Hydroxychloroquine Based Immunomodulatory Therapy Improves Pregnancy Outcomes in Women with Recurrent Implantation Failure Undergoing in Vitro Fertilization and Embryo Transfer

Problem Recurrent implantation failure (RIF) remains a significant challenge in reproductive medicine, with immune dysfunction being a key contributing factor to implantation failure. However, data on the effectiveness of immunomodulatory therapy in RIF patients remain limited. This study aimed to assess the impact of immunomodulatory therapy on pregnancy outcomes in women with RIF undergoing in Vitro fertilization‐embryo transfer (IVF‐ET). Method of Study This retrospective cohort study included women with RIF between 2016 and 2019. Patients in the treatment group received hydroxychloroquine (HCQ)‐based immunomodulatory therapy after immunological evaluation, while those in the control group did not receive immunomodulatory treatment. Generalized estimating equations assessed the association between HCQ‐based immunomodulatory therapy and pregnancy outcomes. Additionally, patients were stratified based on autoimmune antibody status, and subgroup analyses were conducted to further evaluate treatment effects. Results A total of 320 patients were included in the study, with 74 receiving HCQ‐based immunomodulatory therapy (treatment group) and 246 undergoing IVF‐ET alone (control group). The treatment group showed higher biochemical pregnancy (49.5% vs. 31.7%, p < 0.001), clinical pregnancy (43.8% vs. 24.3%, p < 0.001), embryo implantation (30.7% vs. 17.3%, p < 0.001), and live birth rates (33.3% vs. 12.6%, p < 0.001). Multivariate regression identified HCQ‐based immunomodulatory therapy as an independent predictor of biochemical pregnancy (OR = 2.049, 95% CI: 1.440‐2.915, P <0.001), clinical pregnancy (OR = 2.424, 95% CI: 1.613‐3.644, P <0.001), and live birth (OR = 3.555, 95% CI: 2.235‐5.652, P <0.001). Stratified analysis confirmed its benefit in both autoimmune antibody positive and negative patients. Conclusions Real‐world evidence revealed the potential role of HCQ‐based immunomodulatory therapy in improving pregnancy outcomes in IVF‐ET in patients with RIF.