Genetic and Autoimmune Factors in Primary Ovarian Insufficiency

Abstract Primary ovarian insufficiency (POI) is a heterogeneous disorder with diverse genetic and autoimmune contributors. This narrative review examines selected evidence on these contributors and their relevance to the evaluation and counselling of women with POI. Genetic studies have identified established and candidate abnormalities involving chromosomes, FMR1, folliculogenesis, meiosis, DNA repair, and mitochondrial function, although the clinical significance of many rare variants remains uncertain. Autoimmune associations are most consistently described in relation to thyroid, adrenal, and polyglandular autoimmune disorders, while evidence for broader inflammatory mechanisms remains less established. These findings support targeted genetic and autoimmune evaluation rather than indiscriminate testing. Hormone replacement therapy remains the foundation of long-term care, and fertility counselling should acknowledge the possibility of intermittent ovarian activity while maintaining realistic expectations regarding autologous pregnancy. Emerging regenerative approaches remain experimental. Overall, genetic and autoimmune evidence can refine aetiological assessment and counselling in selected patients, but substantial uncertainty remains regarding many proposed molecular and immunological contributors.