Human Reproduction, Vol.35, No.12, pp. 2725–2734, 2020 Advance Access Publication on November 30, 2020 doi:10.1093/humrep/deaa241 ORIGINAL ARTICLE Infertility Developing a core outcome set for future infertility research: an international consensus development study† ‡ Downloaded from https://academic.oup.com/humrep/article/35/12/2725/6010638 by guest on 17 October 2023 J.M.N. Duffy1,2,*, H. AlAhwany3, S. Bhattacharya4, B. Collura5, C. Curtis6,7, J.L.H. Evers8, R.G. Farquharson9, S. Franik10, L.C. Giudice11,12, Y. Khalaf13, J.M.L. Knijnenburg14, B. Leeners15, R.S. Legro16, S. Lensen17, J.C. Vazquez-Niebla18, D. Mavrelos19, B.W.J. Mol20, C. Niederberger21, E.H.Y. Ng22,23, A.S. Otter24, L. Puscasiu25, S. Rautakallio-Hokkanen26, S. Repping27, I. Sarris1, J.L. Simpson28, A. Strandell29, C. Strawbridge30, H.L. Torrance31, A. Vail32, M. van Wely27, M.A. Vercoe33, N.L. Vuong34, A.Y. Wang35, R. Wang20, J. Wilkinson32, M.A. Youssef36, C.M. Farquhar33, and the Core Outcome Measure for Infertility Trials (COMMIT) initiative§ 1 King’s Fertility, Fetal Medicine Research Institute, London, UK 2Institute for Women’s Health, University College London, London, UK 3 School of Medicine, University of Nottingham, Derby, UK 4School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, UK 5RESOLVE: The National Infertility Association, VA, USA 6Fertility New Zealand, Auckland, New Zealand 7School of Psychology, University of Waikato, Hamilton, New Zealand 8Maastricht University Medical Centre, Maastricht, The Netherlands 9Department of Obstetrics and Gynaecology, Liverpool Women’s NHS Foundation Trust, Liverpool, UK 10Department of Obstetrics and Gynaecology, Münster University Hospital, Münster, Germany 11Center for Research, Innovation and Training in Reproduction and Infertility, Center for Reproductive Sciences, University of California, San Francisco, CA, USA 12International Federation of Fertility Societies, Philadelphia, PA, USA 13Department of Women and Children’s Health, King’s College London, Guy’s Hospital, London, UK 14Freya Dutch Infertility Association, Gorinchem, The Netherlands 15Department of Reproductive Endocrinology, University Hospital Zurich, Zurich, Switzerland 16 Department of Obstetrics and Gynaecology, Penn State College of Medicine, PA, USA 17Department of Obstetrics and Gynaecology, University of Melbourne, VIC, Australia 18Cochrane Iberoamerica, Biomedical Research Institute Sant Pau, Barcelona, Spain 19 Reproductive Medicine Unit, University College Hospital, London, UK 20Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia 21Department of Urology, University of Illinois at Chicago College of Medicine, Chicago, IL, USA 22 Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong 23Shenzhen Key Laboratory of Fertility Regulation, The University of Hong Kong-Shenzhen Hospital, China 24Osakidetza OSI, Bilbao, Basurto, Spain 25University of Medicine, Pharmacy, Sciences and Technology, Targu Mures, Romania 26Fertility Europe, Evere, Belgium 27Center for Reproductive Medicine, Amsterdam Reproduction and Development Institute, Amsterdam University Medical Centres, Amsterdam, The Netherlands 28 Department of Human and Molecular Genetics, Florida International University, FL, USA 29Department of Obstetrics and Gynecology, Sahlgrenska Academy, University of Gothenburg, Göteborg, Sweden 30Fertility Network UK, London, UK 31Department of Reproductive Medicine, University Medical Centre Utrecht, Utrecht, the Netherlands 32Centre for Biostatistics, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK 33Cochrane Gynaecology and Fertility Group, University of Auckland, Auckland, New Zealand 34Department of Obstetrics and Gynaecology, University of Medicine and Pharmacy in Ho Chi Minh City, Ho Chi Minh City, Vietnam 35Faculty of Health, University of Technology, Sydney, Broadway, Australia 36Department of Obstetrics and Gynaecology, Faculty of Medicine, Cairo University, Cairo, Egypt *Correspondence address. King’s Fertility, Fetal Medicine Research Institute, London, UK. E-mail: james.duffy3@nhs.net Submitted on May 12, 2020; resubmitted on July 8, 2020; editorial decision on July 22, 2020 STUDY QUESTION: Can a core outcome set to standardize outcome selection, collection and reporting across future infertility research be developed? SUMMARY ANSWER: A minimum data set, known as a core outcome set, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential treatments for infertility. † This article has not been externally peer reviewed. ‡ This article has been published simultaneously in Fertility and Sterility. § Members of the COMMIT initiative are listed in the Appendix. C The Author(s) 2020. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. V This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com 2726 Duffy et al. WHAT IS KNOWN ALREADY: Complex issues, including a failure to consider the perspectives of people with fertility problems when selecting outcomes, variations in outcome definitions and the selective reporting of outcomes on the basis of statistical analysis, make the results of infertility research difficult to interpret. STUDY DESIGN, SIZE, DURATION: A three-round Delphi survey (372 participants from 41 countries) and consensus development workshop (30 participants from 27 countries). PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, researchers and people with fertility problems were brought together in an open and transparent process using formal consensus science methods. MAIN RESULTS AND THE ROLE OF CHANCE: The core outcome set consists of: viable intrauterine pregnancy confirmed by ultra- sound (accounting for singleton, twin and higher multiple pregnancy); pregnancy loss (accounting for ectopic pregnancy, miscarriage, still- birth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Time to pregnancy leading to live birth should be reported when applicable. Downloaded from https://academic.oup.com/humrep/article/35/12/2725/6010638 by guest on 17 October 2023 LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods which have inherent limitations, including the representativeness of the participant sample, Delphi survey attrition and an arbitrary consensus threshold. WIDER IMPLICATIONS OF THE FINDINGS: Embedding the core outcome set within RCTs and systematic reviews should ensure the comprehensive selection, collection and reporting of core outcomes. Research funding bodies, the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) statement, and over 80 specialty journals, including the Cochrane Gynaecology and Fertility Group, Fertility and Sterility and Human Reproduction, have committed to implementing this core outcome set. