ESPE Abstracts

Background: Gonadal dysfunction and fertility impairment are some of the many clinical manifestations described among patients with Fanconi anemia (FA). Many who receive hematopoietic stem cell transplantation (HSCT) suffer additionally from infertility due to gonadal damage from their preparative regimen. The effect of HSCT on gonadal insufficiency and fertility potential among children with FA is largely unknown.

Methods: We performed a retrospective analysis of male and female patients with FA who had pubertal and hormonal data from their follow-up visits at CCHMC from July 1990 to June 2020 to evaluate the incidence of primary ovarian insufficiency (POI) and testicular failure (TF) among transplanted patients. We defined POI in pre-pubertal females as undetectable anti-Mullerian hormone (AMH) and in pubertal females as follicle stimulating hormone (FSH) >20 mIU/l, or undetectable AMH with absent menstrual periods. Among pubertal males, TF was defined as FSH >20 mIU/l and/or luteinizing hormone (LH) >10 mIU/L. Inhibin B (Pg/mL) levels were also collected as markers of spermatogenesis and fertility recovery.

Results: Median follow-up time after HSCT for the entire cohort was 6.18 years (range 0.05-30.4 years). Among 57 transplanted female FA patients, we identified POI among 30 (52.6%) female patients who developed POI at any time point from HSCT. The media age at diagnosis was 13.82 years (range 5.78-26.86 years) and the median time after HSCT for diagnosis was 3.81 years (range 0.58-13.99 years). Among 41 male patients, we identified TF in 20 (48.4%) patients, at a median time of 5.2 years (range 0.73-30.4 years) from HSCT. Among all patients with POI, AMH levels negatively correlated with time from transplant (r² = 0.21, P=0.001). Additionally, FSH levels did not increase significantly with time from HSCT among female POI patients, (r²=0.01, P=0.26). In contrast, FSH increased significantly with time from HSCT among male patients (r²=0.17, P=0.005). Inhibin B levels also declined among male patients who had gonadal insufficiency following HSCT (r²=0.14, P=0.01).

Conclusions: POI and TF are prevalent among FA patients who have undergone HSCT. AMH declined among female patients diagnosed with POI after HSCT. AMH may serve as a more precise marker for POI diagnosis among female FA patients who have undergone HSCT. Increasing FSH and decreasing inhibin B correlated with time from HSCT among male FA patients. Because of the latency to gonadal insufficiency following HSCT, extended timepoints may be needed among these patients to monitor gonadal function.