{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:21:58Z","timestamp":1787008918891,"version":"build-2736575974"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2023,8,26]],"date-time":"2023-08-26T00:00:00Z","timestamp":1693008000000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Elphinstone scholarship scheme at the University of Aberdeen"},{"name":"Assisted Reproduction Unit at Aberdeen Fertility Centre, University of Aberdeen"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,10,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>STUDY QUESTION<\/jats:title>\n                    <jats:p>Can two prediction models developed using data from 1999 to 2009 accurately predict the cumulative probability of live birth per woman over multiple complete cycles of IVF in an updated UK cohort?<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>SUMMARY ANSWER<\/jats:title>\n                    <jats:p>After being updated, the models were able to estimate individualized chances of cumulative live birth over multiple complete cycles of IVF with greater accuracy.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WHAT IS KNOWN ALREADY<\/jats:title>\n                    <jats:p>The McLernon models were the first to predict cumulative live birth over multiple complete cycles of IVF. They were converted into an online calculator called OPIS (Outcome Prediction In Subfertility) which has 3000 users per month on average. A previous study externally validated the McLernon models using a Dutch prospective cohort containing data from 2011 to 2014. With changes in IVF practice over time, it is important that the McLernon models are externally validated on a more recent cohort of patients to ensure that predictions remain accurate.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY DESIGN, SIZE, DURATION<\/jats:title>\n                    <jats:p>A population-based cohort of 91\u200a035 women undergoing IVF in the UK between January 2010 and December 2016 was used for external validation. Data on frozen embryo transfers associated with these complete IVF cycles conducted from 1 January 2017 to 31 December 2017 were also collected.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PARTICIPANTS\/MATERIALS, SETTING, METHODS<\/jats:title>\n                    <jats:p>Data on IVF treatments were obtained from the Human Fertilisation and Embryology Authority (HFEA). The predictive performances of the McLernon models were evaluated in terms of discrimination and calibration. Discrimination was assessed using the c-statistic and calibration was assessed using calibration-in-the-large, calibration slope, and calibration plots. Where any model demonstrated poor calibration in the validation cohort, the models were updated using intercept recalibration, logistic recalibration, or model revision to improve model performance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>MAIN RESULTS AND THE ROLE OF CHANCE<\/jats:title>\n                    <jats:p>Following exclusions, 91\u200a035 women who underwent 144\u200a734 complete cycles were included. The validation cohort had a similar distribution age profile to women in the development cohort. Live birth rates over all complete cycles of IVF per woman were higher in the validation cohort. After calibration assessment, both models required updating. The coefficients of the pre-treatment model were revised, and the updated model showed reasonable discrimination (c-statistic: 0.67, 95% CI: 0.66 to 0.68). After logistic recalibration, the post-treatment model showed good discrimination (c-statistic: 0.75, 95% CI: 0.74 to 0.76). As an example, in the updated pre-treatment model, a 30-year-old woman with 2\u2009years of primary infertility has a 41% chance of having a live birth in the first complete ICSI cycle and a 75% chance over three complete cycles. In a couple with 2\u2009years of primary male factor infertility where a 30-year-old woman has 15 oocytes collected in the first cycle, a single fresh blastocyst embryo transferred in the first cycle and spare embryos cryopreserved, the estimated chance of live birth provided by the post-treatment model is 40% in the first complete ICSI cycle and 75% over three complete cycles.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>LIMITATIONS, REASONS FOR CAUTION<\/jats:title>\n                    <jats:p>Two predictors from the original models, duration of infertility and previous pregnancy, which were not available in the recent HFEA dataset, were imputed using data from the older cohort used to develop the models. The HFEA dataset does not contain some other potentially important predictors, e.g. BMI, ethnicity, race, smoking and alcohol intake in women, as well as measures of ovarian reserve such as antral follicle count.