{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T13:53:33Z","timestamp":1762005213684,"version":"build-2065373602"},"reference-count":20,"publisher":"Knowledge E DMCC","issue":"9","license":[{"start":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T00:00:00Z","timestamp":1761955200000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0"}],"content-domain":{"domain":["knepublishing.com"],"crossmark-restriction":true},"short-container-title":["IJRM"],"abstract":"<jats:p>Background: Recurrent implantation failure in assisted reproductive technology is a major challenge. Intrauterine human chorionic gonadotropin (hCG) infusion and hyaluronic acid enriched embryo transfer media have shown individual effects, but their combined effect in these cases undergoing frozen-thawed embryo transfer is unknown.\r\nObjective: This study aims to investigate the effect of combined therapy on pregnancy outcomes.\r\nMaterials and Methods: This is a single-blind, randomized controlled trial on 158 participants. The cases were randomly assigned to either the intervention group (pretransfer intrauterine hCG infusion and embryo loaded with hyaluronic acid-enriched embryo transfer medium at the time of transfer) or the control group (standard embryo transfer medium). The outcomes were chemical and clinical pregnancy rates, implantation, abortion, and ongoing pregnancy rates.\r\nResults: A total of 158 participants were enrolled in this study in 2 equal groups. The intervention did not significantly improve the overall pregnancy rate compared to control (24% vs. 33.7%, p = 0.30). The results showed that, by controlling variables, the chance of clinical pregnancy in the intervention group was 12% lower than in the control group, although the difference was not statistically significant (p = 0.879). With each increase in the number of embryos, the chance of a pregnancy would be 2.26 times higher. Also, the chance of pregnancy in the morula stage was 68% lower than in the cleavage stage (p &lt; 0.05).\r\nConclusion: The combined approach of intrauterine hCG infusion and the hyaluronan-enriched embryo transfer medium did not significantly improve the overall pregnancy rate but had a significant effect on specific cases using the embryo at the cleavage stage for transfer and cases that received more than one embryo for transfer.<\/jats:p>","DOI":"10.18502\/ijrm.v23i9.20158","type":"journal-article","created":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T13:21:54Z","timestamp":1762003314000},"page":"701-712","update-policy":"https:\/\/doi.org\/10.18502\/knecrossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Impact of intrauterine infusion of human chorionic gonadotropin and hyaluronic acid enriched medium on pregnancy outcomes in frozen-thawed cycles with recurrent implantation failure: An RCT"],"prefix":"10.18502","volume":"23","author":[{"family":"Sepideh Peivandi","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pegah","family":"Jafarifard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marzieh","family":"Zamaniyan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jamshid","family":"Yazdani-charati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"7770","published-online":{"date-parts":[[2025,11,1]]},"reference":[{"key":"307848","doi-asserted-by":"crossref","unstructured":"[1] Ma J, Gao W, Li D. Recurrent implantation failure: A comprehensive summary from etiology to treatment. Front Endocrinol 2023; 13: 1061766.","DOI":"10.3389\/fendo.2022.1061766"},{"key":"307849","doi-asserted-by":"crossref","unstructured":"[2] Bashiri