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Protocol for developing a core outcome set for male infertility research: an international consensus development study

Michael P. Rimmer 1 , Ruth A. Howie 2 , Richard A. Anderson 1,2, Christopher L.R. Barratt 3 , Kurt T. Barnhart4 , Yusuf Beebeejaun 5 , Ricardo Pimenta Bertolla 6 , Siladitya Bhattacharya 7 , Lars Bjo¨ rndahl 8 , Pietro Bortoletto 9 , Robert E. Brannigan10, Astrid E.P. Cantineau11, Ettore Caroppo 12, Barbara L. Collura13, Kevin Coward 14,15, Michael L. Eisenberg 16, Christian De Geyter 17, Dimitrios G. Goulis 18, Ralf R. Henkel 19, Vu N.A. Ho 20, Alayman F. Hussein 21, Carin Huyser22, Jozef H. Kadijk23, Mohan S. Kamath24, Shadi Khashaba25,26, Yoshitomo Kobori27, Julia Kopeika28, Tansu Kucuk29, Saturnino Luja´n 30, Thabo Christopher Matsaseng 31,32, Raj S. Mathur 33, Kevin McEleny 34, Rod T. Mitchell 1 , Ben W. Mol 7,35, Alfred M. Murage36, Ernest H.Y. Ng 37, Allan Pacey 38, Antti H. Perheentupa 39, Stefan Du Plessis 40,41, Nathalie Rives42, Ippokratis Sarris5,43, Peter N. Schlegel 9 , Majid Shabbir 28, Maciej Smiechowski [1] 44, Venkatesh Subramanian 5 , Sesh K. Sunkara 43, Basil C. Tarlarzis 18, Frank Tu¨ ttelmann 45, Andy Vail 46, Madelon van Wely 47,48, Mo´ nica H. Vazquez-Levin 49, Lan N. Vuong 50,51, Alex Y. Wang 52, Rui Wang 53, Armand Zini54, Cindy M. Farquhar 55,56, Craig Niederberger 57,58,* and James M.N. Duffy1

1 MRC Centre for Reproductive Health, Queens Medical Research Institute, University of Edinburgh, Edinburgh, UK

2 Edinburgh Fertility Centre, Simpsons Centre for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh, UK

3 Reproductive Medicine Research Group, University of Dundee, Ninewells Hospital and Medical School, Dundee, UK

4 Department of Obstetrics and Gynaecology, University of Pennsylvania School of Medicine, Philadelphia, PA, USA

5 King’s Fertility, The Fetal Medicine Research Unit, King’s College London, London, UK

6 Division of Urology, Department of Surgery, Universidade Federal de Sao Paulo, Sao Paulo, Brazil

7 University of Aberdeen, Aberdeen, UK

8 ANOVA—Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden

9 The Ronald O. Perelman and Claudia Cohen Centre for Reproductive Medicine, Weill Cornell Medicine, New York, NY, USA

10 Northwestern University, Feinberg School of Medicine, Chicago, IL, USA

11 University of Groningen, University Medical Centre, Groningen, Centre of Reproductive Medicine, Groningen, Netherlands

12 Asl Bari, Reproductive Unit and Andrology Clinic, Conversano (Ba), Italy

13 RESOLVE: The National Infertility Association, McLean, VA, USA

14 Nuffield Department of Women’s and Reproductive Health, University of Oxford, Oxford, UK

15 Women’s Centre, John Radcliffe Hospital, Headington, Oxford, UK

16 Stanford University, Stanford, CA, USA

17 Reproductive Medicine and Gynaecological Endocrinology (RME), University Hospital, University of Basel, Basel, Switzerland

18 Units of Human Reproduction and Reproductive Endocrinology, 1st Department of Obstetrics and Gynaecology, Medical School, Aristotle University of Thessaloniki, Thessaloniki, Greece

19 Department of Digestion, Metabolism and Reproduction, Imperial College London, London, UK

20 IVFMD, My Duc Hospital, HOPE Research Centre, My Duc Hospital, Ho Chi Minh City, Vietnam

21 Minia University, Minia, Egypt

22 Reproductive Biology Laboratory, Department of Obstetrics and Gynaecology, University of Pretoria, Steve Biko Academic Hospital, Pretoria, South Africa

