Older Oligoasthenozoospermic Men Have Altered Telomere Biology and Less Chances Than Controls for Assisted Reproductive Technology Outcomes (Art)

Abstract

To determine the longitudinal impact of adjuvant chemotherapy and tamoxifen-only treatments on the ovarian reserve recovery patterns of women with breast cancer by using a ultra-sensitive Anti-Mullerian Hormone (AMH) assay.DESIGN: Multi-Center Prospective Longitudinal. MATERIALS AND METHODS: One-hundred.-and-forty-two women with a primary diagnosis of breast cancer were prospectively followed with serum AMH assessments before the initiation, and 12, 18 and 24 months after the completion of adjuvant chemotherapy or the start of tamoxifen-only treatment. The chemotherapy regimens were classified into Anthracycline-Cyclophosphamide-based (AC-based) and Cyclophosphamide-Metho-trexate+5-Fluorouracil (CMF). Longitudinal data were analyzed by mixed effects model for treatment effects over time, adjusting for baseline age and BMI.RESULTS: Both chemotherapy regimens resulted in significant decline in ovarian reserve compared to the tamoxifen-only treatment (p<0.0001 either regimen vs. tamoxifen for overall trend). The AMH levels sharply declined at 12 months and the level of decline did not differ between the two chemotherapy groups (p¼0.53).There was no significant recovery from 12 to 18 and 18 to 24 months after the completion of AC-based or CMF regimens (p¼0.97). While the mean/median AMH level was 0.34/0.09 ng/dl at the 12-month time point, it was 0.40/0.06 ng/dl and 0.42/0.07 ng/dl at 18-and 24-month time points for the AC-based regimens group. These values were 0.11/0.03, 0.12/0.02 and 0.20/0.03 at the 3 time points for the CMF group. These mean levels are substantially below the threshold for normal ovarian reserve, which is generally 1.1 ng/mL or higher for the age group. AMH levels remained undetectable in 20% (15/76) vs. 38% (5/13) of women in the AC-based regimens vs. CMF groups at 24 months (p¼0.16 from Fisher exact test). In contrast, tamoxifen-only treatment did not significantly alter the age-adjusted serum AMH levels over the 24-month follow up. Likewise, the use of adjuvant tamoxifen following AC-based regimens did not affect AMH recovery.CONCLUSIONS: Our study is the first to assess ovarian reserve changes with serum AMH in a prospective longitudinal fashion, with multiple time points up to 24-month post-completion of chemotherapy, and in comparison with tamoxifen-only treatments. It shows that both AC-based regimens and CMF significantly compromise ovarian reserve, without a recovery beyond 12 months post-chemotherapy. In contrast, tamoxifen-only treatment does not alter serum AMH levels. The latter also indicates that the ovarian reserve of women who are on long-term tamoxifen treatment can be reliably assessed by serum AMH. This study provides novel information which will be useful in counseling young women with breast cancer for fertility preservation and in assessing post-chemotherapy ovarian damage and recovery.