Assessment of ovarian function in adolescents and young adults after childhood cancer treatment—How accurate are young adult/parent proxy‐reported outcomes?

Abstract

Background : Providers often rely on self‐reported ovarian function in adolescent and young adult (AYA)‐aged childhood cancer survivors when making clinical decisions. This study described reported menstrual patterns and the agreement between respondent‐reported and biochemical premature ovarian insufficiency (POI) in this population. Procedure This was a cross‐sectional study of survivors (or their parent proxy) aged 13‐21.9 years who received gonadotoxic therapy and were enrolled in a longitudinal health survey. Participants reported menstrual regularity, hormone‐replacement therapy (HRT) use, and ovarian dysfunction. Respondent‐reported POI was defined as the survivor taking HRT for ovarian failure or having been told she had ovarian failure. Biochemical POI was defined as follicle‐stimulating hormone (FSH) level ≥40 mIU/mL. The agreement between respondent‐reported and biochemical POI was determined using Cohen's kappa coefficient (κ) and analyzed by demographic and clinical factors. Results Among 182 AYA‐aged survivors (72.5% non‐Hispanic White, 46.7% leukemia survivors), 14.8% reported requiring HRT to have menses but 55.5% reported regular menses without HRT use. Among survivors with FSH measurements (n = 130), 17.7% reported POI whereas 18.5% had FSH ≥40 mIU/mL (κ = 0.66, sensitivity 70.8%, specificity 94.3%). The highest agreement between respondent‐reported and biochemical POI was with young adult self‐report (κ = 0.78) and survivors with >5 survivor clinic (κ = 0.83) and/or >5 endocrinologist (κ = 1.00) visits. Conclusions The majority of AYA‐aged survivors reported having regular menses without HRT support. The accuracy of respondent‐reported POI increased with repeated survivor clinic or endocrinologist visits, highlighting the importance of continued education. Survivors must be informed about their ovarian function to enable them to advocate for their reproductive health.

Perceived and Objective Fertility Risk Among Female Survivors of Adolescent and Young Adult Cancer

“…A similar κ value (κ = 0.19) was found in a study among survivors of childhood cancer between perceived and gonadal function–defined fertility risk . In contrast, AYA-aged survivors of childhood cancer had moderate agreement (κ = 0.66) between FSH levels and self-reported premature ovarian insufficiency; repeated interactions with pediatric cancer survivorship clinics or endocrinologists were associated with high agreement (κ = 0.83 and κ = 1.0, respectively) . Higher agreement may be because the premature ovarian insufficiency phenotype of prolonged amenorrhea is known to the patient or because participants received appropriate survivorship care.…”

“…Using AMH and FSH in combination with hormonal therapy and menstrual pattern allowed for better estimation of ovarian function in this study and follows expert recommendations for AYA cancer survivors . Other studies mainly used treatment gonadotoxicity to estimate impaired fertility and only a few included biomarkers, most often limited to FSH . Another strength was a sufficient population to assess associations with both under- and overestimation of risk.…”

“…Data on fertility perceptions of AYA cancer survivors and their alignment with objective infertility risk are scant. Prior studies, largely in childhood cancer survivors, report that survivors often overestimate or underestimate their infertility risk . Lehmann et al found low agreement between survivors’ perception of their infertility risk and their objective gonadal function.…”

Disparities in Female Pediatric, Adolescent and Young Adult Oncofertility: A Needs Assessment

“…Despite the growing body of knowledge around ORT, there remains no single best approach for monitoring ovarian reserve after gonadotoxic therapy and thus many patients lose the opportunity to pursue fertility in survivorship [88][89][90]. Based on the best available evidence, a reasonable approach to ovarian reserve monitoring may be to perform AMH and FSH 1-year post-treatment and refer to REI based on the values [50,89,91,92]. If FSH levels are <10 mIU/mL and/or AMH is ≥1 ng/mL, and thus normal, providers may consider retesting every 6-12 months if the patient is not interested in pursuing ART at that time.…”

Gynecological cancer among adolescents and young adults (AYA)

“…Despite the effort to optimize cancer treatment to guarantee excellent outcomes, clinicians should have the concern about the enhanced risk of adverse reproductive effects of radiotherapy, chemotherapy and surgery adopted for gynecologic cancer treatment (83).…”