Metaphase-II spindle disruption in oocytes from anti-centromere antibody-positive patients leads to multi-pronuclear...

Anti-centromere antibody (ACA), a specific antinuclear antibody (ANA) subset targeting constitutive kinetochore proteins, is recognized as a potent immunological factor impairing reproductive outcomes. While these antibodies interfere with the kinetochore-microtubule interface essential for chromosome segregation, the relationship between meiotic progression involving spindle formation in human oocytes and subsequent fertilization remains largely unknown. This retrospective cohort study analyzed ovum pick-up cycles, comparing ACA-positive patients with ACA-negative and ANA-positive controls. To account for potential intra-patient correlation, a mixed-effects logistic regression model was employed, incorporating patient identification as a random effect and adjusting for age, body mass index, and anti-Müllerian hormone as fixed effects. We found that oocytes derived from ACA-positive patients had significantly lower metaphase-II maturation rates due to increased metaphase-I arrest. Following intracytoplasmic sperm injection, these oocytes demonstrated a markedly reduced two-pronuclear rate and a dramatic increase in multi-pronuclear formation. Non-invasive imaging via polarized light microscopy revealed that metaphase-II spindle visibility was significantly impaired in oocytes from ACA-positive patients. Crucially, spindle-absent oocytes within this group exhibited a higher frequency of multi-pronuclear formation and completely failed to reach the blastocyst stage. These findings suggest that the clinical presence of ACA is associated with disrupted meiotic spindle assembly, which leads to chromosomal segregation errors and subsequent developmental failure. We conclude that spindle assessment provides a valuable non-invasive prognostic indicator of oocyte quality in ACA-positive patients.