A core outcome set for future male infertility research: development of an international consensus

Michael Rimmer; Ruth A. Howie; Richard A Anderson; Christopher L. R. Barratt; Kurt T  Barnhart; Yusuf Beebeejaun; Ricardo Pimenta Bertolla; Pietro Bortoletto; Robert E.  Brannigan; Astrid E P Cantineau  Cantineau; Ettore Caroppo; Barbara L Collura; Kevin Coward; William Colin Duncan; Michael L.  Eisenberg; Steven A. Gellatly; Christian De Geyter; Dimitrios G. Goulis; Ralf R  Henkel; Vu NA  Ho; Alayman F  Hussein; Carin Huyser; Jozef H Kadijk; Mohan S Kamath; Shadi Khashaba; Hajra Khattak; Yoshitomo Kobori; Julia  Kopeika; Tansu  Kucuk; Saturnino   Luján; Thabo Christopher   Matsaseng; Raj S Mathur; Kevin McEleny; Rod T Mitchell; Ben W Mol; Alfred M. Murage; Ernest HY   Ng; Allan Pacey; Antti H  Perheentupa; Stefan Du Plessis; Nathalie Rives; Ippokratis  Sarris; Peter N. Schlegel; Majid Shabbir; Maciej Smiechowski; Venkatesh Subramanian; Sesh K Sunkara; Basil C Tarlarzis; Frank Tüttelmann; Andy Vail; Madelon   van Wely; Monica H. Vazquez-Levin; Lan N. Voung; Alex Y  Wang; Rui Wang; James M N  Duffy; Cindy M. Farquhar; Craig  Craig Niederberger

doi:10.1093/humrep/deaf039

A core outcome set for future male infertility research: development of an international consensus

Michael Rimmer, Ruth A. Howie, Richard A Anderson, Christopher L. R. Barratt, Kurt T Barnhart , Yusuf Beebeejaun , Ricardo Pimenta Bertolla, Pietro Bortoletto , Robert E. Brannigan, Astrid E P Cantineau Cantineau , Ettore Caroppo , Barbara L Collura , Kevin Coward, William Colin Duncan, Michael L. Eisenberg, Steven A. Gellatly, Christian De Geyter , Dimitrios G. Goulis, Ralf R Henkel , Vu NA HoAlayman F Hussein , Carin Huyser , Jozef H Kadijk , Mohan S Kamath , Shadi Khashaba , Hajra Khattak, Yoshitomo Kobori , Julia Kopeika , Tansu Kucuk , Saturnino Luján , Thabo Christopher Matsaseng , Raj S Mathur , Kevin McEleny , Rod T Mitchell, Ben W Mol, Alfred M. Murage , Ernest HY Ng , Allan Pacey, Antti H Perheentupa , Stefan Du Plessis, Nathalie Rives , Ippokratis Sarris , Peter N. Schlegel, Majid Shabbir , Maciej Smiechowski, Venkatesh Subramanian, Sesh K Sunkara , Basil C Tarlarzis , Frank Tüttelmann , Andy Vail, Madelon van Wely , Monica H. Vazquez-Levin, Lan N. Voung, Alex Y Wang , Rui Wang, James M N Duffy, Cindy M. Farquhar, Craig Craig Niederberger

Research output: Contribution to journal › Article › peer-review

Abstract

Study Question
Can a core outcome set be developed through a global consensus to standardise outcome selection, collection, comparison, and reporting in future male infertility trials?
Summary Answer
A minimum data set, known as a “core outcome set”, has been developed for randomised controlled trials (RCTs) and systematic reviews evaluating potential interventions for male infertility.
What is already known?
Numerous factors, including a failure to consider the perspectives of men with lived experiences of infertility or their partners when developing and conducting RCTs can limit their clinical utility. Selection of outcomes, variations in outcome definitions and the selective reporting of outcomes based on statistical analysis make the results of infertility research challenging to interpret, compare and implement. For male infertility, this is further compounded by there being potentially three participants, the male, their female partner and any offspring born, all with outcomes to be reported. This has led to significant heterogeneity in trial design and reporting. While a core outcome set for general infertility trials has been developed, there is no such outcome set for male infertility trials.
Study design, size, duration
A two-round Delphi survey (334 participants from 39 countries) and consensus development workshops (44 participants from 21 countries).
Participant/materials, setting, methods
Healthcare professionals, researchers and men and women with infertility were brought together in a transparent process using formal consensus science methods.
Main results and the role of chance
The core outcome set for male infertility trials has been developed by the inclusion of specific male-factor outcomes in addition to the general infertility core outcome set. These
outcomes include assessment of semen using the World Health Organisation recommendations for semen analysis; viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancies); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Although not a requirement as part of the core outcome set, other outcomes were identified as potentially useful in certain study settings.
Limitations, reasons for caution
We used consensus development methods in this work, 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, which are inconsistently reported at present. 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 for male infertility trials.
Study funding / competing interest(s)
This research was funded by The Urology Foundation, UK.
Trial registration number
Core Outcome Measures in Effectiveness Trials (COMET) initiative registration No: 1586. Available at www.comet-initiative.org/Studies/Details/1586.