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the Catalyst Fund, Royal Society of New Zealand, Auckland Medical Research Fund and Maurice and Phyllis Paykel Trust. The funder had no role in the design and conduct of the study, the collection, management, analysis or interpretation of data, or manuscript preparation. B.W.J.M. is supported by a National Health and Medical Research Council Practitioner Fellowship (GNT1082548). S.B. was supported by University of Auckland Foundation Seelye Travelling Fellowship. S.B. reports being the Editor-in-Chief of Human Reproduction Open and an editor of the Cochrane Gynaecology and Fertility group. J.L.H.E. reports being the Editor Emeritus of Human Reproduction. J.M.L.K. reports research sponsorship from Ferring and Theramex. R.S.L. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. B.W.J.M. reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. A.S. reports consultancy fees from Guerbet. E.H.Y.N. reports research sponsorship from Merck. N.L.V. reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the work presented. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: Core Outcome Measures in Effectiveness Trials Initiative: 1023. Key words: Consensus development study / core outcome sets / modified Delphi method / modified Nominal Group Technique / outcome measures; outcomes .. Introduction .. been inconsistently defined, using different definitions, including a viable .. fetus after 24 weeks of gestation, pregnancy continuation beyond .. Randomized controlled trials (RCTs) evaluating potential fertility treat- .. 28 weeks of gestation and delivery of a living baby (Wilkinson et al., ments should select, collect and report outcomes that are relevant to .. 2016). Such variation provides sufficient flexibility for researchers to se- .. people with infertility and reflect the realities of clinical practice (Duffy .. lectively report favorable results based on statistical significance. Selective et al., 2017a). Unfortunately, many infertility trials fall short of this re- .. .. reporting of outcomes based on statistical significance, commonly re- quirement (Wilkinson et al., 2019a). Complex issues, including a failure .. ferred to as result cherry picking, is thought to be widespread across in- to take into account the perspectives of people with infertility when .. .. fertility research and can result in the overestimation of treatment designing RCT, variations in outcomes and selective reporting of out- .. efficacy and underestimation of harm (Duffy et al., 2019a). Without con- .. comes, make research evidence difficult to interpret, undermining the .. sistent outcome selection, collection and reporting, evidence synthesis translation of research into clinical practice (Duffy et al., 2019a). .. can be challenging and can make comparisons and combining these data Historically, there has been a limited emphasis upon the engagement ... within a meta-analysis impossible (Braakhekke et al., 2014). .. of people with fertility problems in the design of research, which may .. These problems can be addressed by the development of a core have inadvertently led to the selection of outcomes based upon the .. outcome set for RCT and systematic reviews evaluating potential .. preferences of researchers. A systematic review has characterized out- .. treatments for infertility. A core outcome set represents a minimum .. come reporting across infertility trials and demonstrates the wide varia- .. collection of particularly important outcomes and outcome measures tion in reporting, for example, the majority of infertility trials have not .. which have been developed using formal consensus methods engaging .. reported live birth, major congenital anomalies and adverse events .. health care professionals, researchers and people with fertility prob- (Dapuzzo et al., 2011). Even when relevant outcomes are reported, dif- .. lems (Duffy et al., 2017a). Core outcomes should be routinely utilized .. ferent definitions can limit interpretation. For example, live birth has . by researchers, collected in a standardized manner and reported Core outcomes for infertility research 2727 .. consistently in the final publication (Core Outcomes in Women’s and .. (Murphy et al., 1998). Anticipating a 20% attrition rate, we aimed to Newborn Health Initiative, 2014). .. recruit 18 participants for each stakeholder group. .. Motivated by the desire to increase the utility of future infertility re- .. The modified Delphi method was delivered through sequential on- search, an international collaboration embedded within the Cochrane ... line surveys using Delphi survey software (Delphi Manager, University Gynaecology and Fertility Group, has brought health care professio- .. of Liverpool, Liverpool, UK). Potential participants received an explan- .. nals, researchers and people with fertility problems together to de- .. atory video abstract, a plain language summary and Delphi survey velop a core outcome set for future infertility research. .. instructions. In round one, participants scored individual outcomes on .. .. a nine-point Likert scale. Participants were able to select an ‘unable to .. score’ category if they considered themselves not to have sufficient ex- .. Materials and methods .. pertise or experience to score an individual outcome. Before complet- .. ing the survey, participants were able to suggest additional outcomes. .. The study was prospectively registered with the Core Outcome .. After the round one survey had closed, the scores for each outcome .. Downloaded from https://academic.oup.com/humrep/article/35/12/2725/6010638 by guest on 17 October 2023 Measures in Effectiveness Trials (COMET) initiative, registration num- .. were aggregated across individual stakeholder groups. The percentage ber 1023. An international steering group, including health care profes- .. of participants scoring each outcome at every possible response from sionals, researchers and people with fertility problems, was .. one to nine was calculated and tabulated for individual stakeholder .. established. The steering group was convened during the development .. groups: healthcare professionals, researchers and people with fertility of the study protocol, before the launch of the Delphi survey and be- .. problems. Additional outcomes were considered by the steering group .. fore the consensus