{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T01:34:27Z","timestamp":1768354467176,"version":"3.49.0"},"reference-count":49,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:00:00Z","timestamp":1684454400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Endometriosis and autoimmune diseases share a hyper-inflammatory state that might negatively impact the embryo\u2013endometrium 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\u2013embryo 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\u20130.90) 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.<\/jats:p>","DOI":"10.3390\/jcm12103557","type":"journal-article","created":{"date-parts":[[2023,5,19]],"date-time":"2023-05-19T00:55:29Z","timestamp":1684457729000},"page":"3557","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Concomitant Autoimmunity in Endometriosis Impairs Endometrium\u2013Embryo Crosstalk at the Implantation Site: A Multicenter Case-Control Study"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3239-3799","authenticated-orcid":false,"given":"Noemi","family":"Salmeri","sequence":"first","affiliation":[{"name":"Gynecology\/Obstetrics Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4390-9428","authenticated-orcid":false,"given":"Gianluca","family":"Gennarelli","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology, Physiopathology of Reproduction and IVF Unit, Department of Surgical Sciences, Sant\u2019Anna Hospital, University of Torino, 10124 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valeria Stella","family":"Vanni","sequence":"additional","affiliation":[{"name":"Gynecology\/Obstetrics Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefano","family":"Ferrari","sequence":"additional","affiliation":[{"name":"Gynecology\/Obstetrics Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandro","family":"Ruffa","sequence":"additional","affiliation":[{"name":"Obstetrics and Gynecology, Physiopathology of Reproduction and IVF Unit, Department of Surgical Sciences, Sant\u2019Anna Hospital, University of Torino, 10124 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrizia","family":"Rovere-Querini","sequence":"additional","affiliation":[{"name":"Division of Immunology, Transplantation, and Infectious Diseases, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3960-7454","authenticated-orcid":false,"given":"Luca","family":"Pagliardini","sequence":"additional","affiliation":[{"name":"Gynecology\/Obstetrics Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"},{"name":"Department of Brain and Behavioral Sciences, University of Pavia, 27100 Pavia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Candiani","sequence":"additional","affiliation":[{"name":"Gynecology\/Obstetrics Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Enrico","family":"Papaleo","sequence":"additional","affiliation":[{"name":"Gynecology\/Obstetrics Unit, IRCCS San Raffaele Scientific Institute, 20132 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1789","DOI":"10.1016\/S0140-6736(04)17403-5","article-title":"Endometriosis","volume":"364","author":"Giudice","year":"2004","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1097\/GRF.0b013e3181db7c33","article-title":"Immunology of endometriosis","volume":"53","author":"Barrier","year":"2010","journal-title":"Clin. Obstet. Gynecol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/jog.13559","article-title":"Involvement of immune cells in the pathogenesis of endometriosis","volume":"44","author":"Izumi","year":"2018","journal-title":"J. Obs. Gynaecol. Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1093\/humrep\/17.10.2715","article-title":"High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: A survey analysis","volume":"17","author":"Sinaii","year":"2002","journal-title":"Hum. Reprod."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1093\/humupd\/dmz014","article-title":"The association between endometriosis and autoimmune diseases: A systematic review and meta-analysis","volume":"25","author":"Shigesi","year":"2019","journal-title":"Hum. Reprod. Update"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1475","DOI":"10.1093\/humrep\/dew085","article-title":"A prospective cohort study of endometriosis and subsequent risk of infertility","volume":"31","author":"Prescott","year":"2016","journal-title":"Hum. Reprod."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e13384","DOI":"10.1111\/aji.13384","article-title":"Endometriosis with infertility: A comprehensive review on the role of immune deregulation and immunomodulation therapy","volume":"85","author":"Kolanska","year":"2021","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1034\/j.1600-0897.2003.01207.x","article-title":"The role of cytokines in endometriosis","volume":"49","author":"Wu","year":"2003","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1093\/humupd\/6.1.67","article-title":"Follicular hormonal environment and embryo quality in women with endometriosis","volume":"6","author":"Garrido","year":"2000","journal-title":"Hum. Reprod. Update"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Simopoulou, M., Rapani, A., Grigoriadis, S., Pantou, A., Tsioulou, P., Maziotis, E., Tzanakaki, D., Triantafyllidou, O., Kalampokas, T., and Siristatidis, C. (2021). Getting to Know Endometriosis-Related Infertility Better: A Review on How Endometriosis Affects Oocyte Quality and Embryo Development. Biomedicines, 9.","DOI":"10.3390\/biomedicines9030273"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1093\/humrep\/10.suppl_2.91","article-title":"Exploring the mechanism(s) of endometriosis-related infertility: An analysis of embryo development and implantation in assisted reproduction","volume":"10","author":"Pellicer","year":"1995","journal-title":"Hum. Reprod."