Original language	English
Pages (from-to)	865-875
Journal	Human Reproduction
Volume	40
Issue number	5
DOIs	https://doi.org/10.1093/humrep/deaf039
Publication status	Published - 16 Apr 2025

Keywords / Materials (for Non-textual outputs)

Consensus
Delphi Technique
Female
Humans
Infertility, Male/therapy
Male
Pregnancy
Randomized Controlled Trials as Topic
Research Design

Access to Document

10.1093/humrep/deaf039

Attached file- HR-25-0184-JMH-Edits_MPR TRACK_Michael RimmerAccepted author manuscript, 776 KB
deaf039Final published version, 1.38 MB

Protecting spermatogonial stem cells from chemotherapy-induced damage for fertility preservation in childhood cancer
Mitchell, R. (Principal Investigator) & Carragher, N. (Co-investigator)
UKRI (formerly RCUK)
1/05/24 → 30/04/27
Project: Research

Cite this

Rimmer, M., Howie, R. A., Anderson, R. A., Barratt, C. L. R., Barnhart , K. T., Beebeejaun , Y., Pimenta Bertolla, R., Bortoletto , P., Brannigan, R. E., Cantineau , A. E. P. C., Caroppo , E., Collura , B. L., Coward, K., Duncan, W. C., Eisenberg, M. L., Gellatly, S. A., De Geyter , C., Goulis, D. G., Henkel , R. R., ... Craig Niederberger , C. (2025). A core outcome set for future male infertility research: development of an international consensus. Human Reproduction, 40(5), 865-875. https://doi.org/10.1093/humrep/deaf039

@article{f54b44a74c33450aa74b5e95c5705bce,

title = "A core outcome set for future male infertility research: development of an international consensus",

abstract = "Study Question Can a core outcome set be developed through a global consensus to standardise outcome selection, collection, comparison, and reporting in future male infertility trials? Summary Answer A minimum data set, known as a “core outcome set”, has been developed for randomised controlled trials (RCTs) and systematic reviews evaluating potential interventions for male infertility. What is already known? Numerous factors, including a failure to consider the perspectives of men with lived experiences of infertility or their partners when developing and conducting RCTs can limit their clinical utility. Selection of outcomes, variations in outcome definitions and the selective reporting of outcomes based on statistical analysis make the results of infertility research challenging to interpret, compare and implement. For male infertility, this is further compounded by there being potentially three participants, the male, their female partner and any offspring born, all with outcomes to be reported. This has led to significant heterogeneity in trial design and reporting. While a core outcome set for general infertility trials has been developed, there is no such outcome set for male infertility trials. Study design, size, duration A two-round Delphi survey (334 participants from 39 countries) and consensus development workshops (44 participants from 21 countries). Participant/materials, setting, methods Healthcare professionals, researchers and men and women with infertility were brought together in a transparent process using formal consensus science methods. Main results and the role of chance The core outcome set for male infertility trials has been developed by the inclusion of specific male-factor outcomes in addition to the general infertility core outcome set. These outcomes include assessment of semen using the World Health Organisation recommendations for semen analysis; viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancies); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Although not a requirement as part of the core outcome set, other outcomes were identified as potentially useful in certain study settings. Limitations, reasons for caution We used consensus development methods in this work, 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, which are inconsistently reported at present. 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 for male infertility trials. Study funding / competing interest(s) This research was funded by The Urology Foundation, UK. Trial registration number Core Outcome Measures in Effectiveness Trials (COMET) initiative registration No: 1586. Available at www.comet-initiative.org/Studies/Details/1586.",

keywords = "Consensus, Delphi Technique, Female, Humans, Infertility, Male/therapy, Male, Pregnancy, Randomized Controlled Trials as Topic, Research Design",