development meeting, to obtain advice regarding .. and novel outcomes were entered into the round two survey. the participant sample, data collection and data analysis. .. In round two, participants were asked to reflect on their own .. The core outcome set was developed in a three-stage process using .. scores and on the scores of other participants, before rescoring each consensus science methods advocated by the COMET initiative .. .. outcome. Before completing the survey, participants were able to (Williamson et al., 2017). A protocol describing the methods has pre- .. score additional outcomes suggested by participants in the round one viously been published (Duffy et al., 2018). The protocol was informed .. .. survey. After the round two surveys had closed, the percentage of by a systematic review of registered, progressing and completed core .. participants scoring each outcome at every possible response from .. outcome sets relevant to women’s and newborn health (Duffy et al., .. one to nine was calculated and tabulated for individual stakeholder 2017b) and the experiences of steering group members involved in .. groups. An a priori consensus definition, a median score of eight in .. other core outcome set development studies (Duffy et al., 2016; .. each stakeholder group, was applied to identify consensus outcomes. Hirsch et al., 2016a,b; Khalil et al., 2017, 2019; Webbe et al., 2017; .. The round two Delphi survey results were reviewed by the steering .. Whitehouse et al., 2017). .. group to consider whether a further Delphi survey round was re- The important work of the Harbin Consensus Working Group .. quired. The steering group members concluded it was unlikely a fur- .. (Harbin Consensus Conference Workshop Group, 2014) and .. ther Delphi survey round would identify additional consensus International Committee for Monitoring Assisted Reproductive .. outcomes. However, as there is uncertainty regarding the use of the .. Technologies (Zegers-Hochschild et al., 2017) is complementary to .. modified Delphi method in core outcome set development, the steer- this study. .. ing group recommended proceeding with a third Delphi survey round, .. A comprehensive inventory of outcomes was developed by extracting .. to ensure that no further consensus outcomes would have been iden- outcomes from systematic reviews that had already quantified outcome .. tified (Williamson et al., 2017). .. reporting across infertility trials (Dapuzzo et al., 2011; Braakhekke et al., .. Following the round two survey, a face-to-face consensus develop- 2014; Wilkinson et al., 2016). Lay definitions were developed for individ- .. ment meeting was arranged. A modified Nominal Group Technique .. ual outcomes. The outcome inventory and lay definitions were entered .. was used to further prioritize consensus outcomes. Healthcare profes- into a modified Delphi method (Murphy et al., 1998). .. sionals, researchers and people with fertility problems who had com- .. The study aimed to recruit key stakeholders including health care .. pleted all three rounds of the Delphi survey were invited to professionals, researchers and people with fertility problems. .. .. participate. The modified Nominal Group Technique does not depend Healthcare professionals and researchers were recruited through the .. on statistical power. In consultation with the steering group, we aimed .. British Fertility Society, Core Outcomes in Women’s and Newborn .. to recruit between 10 and 15 participants, as this number has yielded Health initiative, Cochrane Gynaecology and Fertility Group, .. sufficient results and assured validity in other settings (Murphy et al., .. International Federation of Fertility Societies, the International .. 1998). Federation of Gynecology and Obstetrics Committee for .. The modified Nominal Group Technique provides an opportunity .. Reproductive Medicine, Endocrinology and Infertility, Reproductive .. to generate ideas, which are discussed, and ranked by a group of Medicine Clinical Study Group and Royal College of Obstetricians and .. experts (Murphy et al., 1998). At the start of the meeting, the results .. Gynaecologists. People with fertility problems were recruited through .. of the Delphi survey were reviewed. All potential core outcomes Fertility Europe, Fertility Network UK, Fertility New Zealand and .. reaching the standardized consensus definition were entered into the .. RESOLVE: The National Infertility Association. Recruitment was sup- .. process. Participants were able to enter other potential core out- ported by an active social media campaign. The Delphi method does .. comes which had not reached the standardized consensus definition, .. not depend on statistical power. Working from its underlying princi- .. upon request. Each participant was asked to contribute their opinions. ples, group error should decrease and the decision quality increase as .. Following the initial discussion, outcomes were divided into three initial .. the number of participants increases. Between 10 and 15 participants .. categories: outcomes to be considered for inclusion in the final core have been demonstrated to yield sufficient results and assure validity .. outcome set; outcomes where no consensus existed; and outcomes 2728 Duffy et al. .. which should not be considered for inclusion in the final core outcome .. the steering group added 32 additional outcomes to round two, in- set. Participants were invited to discuss the ordering of the outcomes .. cluding cumulative live birth, experimental intervention feasibility and .. within each category. The discussion focused upon ranking the out- .. cost effectiveness. Therefore, 133 outcomes were scored during comes being considered for inclusion in the final core outcome set .. round two. Following round two, 28 outcomes reached the consensus .. and the outcomes where no consensus existed. During the discussion, .. threshold. No additional consensus outcomes were identified following .. the outcomes could be moved between the categories. Finally, the .. the completion of the round three survey. core outcome set was agreed. .. Fifteen healthcare professionals, six researchers and nine people .. .. with fertility problems, including four men with fertility problems, from .. 