DNA repair genes Minichromosome maintenance complex component (MCM) 8 and 9 have been linked with gonadal development, primary ovarian insufficiency (POI), and age at menopause. Our objectives were to characterize MCM 8/9 gene expression in the menstrual cycle and to compare MCM 8/9 expression in POI subjects with normo-ovulatory controls. Prospective cohort Normo-ovulatory controls (n=11) and unexplained POI subjects (n=6) were recruited. For 5 of 11 controls, 3 blood samples were taken within a single menstrual cycle: 1) early follicular phase, 2) ovulation, 3) mid-luteal phase. Controls who were unable to provide multiple blood samples (n=6/11) were drawn only in the follicular phase. All POI patients were amenorrheic and provided a single, random blood sample. RNA was extracted from whole blood and cDNA synthesis performed. MCM8 and 9 mRNA expression was assessed with quantitative real-time PCR. To compare differences across different menstrual cycle phases, a random effects ANOVA analysis was performed. Two-sample t-tests were used to compare two groups. All analyses were performed using delta-Ct measurements; group differences were transformed to a fold change (FC) and confidence interval (CI) for interpretation. In normo-ovulatory subjects (n=5) who submitted 3 samples within the same cycle, significantly higher MCM8 gene expression was noted in the early follicular phase, when compared to ovulation and mid-luteal phase. The FC was 0.69 in the luteal vs follicular phase (p= 0.012, CI = 0.53, 0.90); and 0.65 in the ovulatory vs follicular phase (p=0.0057, CI = 0.50, 0.85). No significant change in MCM9 gene expression was noted throughout the menstrual cycle phases. The FC= 0.84 in the luteal vs follicular phase (p= 0.512, CI = 0.48, 1.49) and 1.18 in the ovulatory vs follicular phase (p=0.523, CI = 0.67, 2.07). There was no statistically significant difference seen in MCM8 or 9 expression when comparing POI subjects (n=6) to control subjects in the follicular phase (n=11) or in the ovulatory/luteal phases (n=5); however ovulatory values for both MCM8 and 9 trend toward significance. MCM8 showed FC = 1.11 (p = 0.5875, CI= 0.74, 1.65) for POI subjects relative to controls in the follicular phase; FC= 1.53 (p=0.104, CI=0.9, 2.62) at ovulation; and FC = 1.45 (p= 0.115, CI= 0.9, 2.35) in the luteal phase. MCM9 showed FC= 0.75 (p = 0.316, CI= 0.41, 1.36) in the follicular phase; FC= 0.56 (p=0.059, CI=0.31, 1.03) at ovulation; and FC = 0.79 (p= 0.466, CI= 0.38, 1.61) in the luteal phase. Our study showed greater MCM8 gene expression in the follicular phase of the menstrual cycle, compared to the ovulatory and luteal phases. This cyclical change was not seen with MCM9. Due to small sample size, significant differences in MCM8/9 gene expression were not detected between POI and controls, although there is some evidence of greater MCM8 and lower MCM9 expression relative to controls at ovulation. We recommend further investigation with a larger sample population to explore this potential effect.