{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T21:47:50Z","timestamp":1778795270902,"version":"3.51.4"},"reference-count":61,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,9,11]],"date-time":"2022-09-11T00:00:00Z","timestamp":1662854400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Problem<\/jats:title><jats:p>What is the impact of an empirical immune therapy protocol of prednisolone and enoxaparin (clexane) (the \u2018Bondi protocol\u2019) on women with repeated in vitro fertilization (IVF) failure?<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of study<\/jats:title><jats:p>This was a retrospective review of live birth outcomes conducted on all transfer cycles performed by a single clinician (GS) at IVFAustralia between February 2016 and April 2020. This study consisted of 1786 transfer cycles, including 460 cycles treated with the Bondi protocol and 1326 without. Women with repeated IVF failure were given the Bondi protocol based on blood NK cell activity. Primary outcome was live birth and statistical analysis was performed with GraphPad Prism software with significance for <jats:italic>P<\/jats:italic>\u2010values\u00a0&lt;\u00a0.05.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Overall \u2018Bondi\u2019 and \u2018normal\u2019 protocol cycles had similar rates of IVF\/ICSI, fresh\/frozen transfers and use of preimplantation genetic testing (PGT). Women given the Bondi protocol were older, had more previous cycles and had higher blood NK cell activity. There was no significant difference in live birth rates (Bondi 26%, normal 28%). Bondi protocol live birth rates per transfer cycle were as high as 40% in patients under 38 years old. The Bondi protocol was more effective as NK activity increased from \u2018normal\u2019 to \u2018borderline\u2019 to \u2018high\u2019. For high NK cell activity levels, live birth rates were over four times higher for women on the Bondi protocol (28%) than those on normal protocols (6%, <jats:italic>P<\/jats:italic>\u00a0=\u00a0.0007).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>This study describes a simple and relatively safe immune therapy protocol that may improve IVF success rates in women with evidence of immune dysfunction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/aji.13616","type":"journal-article","created":{"date-parts":[[2022,9,6]],"date-time":"2022-09-06T21:22:53Z","timestamp":1662499373000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Prednisolone and enoxaparin (clexane) therapy (\u2018the Bondi protocol\u2019) for repeated IVF failure"],"prefix":"10.1111","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0960-5431","authenticated-orcid":false,"given":"Gavin","family":"Sacks","sequence":"first","affiliation":[{"name":"IVFAustralia  Sydney Australia"},{"name":"Department of Women\u2019s and Children\u2019s Health University of New South Wales  Sydney Australia"},{"name":"St George Hospital and Royal Hospital for Women  Sydney Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jessica","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Women\u2019s and Children\u2019s Health University of New South Wales  Sydney Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,9,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12958-018-0414-2"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2017.04.009"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dev096"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1472-6483(10)61110-8"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1479-828X.2007.00702.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(98)01393-0"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2010.00836.x"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dew186"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2021.607669"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/oxfordjournals.humrep.a136451"},{"key":"e_1_2_9_12_1","first-page":"889","article-title":"Increasing clinical pregnancy rates after IVF\/ET. Can immunosuppression help?","volume":"41","author":"Mottla G","year":"1996","journal-title":"J Reprod Med"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0015-0282(00)01622-8"},{"issue":"3","key":"e_1_2_9_14_1","first-page":"CD004752","article-title":"Glucocorticoid supplementation during ovarian stimulation for IVF or ICSI","volume":"3","author":"Kalampokas T","year":"2017","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI68107"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00251-017-1001-y"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.13291"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciimmunol.aat6114"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dev098"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1472-6483(10)60575-5"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.01812"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02317"},{"key":"e_1_2_9_23_1","unstructured":"SacksG VarnierN Natural killer cell testing: comparative analysis demonstrates high blood levels are closely correlated with uterine levels are more discriminatory of a specific patient subpopulation and are proposed to be a valid immune test for further immune therapy trials.Oral presentation at Fertility Society of Australia & New Zealand Annual meeting2013;Brisbane Australia."},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2012.01105.x"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dep349"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1080\/14647273.2016.1219072"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(00)03231-1"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.3109\/01443615.2012.693988"},{"key":"e_1_2_9_29_1","unstructured":"SacksG GowenE Prednisolone and Clexane Therapy in Women with Repeated Reproductive Failure and Raised Peripheral Blood Natural Killer Cells: cumulative livebirth rates.Oral presentation at Fertility Society of Australia & New Zealand Annual meeting2012;Auckland NZ."},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/dep086"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/aogs.13483"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2004.05304.x"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1093\/humupd\/dmn031"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fertnstert.2005.05.012"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2007.00574.x"},{"key":"e_1_2_9_36_1","first-page":"CD005996","article-title":"Macklon NS. Peri\u2010implantation glucocorticoid administration for assisted reproductive technology cycles","volume":"6","author":"Boomsma CM","year":"2012","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_9_37_1","first-page":"13","article-title":"P\u20106: prednisolone Administration in the Luteal Phase in ICSI","volume":"85","author":"Agameya A\u2010F","year":"2006","journal-title":"Fert Steril"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-013-3020-8"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/09513590.2017.1380182"},{"key":"e_1_2_9_40_1","volume-title":"Assisted reproductive technology in Australia and New Zealand 2019","author":"Newman JEPR","year":"2021"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-014-3262-0"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12493"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1142\/S2661318219500178"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2021.08.012"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2012.01183.x"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.1996.tb00497.x"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh378"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.imbio.2013.09.002"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-1977"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.12373"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.101063"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1002\/bdra.23248"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2017.02.006"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-9926(200012)62:6<385::AID-TERA5>3.0.CO;2-Z"},{"key":"e_1_2_9_55_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2003.10.007"},{"key":"e_1_2_9_56_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0272.2012.01295.x"},{"key":"e_1_2_9_57_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.39471.430451.BE"},{"key":"e_1_2_9_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.rbmo.2020.06.002"},{"key":"e_1_2_9_59_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1513873"},{"key":"e_1_2_9_60_1","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/det414"},{"key":"e_1_2_9_61_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13063-020-04630-6"},{"key":"e_1_2_9_62_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2021.103369"}],"container-title":["American Journal of Reproductive Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aji.13616","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/aji.13616","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aji.13616","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,22]],"date-time":"2023-08-22T05:40:47Z","timestamp":1692682847000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/aji.13616"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,11]]},"references-count":61,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2022,11]]}},"alternative-id":["10.1111\/aji.13616"],"URL":"https:\/\/doi.org\/10.1111\/aji.13616","archive":["Portico"],"relation":{},"ISSN":["1046-7408","1600-0897"],"issn-type":[{"value":"1046-7408","type":"print"},{"value":"1600-0897","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,11]]},"assertion":[{"value":"2022-02-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-08-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-09-11","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13616"}}