The diagnostic experience of women with fragile X-associated primary ovarian insufficiency (FXPOI)

Purpose: The fragile X premutation occurs when there are 55-200 CGG repeats in the 5' UTR of the FMR1 gene. An estimated 1 in 148 women carry a premutation, with 20-30% of these individuals at risk for fragile X-associated primary ovarian insufficiency (FXPOI). Diagnostic experiences of FXPOI have not previously been included in the literature, limiting insight on experiences surrounding the diagnosis. This study identifies barriers and facilitators to receiving a FXPOI diagnosis and follow-up care, which can inform care and possibly improve quality of life.

Methods: We conducted qualitative interviews with 24 women with FXPOI exploring how FMR1 screening, physician education, and supportive care impacted their experience. Three subgroups were compared: women diagnosed through family history who have biological children, women diagnosed through family history who do not have biological children, and women diagnosed through symptoms of POI.

Results: Themes from interviews included hopes for broader clinician awareness of FXPOI, clear guidelines for clinical treatment, and proper fertility workups to expand reproductive options prior to POI onset. Participants also spoke of difficulty finding centralized sources of care.

Conclusions: Our results indicate a lack of optimal care of women with a premutation particularly with respect to FMR1 screening for molecular diagnosis, short- and long-term centralized treatment, and clinical and emotional support. The creation of a "FXPOI health navigator" could serve as a centralized resource for the premutation patient population, assisting in connection to optimal treatment and appropriate referrals, including genetic counseling, mental health resources, advocacy organizations, and better-informed physicians.