What are the most common causes of primary ovarian insufficiency (POI)?

• A. Infections
• B. Pregnancy-related
• C. Genetic, autoimmune, and iatrogenic (chemotherapy, radiation)
• D. Unknown cases only

Answer: (C)

Primary ovarian insufficiency results from a range of causes, but the most commonly recognized categories are genetic abnormalities, autoimmune processes, and damage from gonadotoxic treatments. Genetically driven POI includes chromosomal issues such as Turner syndrome or X-chromosome abnormalities, and specifically the Fragile X premutation, all of which can disrupt ovarian function. Autoimmune POI occurs when the immune system targets ovarian tissue, leading to diminished follicle reserve. Iatrogenic POI refers to loss of ovarian function after treatments like alkylating chemotherapy or pelvic radiation, which can destroy growing follicles.

Infections and events during pregnancy are not the typical drivers of POI, and while many cases are idiopathic, focusing on these three broad etiologies captures the main known contributors clinicians most often encounter. Understanding these helps guide evaluation (karyotype, Fragile X testing, autoimmune screening) and management, including counseling about fertility preservation before gonadotoxic therapy.