Anticentromere antibodies are the most potent antinuclear antibodies in reducing live birth outcomes after ICSI.

RESEARCH QUESTION: How, and to what extent, do anticentromere antibodies (ACA) reduce live birth outcomes after ICSI?

STUDY

DESIGN

Retrospective cohort study of infertile women aged 30-43 years who underwent ICSI between September 2016 and March 2021. Women with a history or current diagnosis of symptomatic connective tissue disease were excluded. Immunofluorescence staining detected antinuclear antibodies (ANA). Staining pattern and titre (cut-off, 1:160) were used to divide infertile women into three groups: positive for ACA (ACA+) (n = 28); positive for ANA other than ACA (ANA+) (n = 77); and negative for both ACA and ANA (control) (n = 3723).

RESULTS

Cumulative live birth rate (CLB) was lowest in ACA+ (7%, 31% and 46% in ACA+, ANA+ and control, respectively) (ACA+ versus control, P < 0.0001; ACA+ versus ANA+, P = 0.011; ANA+ versus control, P = 0.012). A small impairment in meiosis I and a larger impairment in meiosis II, fertilization and embryo cleavage caused the decrease. Multiple pronuclei formation increased (RR versus control, 5.33; 95% CI 4.26 to 6.65) and good-quality blastocyst development decreased (RR 0.34; 95% CI 0.22 to 0.53). Multiple logistic regression analysis showed that ACA was associated with CLB outcome (OR 0.08, 95% CI 0.02 to 0.36); the other four ANA staining patterns were not.

CONCLUSIONS

The effect of ACA on live birth outcomes is strongest after ICSI among ANA, primarily through the impairment of meiosis II and subsequent stages. Repeated ICSI failure and eggs with multiple pronuclei may warrant specific testing for ACA.