{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T22:52:43Z","timestamp":1776293563448,"version":"3.50.1"},"reference-count":56,"publisher":"Oxford University Press (OUP)","issue":"8","license":[{"start":{"date-parts":[[2020,7,2]],"date-time":"2020-07-02T00:00:00Z","timestamp":1593648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"University College Dublin Wellcome Institutional Strategic Support Fund"},{"DOI":"10.13039\/501100001631","name":"University College Dublin","doi-asserted-by":"publisher","award":["SFI-HRB"],"award-info":[{"award-number":["SFI-HRB"]}],"id":[{"id":"10.13039\/501100001631","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,8,1]]},"abstract":"Abstract<\/jats:title>STUDY QUESTION<\/jats:title>Which transcriptomic alterations in mid-luteal endometrial scratch biopsies, taken prior to the assisted reproductive treatment (ART) treatment cycle are associated with unsuccessful pregnancy?<\/jats:p><\/jats:sec>SUMMARY ANSWER<\/jats:title>Dysregulated interleukin-17 (IL-17) pathway components are demonstrated in women who fail to become pregnant after ART.<\/jats:p><\/jats:sec>WHAT IS KNOWN ALREADY<\/jats:title>Implantation failure is now recognised as a critical factor in unexplained infertility and may be an important component of failed ART.<\/jats:p><\/jats:sec>STUDY DESIGN, SIZE, DURATION<\/jats:title>Using a prospective longitudinal study design, 29 nulliparous women with unexplained infertility undergoing ART were recruited between October 2016 and February 2018. Mid-luteal stage endometrium and matched serum samples were collected, and patients underwent a single embryo transfer in the subsequent cycle. RNA-seq analysis of endometrial biopsies was performed on the discovery cohort (n = 20).<\/jats:p><\/jats:sec>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>Gene set enrichment analysis of the differentially expressed genes (DEGs) was performed. Endometrium and serum were then prepared for IL-17A analysis by ELISA.<\/jats:p><\/jats:sec>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>There were 204 differentially expressed protein-coding genes identified in tissue from women who became pregnant (n = 9) compared with tissue from women who failed to become pregnant (n = 11) (false discovery rate; P &lt; 0.05). Of the 204 DEGs, 166 were decreased while 38 were increased in the pregnant compared to the non-pregnant groups. Gene set enrichment analysis of the DEGs identified an over-representation of IL-17 and Pl3K-Akt signalling pathways. All the DEGs within the IL-17 signalling pathway (MMP3, MMP1, IL1\u03b2, LCN2, S100A9 and FOSL1) demonstrated decreased expression in the pregnant group. Serum IL-17 protein levels were increased in the non-pregnant discovery cohort (n = 11) and these findings were confirmed a validation cohort (n = 9).<\/jats:p><\/jats:sec>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>Limitations of our study include the cohort size and the lack of aneuploidy data for the embryos; however, all embryos transferred were single good or top-quality blastocysts.<\/jats:p><\/jats:sec>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>These findings demonstrate dysregulated IL-17 pathway components in women who fail to become pregnant after ART. Elevated serum levels of the pro-inflammatory cytokine IL-17 may predict failure of ART in women with unexplained infertility. Future trials of anti-IL-17 therapies in this cohort warrant further investigation.<\/jats:p><\/jats:sec>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>Funding from the UCD Wellcome Institutional Strategic Support Fund, which was financed jointly by University College Dublin and the SFI-HRB-Wellcome Biomedical Research Partnership (ref 204844\/Z\/16\/Z), is acknowledged. The authors have no competing interests.<\/jats:p><\/jats:sec>TRIAL REGISTRATION NUMBER<\/jats:title>NA.<\/jats:p><\/jats:sec>","DOI":"10.1093\/humrep\/deaa111","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T20:05:48Z","timestamp":1588190748000},"page":"1875-1888","source":"Crossref","is-referenced-by-count":22,"title":["Dysregulation of the interleukin-17A pathway in endometrial tissue from women with unexplained infertility affects pregnancy outcome following assisted reproductive treatment"],"prefix":"10.1093","volume":"35","author":[{"given":"D A","family":"Crosby","sequence":"first","affiliation":[{"name":"Department of Reproductive Medicine, Merrion Fertility Clinic, Dublin, D2, Ireland"},{"name":"Department of Obstetrics and Gynaecology, National Maternity Hospital, Dublin, D2, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"L E","family":"Glover","sequence":"additional","affiliation":[{"name":"Department of 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