27 countries, participated in the consensus development meeting. .. .. Twenty-eight consensus outcomes were entered into the modified Results .. Nominal Group Technique. Participants entered an additional eight no .. An outcome inventory, which included 101 outcomes, was developed .. consensus outcomes into the process. These outcomes had been Downloaded from https://academic.oup.com/humrep/article/35/12/2725/6010638 by guest on 17 October 2023 .. (Supplementary Table SI). These outcomes were thematically ordered .. highly scored by people with infertility (median score nine), however, into 23 thematic domains, including early pregnancy outcomes, .. had not met the consensus threshold because of lower scores in other .. patient-reported outcomes and adverse events immediately following .. stakeholder groups. Participants prioritized outcomes for inclusion in treatment. Outcome domains, outcomes and lay definitions were en- .. the core outcome set for infertility (Fig. 2). .. tered into the modified Delphi method. .. When considering the Delphi survey, round one was completed by .. .. 261 healthcare professionals, 57 researchers and 54 people with fertil- .. ity problems, from 41 countries (Table I). Round two was completed .. .. Discussion by 275 participants and round three was completed by 227 partici- .. Using formal consensus science methods, health care professionals, .. pants. One hundred and one outcomes were entered into the Delphi .. researchers and people with fertility problems have developed a core survey (Fig. 1). In response to the outcomes suggested by participants, .. outcome set which should be used to standardize outcome selection, Table I Participant characteristics. Modified Delphi method Modified nominal group technique Round 1 n 5 372 Round 2 n 5 275 Round 3 n 5 227 Withdrawals n 5 145 n 5 30 ............................................................................................................................................................................................................................ Stakeholder group, n Health professionals 261 203 176 85 15 Researchers 57 44 38 19 6 People with infertility 54 28 13 41 9 Gender, n Male 124 94 76 48 15 Female 244 178 148 96 13 Not stated 4 3 3 1 2 Age (years), n Under 29 75 64 62 13 3 30 to 39 116 81 66 50 6 40 to 49 76 54 39 37 5 50 to 59 7 54 44 34 8 Over 60 22 18 12 10 6 Prefer not to say 5 4 4 1 0 Geographical location, n Africa 13 5 5 8 1 Asia 118 99 94 24 2 Australia and New Zealand 42 34 29 13 3 Europe 134 92 70 64 17 North America 37 26 18 19 4 South America 15 9 5 10 2 Prefer not to say 13 10 6 7 1 Core outcomes for infertility research 2729 Systematic review 101 potential core outcomes Delphi survey round 1 101 potential core outcomes 261 healthcare professionals 57 researchers 54 patients 41 countries 32 additional outcomes entered Delphi survey round 2 133 potential core outcomes scored Downloaded from https://academic.oup.com/humrep/article/35/12/2725/6010638 by guest on 17 October 2023 203 healthcare professionals 44 researchers 28 patients Consensus meeting 28 consensus outcomes entered 15 healthcare professionals 6 researchers 9 patients 27 countries 8 outcomes entered by participants Final consensus Core outcome set for future infertility research Figure 1. Flow of participants and outcomes. Viable intrauterine pregnancy confirmed by ultrasound. Accounting for singleton pregnancy, twin pregnancy, and higher multiple pregnancy. Pregnancy loss. Accounting for ectopic pregnancy, miscarriage, stillbirth, and termination of pregnancy. Live birth. Gestational age at delivery. Birth weight. Neonatal mortality. Major congenital anomaly. * When applicable → time to pregnancy leading to live birth. Figure 2. A core outcome set for future infertility research. .. collection and reporting across RCT and systematic reviews evaluating .. study has met these standards. With 372 participants, from 41 coun- potential treatments for infertility. .. tries, participating in the Delphi survey and 30 participants, from 27 .. The COMET initiative has recently published methodological stand- .. countries, participating in the consensus development meeting, the ards for core outcome set development (Kirkham et al., 2017). This .. global participation achieved in this study should secure the 2730 Duffy et al. .. generalizability of the results across diverse research settings. The .. This study has established a core outcome set for infertility, how- study included people with fertility problems as steering group mem- .. ever different definitions exist for individual core outcomes. The study .. bers and participants. As participants, they shared their views regarding .. has recently developed standardized definitions, using formal consen- the importance of potential core outcomes during the Delphi survey ... sus development methods, for individual core outcomes. This addi- and participated fully in the consensus development meeting, which .. tional harmony across future infertility trials should ensure secondary .. prioritized the final core outcome set. This contribution should ensure .. research can be undertaken prospectively, efficiently and harmoniously the final core outcome set holds the necessary reach and relevance to .. (Duffy et al., 2020b). This standardization will be supported by the de- .. people with fertility problems. .. velopment of a freely available electronic case report form and data This consensus study is not without limitations. Consideration .. repository, which future researchers will be encouraged to use for .. should be given to the representativeness of the study’s participants. .. data collection (COMMIT-Collection). Several core outcomes, includ- When considering the Delphi survey, there was a higher response .. ing live birth, birthweight and neonatal mortality, are common to other .. from participants who lived in Europe (134 participants; 36%). To par- .. core outcome sets developed for hyperemesis gravidarum, multiple .. Downloaded from https://academic.oup.com/humrep/article/35/12/2725/6010638 by guest on 17 October 2023 ticipate in the Delphi survey, English proficiency, a computer and inter- .. pregnancy research and neonatal care (Perry et al., 2019; Webbe net access were required. We appreciate limitations in the .. et al., 2020a; Jansen et al., 2020; Townsend et al., 2020a). Additional representativeness of the sample could have impacted upon the out- .. consistency could be achieved across our specialty if the consensus .. comes prioritized. .. definitions developed within this initiative were embedded within these There is considerable uncertainty regarding core outcome set devel- .. core outcome sets. .. opment methods (Duffy and McManus, 