Concomitant Autoimmunity in Endometriosis Impairs Endometrium–Embryo Crosstalk at the Implantation Site: A Multicenter Case-Control Study

Abstract

Endometriosis and autoimmune diseases share a hyper-inflammatory state that might negatively impact the embryo–endometrium crosstalk. Inflammatory and immune deregulatory mechanisms have been shown to impair both endometrial receptivity and embryo competence at the implantation site. The aim of this study was to investigate the potential additional impact of co-existing autoimmunity in women affected by endometriosis on the early stages of reproduction. This was a retrospective, multicenter case-control study enrolling N = 600 women with endometriosis who underwent in vitro fertilization–embryo transfer cycles between 2007 and 2021. Cases were women with endometriosis and concomitant autoimmunity matched based on age and body mass index to controls with endometriosis only in a 1:3 ratio. The primary outcome was the cumulative clinical pregnancy rate (cCPR). The study found significantly lower cleavage (p = 0.042) and implantation (p = 0.029) rates among cases. Autoimmunity (p = 0.018), age (p = 0.007), and expected poor response (p = 0.014) were significant negative predictors of cCPR, with an adjusted odds ratio of 0.54 (95% CI, 0.33–0.90) for autoimmunity. These results suggest that the presence of concomitant autoimmunity in endometriosis has a significant additive negative impact on embryo implantation. This effect might be due to several immunological and inflammatory mechanisms that interfere with both endometrial receptivity and embryo development and deserves further consideration.

Autoantibodies research in patients with endometriosis: A cross-sectional study

“…Autoimmunity may not only enable the endometriosis appearance, but it also appears to have an in uence on endometriosis ndings. According to Almeri et al [10] the coexistence of autoimmunity in patients with endometriosis may have an additive role in problems with embryo implantation, favouring infertility in this situation. Infertility is one of the major concerns in endometriosis affecting from 30-50% of women with this disease.…”

“…[1] Autoantibodies recognizing endometrial antigens resulting from polyclonal B cell activation have also been documented in this setting. [1,[4][5][6] Other systemic and organ-speci c autoimmune diseases associated with endometriosis include systemic lupus erythematosus, [7] rheumatoid arthritis, [8] and Hashimoto thyroiditis, [9] in ammatory bowel disease, [10] and psoriasis. [10] The objective of this study was to examine the prevalence of autoantibodies such as antinuclear antibodies (ANA), antiphospholipid antibodies and anti-endomysial autoantibodies in the sera of patients with endometriosis.…”

An Estrogen–NK Cells Regulatory Axis in Endometriosis, Related Infertility, and Miscarriage

“…However, in endometriosis, estrogen-mediated signaling abnormalities may lead to decreased endometrial receptivity, impacting embryo implantation and reducing pregnancy rates in mice [ 89 , 90 ]. It was also reported that immunological and inflammatory mechanisms in endometriosis have a significant additive negative impact on embryo implantation [ 91 ]. Within this process, NK cells may play a crucial regulatory role.…”

Microbiota in Irritable Bowel Syndrome and Endometriosis: Birds of a Feather Flock Together—A Review

“…This observation aligns with the growing understanding of endometriosis as a multisystem condition characterized by diverse genetic and somatic traits [ 127 , 128 ], along with a significant association with various comorbidities, primarily autoimmune [ 129 ] and immune-related diseases [ 130 ], but also fibromyalgia [ 131 ], migraine [ 132 ], and multiple pregnancy-related disorders [ 133 , 134 , 135 ]. The etiology of these comorbidities, whether resulting from a shared pathogenesis or the chronic inflammatory response to the endometriotic lesions, remains unknown [ 136 ], although the severity of endometriosis is known to increase with the co-occurrence of comorbidities [ 137 , 138 , 139 ].…”