(44) Follicular findings in autoimmune oophoritis: 2 cases from the NIH ovarian tissue cryopreservation protocol

Background: Autoimmune oophoritis and subsequent diminished ovarian reserve (DOR) or premature ovarian insufficiency (POI) is a rare cause of subfertility, representing approximately 4% of spontaneous POI. It often coexists with thyroid and/or adrenal autoimmunity, or can be a part of Polyglandular Autoimmune Syndrome (APS), Type I and Type II. The purpose of this study is to describe several cases of autoimmune DOR/POI in children/adolescents, as well as their ovarian tissue findings to help inform management of this rare condition.

Case: Patient A is a 16-year-old female with a history of Factor V Leiden heterozygous, who was diagnosed with POI during workup of sudden alopecia with labs notable for elevated FSH (129 mIU/mL) and undetectable estradiol. She was also noted to have anti-thyroid peroxidase antibodies, anti-thyroglobulin antibodies, and anti-adrenal antibodies, raising concern for polyglandular autoimmune failure. Menarche occurred at age 12 and she had regular menses, which became lighter but ongoing the time of her diagnosis. She underwent laparoscopic right oophorectomy and ovarian tissue cryopreservation. Ovarian histology demonstrated no ovarian follicles.

Patient B is a 13-year-old who initially presented with weight loss, palpitations, and secondary amenorrhea. Menarche occurred at age 11 with subsequent regular menses until an abrupt stop at 13 years old. Labs demonstrated hyperthyroidism due to Grave’s disease (TSH < 0.005 mIU/L, T4 15.8 mcg/dL, thyroid-stimulating immunoglobulin 413 IU/L) and hypergonadotropic hypogonadism consistent with POI (FSH 59.3 mIU/mL, LH 15.5 IU/L. estradiol 8 pg/mL, AMH 0.01 ng/m). She underwent laparoscopic right oophorectomy and ovarian tissue cryopreservation. Ovarian histology demonstrated no ovarian follicles.

Comments: This study demonstrated no follicles in either of the subjects with POI due to autoimmune oophoritis. It is possible that the absence of follicles represents generally worse outcomes of ovarian tissue cryopreservation for patients with autoimmune POI compared to other causes of POI. That said, little is known about the chronology of this condition, and earlier detection and recognition of autoimmune oophoritis might allow for improved fertility outcomes. Notably both of these patients were post-pubertal. It is unknown if fertility preservation outcomes for patients with autoimmune POI differ by pubertal status. More studies are needed to determine who are optimal candidates for ovarian tissue cryopreservation, especially for rare causes of POI like autoimmune oophoritis.