{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T14:55:23Z","timestamp":1789052123251,"version":"build-2803163510"},"reference-count":31,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,6,28]],"date-time":"2026-06-28T00:00:00Z","timestamp":1782604800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Unexplained infertility (UI) accounts for an estimated 15\u201330% of infertility but its biological basis remains poorly defined. Plasma haemostatic abnormalities have been implicated in recurrent pregnancy loss; however, whether the circulating coagulation\u2013fibrinolysis axis differs between women with UI and those with infertility attributable to other causes has not been characterised. The aim of this study was to compare 20 coagulation- and fibrinolysis-related proteins between women with UI and women with male-factor infertility (MFI) as control. In this exploratory case\u2013control study, plasma from 11 women with UI and 14 women with MFI were analysed using SOMAscan proteomics. Group means were compared using Welch\u2019s two-sample t-test, Cohen\u2019s d with 95% confidence intervals, and a two-sided permutation test on the mean difference (20,000 random label permutations). False discovery rate (FDR) was used for multiple comparisons. Pairwise Pearson and Spearman correlations were performed. Three proteins differed between groups (p &lt; 0.05), all lower in UI than in MFI: vitamin K-dependent protein S (Cohen\u2019s d = \u22121.11, 95% CI \u22121.95 to \u22120.26; Welch p = 0.016; permutation p = 0.015), antithrombin-III (d = \u22121.00, 95% CI \u22121.84 to \u22120.16; p = 0.024; permutation p = 0.020) and \u03b12-antiplasmin (d = \u22120.82, 95% CI \u22121.64 to 0.00; p = 0.051; permutation p = 0.054). No protein survived FDR correction. Within UI, the three proteins co-varied positively, with significant pairwise correlations between protein S and antithrombin-III (r = 0.67, p = 0.024) and between antithrombin-III and \u03b12-antiplasmin (r = 0.71, p = 0.015). Within MFI, antithrombin-III and \u03b12-antiplasmin remained tightly correlated (r = 0.70, p = 0.006) but protein S decoupled from both (r = 0.20 and 0.10, both non-significant). In this hypothesis-generating study, women with UI showed reduction in three plasma regulators of anticoagulant and antifibrinolytic capacity, protein S, antithrombin-III and \u03b12-antiplasmin relative to women with MFI, raising the possibility that UI may be in part a subtle immunothrombotic\/endothelial implantation disorder.<\/jats:p>","DOI":"10.3390\/ijms27135841","type":"journal-article","created":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T00:55:11Z","timestamp":1782780911000},"page":"5841","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["An Exploratory Pilot Study of Coagulation- and Fibrinolysis-Related Proteins in Unexplained Infertility"],"prefix":"10.3390","volume":"27","author":[{"given":"Manjula","family":"Nandakumar","sequence":"first","affiliation":[{"name":"Research Department, Royal College of Surgeons in Ireland Bahrain, Adliya, Manama P.O. Box 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5342-2501","authenticated-orcid":false,"given":"Abu Saleh Md","family":"Moin","sequence":"additional","affiliation":[{"name":"Research Department, Royal College of Surgeons in Ireland Bahrain, Adliya, Manama P.O. Box 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3544-2231","authenticated-orcid":false,"given":"Thozhukat","family":"Sathyapalan","sequence":"additional","affiliation":[{"name":"Academic Endocrinology, Diabetes and Metabolism, Hull York Medical School, Hull HU6 7RX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5762-3917","authenticated-orcid":false,"given":"Alexandra E.","family":"Butler","sequence":"additional","affiliation":[{"name":"Research Department, Royal College of Surgeons in Ireland Bahrain, Adliya, Manama P.O. Box 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5887-7257","authenticated-orcid":false,"given":"Stephen L.","family":"Atkin","sequence":"additional","affiliation":[{"name":"Research Department, Royal College of Surgeons in Ireland Bahrain, Adliya, Manama P.O. Box 15503, Bahrain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,28]]},"reference":[{"key":"ref_1","unstructured":"WHO (2023). Infertility Prevalence Estimates, 1990\u20132021, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Practice Committee of the American Society for Reproductive Medicine (2020). Definitions of infertility and recurrent pregnancy loss: A committee opinion. Fertil. 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