A, Halper KI, Orvieto R. Recurrent implantation failure-update overview on etiology, diagnosis, treatment and future directions. Reprod Biol Endocrinol 2018; 16: 121.","DOI":"10.1186\/s12958-018-0414-2"},{"key":"307850","doi-asserted-by":"crossref","unstructured":"[3] Dos Santos MM, Silva AA, Barbosa ACP, Brum G, Nakagawa HM, Cabral I, et al. Embryo placement in IVF and reproductive outcomes: A cohort analysis and review. JBRA Assist Reprod 2019; 23: 210\u2013214.","DOI":"10.5935\/1518-0557.20190003"},{"key":"307851","doi-asserted-by":"crossref","unstructured":"[4] Pavlovi\u0107-Vasi\u0107 D, Sibin\u010di\u0107 S, Milakovi\u0107 I, Luka\u010d S, Vujni\u0107 S, Gvero M, et al. Influence of EmbryoGlue\u00ae transfer medium on implantation of human embryos. Scr Med 2021; 52: 119\u2013123.","DOI":"10.5937\/scriptamed52-31728"},{"key":"307852","doi-asserted-by":"crossref","unstructured":"[5] Paiva P, Hannan NJ, Hincks C, Meehan KL, Pruysers E, Dimitriadis E, et al. Human chorionic gonadotrophin regulates FGF2 and other cytokines produced by human endometrial epithelial cells, providing a mechanism for enhancing endometrial receptivity. Hum Reprod 2011; 26: 1153\u20131162.","DOI":"10.1093\/humrep\/der027"},{"key":"307853","doi-asserted-by":"crossref","unstructured":"[6] Heymann D, Vidal L, Or Y, Shoham Z. Hyaluronic acid in embryo transfer media for assisted reproductive technologies. Cochrane Database Syst Rev 2020; 9: CD007421.","DOI":"10.1002\/14651858.CD007421.pub4"},{"key":"307854","doi-asserted-by":"crossref","unstructured":"[7] Karadbhajne P, More A. Effect of hyaluronic acid-enriched media in embryo implantation. Cureus 2022; 14: e27083.","DOI":"10.7759\/cureus.27083"},{"key":"307855","doi-asserted-by":"crossref","unstructured":"[8] Balakier H, Kuznyetsova I, Librach CL. The impact of hyaluronan-enriched culture medium and intrauterine infusion of human chorionic gonadotropin on clinical outcomes in blastocyst transfer cycles. Syst Biol Reprod Med 2020; 66: 79\u201388.","DOI":"10.1080\/19396368.2020.1727995"},{"key":"307856","doi-asserted-by":"crossref","unstructured":"[9] Laokirkkiat P, Thanaboonyawat I, Boonsuk S, Petyim S, Prechapanich J, Choavaratana R. Increased implantation rate after intrauterine infusion of a small volume of human chorionic gonadotropin at the time of embryo transfer: A randomized, double-blind controlled study. Arch Gynecol Obstet 2019; 299: 267\u2013275.","DOI":"10.1007\/s00404-018-4962-7"},{"key":"307857","doi-asserted-by":"crossref","unstructured":"[10] Horiuchi Y, Yanaihara A, Hatakeyama S, Taga Y, Kondou T, Kuramoto G, et al. Efficacy of hyaluronan-enriched transfer medium for low-grade frozen embryo transfer. Cureus 2023; 15: e39210.","DOI":"10.7759\/cureus.39210"},{"key":"307858","doi-asserted-by":"crossref","unstructured":"[11] Nakagawa K, Horikawa T, Orita Y, Yamashiro E, Watanabe H, Shirai A, et al. Hyaluronan-enriched transfer medium (HETM) can improve the implantation rate in morphologically poor euploid blastocyst transfer. Arch Gynecol Obstet 2023; 308: 611\u2013619.","DOI":"10.1007\/s00404-023-07083-9"},{"key":"307859","doi-asserted-by":"crossref","unstructured":"[12] Hafezi M, Madani T, Arabipoor A, Zolfaghari Z, Sadeghi M, Ramezanali F. The effect of intrauterine human chorionic gonadotropin flushing on live birth rate after vitrified-warmed embryo transfer in programmed cycles: A randomized clinical trial. Arch Gynecol Obstet 2018; 297: 1571\u20131576.","DOI":"10.1007\/s00404-018-4752-2"},{"key":"307860","doi-asserted-by":"crossref","unstructured":"[13] Yung SSF, Lai SF, Lam MT, Lui EMW, Ko