Genetics of Primary Ovarian Insufficiency

Primary ovarian insufficiency (POI) is a heterogeneous condition that worldwide affects up to 3.7% of women under 40 years of age. POI manifestations are diverse, ranging from ovarian dysgenesis and primary amenorrhea to a later onset ovarian dysfunction, secondary amenorrhea, and diminished ovarian reserve. These conditions result in infertility and elevated risk for osteoporosis and cardiovascular disease. Over the past decade, substantial progress has been made in understanding the complexities of ovarian biology and oocyte development, particularly in identifying involved pathways, etiology, underlying mechanisms, and POI-associated genes. In this review, we focus on chromosomal and monogenic causes of POI leading to syndromic and isolated forms in humans. We provide an updated summary on 272 genes reported in at least two unrelated individuals with a clinical diagnosis of POI. This information supports healthcare professionals in making informed decisions regarding genetic testing and genetic counseling. This review underlines the critical role of molecular diagnosis in understanding and managing POI, highlighting both the current progress and the existing limitations in translating genetic findings and knowledge into effective diagnostic practice.