Measures of ovarian reserve in female cancer patients compared to naturally aging women

Abstract

OBJECTIVE: To determine if measures of ovarian reserve differ between female cancer survivors compared to age matched and naturally aging women. DESIGN: Prospective cohort. MATERIALS AND METHODS: Measures of ovarian function were compared between menstruating female cancer survivors diagnosed with cancer at less than 26 years of age at least 2 years post alkylator therapy (mean age 23.1) and 2 menstruating control populations (18 subjects per group). Controls groups were: 1) healthy age matched women (mean age 24.8) and 2) healthy late reproductive age women at least 40 years of age (mean age 45.6). On cycle day 1-4, serum hormone levels (FSH, LH, Estradiol, Inhibin B, AMH) and ovarian ultrasound measurements (ovarian volume and Antral Follicle Counts) were obtained. Survivors were categorized into 2 dose groups; a high dose chemotherapy group (treatment with cytoxan > 15 g/m2 and/or ifosfamide > 40 g/m2 and/or bone marrow transplant), and a low dose chemotherapy group (other therapy). Hormones (log transformed) and ultrasound measures were compared between survivors overall, dose groups and control groups using linear regression models. Pairwise comparisons were made between using ttests. Two tailed p value<0.05 considered statistically significant. RESULTS: Baseline characteristics were similar between groups. AMH, Inhibin B and total AFC were significantly different between cancer survivors vs. age matched controls (AMH: P< 0.001; Inhibin B: P=0.046; AFC: P<0.001). Comparison of chemotherapy dose groups revealed significant differences in AMH (P=0.008) and AFC (P<0.026) with increasing dose. Measures were similar between women who received high dose chemotherapy and late reproductive age women.TableControlLow DoseHigh DoseLate Repro Controlp valueAge24.822.32445.6FSH (Miu/ml)7.998.7113.4912.130.07E2 (pg/ml)39.0624.9026.9947.270.45Inh B (pg/ml)43.3443.3336.9014.34<0.001AMH (ng/L)3298.71510.1417.8532.5<0.001Ovarian vol8.529.066.426.640.34AFC11.676.793.53.92<0.001Linear regression results adjusted for BMI and race. Open table in a new tab Linear regression results adjusted for BMI and race. CONCLUSIONS: Ovarian function is impaired in female cancer survivors compared to similar aged controls, particularly among those who received high dose therapy. Ovarian function of women who received high dose therapy is similar to women in their mid 40′s. Prospective studies are needed to determine whether these measures correlate with fertility and age at menopause.