Fertility outcomes and ovarian function recovery after anti-NMDAR encephalitis: A retrospective cohort study

Anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis predominantly affects women of reproductive age and is frequently associated with ovarian teratomas. While acute neurological outcomes are well described, the long-term impact on ovarian endocrine function and fertility-particularly in tumor-associated cases-remains poorly understood, creating significant uncertainty in survivorship counseling.

We conducted a retrospective cohort study involving 106 women diagnosed with anti-NMDAR encephalitis at a tertiary academic hospital between 2015 and 2024. Primary outcomes included the recovery of ovarian endocrine function, measured by serial sex hormone levels and fertility outcomes. Secondary analyses assessed disease severity, tumor markers, and neuroimaging features between teratoma-associated cases and non-teratoma cases.

Patients with teratoma-associated encephalitis (n = 23) exhibited greater acute disease severity, necessitating higher rates of ICU admission (p = 0.012) and mechanical ventilation (p = 0.021). During the acute phase of illness, 38% of all patients experienced HPO axis suppression, primarily manifesting as amenorrhea. However, longitudinal monitoring revealed substantial recovery, with significant improvements in both luteinizing hormone (p = 0.01) and estradiol levels (p = 0.01) during convalescence. Notably, pregnancy rates were comparable between the teratoma (80%) and non-teratoma (83.3%) groups (p = 0.68).

Ovarian dysfunction in anti-NMDAR encephalitis is often reversible, and long-term fertility remains favorable even in teratoma-associated cases. These findings provide valuable guidance for fertility counseling and highlight the importance of incorporating reproductive health monitoring into the long-term care of young women with tumor-related autoimmune encephalitis.