ESPE Abstracts

Introduction: Female patients treated with alkylating agents in childhood are at risk for ovarian impairment. We aimed at describing the pattern of residual ovarian function in a cohort of hematological cancer survivors, assessing the relationship between the cumulative dose of alkylating agents administered (expressed as Cyclophosphamide Equivalent Dose - CED) and Anti-Müllerian Hormone (AMH) levels.

Methods: Gonadal health was assessed in 81 post-menarchal survivors treated for pediatric lymphoma or leukemia at a mean age of 11.75 ± 5.02 years and aged 20.05±4.13 years upon data collection. Clinical and biochemical (LH, FSH, AMH) data were gathered in all the patients enrolled.

Results: Eighty-one patients were treated with alkylating agents with a CED (mg/m²) < 4000, between 4000 and 8000 and > 8000 in 39%, 57% and 4% of patients, respectively. Abdomino-pelvic irradiation was administered to 11/81 patients (13.4%). Seventy-eight patients presented with regular menses (96.3%), whereas 3 (3.7%) showed secondary amenorrhea, raised FSH and undetectable AMH levels, profiling an overt “premature ovarian insufficiency” (POI). Among 78 women with retained menses and normal FSH levels, milder “diminished ovarian reserve” (DOR), identified by AMH-SDS below -1.65 (5^th centile) was detected in 18 patients (22.2% of the whole cohort). Mean AMH-SDS values were -0.48±1.43 SDS. Among not irradiated patients, increasing CED values were associated with lower AMH-SDS (P 0.05), with the threshold of 7200 g/m² being the best discriminator between impaired and normal ovarian function (AUC: 0.75 on ROC analysis) and with an observed decrease of 0.14 AMH-SDS for each CED increase of 1 gr/m2. In addition, pelvic irradiation played a detrimental role on ovarian reserve (P 0.0297). At last, age at diagnosis below 10 years was associated with normal ovarian function in 100% of cases and with greater AMH values than those of patients diagnosed beyond 10 years (P < 0.0001), with an observed decrease of 0.11 AMH-SDS for each 1-year increase (P value = 0.004).

Conclusions: In the present study we used an AMH-driven approach to identify the cut off of CED that best discriminates between women with diminished versus normal ovarian reserve (7200 mg/m²). This value is consistent with the threshold already reported in Literature (8000 mg/m²), beyond which the incidence of POI is increased. The harmony between these two values supports the reliability of age-standardized AMH as a tool for the earlier detection of ovarian impairment. In addition, our findings suggest that younger age at diagnosis plays a protective role on ovarian reserve.