2016; Williamson et al., 2017; .. The CROWN initiative, supported by over 80 specialty journals, in- Duffy et al., 2019b). The optimal approaches to selecting participants, .. cluding the Cochrane Gynaecology and Fertility Group, Fertility and .. structuring interactions, and methods of synthesizing individual judg- .. Sterility and Human Reproduction, has resolved to implement this core .. ments are unclear (Murphy et al., 1998). Further methodological re- .. outcome set (Core Outcomes in Women’s and Newborn Health search is required to inform future core outcome set development .. Initiative, 2014). CROWN initiative journals will advise researchers to .. (Williamson et al., 2017). .. report the core outcome set for infertility within trial reports and offer The Delphi survey’s overall attrition rate was 38%, which is compa- .. conclusions based on these outcomes. Where core outcome sets .. rable to other core outcome development studies (Duffy et al., .. have not been collected, the researchers will be asked to report this 2017b). Participants who identified as people with fertility problems .. deficiency and its implications for their findings. The COMMIT initiative .. were more likely to withdraw. It may have been possible to reduce at- .. is currently developing reporting tools and templates to assist trition by reducing the length of the survey; for example, limiting the .. researchers to clearly report core outcomes within their manuscripts .. outcomes entered into the Delphi survey, removing outcomes which .. (COMMIT-Reporting). reached consensus in subsequent survey rounds, or reducing the num- .. Analyses of data arising from infertility trials, particularly for studies .. ber of survey rounds. However, attrition needed to be balanced with .. related to ART, are frequently undermined by the use of an inappro- the requirement to enter a comprehensive long list of potential core .. priate denominator (Wilkinson, et al., 2016). Two main issues exist. .. outcomes into the Delphi survey and for participants to be able to re- .. The first is the use of a post-randomization denominator, for example, flect on and rescore individual outcomes in relation to each other. .. when live birth rates are calculated per embryo transferred, rather .. Further methodological research is required to understand the impact .. than per woman randomized. Analyses conducted on this basis do not of attrition on the development of consensus within core outcome set .. reflect the randomized comparisons as the groups being compared .. development studies. .. may differ with respect to their characteristics, and therefore, also Many international initiatives, professional societies and colleagues .. with respect to their outcomes (Hirji and Fagerland, 2009). The sec- .. have strongly advocated for the collection and reporting of many of .. ond issue relates to analyses which commit a unit of analysis error the core outcomes, including live birth, pregnancy loss and adverse .. (Vail and Gardener, 2003). This error occurs when proportions are .. events (Barnhart, 2014; Harbin Consensus Conference Workshop .. calculated using an inappropriate denominator, for example, the num- .. Group, 2014). Despite the clear articulation of the importance of .. ber of oocytes or number of embryos. Unit of analysis errors com- these outcomes, poor reporting persists with only one-third of infertil- .. monly occur when researchers calculate the pregnancy rate by dividing .. ity trials reporting live birth (Wilkinson et al., 2016). Why will this time .. the number of gestational sacs on ultrasound by the number of em- be different? The Core Outcome Measure for Infertility Trials .. bryos transferred. As the outcomes of a couple’s embryos are corre- .. (COMMIT) initiative has developed a strategic plan in consultation .. lated, this approach is incorrect as standard statistical tests assume with a broad range of stakeholders across the research pipeline to uti- .. that the tested observations are independent. To address these im- .. lize available enablers to secure the routine selection, collection and .. portant issues the COMMIT initiative has resolved to reach clear rec- reporting of core outcomes across future fertility research (Devall .. ommendations regarding the selection of the most appropriate .. et al., 2020). .. denominator (Duffy et al., 2020b). Research funding bodies are increasingly advocating for the use of .. The Cochrane Gynaecology and Fertility Group have published over .. core outcome sets within the research they fund. It is considered .. 100 systematic reviews evaluating potential treatments for infertility good practice for researchers planning RCT to follow the SPIRIT state- .. and has committed to implementing the core outcome set for infertil- .. ment, which outlines the scientific, ethical and administrative elements .. ity when new and updated reviews are being prepared. Secondary re- that should be incorporated in a clinical trial protocol (Chan et al., .. search, including pairwise meta-analyses, individual participant data .. 2013). This statement specifically recommends the collection of core .. meta-analyses and network meta-analyses, will be more influential outcomes. .. when infertility trials routinely collect and report core outcomes. Core outcomes for infertility research 2731 .. The COMMIT initiative has committed to undertaking further re- .. .. Supplementary data search to assess the uptake and implementation of the core outcome .. Supplementary data are available at Human Reproduction online. set for infertility (COMMIT-Implementation). Objectively demonstrat- .. ing the uptake of the core outcome set for infertility is important to ... quantify its contribution to improve the value of future research. .. Acknowledgements .. Assessing the uptake of the core outcome set will be undertaken by .. .. We would like to thank the Delphi survey and consensus development examining registry records, published protocols, RCT and systematic .. meeting participants and colleagues at the Cochrane Gynaecology and reviews, and undertaking a citation analysis. Further research is .. .. Fertility Group, University of Auckland, New Zealand. planned to examine and understand the reasons why researchers do, .. and do not, implement the core outcome set for infertility. By identify- .. .. Authors’ roles ing perceived barriers to implementation, strategies informed by imple- .. mentation science will be developed to limit, and hopefully overcome, .. .. Study