{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T05:19:10Z","timestamp":1790745550110,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2023,12,26]],"date-time":"2023-12-26T00:00:00Z","timestamp":1703548800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council Centre for Research Excellence in Women\u2019s Health in Reproductive Life","award":["App 1171592"],"award-info":[{"award-number":["App 1171592"]}]},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"publisher","award":["GNT2016729"],"award-info":[{"award-number":["GNT2016729"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"publisher","award":["GNT20009767"],"award-info":[{"award-number":["GNT20009767"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"NHMRC","doi-asserted-by":"publisher","award":["GNT1176437"],"award-info":[{"award-number":["GNT1176437"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>BACKGROUND<\/jats:title>\n                  <jats:p>IVF and IUI with ovarian stimulation (IUI-OS) are widely used in managing unexplained infertility. IUI-OS is generally considered first-line therapy, followed by IVF only if IUI-OS is unsuccessful after several attempts. However, there is a growing interest in using IVF for immediate treatment because it is believed to lead to higher live birth rates and shorter time to pregnancy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>OBJECTIVE AND RATIONALE<\/jats:title>\n                  <jats:p>Randomized controlled trials (RCTs) comparing IVF versus IUI-OS had varied study designs and findings. Some RCTs used complex algorithms to combine IVF and IUI-OS, while others had unequal follow-up time between arms or compared treatments on a per-cycle basis, which introduced biases. Comparing cumulative live birth rates of IVF and IUI-OS within a consistent time frame is necessary for a fair head-to-head comparison. Previous meta-analyses of RCTs did not consider the time it takes to achieve pregnancy, which is not possible using aggregate data. Individual participant data meta-analysis (IPD-MA) allows standardization of follow-up time in different trials and time-to-event analysis methods. We performed this IPD-MA to investigate if IVF increases cumulative live birth rate considering the time leading to pregnancy and reduces multiple pregnancy rate compared to IUI-OS in couples with unexplained infertility.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>SEARCH METHODS<\/jats:title>\n                  <jats:p>We searched MEDLINE, EMBASE, CENTRAL, PsycINFO, CINAHL, and the Cochrane Gynaecology and Fertility Group Specialised Register to identify RCTs that completed data collection before June 2021. A search update was carried out in January 2023. RCTs that compared IVF\/ICSI to IUI-OS in couples with unexplained infertility were eligible. We invited author groups of eligible studies to join the IPD-MA and share the deidentified IPD of their RCTs. IPD were checked and standardized before synthesis. The quality of evidence was assessed using the Risk of Bias 2 tool.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>OUTCOMES<\/jats:title>\n                  <jats:p>Of eight potentially eligible RCTs, two were considered awaiting classification. In the other six trials, four shared IPD of 934 women, of which 550 were allocated to IVF and 383 to IUI-OS. Because the interventions were unable to blind, two RCTs had a high risk of bias, one had some concerns, and one had a low risk of bias. Considering the time to pregnancy leading to live birth, the cumulative live birth rate was not significantly higher in IVF compared to that in IUI-OS (4 RCTs, 908 women, 50.3% versus 43.2%, hazard ratio 1.19, 95% CI 0.81\u20131.74, I2\u2009=\u200942.4%). For the safety primary outcome, the rate of multiple pregnancy was not significantly lower in IVF than IUI-OS (3 RCTs, 890 women, 3.8% versus 5.2% of all couples randomized, odds ratio 0.78, 95% CI 0.41\u20131.50, I2\u2009=\u20090.0%).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>WIDER IMPLICATIONS<\/jats:title>\n                  <jats:p>There is no robust evidence that in couples with unexplained infertility IVF achieves pregnancy leading to live birth faster than IUI-OS. IVF and IUI-OS are both viable options in terms of effectiveness and safety for managing unexplained infertility. The associated costs of interventions and the preference of couples need to be weighed in clinical decision-making.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/humupd\/dmad033","type":"journal-article","created":{"date-parts":[[2023,12,27]],"date-time":"2023-12-27T01:31:06Z","timestamp":1703640666000},"page":"174-185","source":"Crossref","is-referenced-by-count":10,"title":["IVF versus IUI with ovarian stimulation for unexplained infertility: a collaborative individual participant data meta-analysis"],"prefix":"10.1093","volume":"30","author":[{"given":"Shimona","family":"Lai","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Monash University , Clayton, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6622-8134","authenticated-orcid":false,"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Monash University , Clayton, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8263-213X","authenticated-orcid":false,"given":"Madelon","family":"van Wely","sequence":"additional","affiliation":[{"name":"Centre for Reproductive Medicine, Amsterdam UMC, Location AMC , Amsterdam, The Netherlands"},{"name":"Department of Epidemiology & Data Science, Amsterdam UMC, Location VUmc , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Costello","sequence":"additional","affiliation":[{"name":"Women\u2019s Health, School of Clinical Medicine, University of New South Wales & Royal Hospital for Women and Monash IVF , Sydney, NSW, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Farquhar","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, University of Auckland , Auckland, New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra J","family":"Bensdorp","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Amsterdam UMC , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Inge M","family":"Custers","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Amsterdam UMC , Amsterdam, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelique J","family":"Goverde","sequence":"additional","affiliation":[{"name":"Department of Reproductive Medicine and Gynaecology, University Medical Centre Utrecht , Utrecht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hossam","family":"Elzeiny","sequence":"additional","affiliation":[{"name":"Royal Women\u2019s Hospital, Melbourne IVF , Melbourne, VIC, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8337-550X","authenticated-orcid":false,"given":"Ben W","family":"Mol","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Monash University , Clayton, VIC, Australia"},{"name":"Aberdeen Centre for Women\u2019s Health Research, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen , Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8980-0909","authenticated-orcid":false,"given":"Wentao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynaecology, Monash University , Clayton, VIC, Australia"},{"name":"National Perinatal Epidemiology and Statistics Unit (NPESU), Centre for Big Data Research in Health, and School of Clinical Medicine, Faculty of Medicine, University of New South Wales, Sydney, 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