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Ferroptosis is a novel type of programmed cell death dependent on iron and characterized by the accumulation of lipid peroxides in cells and is closely related to various diseases. Female infertility is a global health concern, which is associated with a variety of factors. The etiology remains unknown in many women with infertility. With further investigation into the pathogenesis of infertility, a growing number of studies have demonstrated the close connections between infertility and ferroptosis. Through a literature review, it is found that ferroptosis is closely involved in endometriosis- and polycystic ovarian syndrome (PCOS)-associated infertility and tubal factor infertility. Iron overload increases the resistance to ferroptosis, and ferroptosis in some cells accelerates endometrial lesion growth. Moreover, iron overload may be hazardous to oocytes. This review may shed some light on the diagnosis and treatment of female infertility.

Ovulation disorders are the leading cause of female infertility, primarily due to abnormal regulation of the hypothalamic-pituitary-ovarian (HPO) axis or dysfunction of target organs. The most common conditions in this category are polycystic ovary syndrome (PCOS) and premature ovarian insufficiency (POI), with the core mechanisms involving follicular developmental abnormalities and impaired oocyte quality. However, the pathophysiological mechanisms underlying PCOS and POI are not yet fully understood. Recent studies have shown that epigenetic regulatory mechanisms play a crucial role in the pathological processes of PCOS and POI, with DNA methylation key epigenetic modification emerging as a focal point of research. Aberrant DNA methylation regulation has been closely linked to follicular developmental disorders and endocrine dysfunction in reproduction. Although research on the role of DNA methylation in PCOS/POI pathology is still in its early stages, it has already demonstrated significant potential as a key epigenetic target. In this study, we comprehensively review the relationship between DNA methylation abnormalities and the pathogenesis of PCOS/POI, exploring their mechanisms of action. We also discuss new research directions and potential epigenetic biomarkers for treating associated comorbidities and improving the quality of life in female patients with ovarian dysfunction. This provides a theoretical foundation for advancing epigenetic diagnostic marker screening, targeted intervention strategies, and accelerating the translation of epigenetic regulatory mechanisms into clinical diagnostic and therapeutic applications. Graphical abstract

Background: Menopause in women marks the knot of reproductive life, and menopause is defined as the last menstrual period in a woman, but this is caused by the failure of the ovarian reserve. The average age of natural menopause in the general population of women has remained around 50–52 years. Premature ovarian insufficiency (POI) is a debilitating clinical syndrome that manifests as a decline in ovarian function in women under 40. This condition is a prominent cause of female infertility. Summary: POI is a debilitating condition that not only wreaks havoc on patients’ physical and mental well-being but also imposes substantial mental, psychological, and economic burdens, particularly on women. In addition to diminished fertility, individuals afflicted with POI face an elevated risk of developing debilitating conditions such as osteoporosis and cardiovascular disease. The etiologies of POI are highly heterogeneous, and it can be caused by spontaneous genetic defects or induced by autoimmune diseases, infections, and iatrogenic or environmental factors. Alarmingly, idiopathic POI, a subtype characterized by an unknown etiology, accounts for more than half of all POI cases. Currently, clinical interventions for POI primarily consist of hormone replacement therapy. Fertility preservation methods are cryopreservation of embryos, oocytes, and ovarian tissue. Immunological interventions, gene editing techniques, and stem cell-based therapies are being explored to unravel the diverse etiologies and underlying mechanisms of POI, thereby enabling the identification of optimal therapeutic interventions. These innovative approaches offer unprecedented opportunities to advance the field of reproductive medicine. Key Messages: The main aim of this paper was to offer a succinct summary of the latest research breakthroughs concerning the elucidation of the mechanisms governing the origin and management of POI.