{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T08:40:28Z","timestamp":1783068028837,"version":"3.54.6"},"reference-count":31,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,8,13]],"date-time":"2012-08-13T00:00:00Z","timestamp":1344816000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJOG"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:p>\n                    <jats:bold>Objective\u2002<\/jats:bold>\n                    Previous trials have shown little benefit for preventing preterm birth in twin pregnancies using 90\u2013200\u2003mg of daily vaginal natural progesterone. Higher doses have not been tested. Our aim was to determine the efficacy and safety of two different daily doses of vaginal natural progesterone (200 and 400\u2003mg), compared with placebo, for preventing preterm birth in unselected twin pregnancies.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Design\u2002<\/jats:bold>\n                    Randomised controlled double\u2010blind multicentre trial (1:1:1).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Setting\u2002<\/jats:bold>\n                    The study was carried out in five university centres from Valencia, Murcia and Alicante (Spain).\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Population\u2002<\/jats:bold>\n                    Women with dichorionic diamniotic twin pregnancies.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Methods\u2002<\/jats:bold>\n                    The women self\u2010inserted two vaginal pessaries daily, containing placebo (\n                    <jats:italic>n<\/jats:italic>\n                    \u2003=\u200396), 200\u2003mg of natural progesterone (\n                    <jats:italic>n<\/jats:italic>\n                    \u2003=\u200397) or 400\u2003mg of natural progesterone (\n                    <jats:italic>n<\/jats:italic>\n                    \u2003=\u200397), from 20 to 34\u2003weeks of gestation or delivery. Randomisation was performed by an external centre. Data were analysed on an intention\u2010to\u2010treat basis.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Main outcome measure\u2002<\/jats:bold>\n                    Preterm birth rate.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Results\u2002<\/jats:bold>\n                    The baseline characteristics for placebo and progesterone groups were similar. Comparison of the three groups and analysis of progesterone\u2010treated versus untreated women showed similar pregnancy and neonatal outcomes. The proportion of preterm and very preterm births, low birthweight, perinatal mortality and neonatal morbidity showed no differences between the three groups. Similar results were also obtained when comparing the 200\u2010 versus 400\u2010mg progesterone groups. No serious adverse effects were encountered.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>Conclusions\u2002<\/jats:bold>\n                    Vaginal progesterone therapy was generally well tolerated, but failed to prevent preterm births in unselected dichorionic diamniotic twin pregnancies. The 400\u2010mg progesterone dose offered no advantages over the 200\u2010mg regimen.\n                  <\/jats:p>","DOI":"10.1111\/j.1471-0528.2012.03448.x","type":"journal-article","created":{"date-parts":[[2012,8,13]],"date-time":"2012-08-13T06:15:13Z","timestamp":1344838513000},"page":"50-57","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":89,"title":["Increased doses of vaginal progesterone for the prevention of preterm birth in twin pregnancies: a randomised controlled double\u2010blind multicentre trial"],"prefix":"10.1111","volume":"120","author":[{"given":"V","family":"Serra","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Perales","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Meseguer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JJ","family":"Parrilla","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C","family":"Lara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J","family":"Bellver","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R","family":"Grifol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Alcover","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M","family":"Sala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JC","family":"Mart\u00ednez\u2010Escoriza","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A","family":"Pellicer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,8,13]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0020-7292(99)00223-4"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2010.04.031"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.siny.2010.06.006"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.1990.tb01740.x"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa067815"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/uog.9017"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2003.41"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0b013e31818b1ff6"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa035140"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa070641"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(09)60947-8"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2010.06.016"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2010.12.042"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1097\/SMJ.0b013e3181afee12"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.3109\/14767051003702786"},{"key":"e_1_2_6_17_2","first-page":"692","article-title":"Inefficacy of 17 alpha\u2010hydroxyprogesterone caproate in the prevention of prematurity in twin pregnancy","volume":"56","author":"Hartikainen\u2010Sorri AL","year":"1980","journal-title":"Obstet Gynecol"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00404-009-1351-2"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.3109\/00016340903280982"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1186\/1741-7015-8-18"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.2337\/dc07-0564"},{"key":"e_1_2_6_22_2","first-page":"165","article-title":"Effets de la progest\u00e9rone naturelle micronis\u00e9e sur le foie au cours du trosi\u00e8me trimestre de la grossesse","volume":"25","author":"Benifla JL","year":"1997","journal-title":"Contracept Fertil Sex"},{"key":"e_1_2_6_23_2","first-page":"102","article-title":"Cytolyse h\u00e9patique lors d\u2019un traitement tocolytique par la progest\u00e9rone naturelle micronis\u00e9e","volume":"25","author":"Magnin G","year":"1996","journal-title":"Presse Med"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1093\/humrep\/deh146"},{"key":"e_1_2_6_25_2","volume-title":"Scottish, Reproductive, Health, Programme. 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