concept and design: J.M.N.D., H.A., S.B., B.C., C.C., J.L.H.E., Downloaded from https://academic.oup.com/humrep/article/35/12/2725/6010638 by guest on 17 October 2023 any perceived barriers. .. L.C.G., R.G.F., S.F., Y.K., R.S.L., J.M.L.K., D.M., B.W.J.M., B.L., S.L., .. The core outcome set reported in this study is intended to be used .. C.N., E.H.Y.N., A.S.O., L.P., S.R.H., S.R., I.S., J.L.S., A.S., C.S., H.L.T., across trials evaluating a broad range of potential fertility treatments, .. A.V., M.v.W., M.A.V., N.L.V., A.Y.W., R.W., J.W., M.A.Y. and C.M.F. .. for example, male endocrine stimulation protocols, lifestyle interven- .. Acquisition of data: J.M.N.D., H.A., S.B., B.C., C.C., J.L.H.E., L.C.G., tions for people with fertility problems, and methods for embryo se- .. R.G.F., S.F., Y.K., R.S.L., J.M.L.K., D.M., B.W.J.M., B.L., S.L., C.N., .. lection during IVF cycles. Extensions to the current core outcome set .. E.H.Y.N., A.S.O., L.P., S.R.H., S.R., I.S., J.L.S., A.S., C.S., H.L.T., A.V., .. M.v.W., M.A.V., N.L.V., A.Y.W., R.W., J.W., M.A.Y. and C.M.F. are planned or currently in development for different patient popula- .. tions, including men with fertility problems (COMMIT-Male Infertility), .. Analysis and interpretation of data: J.M.N.D., H.A., S.B., B.C., C.C., .. women with endometriosis (Duffy et al., 2020c) and interventions in- .. J.L.H.E., L.C.G., R.G.F., S.F., Y.K., R.S.L., J.M.L.K., D.M., B.W.J.M., B.L., cluding IVF (COMMIT-IVF). Other extensions are planned to ensure .. S.L., C.N., E.H.Y.N., A.S.O., L.P., S.R.H., S.R., I.S., J.L.S., A.S., C.S., .. future infertility trials and systematic reviews routinely collect and re- .. H.L.T., A.V., M.v.W., M.A.V., N.L.V., A.Y.W., R.W., J.W., M.A.Y. and port harms (COMMIT-Harms). Although quality of life was not se- .. C.M.F. Drafting of the manuscript: J.M.N.D. and C.M.F. Critical revision .. lected as a core outcome, the COMMIT initiative has committed to .. of the manuscript for important intellectual content: H.A., S.B., B.C., .. C.C., J.L.H.E., L.C.G., R.G.F., S.F., Y.K., R.S.L., J.M.L.K., D.M., undertaking a systematic review and methodological assessment of .. measurement instruments capable of measuring quality of life and will .. B.W.J.M., B.L., S.L., C.N., E.H.Y.N., A.S.O., L.P., S.R.H., S.R., I.S., .. J.L.S., A.S., C.S., H.L.T., A.V., M.v.W., M.A.V., N.L.V., A.Y.W., R.W., make recommendations to inform the design of future infertility trials .. (COMMIT-QoL). .. J.W. and M.A.Y. Statistical analysis: J.M.N.D. and J.W. Study supervi- .. This comprehensive strategy could make a significant contribution in .. sion: C.M.F. reducing research waste across future fertility research. This approach .. .. has acted as a template for other areas of women’s health seeking to .. Funding .. tackle research waste, including twin and multiple pregnancy research .. This research was funded by the Catalyst Fund, Royal Society of New (Townsend et al., 2020b). The variation in outcome reporting and sus- .. .. Zealand, Auckland Medical Research Fund and Maurice and Phyllis pected outcome reporting bias has been characterized across wom- .. en’s and newborn health, including endometriosis, twin-twin .. Paykel Trust. The funder had no role in the design and conduct of the .. study, the collection, management, analysis or interpretation of data, transfusion syndrome and neonatal care. This study should inform the .. .. or manuscript preparation. B.W.J.M. is supported by a National Health development of other core outcome sets seeking to tackle poorly se- .. and Medical Research Council Practitioner Fellowship (GNT1082548). lected, collected and reported outcomes (Hirsch et al., 2016a,b; Perry .. .. S.B. was supported by University of Auckland Foundation Seelye et al., 2018; Webbe et al., 2020a,b). .. Travelling Fellowship. Research priority setting presents an opportunity to develop a prior- .. .. itized research agenda (Graham et al., 2020). A research priority set- .. ting study has recently been completed for infertility and identified .. .. Conflict of interest research priorities related to the prevention, diagnosis and treatment .. S.B. reports being the Editor-in-Chief of Human Reproduction Open and .. of male, female and unexplained infertility (Duffy et al., 2020a). .. an editor of the Cochrane Gynaecology and Fertility group. J.L.H.E. Undertaking an RCT is the only appropriate method to answer many .. reports being the Editor Emeritus of Human Reproduction. J.M.L.K. .. of these research priorities (Wilkinson et al., 2019b). Therefore, it is .. reports research sponsorship from Ferring and Theramex. R.S.L. important for our specialty to work together to improve the design, .. .. reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud delivery and reporting of future trials. .. Pharma and Kindex and research sponsorship from Guerbet and Hass In summary, this study used formal consensus methods to develop .. .. Avocado Board. B.W.J.M. reports consultancy fees from Guerbet, a core outcome set for future RCT and systematic reviews evaluating .. iGenomix, Merck, Merck KGaA and ObsEva. C.N. reports being the .. potential treatments for infertility. Embedding the core outcome set .. Co Editor-in-Chief of Fertility and Sterility and Section Editor of the within future infertility research could make a profound contribution to .. Journal of Urology, research sponsorship from Ferring, and retains a fi- .. advancing the usefulness of research to inform clinical practice and en- .. nancial interest in NexHand. A.S. reports consultancy fees from hance the care people with infertility problems receive. .. Guerbet. E.H.Y.N. reports research sponsorship from Merck. N.L.V. 2732 Duffy et al. .. reports consultancy and conference fees from Ferring, Merck and .. Professor Charalampos S. Siristatidis, Greece; Dr Akanksha Sood, St. Merck Sharp and Dohme. The remaining authors declare no competing .. Mary’s Hospital, UK; Dr Cam Tu Tran, Vietnam; Emma L. Votteler, .. interests in relation to the work presented. All authors have completed .. Bath Fertility Centre, UK; Professor Chi Chiu Wang, The Chinese the disclosure form. ... University of Hong Kong, Hong Kong; Dr Andrew Watson, Tameside .. Foundation Trust, UK; and Dr Menem Yossry, City Hospital .. .. Sunderland, UK. Appendix. Core Outcome .. .. Measure for Infertility Trials .. .. (COMMIT) initiative .. References .. .. Barnhart KT. Live birth is the correct outcome for clinical trials evalu- Professor Ahmed M. Abou-Setta, University of Manitoba, Canada; Dr .. Juan J. Aguilera, Argentina; Dr Oluseyi O.A. Atanda, Ladoke Akintola .. ating therapy for the infertile couple. Fertil Steril 2014;101: .. Downloaded from https://academic.oup.com/humrep/article/35/12/2725/6010638 by guest on 17 October 2023 University of Technology Teaching Hospital, Nigeria; Eva M.E. .. 