Causal Relationship Between Antibody‐Mediated Immune Responses of Chlamydia trachomatis Infection and Reproductive Tract Complications: A Bidirectional Mendelian Randomization Study

ABSTRACT Purpose Characterized as a prevalent sexually transmitted infection, Chlamydia trachomatis is intimately associated with reproductive tract complications, including pelvic inflammatory disease (PID) and infertility. However, the causal relationships between C. trachomatis infection and reproductive tract complications remain elusive. Methods To investigate the causal relationships between C. trachomatis antibodies and seven reproductive tract complications, we conducted a bidirectional Mendelian randomization (MR) analysis. The fundamental data were originated from the genome‐wide association studies (GWAS) database. While the influences of C. trachomatis antibodies on reproductive tract complications such as tubal factor infertility (TFI) and PID have been assessed, the reverse MR analysis examined how these complications impacted C. trachomatis antibodies. Results The forward MR analysis revealed that the upregulation of MOMP A antibodies was significantly associated with a reduced risk of TFI (OR = 0.932, p = 0.007), while MOMP D antibodies were associated with a reduced risk of ectopic pregnancy (EP) (OR = 0.923, p = 0.005). However, no significant causal interactions were identified for other reproductive complications. Moreover, the reverse MR analysis indicated that cervicitis was significantly correlated with lower MOMP A antibody levels (OR = 0.900, p = 0.016). Conclusions This study demonstrates the protective effects of C. trachomatis antibodies, particularly MOMP A and MOMP D, against TFI and EP, respectively. It also emphasizes the potential role of cervical inflammation in shaping immune responses to C. trachomatis . These insights provide a foundation for future research to develop immune‐targeted therapies and integrated approaches for preventing and managing C. trachomatis ‐related reproductive tract complications.