{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T10:14:47Z","timestamp":1788257687754,"version":"build-2803163510"},"reference-count":39,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T00:00:00Z","timestamp":1712102400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Chang Gung Memorial Hospital Research","award":["CMRPG3L0761"],"award-info":[{"award-number":["CMRPG3L0761"]}]},{"name":"Chang Gung Memorial Hospital Research","award":["CMRPG3M0791"],"award-info":[{"award-number":["CMRPG3M0791"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The implantation of human embryos is a complex process involving various cytokines and receptors expressed by both endometrium and embryos. However, the role of cytokines produced by a single embryo in successful implantation is largely unknown. This study aimed to investigate the role of IL-1\u03b2 expressed in a single-embryo-conditioned medium (ECM) in embryo implantation. Seventy samples of single ECM were analyzed by a specially designed magnetic-beads-based microfluidic chip from 15 women. We discovered that IL-1\u03b2 level increased as the embryo developed, and the difference was significant. In addition, receiver operator characteristic (ROC) curves analysis showed a higher chance of pregnancy when the IL-1\u03b2 level on day 5 ECM was below 79.37 pg\/mL and the difference between day 5 and day 3 was below 24.90 pg\/mL. Our study discovered a possible association between embryonic proteomic expression and successful implantation, which might facilitate single-embryo transfer in the future by helping clinicians identify the embryo with the greatest implantation potential.<\/jats:p>","DOI":"10.3390\/ijms25074006","type":"journal-article","created":{"date-parts":[[2024,4,3]],"date-time":"2024-04-03T11:01:41Z","timestamp":1712142101000},"page":"4006","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Detection of Interleukin-1 \u03b2 (IL-1\u03b2) in Single Human Blastocyst-Conditioned Medium Using Ultrasensitive Bead-Based Digital Microfluidic Chip and Its Relationship with Embryonic Implantation Potential"],"prefix":"10.3390","volume":"25","author":[{"given":"Tian-Chi","family":"Tsai","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, 5 Fu-Shin Street, Taoyuan 33301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Wen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, 5 Fu-Shin Street, Taoyuan 33301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Shiue","family":"Lee","sequence":"additional","affiliation":[{"name":"Institute of Molecular Medicine and Bioengineering, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Ning","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, 5 Fu-Shin Street, Taoyuan 33301, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0189-9578","authenticated-orcid":false,"given":"Wensyang","family":"Hsu","sequence":"additional","affiliation":[{"name":"Department of Mechanical Engineering, National Yang Ming Chiao Tung University, Hsinchu 30010, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6631-780X","authenticated-orcid":false,"given":"Da-Jeng","family":"Yao","sequence":"additional","affiliation":[{"name":"Mechanical and Mechatronics System Research Laboratories, Industrial Technology Research Institute, Hsinchu 310401, Taiwan"},{"name":"Department of Power Mechanical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong-Yuan","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital, Linkou Medical Center, 5 Fu-Shin Street, Taoyuan 33301, Taiwan"},{"name":"Department of Obstetrics and Gynecology, College of Medicine, Chang Gung University, Taoyuan 33305, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1093\/humupd\/dmaa054","article-title":"Embryo implantation in the laboratory: An update on current techniques","volume":"27","author":"Ojosnegros","year":"2021","journal-title":"Hum. Reprod. Update"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/j.mam.2012.12.011","article-title":"Physiological and molecular determinants of embryo implantation","volume":"34","author":"Zhang","year":"2013","journal-title":"Mol. Asp. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1016\/j.fertnstert.2019.02.009","article-title":"What exactly is endometrial receptivity?","volume":"111","author":"Lessey","year":"2019","journal-title":"Fertil. Steril."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jri.2012.05.004","article-title":"Interleukin-6 in pregnancy and gestational disorders","volume":"95","author":"Prins","year":"2012","journal-title":"J. Reprod. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1093\/molehr\/gaq079","article-title":"The molecular basis of recurrent pregnancy loss: Impaired natural embryo selection","volume":"16","author":"Teklenburg","year":"2010","journal-title":"Mol. Hum. Reprod."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.rbmo.2021.09.012","article-title":"A microenvironment of high lactate and low pH created by the blastocyst promotes endometrial receptivity and implantation","volume":"44","author":"Gurner","year":"2021","journal-title":"Reprod. Biomed. Online"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3894","DOI":"10.1038\/srep03894","article-title":"Uterine Selection of Human Embryos at Implantation","volume":"4","author":"Brosens","year":"2014","journal-title":"Sci. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1093\/humupd\/dmg021","article-title":"Selection based on morphological assessment of oocytes and embryos at different stages of preimplantation development: A review","volume":"9","author":"Ebner","year":"2003","journal-title":"Hum. Reprod. Update"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1093\/humupd\/dmz042","article-title":"Identifying biomarkers for predicting successful embryo implantation: Applying single to multi-OMICs to improve reproductive outcomes","volume":"26","year":"2020","journal-title":"Hum. Reprod. Update"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1016\/S0015-0282(00)00518-5","article-title":"Blastocyst score affects implantation and pregnancy outcome: Towards a single blastocyst transfer","volume":"73","author":"Gardner","year":"2000","journal-title":"Fertil. Steril."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"908","DOI":"10.1016\/j.fertnstert.2015.06.032","article-title":"New strategy for diagnosing embryo implantation potential by combining proteomics and time-lapse technologies","volume":"104","author":"Dominguez","year":"2015","journal-title":"Fertil. Steril."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1093\/humupd\/dmu064","article-title":"Diagnosis of human preimplantation embryo viability","volume":"21","author":"Gardner","year":"2015","journal-title":"Hum. Reprod. Update"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1034\/j.1600-0897.2002.1o047.x","article-title":"Expression of Pro-inflammatory Cytokines in Mouse Blastocysts During Implantation: Modulation by Steroid Hormones","volume":"47","author":"Basak","year":"2002","journal-title":"Am. J. Reprod. Immunol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/S0165-0378(97)00030-2","article-title":"Different pattern of interleukin-1\u03b2-(IL-1\u03b2), interleukin-1 receptor antagonist-(IL-1ra) and interleukin-1 receptor type I-(IL-1R tI) mRNA-expression in single preimplantation mouse embryos at various developmental stages","volume":"34","author":"Kruessel","year":"1997","journal-title":"J. Reprod. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"17125","DOI":"10.1016\/S0021-9258(17)32529-2","article-title":"Interleukin-1 beta regulates human cytotrophoblast metalloproteinase activity and invasion in vitro","volume":"269","author":"Librach","year":"1994","journal-title":"J. Biol. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Pantos, K., Grigoriadis, S., Maziotis, E., Pistola, K., Xystra, P., Pantou, A., Kokkali, G., Pappas, A., Lambropoulou, M., and Sfakianoudis, K. (2022). The Role of Interleukins in Recurrent Implantation Failure: A Comprehensive Review of the Literature. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23042198"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"103283","DOI":"10.1016\/j.jri.2021.103283","article-title":"Interleukin-1 beta is significantly upregulated in the decidua of spontaneous and recurrent miscarriage placentas","volume":"144","author":"Amann","year":"2021","journal-title":"J. Reprod. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Hsu, W., Shih, Y.-T., Lee, M.-S., Huang, H.-Y., and Wu, W.-N. (2022). Bead Number Effect in a Magnetic-Beads-Based Digital Microfluidic Immunoassay. Biosensors, 12.","DOI":"10.3390\/bios12050340"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"hoaa008","DOI":"10.1093\/hropen\/hoaa008","article-title":"Good practice recommendations for the use of time-lapse technology","volume":"2020","author":"Apter","year":"2020","journal-title":"Hum. Reprod. Open"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1016\/j.rbmo.2020.02.017","article-title":"Cytoplasmic halo characteristics during fertilization and their implications for human preimplantation embryo development and pregnancy outcome","volume":"41","author":"Ezoe","year":"2020","journal-title":"Reprod. Biomed. Online"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lee, C.-I., Huang, C.-C., Lee, T.-H., Chen, H.-H., Cheng, E.-H., Lin, P.-Y., Yu, T.-N., Chen, C.-I., Chen, C.-H., and Lee, M.-S. (2024). Associations between the artificial intelligence scoring system and live birth outcomes in preimplantation genetic testing for aneuploidy cycles. Reprod. Biol. Endocrinol., 22.","DOI":"10.1186\/s12958-024-01185-y"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1093\/molehr\/gap012","article-title":"The role of proteomics in defining the human embryonic secretome","volume":"15","author":"McReynolds","year":"2009","journal-title":"Mol. Hum. Reprod."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1993","DOI":"10.1093\/humrep\/den205","article-title":"Comparative protein-profile analysis of implanted versus non-implanted human blastocysts","volume":"23","author":"Dominguez","year":"2008","journal-title":"Hum. Reprod."