1205–1208. Balkenende, University of Amsterdam, The Netherlands; Dr Kurt T. .. Braakhekke M, Kamphuis EI, van Rumste MM, Mol F, van der Veen .. Barnhart, Universtity of Pennsylvania, USA; Dr Yusuf Beebeejaun, .. F, Mol BW. How are neonatal and maternal outcomes reported in .. randomised controlled trials (RCTs) in reproductive medicine? King’s Fertility, Fetal Medicine Research Institute, UK; Dr Sohinee .. Bhattacharya, University of Aberdeen, UK; Megan Black, New .. Hum Reprod 2014;29:1211–1217. .. Chan A-W, Tetzlaff JM, Altman DG, Laupacis A, Gøtzsche PC, Zealand; Magdalena Bofill, University of Auckland, New Zealand; .. Associate Professor Georgina M. Chambers, University of New South .. Krleza-Jeric K, Hróbjartsson A, Mann H, Dickersin K, Berlin JA et .. al. SPIRIT 2013 statement: defining standard protocol items for Wales, Australia; Dr Abrar A. Chughtai, University of New South .. Wales, Australia; Dr Javier A. Crosby, Clinica Las Condes, Chile; Dr .. clinical trials. Ann Intern Med 2013;158:200–207. .. Core Outcomes in Women’s and Newborn Health Initiative. The Irene Cuevas-Sáiz, Hospital General Universitario de Valencia, Spain; .. Dr Arianna D’Angelo, Wales Fertility Institute, UK; Danielle D. .. CROWN Initiative: journal editors invite researchers to develop .. Dubois, Ottawa Fertility Centre, Canada; Dr Kirsten Duckitt, .. core outcomes in women’s health. Hum Reprod 2014;29: University of British Columbia, Canada; Dr Carlos Encinas, Geneva .. 1349–1350. .. Foundation for Medical Education and Research, Bolivia; Anita .. Dapuzzo L, Seitz FE, Dodson WC, Stetter C, Kunselman AR, Legro .. RS. Incomplete and inconsistent reporting of maternal and fetal Fincham, Fertility Europe, Belgium; Dr Marie-Odile Gerval, Chelsea .. and Westminster Hospital NHS Foundation Trust, UK; Dr Nhu H. .. outcomes in infertility treatment trials. Fertil Steril 2011;95: .. 2527–2530. Giang, Vietnam; Dr Ahmed Gibreel, Mansoura University, Egypt; .. Lynda J. Gingel, UK; Dr Elizabeth J. Glanville, Fertility Plus, National .. Devall AJ, Out JH, Mol BWJ, Duffy JMN, Collura B, Dyer S. .. Coordination and planning of clinical research on a national and Women’s Hospital, New Zealand; Dr Demian Glujovsky, CEGYR .. Medicina Reproductiva, Argentina; Dr Ingrid Granne, University of .. global level. Fertil Steril 2020;113:1100–1106. .. Oxford, UK; Professor Georg Griesinger, University Hospital of .. Duffy JMN, Adamson GD, Benson E, Bhattacharya S, Bhattacharya S, Schleswig-Holstein, Germany; Dr Devashana Gupta, Repromed, New .. Bofill M, Brain K, Collura B, Curtis C, Evers JLH et al. Priorities for .. Zealand; Associate Professor Zeinab Hamzehgardeshi, Mazandaran .. future infertility research: an international consensus development University of Medical Sciences, Iran; Professor Martha Hickey, .. study. Hum Reprod 2020a;35:2715–2724. .. University of Melbourne, Australia; Dr Martin Hirsch, University .. Duffy JMN, Bhattacharya S, Bhattacharya S, Bofill M, Collura B, .. Curtis C, Evers JLH, Giudice LC, Farquharson RG, Franik S et al. College London Hospitals, UK; Dr Marcos Horton, Pregna .. Reproductive Medicine, Argentina; Associate Professor M. Louise Hull, .. Standardizing definitions for the infertility core outcome set: an in- .. ternational consensus development study. Hum Reprod 2020b;35: University of Adelaide, Australia; Dr Shikha Jain, Dreamz IVF, India; Dr .. Marta Jansa Perez, UK; Dr Claire A. Jones, University of Toronto, .. 2735–2745. .. Canada; Dr Vanessa Jordan, University of Auckland, New Zealand; .. Duffy JMN, Bhattacharya S, Curtis C, Evers JLH, Farquharson RG, Professor Mohan S. Kamath, Christian Medical College, Vellore, India; .. Franik S, Khalaf Y, Legro RS, Lensen S, Mol BW et al.; COMMIT: .. Dr Elena Kostova, Cochrane Gynaecology and Fertility, The .. Core Outcomes Measures for Infertility Trials. A protocol devel- Netherlands; Professor Antonio La Marca, University Hospital of .. oping, disseminating and implementing a core outcome set for in- .. Modena, Italy; Dr Tien Khac Le, Vietnam; Dr Arthur Leader, Ottawa .. fertility. Hum Reprod Open 2018;2018:hoy007. Hospital Research Institute, Canada; Dr Jian Li, Chinese University of .. Duffy JMN, Bhattacharya S, Herman M, Mol B, Vail A, Wilkinson J, .. Hong Kong, China; Professor Olabisi M. Loto, Obafemi Awolowo .. Farquhar C; the Cochrane Gynaecology and Fertility Group. .. Reducing research waste in benign gynaecology and fertility re- University, Nigeria; Karen L. Marks, UK; Alison R. McTavish, .. University of Aberdeen, UK; David J. Mills, UK; Dr Raju R. Nair, .. search. BJOG 2017a;124:366–369. .. Mitera Hospital, India; Dr Dung Thi Phuong Nguyen, Vietnam; .. Duffy JMN, Hirsch M, Vercoe M, Abbott J, Barker C, Collura B, Professor Allan A. Pacey, University of Sheffield, UK; Dr Lynn C. .. Drake R, Evers J, Hickey M, Horne AW et al.; endo:outcomes - an .. Sadler, Auckland District Health Board, New Zealand; Dr Peggy Sagle, .. International Collaboration Harmonising Outcomes and Outcome University of Alberta, Canada; Dr Juan-Enrique Schwarze, Clinica Las .. Measures for Endometriosis Research. A core outcome set for fu- .. Condes, Chile; Dr Heather M. Shapiro, University of Toronto, .. ture endometriosis research: an international consensus develop- Canada; Marian Showell, University of Auckland, New Zealand; .. ment study. BJOG 2020c;127:967–974. Core outcomes for infertility research 2733 .. Duffy JMN, Hirsch M, Ziebland S, McManus RJ, Brown M, Gale C, .. Collaboration to Harmonise Outcomes for Twin–Twin Grobman W, Fitzpatrick R, Karumanchi SA, Lucas N et al.; the .. Transfusion Syndrome (CHOOSE). Twin–Twin Transfusion .. International Collaboration to Harmonise Outcomes in Pre- .. Syndrome: study protocol for developing, disseminating, and eclampsia (iHOPE). Methodological decisions influence the identifi- .. implementing a core outcome set. Trials 2017;18:325. .. cation of potential core outcomes in studies related to pre- .. Kirkham JJ, Davis K, Altman DG, Blazeby JM, Clarke M, Tunis S, eclampsia: an analysis informing the development of recommenda- .. Williamson PR. Core Outcome Set-STAndards for development: .. tions for future core outcome set developers. BJOG 2019b;126: .. the COS-STAD recommendations. PLoS Med 2017;14:e1002447. 