{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T22:45:29Z","timestamp":1785451529681,"version":"3.56.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T00:00:00Z","timestamp":1737417600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Foundation for Embryonic Competence"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>STUDY QUESTION<\/jats:title>\n                  <jats:p>Does the use of slush nitrogen (SN) for embryo vitrification improve embryo transfer outcomes compared to liquid nitrogen (LN)?<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>SUMMARY ANSWER<\/jats:title>\n                  <jats:p>SN is a safe method for embryo preservation and significantly improves post-warming survival rates during repeated vitrification\u2013warming cycles; however, after a single freeze\u2013thaw cycle, pregnancy outcomes are not improved when embryos are vitrified with SN compared to LN.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                  <jats:p>SN is a combination of solid and LN, with a temperature lower than regular LN, and it is an alternative to conventional LN in achieving a faster cooling speed. Studies have shown that SN improves survival in non-human embryos and human oocytes. However, it is unknown whether the use of SN reduces blastocyst damage in humans during vitrification\u2014as indicated by increased survival across multiple vitrification\u2013warming cycles\u2014or whether it enhances pregnancy outcomes in a single vitrification\u2013warming cycle.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                  <jats:p>Following the pre-clinical trial assessing embryo survival after repeated freeze\u2013thaw cycles using SN and LN on 50 donated embryos per group, a randomized controlled trial was performed, where 253 patients were enrolled between September 2020 and January 2022, and 245 underwent an IVF stimulation, which resulted in at least one blastocyst for cryopreservation. Of those, 121 were allocated to the SN (study), and 124 were allocated to the LN (control) group. Randomization occurred on the day of blastocyst biopsy using a computer-generated block schema. Groups were assigned via opaque envelopes, opened by the embryologist on vitrification day. The patient, physician, and clinical team were blinded to the intervention.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                  <jats:p>All couples with female aged between 18 and 42\u2009years old undergoing IVF stimulation at one university-affiliated infertility center, with plan for preimplantation genetic testing for aneuploidy and subsequent single, frozen embryo transfer (FET) were eligible for inclusion in this study.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                  <jats:p>The pre-clinical trial demonstrated significant improvements in blastocyst survival, with the SN group achieving a mean of 7.5 survived vitrification\u2013warming cycles (range: 3\u201322), significantly surpassing the mean of 3.0 cycles (range: 0\u201310) in the LN group (P\u2009&amp;lt;\u20090.0001). Following the pre-clinical trial, 223 patients randomized to SN or LN underwent single FET. Baseline characteristics were similar between groups, as were embryology outcomes, including the number of oocytes retrieved, mature oocytes, fertilization rate, and total blastocysts biopsied. No significant differences were observed between the two groups in pregnancy rate, clinical pregnancy rate, sustained implantation rate, or miscarriage rate (P\u2009=\u20090.16, 0.80, 0.49, and 0.74, respectively, using Student\u2019s t-test). A futility analysis indicated no value in continuing recruitment and therefore the study was closed.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                  <jats:p>Neonatal or birth outcomes were not assessed. Termination of the study based on futility analysis precludes a conclusion of equivalence between SN and LN.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                  <jats:p>This study demonstrates that SN is a safe alternative to traditional LN for vitrification; however, it did not demonstrate improvements in the reproductive potential of vitrified embryos.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                  <jats:p>The project was funded by the Foundation for Embryonic Competence<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                  <jats:p>NCT04496284.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>TRIAL REGISTRATION DATE<\/jats:title>\n                  <jats:p>3 August 2020.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>DATE OF FIRST PATIENT\u2019S ENROLLMENT<\/jats:title>\n                  <jats:p>5 September 2020.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/humrep\/deaf003","type":"journal-article","created":{"date-parts":[[2025,1,21]],"date-time":"2025-01-21T20:05:31Z","timestamp":1737489931000},"page":"426-433","source":"Crossref","is-referenced-by-count":1,"title":["A randomized controlled trial comparing embryo vitrification with slush nitrogen to liquid nitrogen in women undergoing frozen embryo transfer: embryology and clinical outcomes"],"prefix":"10.1093","volume":"40","author":[{"given":"A M","family":"Klimczak","sequence":"first","affiliation":[{"name":"IVIRMA Global Research Alliance, IVIRMA New Jersey , Basking Ridge, 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