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.
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).
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).
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.
Research funding: None declared.
Author contributions: FP, SC, RDP for study concepts; FP and SC for study designed; FP, RDP, MN, RB and VV for data collection; FP, GT and SG for quality control of data and algorithms; GT, FP, SZ and SC for data analysis and interpretation; GT for statistical analysis; FP and SG for manuscript preparation; SC, and GT for manuscript editing; RB, SZ and VV for manuscript review; all the authors decided to submit the paper for publication. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Competing interests: None declared.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: All patients and their parents in the case of minors, provided informed consent for the research and for data collection for the purposes of the study, as approved by the institutional review board of Verona. All procedures followed the Italian laws for personal data protection and were in accordance with the tenets of the Helsinki Declaration.
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The online version of this article offers supplementary material (DOI: https://doi.org/10.1515/j_jpem-2020-0272).
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