author = "Michael Rimmer and Howie, {Ruth A.} and Anderson, {Richard A} and Barratt, {Christopher L. R.} and Barnhart, {Kurt T} and Yusuf Beebeejaun and {Pimenta Bertolla}, Ricardo and Pietro Bortoletto and Brannigan, {Robert E.} and Cantineau, {Astrid E P Cantineau} and Ettore Caroppo and Collura, {Barbara L} and Kevin Coward and Duncan, {William Colin} and Eisenberg, {Michael L.} and Gellatly, {Steven A.} and {De Geyter}, Christian and Goulis, {Dimitrios G.} and Henkel, {Ralf R} and Ho, {Vu NA} and Hussein, {Alayman F} and Carin Huyser and Kadijk, {Jozef H} and Kamath, {Mohan S} and Shadi Khashaba and Hajra Khattak and Yoshitomo Kobori and Julia Kopeika and Tansu Kucuk and Saturnino Luj{\'a}n and Matsaseng, {Thabo Christopher} and Mathur, {Raj S} and Kevin McEleny and Mitchell, {Rod T} and Mol, {Ben W} and Murage, {Alfred M.} and Ng, {Ernest HY} and Allan Pacey and Perheentupa, {Antti H} and Plessis, {Stefan Du} and Nathalie Rives and Ippokratis Sarris and Schlegel, {Peter N.} and Majid Shabbir and Maciej Smiechowski and Venkatesh Subramanian and Sunkara, {Sesh K} and Tarlarzis, {Basil C} and Frank T{\"u}ttelmann and Andy Vail and {van Wely}, Madelon and Vazquez-Levin, {Monica H.} and Voung, {Lan N.} and Wang, {Alex Y} and Rui Wang and Duffy, {James M N} and Farquhar, {Cindy M.} and {Craig Niederberger}, Craig",

year = "2025",

month = apr,

day = "16",

doi = "10.1093/humrep/deaf039",

language = "English",

volume = "40",

pages = "865--875",

journal = "Human Reproduction",

issn = "0268-1161",

publisher = "Oxford University Press",

number = "5",

}

Rimmer, M, Howie, RA, Anderson, RA, Barratt, CLR, Barnhart , KT, Beebeejaun , Y, Pimenta Bertolla, R, Bortoletto , P, Brannigan, RE, Cantineau , AEPC, Caroppo , E, Collura , BL, Coward, K, Duncan, WC, Eisenberg, ML, Gellatly, SA, De Geyter , C, Goulis, DG, Henkel , RR, Ho, VNA, Hussein , AF, Huyser , C, Kadijk , JH, Kamath , MS, Khashaba , S, Khattak, H, Kobori , Y, Kopeika , J, Kucuk , T, Luján , S, Matsaseng , TC, Mathur , RS, McEleny , K, Mitchell, RT, Mol, BW, Murage , AM, Ng , EHY, Pacey, A, Perheentupa , AH, Plessis, SD, Rives , N, Sarris , I, Schlegel, PN, Shabbir , M, Smiechowski, M, Subramanian, V, Sunkara , SK, Tarlarzis , BC, Tüttelmann , F, Vail, A, van Wely , M, Vazquez-Levin, MH, Voung, LN, Wang , AY, Wang, R, Duffy, JMN, Farquhar, CM & Craig Niederberger , C 2025, 'A core outcome set for future male infertility research: development of an international consensus', Human Reproduction, vol. 40, no. 5, pp. 865-875. https://doi.org/10.1093/humrep/deaf039

TY - JOUR

T1 - A core outcome set for future male infertility research: development of an international consensus

AU - Rimmer, Michael

AU - Howie, Ruth A.

AU - Anderson, Richard A

AU - Barratt, Christopher L. R.

AU - Barnhart , Kurt T

AU - Beebeejaun , Yusuf

AU - Pimenta Bertolla, Ricardo

AU - Bortoletto , Pietro

AU - Brannigan, Robert E.

AU - Cantineau , Astrid E P Cantineau

AU - Caroppo , Ettore

AU - Collura , Barbara L

AU - Coward, Kevin

AU - Duncan, William Colin

AU - Eisenberg, Michael L.

AU - Gellatly, Steven A.

AU - De Geyter , Christian

AU - Goulis, Dimitrios G.

AU - Henkel , Ralf R

AU - Ho, Vu NA

AU - Hussein , Alayman F

AU - Huyser , Carin

AU - Kadijk , Jozef H

AU - Kamath , Mohan S

AU - Khashaba , Shadi

AU - Khattak, Hajra

AU - Kobori , Yoshitomo

AU - Kopeika , Julia

AU - Kucuk , Tansu

AU - Luján , Saturnino

AU - Matsaseng , Thabo Christopher

AU - Mathur , Raj S

AU - McEleny , Kevin

AU - Mitchell, Rod T

AU - Mol, Ben W

AU - Murage , Alfred M.

AU - Ng , Ernest HY

AU - Pacey, Allan

AU - Perheentupa , Antti H

AU - Plessis, Stefan Du

AU - Rives , Nathalie

AU - Sarris , Ippokratis

AU - Schlegel, Peter N.