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>WIDER IMPLICATIONS OF THE FINDINGS<\/jats:title>\n                    <jats:p>Both updated models show improved predictive ability and provide estimates which are more reflective of current practice and patient case mix. The updated OPIS tool can be used by clinicians to help shape couples\u2019 expectations by informing them of their individualized chances of live birth over a sequence of multiple complete cycles of IVF.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>STUDY FUNDING\/COMPETING INTEREST(S)<\/jats:title>\n                    <jats:p>This study was supported by an Elphinstone scholarship scheme at the University of Aberdeen and Aberdeen Fertility Centre, University of Aberdeen. S.B. has a commitment of research funding from Merck. D.J.M. and M.B.R. declare support for the present manuscript from Elphinstone scholarship scheme at the University of Aberdeen and Assisted Reproduction Unit at Aberdeen Fertility Centre, University of Aberdeen. D.J.M. declares grants received by University of Aberdeen from NHS Grampian, The Meikle Foundation, and Chief Scientist Office in the past 3\u2009years. D.J.M. declares receiving an honorarium for lectures from Merck. D.J.M. is Associate Editor of Human Reproduction Open and Statistical Advisor for Reproductive BioMed Online. S.B. declares royalties from Cambridge University Press for a book. S.B. declares receiving an honorarium for lectures from Merck, Organon, Ferring, Obstetric and Gynaecological Society of Singapore, and Taiwanese Society for Reproductive Medicine. S.B. has received support from Merck, ESHRE, and Ferring for attending meetings as speaker and is on the METAFOR and CAPRE Trials Data Monitoring Committee.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>TRIAL REGISTRATION NUMBER<\/jats:title>\n                    <jats:p>N\/A.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/humrep\/dead165","type":"journal-article","created":{"date-parts":[[2023,8,7]],"date-time":"2023-08-07T16:18:24Z","timestamp":1691425104000},"page":"1998-2010","source":"Crossref","is-referenced-by-count":27,"title":["External validation of models for predicting cumulative live birth over multiple complete cycles of IVF treatment"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9468-6688","authenticated-orcid":false,"given":"Mariam B","family":"Ratna","sequence":"first","affiliation":[{"name":"Institute of Applied Health Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen , Aberdeen, UK"},{"name":"Clinical Trials Unit, Warwick Medical School, University of Warwick , Warwick , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4588-356X","authenticated-orcid":false,"given":"Siladitya","family":"Bhattacharya","sequence":"additional","affiliation":[{"name":"School of Medicine, Medical Sciences & Nutrition, University of Aberdeen , Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8905-2429","authenticated-orcid":false,"given":"David J","family":"McLernon","sequence":"additional","affiliation":[{"name":"Institute of Applied Health Sciences, School of Medicine, Medical Sciences & Nutrition, University of Aberdeen , Aberdeen, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,8,25]]},"reference":[{"key":"2024051411363918000_dead165-B1","doi-asserted-by":"crossref","first-page":"n2281","DOI":"10.1136\/bmj.n2281","article-title":"Risk of bias in studies on prediction models developed using supervised machine learning techniques: systematic review","volume":"375","author":"Andaur Navarro","year":"2021","journal-title":"BMJ"},{"key":"2024051411363918000_dead165-B2","doi-asserted-by":"crossref","first-page":"2971","DOI":"10.1093\/humrep\/des283","article-title":"Simple adaptations to the Templeton model for IVF outcome prediction make it current and clinically useful","volume":"27","author":"Arvis","year":"2012","journal-title":"Hum Reprod"},{"key":"2024051411363918000_dead165-B3","doi-asserted-by":"crossref","first-page":"e1001221","DOI":"10.1371\/journal.pmed.1001221","article-title":"Reporting and methods in clinical prediction research: a systematic review","volume":"9","author":"Bouwmeester","year":"2012","journal-title":"PLoS Med"},{"key":"2024051411363918000_dead165-B4","doi-asserted-by":"crossref","first-page":"3127","DOI":"10.1093\/humrep\/dep340","article-title":"When and why do subfertile couples discontinue their fertility care? 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