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1093\/humupd\/dmm011","article-title":"The role of the endometrium and embryo in human implantation","volume":"13","author":"Diedrich","year":"2007","journal-title":"Hum. Reprod. Update"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/aji.12493","article-title":"Unexplained Recurrent Miscarriage and Recurrent Implantation Failure: Is There a Place for Immunomodulation?","volume":"76","author":"Mekinian","year":"2016","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_14","first-page":"575","article-title":"Does autoimmunity play a role in the risk of implantation failures?","volume":"38","author":"Malinowski","year":"2018","journal-title":"Neuro Endocrinol. Lett."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"100698","DOI":"10.1016\/j.repbio.2022.100698","article-title":"Role of inflammatory factors in the etiology and treatment of recurrent implantation failure","volume":"22","author":"Wang","year":"2022","journal-title":"Reprod. Biol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"752","DOI":"10.1080\/09513590.2018.1442427","article-title":"The influence of thyroid autoimmunity on embryo quality in women undergoing assisted reproductive technology","volume":"34","author":"Andrisani","year":"2018","journal-title":"Gynecol. Endocrinol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1186\/s12958-019-0529-0","article-title":"Serum and follicular fluid thyroid hormone levels and assisted reproductive technology outcomes","volume":"17","author":"Cai","year":"2019","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_18","first-page":"169","article-title":"Basal progesterone level as the main determinant of progesterone elevation on the day of hCG triggering in controlled ovarian stimulation cycles","volume":"290","author":"Papaleo","year":"2014","journal-title":"Arch. Gynecol. Obs."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"15372","DOI":"10.1038\/s41598-021-94877-z","article-title":"Concomitant autoimmunity may be a predictor of more severe stages of endometriosis","volume":"11","author":"Vanni","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"International Working Group of AAGL, ESGE, ESHRE and WES, Vermeulen, N., Abrao, M.S., Einarsson, J.I., Horne, A.W., Johnson, N.P., Lee, T.T.M., Missmer, S., Petrozza, J., and Tomassetti, C. (2021). Endometriosis classification, staging and reporting systems: A review on the road to a universally accepted endometriosis classification. Hum. Reprod. Open, 2021, hoab025.","DOI":"10.1093\/hropen\/hoab025"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"ESHRE working group on Poor Ovarian Response Definition, Ferraretti, A.P., La Marca, A., Fauser, B.C., Tarlatzis, B., Nargund, G., and Gianaroli, L. (2011). ESHRE consensus on the definition of \u2018poor response\u2019 to ovarian stimulation for in vitro fertilization: The Bologna criteria. Hum. Reprod., 26, 1616\u20131624.","DOI":"10.1093\/humrep\/der092"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1270","DOI":"10.1016\/j.fertnstert.2013.06.049","article-title":"Using the ovarian sensitivity index to define poor, normal, and high response after controlled ovarian hyperstimulation in the long gonadotropin-releasing hormone-agonist protocol: Suggestions for a new principle to solve an old problem","volume":"100","author":"Huber","year":"2013","journal-title":"Fertil. Steril."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.fertnstert.2017.06.005","article-title":"The International Glossary on Infertility and Fertility Care, 2017","volume":"108","author":"Adamson","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.fertnstert.2017.05.031","article-title":"Endometrial receptivity in the eutopic endometrium of women with endometriosis: It is affected, and let me show you why","volume":"108","author":"Lessey","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_25","first-page":"564","article-title":"The endometrial immune environment of women with endometriosis","volume":"25","author":"Houshdaran","year":"2019","journal-title":"Hum. Reprod. Update"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3792","DOI":"10.3390\/cimb44090260","article-title":"Inflammation-Related Molecules at the Maternal-Fetal Interface during Pregnancy and in Pathologically Altered Endometrium","volume":"44","author":"Sieg","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1016\/j.fertnstert.2017.06.002","article-title":"Endometrial receptivity in eutopic endometrium in patients with endometriosis: It is not affected, and let me show you why","volume":"108","year":"2017","journal-title":"Fertil. Steril."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e13593","DOI":"10.1111\/aji.13593","article-title":"Oxidative stress-related effects on various aspects of endometriosis","volume":"88","author":"Ansariniya","year":"2022","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1055\/s-0032-1333483","article-title":"Oocyte donation and endometriosis: What are the lessons?","volume":"31","author":"Hauzman","year":"2013","journal-title":"Semin. Reprod. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1034\/j.1600-0897.2003.00042.x","article-title":"Immunology and endometriosis","volume":"50","author":"Berkkanoglu","year":"2003","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"e13633","DOI":"10.1111\/aji.13633","article-title":"The cytokine profiles in follicular fluid and reproductive outcomes in women with endometriosis","volume":"89","author":"Han","year":"2022","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1093\/humupd\/dmac025","article-title":"Bioengineering trends in female reproduction: A systematic review","volume":"28","author":"Lopez","year":"2022","journal-title":"Hum. Reprod. Update"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e13560","DOI":"10.1111\/aji.13560","article-title":"Antinuclear antibodies in follicular fluid may be a risk factor in vitro fertilization and embryo transfer","volume":"88","author":"Wu","year":"2022","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e13289","DOI":"10.1111\/aji.13289","article-title":"Antinuclear antibodies in FF may reduce efficacy of in vitro fertilization and embryo transfer by invading endometrium and granular cells","volume":"84","author":"Li","year":"2020","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"458","DOI":"10.3109\/08820139.2012.660266","article-title":"Antinuclear antibodies predicts a poor IVF-ET outcome: Impaired egg and embryo development and reduced pregnancy rate","volume":"41","author":"Ying","year":"2012","journal-title":"Immunol. Investig."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"680","DOI":"10.1111\/j.1471-0528.1991.tb13455.x","article-title":"Autoreactivity in women with endometriosis","volume":"98","author":"Taylor","year":"1991","journal-title":"Br. J. Obs. Gynaecol."},{"key":"ref_37","first-page":"458","article-title":"Immune abnormalities in endometriosis compromising fertility in IVF-ET patients","volume":"44","author":"Lucena","year":"1999","journal-title":"J. Reprod. Med."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1038\/ncpendmet0846","article-title":"The role of thyroid autoimmunity in fertility and pregnancy","volume":"4","author":"Poppe","year":"2008","journal-title":"Nat. Clin. Pract. Endocrinol. Metab."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Tan, J., Cerrillo, M., Cruz, M., Cecchino, G.N., and Garcia-Velasco, J.A. (2021). Early Pregnancy Outcomes in Fresh Versus Deferred Embryo Transfer Cycles for Endometriosis-Associated Infertility: A Retrospective Cohort Study. J. Clin. Med., 10.","DOI":"10.3390\/jcm10020344"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"hoac016","DOI":"10.1093\/hropen\/hoac016","article-title":"The mid-secretory endometrial transcriptomic landscape in endometriosis: A meta-analysis","volume":"2022","author":"Vargas","year":"2022","journal-title":"Hum. Reprod. Open"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1038\/s41598-019-57207-y","article-title":"Transcriptome meta-analysis reveals differences of immune profile between eutopic endometrium from stage I-II and III-IV endometriosis independently of hormonal milieu","volume":"10","author":"Meola","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Boucher, A., Brichant, G., Gridelet, V., Nisolle, M., Ravet, S., Timmermans, M., and Henry, L. (2022). Implantation Failure in Endometriosis Patients: Etiopathogenesis. J. Clin. Med., 11.","DOI":"10.3390\/jcm11185366"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1111\/aji.12259","article-title":"Characterization of uterine NK cells in women with infertility or recurrent pregnancy loss and associated endometriosis","volume":"72","author":"Giuliani","year":"2014","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_44","first-page":"18","article-title":"Uterine CD56dim and CD16+ Cells in Refractory Antiphospholipid Antibody-Related Pregnancy Loss and Chromosomally Intact Abortuses: A Case-Control Study","volume":"10","author":"Gomaa","year":"2017","journal-title":"J. Hum. Reprod. Sci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/S1472-6483(10)62016-0","article-title":"Endometriosis, recurrent miscarriage and implantation failure: Is there an immunological link?","volume":"13","author":"Tomassetti","year":"2006","journal-title":"Reprod. Biomed. Online"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1016\/S0140-6736(10)60490-4","article-title":"Endometriosis and infertility: Pathophysiology and management","volume":"376","author":"Borghese","year":"2010","journal-title":"Lancet"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Szubert, M., Kozir\u00f3g, E., Olszak, O., Krygier-Kurz, K., Kazmierczak, J., and Wilczynski, J. (2021). Adenomyosis and Infertility-Review of Medical and Surgical Approaches. Int. J. Env. Res. Public Health, 18.","DOI":"10.3390\/ijerph18031235"},{"key":"ref_48","first-page":"CD009591","article-title":"Imaging modalities for the non-invasive diagnosis of endometriosis","volume":"2","author":"Nisenblat","year":"2016","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1016\/j.rbmo.2021.08.008","article-title":"Focus on time-lapse analysis: Blastocyst collapse and morphometric assessment as new features of embryo viability","volume":"43","author":"Sciorio","year":"2021","journal-title":"Reprod. Biomed. Online"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/10\/3557\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T19:38:11Z","timestamp":1760125091000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/10\/3557"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,19]]},"references-count":49,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,5]]}},"alternative-id":["jcm12103557"],"URL":"https:\/\/doi.org\/10.3390\/jcm12103557","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,19]]}}}