{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:48:05Z","timestamp":1790387285068,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2020,9,24]],"date-time":"2020-09-24T00:00:00Z","timestamp":1600905600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100003122","name":"Ferring","doi-asserted-by":"publisher","award":["000323"],"award-info":[{"award-number":["000323"]}],"id":[{"id":"10.13039\/501100003122","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Vietnam National Foundation for Science and Technology Development","award":["FWO.106-YS.2017.02"],"award-info":[{"award-number":["FWO.106-YS.2017.02"]}]},{"name":"Fund for Research Flanders","award":["G.OD97.18N"],"award-info":[{"award-number":["G.OD97.18N"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,11,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>Is one cycle of IVM non-inferior to one cycle of conventional in IVF with respect to live birth rates in women with high antral follicle counts (AFCs)?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>We could not demonstrate non-inferiority of IVM compared with IVF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                    <jats:p>IVF with ovarian hyperstimulation has limitations in some subgroups of women at high risk of ovarian stimulation, such as those with polycystic ovary syndrome. IVM is an alternative ART for these women. IVM may be a feasible alternative to IVF in women with a high AFC, but there is a lack of data from randomized clinical trials comparing IVM with IVF in women at high risk of ovarian hyperstimulation syndrome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>This single-center, randomized, controlled non-inferiority trial was conducted at an academic infertility center in Vietnam from January 2018 to April 2019.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>In total, 546 women with an indication for ART and a high AFC (\u226524 follicles in both ovaries) were randomized to the IVM (n\u2009=\u2009273) group or the IVF (n\u2009=\u2009273) group; each underwent one cycle of IVM with a prematuration step versus one cycle of IVF using a standard gonadotropin-releasing hormone antagonist protocol with gonadotropin-releasing hormone agonist triggering. The primary endpoint was live birth rate after the first embryo transfer. The non-inferiority margin for IVM versus IVF was \u221210%.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>Live birth after the first embryo transfer occurred in 96 women (35.2%) in the IVM group and 118 women (43.2%) in the IVF group (absolute risk difference \u20138.1%; 95% confidence interval (CI) \u201316.6%, 0.5%). Cumulative ongoing pregnancy rates at 12\u2009months after randomization were 44.0% in the IVM group and 62.6% in the IVF group (absolute risk difference \u201318.7%; 95% CI \u201327.3%, \u201310.1%). Ovarian hyperstimulation syndrome did not occur in the IVM group, versus two cases in the IVF group. There were no statistically significant differences between the IVM and IVF groups with respect to the occurrence of pregnancy complications, obstetric and perinatal complications, preterm delivery, birth weight and neonatal complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>The main limitation of the study was its open-label design. In addition, the findings are only applicable to IVM conducted using the prematuration step protocol used in this study. Finally, the single ethnicity population limits the external generalizability of the findings.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>Our randomized clinical trial compares live birth rates after IVM and IVF. Although IVM is a viable and safe alternative to IVF that may be suitable for some women seeking a mild ART approach, the current study findings approach inferiority for IVM compared with IVF when cumulative outcomes are considered. Future research should incorporate multiple cycles of IVM in the study design to estimate cumulative fertility outcomes and better inform clinical decision-making.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                    <jats:p>This work was partly supported by Ferring grant number 000323 and funded by the Vietnam National Foundation for Science and Technology Development (NAFOSTED) and by the Fund for Research Flanders (FWO). LNV has received speaker and conference fees from Merck, grant, speaker and conference fees from Merck Sharpe and Dohme, and speaker, conference and scientific board fees from Ferring; TMH has received speaker fees from Merck, Merck Sharp and Dohme, and Ferring; RJN has received conference and scientific board fees from Ferring, is a minor shareholder in an IVF company, and receives grant funding from the National Health and Medical Research Council (NHMRC) of Australia; BWM has acted as a paid consultant to Merck, ObsEva and Guerbet, and is the recipient of grant money from an NHMRC Investigator Grant; RBG reports grants and fellowships from the NHMRC of Australia; JS reports lecture fees from Ferring Pharmaceuticals, Biom\u00e9rieux, Besins Female Healthcare and Merck, grants from Fund for Research Flanders (FWO), and is co-inventor on granted patents on CAPA-IVM methodology in the US (US10392601B2) and Europe (EP3234112B1); TDP, VQD, VNAH, NHG, AHL, THP and RW have no financial relationships with any organizations that might have an interest in the submitted work in the previous three years, and no other relationships or activities that could appear to have influenced the submitted work.