JKY, Li HWR, et al. Hyaluronic acid-enriched transfer medium for frozen embryo transfer: A randomized, double-blind, controlled trial. Fertil Steril 2021; 116: 1001\u20131009.","DOI":"10.1016\/j.fertnstert.2021.02.015"},{"key":"307861","doi-asserted-by":"crossref","unstructured":"[14] Fancsovits P, Lehner A, Murber A, Kaszas Z, Rigo J, Urbancsek J. Effect of hyaluronan-enriched embryo transfer medium on IVF outcome: A prospective randomized clinical trial. Arch Gynecol Obstet 2015; 291: 1173\u20131179.","DOI":"10.1007\/s00404-014-3541-9"},{"key":"307862","doi-asserted-by":"crossref","unstructured":"[15] Yan Q, Zhao M, Hao F, Zhao R, Teng X, He B, et al. Effect of hyaluronic acid-enriched transfer medium on frozen-thawed embryo transfer outcomes in RIF patients: A single-centre retrospective study. Front Endocrinol 2023; 14: 1170727.","DOI":"10.3389\/fendo.2023.1170727"},{"key":"307863","doi-asserted-by":"crossref","unstructured":"[16] Heymann D, Vidal L, Shoham Z, Kostova E, Showell M, Or Y. The effect of hyaluronic acid in embryo transfer media in donor oocyte cycles and autologous oocyte cycles: A systematic review and meta-analysis. Hum Reprod 2022; 37: 1451\u20131469.","DOI":"10.1093\/humrep\/deac097"},{"key":"307864","doi-asserted-by":"crossref","unstructured":"[17] Kandari S. Time lapse selected elective single embryo transfer in hyaluronon enriched transfer medium in pcos improves live birth rates compared to use of conventional embryo transfer media: A possible alternative to freeze-all cycles in PCOS. Fertil Steril 2019; 112: e47-e48.","DOI":"10.1016\/j.fertnstert.2019.07.252"},{"key":"307865","doi-asserted-by":"crossref","unstructured":"[18] Bhoi NR, Murdia N, Murdia K, Chandra V, Suwalka I, Mistari W, et al. Effect of hyaluronic acid-containing transfer media (EmbryoGlue\u00ae) on the live birth rate in frozen thawed embryo transfer cycles. Cureus 2024; 16: e52713.","DOI":"10.7759\/cureus.52713"},{"key":"307866","doi-asserted-by":"crossref","unstructured":"[19] Singh N, Gupta M, Kriplani A, Vanamail P. Role of embryo glue as a transfer medium in the outcome of fresh non-donor in-vitro fertilization cycles. J Hum Reprod Sci 2015; 8: 214\u2013217.","DOI":"10.4103\/0974-1208.170398"},{"key":"307867","doi-asserted-by":"crossref","unstructured":"[20] Kong X, Tang G, Liu Y, Zheng Z, Li Y, Yan F. Efficacy of intrauterine infusion therapy before embryo transfer in recurrent implantation failure: A systematic review and network meta-analysis. J Reprod Immunol 2023; 156: 103819.","DOI":"10.1016\/j.jri.2023.103819"}],"container-title":["International Journal of Reproductive BioMedicine (IJRM)"],"original-title":[],"link":[{"URL":"https:\/\/knepublishing.com\/index.php\/ijrm\/article\/download\/20158\/30778","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/knepublishing.com\/index.php\/ijrm\/article\/download\/20158\/30778","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,1]],"date-time":"2025-11-01T13:43:11Z","timestamp":1762004591000},"score":1,"resource":{"primary":{"URL":"https:\/\/knepublishing.com\/index.php\/ijrm\/article\/view\/20158"},"secondary":[{"URL":"http:\/\/ijrm.ir\/article-1-3428-en.html","label":"UNIVERSITY"}]},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,1]]},"references-count":20,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2025,11,1]]}},"URL":"https:\/\/doi.org\/10.18502\/ijrm.v23i9.20158","relation":{},"ISSN":["2476-3772","2476-4108"],"issn-type":[{"type":"electronic","value":"2476-3772"},{"type":"print","value":"2476-4108"}],"subject":[],"published":{"date-parts":[[2025,11,1]]}}}