Longitudinal Ovarian Reserve in Female Adolescents/Young Adults With Lymphoma: A Report From Children's Oncology Group Study ALTE11C1.
This prospective COG study reports that female adolescents and young adults with lymphoma had lower AMH than healthy peers at diagnosis and one year after treatment, with low baseline AMH and greater alkylator exposure independently predicting diminished ovarian reserve.
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This prospective COG study reports that female adolescents and young adults with lymphoma had lower AMH than healthy peers at diagnosis and one year after treatment, with low baseline AMH and greater alkylator exposure independently predicting diminished ovarian reserve.
Research significance
The evidence supports using baseline AMH and alkylator exposure as risk-stratification factors for post-treatment diminished ovarian reserve; it is reasonable, but not tested here, to hypothesize that this information could guide earlier fertility-preservation counseling or selection of less gonadotoxic treatment when oncologically appropriate.
Source abstract
BACKGROUND: Children's Oncology Group (COG) study ALTE11C1 prospectively evaluated ovarian reserve in female adolescents/young adults (AYAs) with lymphoma from diagnosis to 1 year post-end of treatment (EOT). Healthy peers provided normative comparisons. PROCEDURE: From 2013 to 2018, female participants ≥6 months post-menarche with newly diagnosed lymphoma were enrolled at COG institutions, along with healthy peers. All completed study entry questionnaires and menstrual cycle-independent blood draws for anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), and estradiol; lymphoma participants had four additional draws during and after treatment. Associations between biomarkers, disease and treatment characteristics were evaluated. Logistic regression and recursive partitioning analyses identified predictors of diminished ovarian reserve (DOR: AMH <1 ng/mL) at 1 year post-EOT. RESULTS: Analyses included 168 participants and 125 healthy peers. Participants had lower AMH than healthy peers at study entry (2.1 vs. 4.1 ng/mL; p < 0.01) and 1 year post-EOT (1.7 vs. 4.1 ng/mL; p < 0.01). AMH declined during treatment, with partial recovery post-EOT to below study entry levels (p < 0.01). Those with advanced stage Hodgkin lymphoma and/or B symptoms had the lowest AMH. By 1 year post-EOT, 34% had DOR; study entry AMH less than 1 ng/mL (p = 0.003) and higher alkylator exposure (p = 0.01) were independent predictors. Most participants with study entry AMH less than 1 ng/mL (76%) or CED ≥6.6 g/m2 (75%) demonstrated DOR at 1 year post-EOT. No participant had acute ovarian failure at 1 year post-EOT. CONCLUSIONS: Lymphoma and its treatments affect ovarian reserve in female AYA patients. Low AMH at diagnosis and high alkylator exposure predict post-therapy DOR and can guide fertility preservation counseling.