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                    <jats:p>NCT03405701 (www.clinicaltrials.gov).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION DATE<\/jats:title>\n                    <jats:p>16 January 2018.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DATE OF FIRST PATENT\u2019S ENROLMENT<\/jats:title>\n                    <jats:p>25 January 2018.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humrep\/deaa240","type":"journal-article","created":{"date-parts":[[2020,8,21]],"date-time":"2020-08-21T08:16:38Z","timestamp":1597997798000},"page":"2537-2547","source":"Crossref","is-referenced-by-count":117,"title":["In-vitro maturation of oocytes versus conventional IVF in women with infertility and a high antral follicle count: a randomized non-inferiority controlled trial"],"prefix":"10.1093","volume":"35","author":[{"given":"Lan N","family":"Vuong","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Medicine and Pharmacy, Ho Chi Minh City, Vietnam"},{"name":"IVFMD, My Duc Hospital and HOPE Research Center, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vu N A","family":"Ho","sequence":"additional","affiliation":[{"name":"IVFMD, My Duc Hospital and HOPE Research Center, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuong M","family":"Ho","sequence":"additional","affiliation":[{"name":"IVFMD, My Duc Hospital and HOPE Research Center, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinh Q","family":"Dang","sequence":"additional","affiliation":[{"name":"IVFMD, My Duc Hospital and HOPE Research Center, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tuan H","family":"Phung","sequence":"additional","affiliation":[{"name":"IVFMD, My Duc Hospital and HOPE Research Center, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nhu H","family":"Giang","sequence":"additional","affiliation":[{"name":"IVFMD, My Duc Hospital and HOPE Research Center, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anh H","family":"Le","sequence":"additional","affiliation":[{"name":"IVFMD, My Duc Hospital and HOPE Research Center, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toan D","family":"Pham","sequence":"additional","affiliation":[{"name":"IVFMD, My Duc Hospital and HOPE Research Center, Ho Chi Minh City, Vietnam"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johan","family":"Smitz","sequence":"additional","affiliation":[{"name":"Follicle Biology Laboratory, Free University of Brussels (VUB), Brussels, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert B","family":"Gilchrist","sequence":"additional","affiliation":[{"name":"School of Women\u2019s and Children\u2019s Health, University of New South Wales Sydney, New South Wales, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"Norman","sequence":"additional","affiliation":[{"name":"Robinson Research Institute and Adelaide Medical School, The University of Adelaide, Adelaide, South Australia, Australia"},{"name":"Fertility SA, Adelaide, South Australia, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben W","family":"Mol","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Victoria, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2020,9,24]]},"reference":[{"key":"2020111005430689300_deaa240-B1","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1016\/j.rbmo.2011.02.001","article-title":"Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting","volume":"22","year":"2011","journal-title":"Reprod Biomed Online"},{"key":"2020111005430689300_deaa240-B2","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1093\/humrep\/deh104","article-title":"The merits of blastocyst versus cleavage stage embryo transfer: a Cochrane review","volume":"19","author":"Blake","year":"2004","journal-title":"Hum Reprod"},{"key":"2020111005430689300_deaa240-B3","doi-asserted-by":"crossref","first-page":"hoz034","DOI":"10.1093\/hropen\/hoz034","article-title":"The perspective of women with an increased risk of OHSS regarding the safety and burden of IVF: a discrete choice experiment","volume":"2020","author":"Braam","year":"2020","journal-title":"Hum Reprod Open"},{"key":"2020111005430689300_deaa240-B4","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1111\/j.1471-0528.1995.tb10840.x","article-title":"Diagnosis, prevention and management of ovarian hyperstimulation syndrome","volume":"102","author":"Brinsden","year":"1995","journal-title":"Br J Obstet