FERTILITY PRESERVATION IN PATIENTS WITH GENETIC CONDITIONS PREDISPOSING TO POI

Advances in genomic medicine have substantially expanded the spectrum of genetic conditions associated with primary ovarian insufficiency (POI), enabling the identification of women and girls at risk of premature reproductive decline before irreversible loss of ovarian reserve occurs. Genetic forms of POI comprise a heterogeneous group of disorders characterized by distinct pathogenic mechanisms, highly variable trajectories of ovarian reserve decline, and markedly different windows of reproductive opportunity. Consequently, fertility preservation requires a disease-specific, individualized approach rather than a uniform management strategy. Current evidence indicates that successful fertility preservation depends on understanding the biological basis of ovarian dysfunction, accurately identifying the optimal window for intervention, and selecting the most appropriate strategy according to the underlying disorder and residual ovarian reserve. This review critically appraises the available evidence across major genetic conditions that predispose to POI or otherwise threaten reproductive potential, including Turner syndrome, FMR1 premutation, classic galactosemia, rare monogenic disorders, and hereditary cancer predisposition syndromes, focusing on mechanisms of reproductive impairment, patient selection, timing of intervention, fertility preservation strategies, reproductive outcomes, safety, and emerging technologies. Current evidence supports early referral following genetic diagnosis and longitudinal monitoring of ovarian reserve, as the opportunity for fertility preservation may be brief and unpredictable in many disorders. In hereditary cancer predisposition syndromes, reproductive risk may derive from intrinsic ovarian vulnerability, gonadotoxic treatment, and/or risk-reducing surgery, even when a direct gene-specific risk of POI is uncertain.