Epigenetic clock measuring age acceleration via DNA methylation levels in blood is associated with decreased oocyte yield.

PURPOSE: To investigate how biologic age (phenotypic age at which your body functions) greater than chronologic age, (age acceleration (AgeAccel)), correlates with oocyte yield. METHODS: Thirty-nine women undergoing ovarian stimulation, inclusive of all infertility diagnoses, were included in this pilot study. Methylome analysis of peripheral blood was utilized to determine biologic age. AgeAccel was defined as biologic age > 2 years older than chronologic age. A negative binomial model was used to obtain the crude association of AgeAccel with number of oocytes. A parsimonious adjusted model for the number of oocytes was obtained using backwards selection (p < 0.05). RESULTS: Measures of age were negatively correlated with number of oocytes (chronological age Pearson ρ = - 0.45, biologic age Pearson ρ = - 0.46) and AMH was positively correlated with number of oocytes (Pearson ρ = 0.91). Patients with AgeAccel were noted to have lower AMH values (1.29 ng/mL vs. 2.29, respectively (p = 0.049)) and lower oocyte yield (5.50 oocytes vs. 14.50 oocytes, respectively (p = 0.0030)). A crude association of a 7-oocyte reduction in the age-accelerated group was found (- 6.9 oocytes (CI - 11.6, - 2.4)). In a model with AMH and antral follicle count, AgeAccel was associated with a statistically significant 3.3 reduction in the number of oocytes (- 3.1; 95% CI - 6.5, - 0.1; p = 0.036). CONCLUSIONS: In this small pilot study, AgeAccel is associated with a lower AMH and lower oocyte yield providing preliminary evidence that biologic age, specifically AgeAccel, may serve as an epigenetic biomarker to improve the ability of predictive models to assess ovarian reserve.