Women of advanced maternal age or carrying the fragile X premutation (55-200 CGG repeat expansion, PM) are at risk for developing diminished ovarian reserve (DOR). DOR in PM patients can also progress into fragile X-associated primary ovarian insufficiency (FXPOI). So far, the cause of DOR in these patients could not be comprehensively examined due to the scarcity of human ovarian tissue and oocytes. From studies in model systems, it has been proposed that molecular abnormalities within the ovaries or a diminished primordial follicle pool may cause DOR. To elucidate the defects instigating DOR in these patients, we are examining human oocytes obtained from PM carriers undergoing in vitro fertilization (IVF). We found that the number of MII oocytes was reduced, suggesting that the maturation of the oocytes is constrained. In anaphase I, these oocytes failed to initiate the protrusion of the first polar body. In addition, these oocytes amassed bundle actin structures, lacked an actin cap, and had elevated profilin1 levels. Profilin1 limits the formation of branched actin structures, which are necessary for actin cap formation and membrane protrusions. We found that an increase in FMRP elevates the profilin1 translation, which leads to cytoskeleton defects and deficiencies in the formation of the first polar body. In addition, we detected that the profilin1 expression and formation of the actin cytoskeleton were dysregulated due to the appearance of cytoplasmic FMRP foci in aged human oocytes. Thus, these results reveal that defects during anaphase I hinder the maturation of human oocytes, resulting in FXDOR/FXPOI in PM carriers and a reduction in mature oocytes in women with advanced maternal age.