding disease mechanisms and therapeutic screening. A systematic search was conducted in the PubMed database for original and review articles published in English until July 2025. Search terms included "endometriosis," "3D model," "spheroid," "organoid," "microfluidic system," "organ-on-a-chip," "bioprinting," "chorioallantoic membrane," "amniotic membrane culture," and "explant." Exclusion criteria included non-English articles and studies not focused on human or relevant animal models. Six major categories of 3D in vitro endometriosis models were identified, each with distinct structural and functional features tailored to specific research questions. Their evolution over time is discussed, along with critical evaluation of their limitations and practical challenges. The insights gained from 3D in vitro models have significant implications for clinical practice, potentially informing targeted therapies and improving patient outcomes. For reproductive health specialists and scientists, these models may lead to more effective diagnostic and treatment strategies, thereby advancing the field. We discuss the future perspectives, of advancing and integrating these models into personalized medicine approaches and exploring novel therapeutic targets.