23 Freya—Dutch Patient Association for Infertility, Gorinchem, The Netherlands

24 Christian Medical College, Vellore, India

25 University of New South Wales, Sydney, Australia

26 IVF Australia, Sydney, Australia

27 Dokkyo Medical University Saitama Medical Center, Mibu, Japan

28 Guy’s and St Thomas Hospital, London, UK

29 Acibadem Maslak Hospital, Istanbul, Turkey

30 Urology Department, Hospital Universitari i Polite`cnic La Fe, Valencia, Spain

31 Stellenbosch University, Stellenbosch, Western Cape, South Africa

32 Tygerberg Academic Hospital, Cape Town, South Africa

33 Manchester University Foundation Trust, Manchester Academic Health Sciences Centre, Manchester, UK

34 Newcastle Fertility, The Newcastle upon Tyne Hospitals NHS Trust, Newcastle upon Tyne, UK

35 Department of Obstetrics and Gynaecology, Monash University, Clayton, Australia

36 Harley Street Fertility Centre, Nairobi, Kenya

37 Department of Obstetrics and Gynaecology, The University of Hong Kong, Hong Kong Special Administrative Region, China

38 Department of Oncology and Metabolism, University of Sheffield, Sheffield, UK

39 Department of Obstetrics and Gynaecology, University of Turku and Turku University Hospital, Turku, Finland

40 College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, UAE

41 Medical Physiology, Stellenbosch University, Tygerberg, South Africa

42 Rouen University Hospital, Biology of Reproduction-CECOS Laboratory, Rouen, France

43 Faculty of Life Sciences and Medicine, King’s College London, London, UK

44 Association for Infertility Treatment and Adoption Support “Our Stork”, Warsaw, Poland

45 Institute of Reproductive Genetics, University of Mu¨nster, Mu¨nster, Germany

46 Centre for Biostatistics, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK

47 Netherlands Satellite of the Cochrane Gynaecology and Fertility Group, Centre for Reproductive Medicine, Amsterdam, Netherlands

48 Reproduction & Development Research Institute, Amsterdam University Medical Centre, Amsterdam, Netherlands

49 Laboratorio de Estudios de Interaccio´n Celular en Reproduccio´n y Ca´ncer, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas de Argentina (CONICET), Fundacio´n IBYME (FIBYME), Buenos Aires, Argentina

50 Department of Obstetrics and Gynaecology, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam

51 HOPE Research Centre, My Duc Hospital, Ho Chi Minh City, Vietnam

52 Faculty of Health, University of Technology Sydney, Ultimo, Australia

53 Department of Obstetrics and Gynaecology, Monash University, Melbourne, Australia

54 Division of Urology, Department of Surgery, McGill University, Montreal, Quebec, Canada

55 Cochrane Gynaecology and Fertility Group, University of Auckland, Auckland, New Zealand

56 Department of Obstetrics and Gynaecology, University of Auckland, Auckland, New Zealand

57 Department of Urology, University of Illinois at Chicago, Chicago, IL, USA

58 Department of Bioengineering, University of Illinois at Chicago College of Engineering, Chicago, IL, USA


We aim to develop, disseminate and implement a minimum data set, known as a core outcome set, for future male infertility research.
Research into male infertility can be challenging to design, conduct and report. Evidence from randomized trials can be difficult to interpret and of limited ability to inform clinical practice for numerous reasons. These may include complex issues, such as variation in outcome measures and outcome reporting bias, as well as failure to consider the perspectives of men and their partners with lived experience of fertility problems. Previously, the Core Outcome Measure for Infertility Trials (COMMIT) initiative, an international consortium of researchers, healthcare professionals and people with fertility problems, has developed a core outcome set for general infertility research. Now, a bespoke core outcome set for male infertility is required to address the unique challenges pertinent to male infertility research.
Stakeholders, including healthcare professionals, allied healthcare professionals, scientists, researchers and people with fertility problems, will be invited to participate. Formal consensus science methods will be used, including the modified Delphi method, modified Nominal Group Technique and the National Institutes of Health’s consensus development conference.
An international steering group, including the relevant stakeholders outlined above, has been established to guide the development of this core outcome set. Possible core outcomes will be identified by undertaking a systematic review of randomized controlled trials evaluating potential treatments for male factor infertility. These outcomes will be entered into a modified Delphi method. Repeated reflection and re-scoring should promote convergence towards consensus outcomes, which will be prioritized during a consensus development meeting to identify a final core outcome set. We will establish standardized definitions and recommend high-quality measurement instruments for individual core outcomes.
This work has been supported by the Urology Foundation small project award, 2021. C.L.R.B. is the recipient of a BMGF grant and received consultancy fees from Exscentia and Exceed sperm testing, paid to the University of Dundee and speaking fees or honoraria paid personally by Ferring, Copper Surgical and RBMO. S.B. received royalties from Cambridge University Press, Speaker honoraria for Obstetrical and Gynaecological Society of Singapore, Merk SMART Masterclass and Merk FERRING Forum, paid to the University of Aberdeen. Payment for leadership roles within NHS Grampian, previously paid to self, now paid to University of Aberdeen. An Honorarium is received as Editor in Chief of Human Reproduction Open. M.L.E. is an advisor to the companies Hannah and Ro. B.W.M. received an investigator grant from the NHMRC, No: GNT1176437 is a paid consultant for ObsEva and has received research funding from Ferring and Merck. R.R.H. received royalties from Elsevier for a book, consultancy fees from Glyciome, and presentation fees from GryNumber Health and Aytu Bioscience. Aytu Bioscience also funded MiOXYS systems and sensors. Attendance at Fertility 2020 and Roadshow South Africa by Ralf Henkel was funded by LogixX Pharma Ltd. R.R.H. is also Editor in Chief of Andrologia and has been an employee of LogixX Pharma Ltd. since 2020. M.S.K. is an associate editor with Human Reproduction Open. K.Mc.E. received an honoraria for lectures from Bayer and Pharmasure in 2019 and payment for an ESHRE grant review in 2019. His attendance at ESHRE 2019 and AUA 2019 was sponsored by Pharmasure and Bayer, respectively. The remaining authors declare no competing interests.
Core Outcome Measures in Effectiveness Trials (COMET) initiative registration No: 1586. Available at


Polymorphisms, FSH receptor, Ovarian stimulation, Progesterone elevation, Estradiol, Progesterone, Ovarian response