},{"key":"ref_24","unstructured":"Biba, M., Keramitsoglou, T., Goukos, D., Varla-Leftherioti, M., and Pantos, K. (2015). Interleukin (IL)-1 Beta and IL-6 Levels in Human Embryo Culture Supernatants and their Role in Implantation Following IVF: A Prospective, Non-randomized Study. J. Immuno. Biol., 1."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Caillaud, M., Duchamp, G., and G\u00e9rard, N. (2005). In vivo effect of interleukin-1beta and interleukin-1RA on oocyte cytoplasmic maturation, ovulation, and early embryonic development in the mare. Reprod. Biol. Endocrinol., 3.","DOI":"10.1186\/1477-7827-3-26"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/S0165-0378(96)00987-4","article-title":"The expression of Interleukin-1\u03b1, Interleukin-1\u03b2, and Interleukin-1 receptor type I mRNA during preimplantation mouse development","volume":"32","author":"Takacs","year":"1996","journal-title":"J. Reprod. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1023\/B:JARG.0000013650.76052.ae","article-title":"Involvement of Interleukin-1 and the Interleukin-1 Receptor Antagonist in In Vitro Embryo Development Among Women Undergoing In Vitro Fertilization\u2013Embryo Transfer","volume":"20","author":"Spandorfer","year":"2003","journal-title":"J. Assist. Reprod. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2206","DOI":"10.1093\/humrep\/13.8.2206","article-title":"Expression of interleukin-1 system mRNA in single blastomeres from human preimplantation embryos","volume":"13","author":"Krussel","year":"1998","journal-title":"Hum. Reprod."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1002\/jcb.29345","article-title":"Interleukin-1 beta induces autophagy of mouse preimplantation embryos and improves blastocyst quality","volume":"121","author":"Pan","year":"2019","journal-title":"J. Cell. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1530\/REP-20-0376","article-title":"Expression of IL-1\u03b2 and implantation serine proteases is required for mouse blastocyst hatching","volume":"161","author":"Pathak","year":"2021","journal-title":"Reproduction"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/S1472-6483(10)61717-8","article-title":"Embryo-maternal signalling: How the embryo starts talking to its mother to accomplish implantation","volume":"6","author":"Herrler","year":"2003","journal-title":"Reprod. Biomed. Online"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"102618","DOI":"10.1016\/j.jri.2019.102618","article-title":"Are the cytokines TNF alpha and IL 1Beta early predictors of embryo implantation? Cross sectional study","volume":"137","author":"Salama","year":"2019","journal-title":"J. Reprod. Immunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1016\/S0015-0282(98)00275-1","article-title":"Interleukin-1 receptor antagonist prevents embryonic implantation by a direct effect on the endometrial epithelium","volume":"70","author":"Valbuena","year":"1998","journal-title":"Fertil. Steril."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1038\/sj.gene.6363812","article-title":"T helper 1-type immunity to trophoblast antigens in women with a history of recurrent pregnancy loss is associated with polymorphism of the IL1B promoter region","volume":"3","author":"Wang","year":"2002","journal-title":"Genes Immun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"S62","DOI":"10.1016\/S0015-0282(01)02199-9","article-title":"Reduced IL-1\u03b2 production is associated with altered T helper 1 (Th1)\/Th2 cytokine profile at the mRNA level in the decidua in unexplained recurrent pregnancy loss (RPL)","volume":"76","author":"Wang","year":"2001","journal-title":"Fertil. Steril."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1016\/j.fertnstert.2022.04.023","article-title":"Immune determinants of endometrial receptivity: A biological perspective","volume":"117","author":"Robertson","year":"2022","journal-title":"Fertil. Steril."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e14887","DOI":"10.1111\/ijcp.14887","article-title":"Interleukin-1\u03b2 as clinically predictive risk marker for recurrent pregnancy loss in women positive for antinuclear antibody","volume":"75","author":"Gao","year":"2021","journal-title":"Int. J. Clin. Pract."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Lee, M.-S., Chang, Y.-C., Huang, H.-Y., and Hsu, W. (2022). Single-type reporter multiplexing with A single droplet through bead-based digital microfluidics. J. Pharm. Biomed. Anal., 219.","DOI":"10.1016\/j.jpba.2022.114877"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Veeck, L.L. (1999). An Atlas of Human Gametes and Conceptuses, CRC Press.","DOI":"10.1201\/9780367803001"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/7\/4006\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T14:23:07Z","timestamp":1760106187000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/7\/4006"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,4,3]]},"references-count":39,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2024,4]]}},"alternative-id":["ijms25074006"],"URL":"https:\/\/doi.org\/10.3390\/ijms25074006","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,4,3]]}}}