Effect of anti-nuclear antibody positivity with negative specific anti-extractable anti-nuclear antibodies on IVF and ICSI embryological outcomes: potential role of sperm concentration.

RESEARCH QUESTION: Anti-extractable nuclear antigens (ENA) and anti-nuclear antibodies (ANA) impair oocyte and embryo quality. What are the embryo laboratory outcomes in ANA-positive but anti-ENA-negative patients?

DESIGN

ANA-positive women (n = 113) undergoing their first IVF/ICSI cycle and matched ANA-negative women (n = 213) were included. Clinical characteristics and IVF/ICSI outcomes were compared between groups. Multivariable linear regression controlled for confounders to assess the relationship between ANA positivity and laboratory outcomes. Subgroup analysis explored the interaction between clinical factors and ANA status. Restricted cubic splines (RCS) examined dose-response relationships. Post-hoc analysis assessed the accuracy and reliability of the results.

RESULTS

ANA-positive infertile patients had significantly fewer two pronuclei (2PN) embryos (P = 0.022), cleavage embryos (P = 0.036), 2PN cleavage embryos (P = 0.025), available embryos (P = 0.009), high-quality embryos (P = 0.010), blastocysts, (P = 0.006) and high-quality blastocysts (P = 0.004) compared with ANA-negative infertile patients, despite similar clinical characteristics. Multivariable regression identified ANA positivity as an independent risk factor for poorer embryo outcomes. Subgroup analysis and RCS indicated that higher sperm concentration improved high-quality blastocyst numbers in the ANA-positive group, but had no effect in the ANA-negative group. Post-hoc analysis showed statistical power exceeding 95.0% before PSM, with an effect size ranging from 0.380 to 0.592. After PSM, statistical power decreased to 57.9-74.2%, with an effect size of 0.252-0.305.

CONCLUSION

ANA positivity in serum, irrespective of ENA status, may adversely affect embryo laboratory outcomes in infertile patients undergoing their first IVF/ICSI cycle. Sperm concentration may improve embryo outcomes in ANA-positive patients. Relevant ANA testing before ART is essential for these patients.