Controversial Roles of Autophagy in Adenomyosis and Its Implications for Fertility Outcomes-A Systematic Review.

Background/Objectives: Adenomyosis is a benign condition where ectopic endometrial glandular tissue is found within the uterine myometrium. Its impact on women's reproductive outcomes is substantial, primarily due to defective decidualization, impaired endometrial receptivity, and implantation failure. The exact pathogenesis of the disease remains unclear, and the role of autophagy in adenomyosis and its associated infertility is not well understood. The aim of this systematic review was to conduct an exhaustive search of the literature to clarify the role of autophagy in the pathogenesis of adenomyosis. Methods: A systematic search was conducted in Medline, Embase, and Scopus databases up to the date of 20 August 2024. We included all English-written publications assessing the role of autophagy in the pathogenesis of adenomyosis. Results: Seventeen eligible articles were identified, including reviews and experimental studies involving human samples and murine models. The results showed that the role of autophagy in adenomyosis is controversial, with studies showing both increased and decreased levels of autophagy in adenomyosis. Conclusions: Autophagy plays a dual role in cell survival and death. Increased autophagy might support the survival and proliferation of ectopic endometrial cells, while decreased autophagy could prevent cell death, leading to abnormal growth. Oxidative stress may trigger pro-survival autophagy, mitigating apoptosis and promoting cellular homeostasis. Hormonal imbalances disrupt normal autophagic activity, potentially impairing endometrial receptivity and decidualization and contributing to infertility. The balance of autophagy is crucial in adenomyosis, with its dual role contributing to the complexity of the disease. Limitations: A few studies have been conducted with heterogeneous populations, limiting comparative analyses.