Gynaecol"},{"key":"2020111005430689300_deaa240-B5","doi-asserted-by":"crossref","first-page":"1044","DOI":"10.1016\/j.fertnstert.2009.04.040","article-title":"The antral follicle count: practical recommendations for better standardization","volume":"94","author":"Broekmans","year":"2010","journal-title":"Fertil Steril"},{"key":"2020111005430689300_deaa240-B6","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1093\/humupd\/4.2.103","article-title":"Maturation in vitro of immature human oocytes for clinical use","volume":"4","author":"Cha","year":"1998","journal-title":"Hum Reprod Update"},{"key":"2020111005430689300_deaa240-B7","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/S0015-0282(16)54068-0","article-title":"Pregnancy after in vitro fertilization of human follicular oocytes collected from nonstimulated cycles, their culture in vitro and their transfer in a donor oocyte program","volume":"55","author":"Cha","year":"1991","journal-title":"Fertil Steril"},{"key":"2020111005430689300_deaa240-B8","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1016\/S0015-0282(01)02853-9","article-title":"In vitro maturation and fertilization of oocytes from unstimulated normal ovaries, polycystic ovaries, and women with polycystic ovary syndrome","volume":"76","author":"Child","year":"2001","journal-title":"Fertil Steril"},{"key":"2020111005430689300_deaa240-B9","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1007\/s10815-018-1216-3","article-title":"Decreased pregnancy and live birth rates after vitrification of in vitro matured oocytes","volume":"35","author":"Cohen","year":"2018","journal-title":"J Assist Reprod Genet"},{"key":"2020111005430689300_deaa240-B10","doi-asserted-by":"crossref","first-page":"1947","DOI":"10.1093\/humrep\/15.9.1947","article-title":"Day 5 versus day 3 embryo transfer: a controlled randomized trial","volume":"15","author":"Coskun","year":"2000","journal-title":"Hum Reprod"},{"key":"2020111005430689300_deaa240-B11","doi-asserted-by":"crossref","first-page":"2411","DOI":"10.1093\/humrep\/dew208","article-title":"The definition of IVM is clear-variations need defining","volume":"31","author":"De Vos","year":"2016","journal-title":"Hum Reprod"},{"key":"2020111005430689300_deaa240-B12","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/S0140-6736(65)92903-X","article-title":"Maturation in vitro of human ovarian oocytes","volume":"286","author":"Edwards","year":"1965","journal-title":"Lancet"},{"key":"2020111005430689300_deaa240-B13","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1038\/221632a0","article-title":"Early stages of fertilization in vitro of human oocytes matured in vitro","volume":"221","author":"Edwards","year":"1969","journal-title":"Nature"},{"key":"2020111005430689300_deaa240-B14","doi-asserted-by":"crossref","first-page":"1182","DOI":"10.1016\/j.fertnstert.2013.01.090","article-title":"In vitro maturation of oocytes: uncommon indications","volume":"99","author":"Grynberg","year":"2013","journal-title":"Fertil Steril"},{"key":"2020111005430689300_deaa240-B15","doi-asserted-by":"crossref","first-page":"1055","DOI":"10.1093\/humrep\/dez060","article-title":"The effectiveness and safety of in vitro maturation of oocytes versus in vitro fertilization in women with a high antral follicle count","volume":"34","author":"Ho","year":"2019","journal-title":"Hum Reprod"},{"key":"2020111005430689300_deaa240-B16","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1146\/annurev-animal-022114-110822","article-title":"Maturation of oocytes in vitro","volume":"4","author":"Lonergan","year":"2016","journal-title":"Annu Rev Anim Biosci"},{"key":"2020111005430689300_deaa240-B17","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1093\/oxfordjournals.humrep.a137702","article-title":"In-vitro fertilization and the ovarian hyperstimulation syndrome","volume":"7","author":"MacDougall","year":"1992","journal-title":"Hum Reprod"},{"key":"2020111005430689300_deaa240-B18","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1056\/NEJMoa053524","article-title":"In vitro fertilization with single blastocyst-stage versus single cleavage-stage embryos","volume":"354","author":"Papanikolaou","year":"2006","journal-title":"N Engl J Med"},{"key":"2020111005430689300_deaa240-B19","doi-asserted-by":"crossref","first-page":"3198","DOI":"10.1093\/humrep\/dei217","article-title":"Live birth rate is significantly higher after blastocyst transfer than after cleavage-stage embryo transfer when at least four embryos are available on day 3 of embryo culture. A randomized prospective study","volume":"20","author":"Papanikolaou","year":"2005","journal-title":"Hum Reprod"},{"key":"2020111005430689300_deaa240-B20","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1093\/humupd\/dmq032","article-title":"Extra- and intra-ovarian factors in polycystic ovary syndrome: impact on oocyte maturation and embryo developmental competence","volume":"17","author":"Qiao","year":"2011","journal-title":"Hum Reprod