Female adolescents and young women previously treated for pediatric malignancies: assessment of ovarian reserve and gonadotoxicity risk stratification for early identification of patients at increased infertility risk

Abstract

Objectives: Childhood and adolescent cancer survivors (CACSs) are at risk of adverse reproductive outcomes. Assessment of follicle-stimulating hormone (FSH) levels is the most common test used to diagnose premature ovarian insufficiency (POI) whereas anti-m|llerian hormone (AMH) and antral follicle count (AFC) have been proposed as ovarian reserve markers. We assessed the correlation between these markers and treatment gonadotoxicity risk (GR) in CACSs.

Methods: A total of 55 female CACSs were enrolled. GR was graded as low, medium, or high according to classifications based on disease and treatments and on cyclophosphamide equivalent dose score. FSH, AMH, and AFC were determined. POI was defined by amenorrhea and FSH>30 IU/L. For remaining patients, diminished ovarian reserve (DOR) was defined by AMH<5th centile. FSH and AFC cut-offs proposed in the literature as DOR markers were also considered (FSH>10 IU/L or >95th centile; AFC<8 or <5th centile).

Results: Ovarian reserve results to be compromised in 23 (41.8%) patients: 14 with DOR and 9 with an established POI. Results showed GR classifications to be a good predictor of ovarian reserve, with significantly lower AMH and AFC in the high-risk groups. AFC resulted to be directly correlated with AMH (r=0.75, p<0.001).

Conclusions: In CACSs, GR classifications correlate with post-treatment AMH and AFC. These are useful tools in the early identification of young patients with DOR, who may benefit from reproductive and fertility preservation counseling. Further studies are needed to determine the rate and time of progression from DOR to POI in this population.

Keywords: anti-m|llerian hormone; antral follicle count; gonadotoxicity risk; ovarian reserve; premature ovarian insufficiency; young childhood cancer survivors.