{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T19:42:25Z","timestamp":1791229345550,"version":"4.1.0"},"reference-count":83,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,1,3]],"date-time":"2023-01-03T00:00:00Z","timestamp":1672704000000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Ultrasound in Obstet &amp;amp; Gyne"],"published-print":{"date-parts":[[2023,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>\n                      To compare the reported rate of any congenital anomaly and perinatal outcome of pregnancy following blastocyst\u2010\n                      <jats:italic>vs<\/jats:italic>\n                      cleavage\u2010stage embryo transfer using a pairwise meta\u2010analysis and to evaluate the same outcomes following fresh\u2010blastocyst, frozen\u2010blastocyst, fresh\u2010cleavage or frozen\u2010cleavage embryo transfer using a network meta\u2010analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A literature search was performed in PubMed, Scopus and CENTRAL and registers for ongoing studies, from inception to February 2022, for randomized controlled trials (RCTs) with any sample size and observational studies including at least 100 live births per group, comparing the rates of any congenital anomaly and perinatal outcome of pregnancy following fresh\/frozen embryo transfer at cleavage (day\u20092\u20133)\n                      <jats:italic>vs<\/jats:italic>\n                      blastocyst (day\u20095\u20137) stage. Risk ratios (RRs) along with their 95%\u2009CIs were pooled via a random\u2010effects model meta\u2010analysis. Within a frequentist network meta\u2010analysis framework, outcomes of all four treatment modalities (i.e. fresh\u2010blastocyst, fresh\u2010cleavage, frozen\u2010blastocyst, frozen\u2010cleavage) were compared further. Any congenital anomaly constituted the primary outcome, whereas preterm delivery (delivery &lt;\u200937\u2009weeks), low birth weight (LBW; &lt;\u20092500\u2009g), gender of the neonate (male), perinatal death and healthy neonate (defined as liveborn neonate, delivered at term, weighing \u2265\u20092500\u2009g, surviving for at least 28\u2009days postbirth and without any congenital anomaly) were considered as secondary outcomes. Subgroup analyses by plurality (liveborn singleton\n                      <jats:italic>vs<\/jats:italic>\n                      multiple pregnancy) were conducted in the pairwise and network meta\u2010analyses. The risk of bias was assessed using the RoB2 tool for RCTs and the ROBINS\u2010I tool for non\u2010randomized studies. Certainty of evidence was assessed using GRADE.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Through the literature search, 550 studies were retrieved and 33 were included in the systematic review. We found no significant difference in the risk for any congenital anomaly between blastocyst\u2010 and cleavage\u2010stage transfer (RR, 0.80 (95%\u2009CI, 0.63\u20131.03); 10 studies;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009192\u2009442;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200985.5%). An increased probability of a male neonate was observed following blastocyst\u2010\n                      <jats:italic>vs<\/jats:italic>\n                      cleavage\u2010stage transfer (RR, 1.07 (95%\u2009CI, 1.06\u20131.09); 18 studies;\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009227\u2009530;\n                      <jats:italic>I<\/jats:italic>\n                      <jats:sup>2<\/jats:sup>\n                      \u2009=\u200932.7%). No significant differences in other secondary outcomes or significant subgroup differences between liveborn singletons and multiple pregnancies were observed.\n                    <\/jats:p>\n                    <jats:p>\n                      The network meta\u2010analysis showed a significantly lower risk for LBW following frozen\u2010blastocyst\n                      <jats:italic>vs<\/jats:italic>\n                      fresh\u2010blastocyst (RR, 0.76 (95%\u2009CI, 0.60\u20130.95)) or fresh\u2010cleavage (RR, 0.74 (95%\u2009CI, 0.59\u20130.93)) transfer. Frozen\u2010blastocyst transfer was associated with an increased risk for perinatal death compared with the fresh\u2010cleavage method (RR, 2.06 (95%\u2009CI, 1.10\u20133.88)). The higher probability of a male neonate following blastocyst transfer remained evident in the network comparisons. All outcomes were assessed to be of very\u2010low certainty of evidence.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Current very\u2010low certainty of evidence shows that there may be little\u2010to\u2010no difference in the risk for congenital anomaly or adverse perinatal outcome of pregnancy following blastocyst\u2010\n                      <jats:italic>vs<\/jats:italic>\n                      cleavage\u2010stage embryo transfer, although there was a slightly increased probability of a male neonate following blastocyst transfer. When considering cryopreservation, frozen\u2010blastocyst transfer was associated with a reduction in the risk for LBW compared with both fresh\u2010transfer modalities, and fresh\u2010cleavage transfer may be associated with a reduction in the risk for perinatal death compared with frozen\u2010blastocyst transfer. High\u2010quality RCTs with separate data on fresh and frozen cycles and consistent reporting of culture conditions and freezing methods are mandatory. Individual participant data meta\u2010analyses are required to address the substantial inconsistency resulting from current aggregate data approaches. \u00a9 2022 The Authors.\n                      <jats:italic>Ultrasound in Obstetrics &amp; Gynecology<\/jats:italic>\n                      published by John Wiley &amp; Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/uog.26019","type":"journal-article","created":{"date-parts":[[2022,6,25]],"date-time":"2022-06-25T13:33:32Z","timestamp":1656164012000},"page":"12-25","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Congenital anomaly and perinatal outcome following blastocyst\u2010\n                    <i>vs<\/i>\n                    cleavage\u2010stage embryo transfer: systematic review and network meta\u2010analysis"],"prefix":"10.1002","volume":"61","author":[{"given":"C.","family":"Siristatidis","sequence":"first","affiliation":[{"name":"Assisted Reproduction Unit, Second Department of Obstetrics and Gynecology, Medical School National and Kapodistrian University of Athens, \u201cAretaieion\u201d University Hospital  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8331-2402","authenticated-orcid":false,"given":"M.","family":"Papapanou","sequence":"additional","affiliation":[{"name":"Assisted Reproduction Unit, Second Department of Obstetrics and Gynecology, Medical School National and Kapodistrian University of Athens, \u201cAretaieion\u201d University Hospital  Athens Greece"},{"name":"Obstetrics, Gynecology and Reproductive Medicine Working Group, Society of Junior Doctors  Athens Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"V.","family":"Karageorgiou","sequence":"additional","affiliation":[{"name":"University of Exeter  Exeter UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7593-5607","authenticated-orcid":false,"given":"W. 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