Effects of Immunosuppressive Treatments on Pregnancy Outcomes in Infertile Women: A Systematic Review of Clinical Trials

Background: Despite recent significant advances in the field of in-vitro fertilization (IVF), repeated implantation failure (RIF) remains a serious challenge for fertility. The suppression and regulation of the immune system by using immunomodulatory or immunosuppressive agents are one of the key ways to reduce RIF. The present study aimed to review the literature on the effect of immunosuppressive drugs on pregnancy outcomes, in infertile women with RIF.
Materials and Methods: In this systematic review, two independent reviewers selected related articles from online databases (Scopus, EMBASE, Cochrane Central Register of Controlled Trials, International Registry Platform for ongoing trials and clinical trails.gov, Web of Science, CINAHL, Medline, and Google Scholar search engine), without time limits from the inception restrictions up to July 2022.
Results: Fertilization, implantation, and clinical pregnancy rates were significantly higher in the prednisone + HCQ group than in the prednisone group. However, abortion rates were not different between the two groups. In a retrospective cohort study, there was no difference between the groups treated with prednisone +‎ hydroxychloroquine + cyclosporine (PDN + HCQ + CsA), prednisone + hydroxychloroquine (PDN + HCQ), and PDN compared with untreated patients in the rate of live birth, implantation, biochemical, and clinical pregnancy (p>0.05). Treatment with HCQ significantly down-regulated Th17-related cytokines and function and up-regulated T-reg-related cytokines and function (p<0.001). Hydroxychloroquine (400 mg/orally per day) treatment significantly decreased the serum level of TNF-α and significantly increased the serum level of IL-10 (p< 0.0001).
Conclusion: Based on the combined results, immunoregulatory agents can be effective in fertilization, clinical pregnancy, live birth, and implantation rates. However, it was not effective in reducing abortion rates and biochemical pregnancy.