Endometriosis with infertility: A comprehensive review on the role of immune deregulation and immunomodulation therapy

Abstract Background Endometriosis is a multifactorial pathology dependent on intrinsic and extrinsic factors, but the immune deregulation seems to play a pivotal role. In endometriosis‐associated infertility, this could raise the benefit of immunomodulatory strategies to improve the results of ART. In this review, we will describe (1) sera and peritoneal fluid cytokines and immune markers; (2) autoantibodies; and (3) immunomodulatory treatments in endometriosis with infertility. Methods The literature research was conducted in MEDLINE, Embase, and Cochrane Library with the following keywords: “endometriosis”, “unexplained miscarriage”, “implantation failure”, “recurrent implantation failure » and « IVF‐ICSI », « biomarkers of autoimmunity”, “TNF‐α”, “TNF‐α antagonists”, “infliximab”, “adalimumab”, “etanercept”, “immunomodulatory treatment”, “steroids”, “intralipids”, “intravenous immunoglobulins”, “G‐CSF”, “pentoxyfylline”. Results Several studies analyzed the levels of pro‐inflammatory cytokines in sera and peritoneal fluid of endometriosis‐associated infertility, in particular TNF‐α. Various autoantibodies have been found in peritoneal fluid and sera of infertile endometriosis women even in the absence of clinically defined autoimmune disease, as antinuclear, anti‐SSA, and antiphospholipid autoantibodies. In few uncontrolled studies, steroids and TNF‐α antagonists could increase the pregnancy rates in endometriosis‐associated infertility, but well‐designed trials are lacking. Conclusion Endometriosis is characterized by increased levels of cytokines and autoantibodies. This suggests the role of inflammation and immune cell deregulation in infertility associated with endometriosis. The strategies of immunomodulation to regulate these immune deregulations are poorly studied, and well‐designed studies are necessary.