1482–1490. .. Murphy M, Sanderson C, Black N, Askham J, Lamping D, Marteau T, .. Duffy JMN, McManus R. Influence of methodology upon the identifi- .. McKee C. Consensus development methods, and their use in clini- cation of potential core outcomes: recommendations for core out- .. .. cal guideline development. Health Technol Assess 1998;2:1–88. come set developers are needed. BJOG 2016;123:1599. .. Perry H, Duffy JMN, Reed K, Baschat A, Deprest J, Hecher K, Lewi Duffy JMN, Rolph R, Gale C, Hirsch M, Khan KS, Ziebland S, ... L, Lopriore E, Oepkes D, Khalil A et al.; the International .. Downloaded from https://academic.oup.com/humrep/article/35/12/2725/6010638 by guest on 17 October 2023 McManus RJ; On behalf of the International Collaboration to .. Collaboration to Harmonise Outcomes for Twin–Twin Harmonise Outcomes in Pre-eclampsia (iHOPE). Core outcome .. Transfusion Syndrome (CHOOSE). Core outcome set for research .. sets in women’s and newborn health: a systematic review. BJOG .. studies evaluating treatments for twin–twin transfusion syndrome. 2017b;124:1481–1489. .. .. Ultrasound Obstet Gynecol 2019;54:255–261. Duffy JMN, van ‘t Hooft J, Gale C, Brown M, Grobman W, .. Perry H, Duffy JMN, Umadia O, Khalil A; the International Fitzpatrick R, Karumanchi SA, Lucas N, Magee L, Mol B et al. A .. .. Collaboration to Harmonise Outcomes for Twin-Twin Transfusion protocol for developing, disseminating, and implementing a core .. Syndrome (CHOOSE). Outcome reporting across randomized tri- outcome set for pre-eclampsia. Pregnancy Hypertens 2016;6: .. .. als and observational studies evaluating treatments for twin–twin 274–278. .. transfusion syndrome: systematic review. Ultrasound Obstet Gynecol Duffy JMN, Ziebland S, von Dadelszen P, McManus RJ. Tackling .. .. 2018;52:577–585. poorly selected, collected, and reported outcomes in obstetrics .. Townsend R, Duffy JMN, Khalil A. Increasing value and reducing re- and gynecology research. Am J Obstet Gynecol 2019a;220: .. .. search waste in obstetrics: towards woman-centered research. 71.e71–71.e74. .. Graham L, Illingworth B, Showell M, Vercoe M, Crosbie E, Gingel L, .. Ultrasound Obstet Gynecol 2020b;55:151–156. .. Townsend R, Duffy JMN, Sileo F, Perry H, Ganzevoort W, Reed K, Farquhar C, Horne A, Prior M, Stephenson J et al. Research prior- .. ity setting in women’s health: a systematic review. BJOG 2020; .. Baschat AA, Deprest J, Gratacos E, Hecher K et al.; International .. Collaboration to Harmonise Outcomes for Selective Fetal Growth 127:694–700. .. .. Restriction (CHOOSE-FGR). Core outcome set for studies investi- Harbin Consensus Conference Workshop Group. Improving the .. gating management of selective fetal growth restriction in twins. reporting of clinical trials of infertility treatments (IMPRINT): modi- .. .. Ultrasound Obstet Gynecol 2020a;55:652–660. fying the CONSORT statement. Hum Reprod 2014;29:2075–2082. .. Vail A, Gardener E. Common statistical errors in the design and Hirji KF, Fagerland MW. Outcome based subgroup analysis: a .. .. analysis of subfertility trials. Hum Reprod 2003;18:1000–1004. neglected concern. Trials 2009;10:33. .. Hirsch M, Duffy JMN, Barker C, Hummelshoj L, Johnson NP, Mol B, .. Webbe J, Brunton G, Ali S, Duffy JM, Modi N, Gale C. Developing, .. implementing and disseminating a core outcome set for neonatal Khan KS, Farquhar C. Protocol for developing, disseminating and .. implementing a core outcome set for endometriosis. BMJ Open .. medicine. BMJ Paediatr Open 2017;1:e000048. .. Webbe JWH, Ali S, Sakonidou S, Webbe T, Duffy JMN, Brunton G, 2016a;6:e013998. .. Hirsch M, Duffy JMN, Kusznir JO, Davis CJ, Plana MN, Khan KS, .. Modi N, Gale C. Inconsistent outcome reporting in large neonatal .. trials: a systematic review. Arch Dis Child Fetal Neonatal Ed 2020b; Duffy JMN, Farquhar C, Hirsch M, Johnson N et al. Variation in .. outcome reporting in endometriosis trials: a systematic review. Am .. 105:69–75. .. J Obstet Gynecol 2016b;214:452–464. .. Webbe JWH, Duffy JMN, Afonso E, Al-Muzaffar I, Brunton G, Jansen LAW, Koot MH, van‘t Hooft J, Dean CR, Duffy JMN, .. Greenough A, Hall NJ, Knight M, Latour JM, Lee-Davey C et al. .. Ganzevoort W, Gauw N, Goes BY, Rodenburg J, Roseboom TJ et .. Core outcomes in neonatology: development of a core outcome .. set for neonatal research. Arch Dis Child Fetal Neonatal Ed 2020a; al. A core outcome set for hyperemesis gravidarum research: an .. international consensus study. BJOG 2020;127:983–992. .. 105:425–431. .. Whitehouse KC, Kim CR, Ganatra B, Duffy JMN, Blum J, Brahmi D, Khalil A, Duffy JMN, Perry H, Ganzevoort W, Reed K, Baschat AA, .. Deprest J, Gratacos E, Hecher K, Lewi L et al.; On behalf of the .. Creinin MD, DePi~neres T, Gemzell-Danielsson K, Grossman D et .. al. Standardizing abortion research outcomes (STAR): a protocol International Collaboration to Harmonise Outcomes for Selective .. Fetal Growth Restriction (CHOOSE-FGR). Study protocol: devel- .. for developing, disseminating and implementing a core outcome .. oping, disseminating, and implementing a core outcome set for se- .. set for medical and surgical abortion. Contraception 2017;95: lective fetal growth restriction in monochorionic twin pregnancies. .. 437–441. .. Trials 2019;20:35. .. Wilkinson J, Bhattacharya S, Duffy JMN, Kamath MS, Marjoribanks J, Khalil A, Perry H, Duffy JMN, Reed K, Baschat A, Deprest J, Hecher .. Repping S, Vail A, Wely M, Farquhar CM. Reproductive medicine: .. K, Lewi L, Lopriore E, Oepkes D; On behalf of the International . still more ART than science? BJOG 2019a;126:138–141. 2734 Duffy et al. .. Wilkinson J, Brison DR, Duffy JMN, Farquhar CM, Lensen S, .. Williamson PR, Altman DG, Bagley H, Barnes KL, Blazeby JM, Mastenbroek S, van Wely M, Vail A. Don’t abandon RCTs in IVF. .. Brookes ST, Clarke M, Gargon E, Gorst S, Harman N et al. The .. We don’t even understand them. Hum Reprod 2019b;34: .. COMET handbook: version 1.0. Trials 2017;18:280. 2093–2098. .. Zegers-Hochschild F, Adamson GD, Dyer S, Racowsky C, de .. Wilkinson J, Roberts SA, Showell M, Brison DR, Vail A. No common .. Mouzon J, Sokol R, Rienzi L, Sunde A, Schmidt L, Cooke ID et al. denominator: a review of outcome measures in IVF RCTs. Hum .. The International Glossary on Infertility and Fertility Care, 2017. .. Reprod 2016;31:2714–2722. . Fertil Steril 2017;108:393–406. Downloaded from https://academic.oup.com/humrep/article/35/12/2725/6010638 by guest on 17 October 2023