Effect of timing of gonadotropin-releasing hormone agonist administration for ovarian protection in patients with breast cancer

Purpose: This study was performed to investigate the effect of the interval between the start of gonadotropin-releasing hormone agonist (GnRHa) and the start of chemotherapy on ovarian protection in patients with breast cancer. Methods: This was a prospective observational cohort study that included 136 patients with breast cancer below 40 years who received GnRHa during chemotherapy for fertility preservation. Plasma anti-Mfillerian hormone (AMH) levels were measured before chemotherapy (baseline) and after chemotherapy. Subjects were divided into 3 groups according to the interval between the start of GnRHa and the start of chemotherapy for analysis: 1-6 days, 7-13 days, and >= 14 days. The ratio of the post-chemotherapy AMH value to the baseline AMH (pcAMH) at each time point were compared among the 3 groups. Ranked analysis of covariance was used for statistical analysis, adjusted for age, body mass index (BMI), and the existence of polycystic ovaries (PCOs). In addition, recovery of ovarian function (AMH >= 1 ng/mL) at 12 months was evaluated. Results: The median age of the patients was 32 years. There was no difference in the baseline AMH levels among the 3 groups (mean +/- standard error: 5.0 +/- 0.4 ng/mL [1-6 days], 5.3 +/- 0.7 ng/mL [7-13 days], and 8.1 +/- 1.3 ng/mL [>= 14 days]; p = 0.250). The pcAMH at 3, 6,12, 24, and 36 months were not significantly different among the 3 groups (p-values were 0.332, 0.732, 0.830, 0.148, and 0.393, respectively). In multivariate analysis, young age (p= 0.024), low BMI (p = 0.013), and the existence of PCO (p = 0.015) were predictors for AMH >= 1 ng/mL at 12 months. Conclusion: There was no difference in the ovarian protective effect according to the difference in the timing of administration of GnRHa