Update"},{"key":"2020111005430689300_deaa240-B21","doi-asserted-by":"crossref","first-page":"2135","DOI":"10.1007\/s10815-019-01551-5","article-title":"Biphasic in vitro maturation (CAPA-IVM) specifically improves the developmental capacity of oocytes from small antral follicles","volume":"36","author":"Sanchez","year":"2019","journal-title":"J Assist Reprod Genet"},{"key":"2020111005430689300_deaa240-B22","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1007\/s10815-015-0528-9","article-title":"vitro maturation (IVM) of oocytes recovered from ovariectomy specimens in the laboratory: a promising \u201cex vivo\u201d method of oocyte cryopreservation resulting in the first report of an ongoing pregnancy in Europe","volume":"32","author":"Segers","year":"2015","journal-title":"J Assist Reprod Genet"},{"key":"2020111005430689300_deaa240-B23","doi-asserted-by":"crossref","first-page":"e0134696","DOI":"10.1371\/journal.pone.0134696","article-title":"In vitro maturation in women with vs. without polycystic ovarian syndrome: a systematic review and meta-analysis","volume":"10","author":"Siristatidis","year":"2015","journal-title":"PLoS One"},{"key":"2020111005430689300_deaa240-B24","article-title":"In vitro maturation in subfertile women with polycystic ovarian syndrome undergoing assisted reproduction","volume":"10","author":"Siristatidis","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"2020111005430689300_deaa240-B25","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1055\/s-0030-1268701","article-title":"The promise of in vitro maturation in assisted reproduction and fertility preservation","volume":"29","author":"Smitz","year":"2011","journal-title":"Semin Reprod Med"},{"key":"2020111005430689300_deaa240-B26","doi-asserted-by":"crossref","first-page":"1534","DOI":"10.1093\/humrep\/deh768","article-title":"Favourable pregnancy results with insemination of in vitro matured oocytes from unstimulated patients","volume":"20","author":"Soderstrom-Anttila","year":"2005","journal-title":"Hum Reprod"},{"key":"2020111005430689300_deaa240-B27","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1093\/humrep\/dey256","article-title":"Recommendations from the international evidence-based guideline for the assessment and management of polycystic ovary syndrome","volume":"33","author":"Teede","year":"2018","journal-title":"Hum Reprod"},{"key":"2020111005430689300_deaa240-B28","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1142\/S2661318219300022","article-title":"The place of in vitro maturation in assisted reproductive technology","volume":"1","author":"Vuong","year":"2019","journal-title":"Fertil Reprod"},{"key":"2020111005430689300_deaa240-B29","doi-asserted-by":"crossref","first-page":"e023413","DOI":"10.1136\/bmjopen-2018-023413","article-title":"Effectiveness and safety of in vitro maturation of oocytes versus in vitro fertilisation in women with high antral follicle count: study protocol for a randomised controlled trial","volume":"8","author":"Vuong","year":"2018","journal-title":"BMJ Open"},{"key":"2020111005430689300_deaa240-B30","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s10815-019-01677-6","article-title":"Live births after oocyte in vitro maturation with a prematuration step in women with polycystic ovary syndrome","volume":"37","author":"Vuong","year":"2020","journal-title":"J Assist Reprod Genet"},{"key":"2020111005430689300_deaa240-B31","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1093\/humrep\/deu248","article-title":"In vitro maturation as an alternative to standard in vitro fertilization for patients diagnosed with polycystic ovaries: a comparative analysis of fresh, frozen and cumulative cycle outcomes","volume":"30","author":"Walls","year":"2015","journal-title":"Hum Reprod"},{"key":"2020111005430689300_deaa240-B32","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.fertnstert.2006.11.070","article-title":"Prospective evaluation of the optimal time for selecting a single embryo for transfer: day 3 versus day 5","volume":"88","author":"Zech","year":"2007","journal-title":"Fertil Steril"}],"container-title":["Human Reproduction"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/humrep\/article-pdf\/35\/11\/2537\/34221783\/deaa240.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/humrep\/article-pdf\/35\/11\/2537\/34221783\/deaa240.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2020,11,10]],"date-time":"2020-11-10T05:43:52Z","timestamp":1604987032000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/humrep\/article\/35\/11\/2537\/5911267"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,24]]},"references-count":32,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,9,24]]},"published-print":{"date-parts":[[2020,11,1]]}},"URL":"https:\/\/doi.org\/10.1093\/humrep\/deaa240","relation":{},"ISSN":["0268-1161","1460-2350"],"issn-type":[{"value":"0268-1161","type":"print"},{"value":"1460-2350","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2020,11]]},"published":{"date-parts":[[2020,9,24]]}}}