AU - Shabbir , Majid

AU - Smiechowski, Maciej

AU - Subramanian, Venkatesh

AU - Sunkara , Sesh K

AU - Tarlarzis , Basil C

AU - Tüttelmann , Frank

AU - Vail, Andy

AU - van Wely , Madelon

AU - Vazquez-Levin, Monica H.

AU - Voung, Lan N.

AU - Wang , Alex Y

AU - Wang, Rui

AU - Duffy, James M N

AU - Farquhar, Cindy M.

AU - Craig Niederberger , Craig

PY - 2025/4/16

Y1 - 2025/4/16

N2 - Study Question Can a core outcome set be developed through a global consensus to standardise outcome selection, collection, comparison, and reporting in future male infertility trials? Summary Answer A minimum data set, known as a “core outcome set”, has been developed for randomised controlled trials (RCTs) and systematic reviews evaluating potential interventions for male infertility. What is already known? Numerous factors, including a failure to consider the perspectives of men with lived experiences of infertility or their partners when developing and conducting RCTs can limit their clinical utility. Selection of outcomes, variations in outcome definitions and the selective reporting of outcomes based on statistical analysis make the results of infertility research challenging to interpret, compare and implement. For male infertility, this is further compounded by there being potentially three participants, the male, their female partner and any offspring born, all with outcomes to be reported. This has led to significant heterogeneity in trial design and reporting. While a core outcome set for general infertility trials has been developed, there is no such outcome set for male infertility trials. Study design, size, duration A two-round Delphi survey (334 participants from 39 countries) and consensus development workshops (44 participants from 21 countries). Participant/materials, setting, methods Healthcare professionals, researchers and men and women with infertility were brought together in a transparent process using formal consensus science methods. Main results and the role of chance The core outcome set for male infertility trials has been developed by the inclusion of specific male-factor outcomes in addition to the general infertility core outcome set. These outcomes include assessment of semen using the World Health Organisation recommendations for semen analysis; viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancies); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Although not a requirement as part of the core outcome set, other outcomes were identified as potentially useful in certain study settings. Limitations, reasons for caution We used consensus development methods in this work, 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, which are inconsistently reported at present. 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 for male infertility trials. Study funding / competing interest(s) This research was funded by The Urology Foundation, UK. Trial registration number Core Outcome Measures in Effectiveness Trials (COMET) initiative registration No: 1586. Available at www.comet-initiative.org/Studies/Details/1586.

AB - Study Question Can a core outcome set be developed through a global consensus to standardise outcome selection, collection, comparison, and reporting in future male infertility trials? Summary Answer A minimum data set, known as a “core outcome set”, has been developed for randomised controlled trials (RCTs) and systematic reviews evaluating potential interventions for male infertility. What is already known? Numerous factors, including a failure to consider the perspectives of men with lived experiences of infertility or their partners when developing and conducting RCTs can limit their clinical utility. Selection of outcomes, variations in outcome definitions and the selective reporting of outcomes based on statistical analysis make the results of infertility research challenging to interpret, compare and implement. For male infertility, this is further compounded by there being potentially three participants, the male, their female partner and any offspring born, all with outcomes to be reported. This has led to significant heterogeneity in trial design and reporting. While a core outcome set for general infertility trials has been developed, there is no such outcome set for male infertility trials. Study design, size, duration A two-round Delphi survey (334 participants from 39 countries) and consensus development workshops (44 participants from 21 countries). Participant/materials, setting, methods Healthcare professionals, researchers and men and women with infertility were brought together in a transparent process using formal consensus science methods. Main results and the role of chance The core outcome set for male infertility trials has been developed by the inclusion of specific male-factor outcomes in addition to the general infertility core outcome set. These outcomes include assessment of semen using the World Health Organisation recommendations for semen analysis; viable intrauterine pregnancy confirmed by ultrasound (accounting for singleton, twin and higher multiple pregnancies); pregnancy loss (accounting for ectopic pregnancy, miscarriage, stillbirth and termination of pregnancy); live birth; gestational age at delivery; birthweight; neonatal mortality; and major congenital anomaly. Although not a requirement as part of the core outcome set, other outcomes were identified as potentially useful in certain study settings. Limitations, reasons for caution We used consensus development methods in this work, 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, which are inconsistently reported at present. 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 for male infertility trials. Study funding / competing interest(s) This research was funded by The Urology Foundation, UK. Trial registration number Core Outcome Measures in Effectiveness Trials (COMET) initiative registration No: 1586. Available at www.comet-initiative.org/Studies/Details/1586.

KW - Consensus

KW - Delphi Technique

KW - Female

KW - Humans

KW - Infertility, Male/therapy

KW - Male

KW - Pregnancy

KW - Randomized Controlled Trials as Topic

KW - Research Design

U2 - 10.1093/humrep/deaf039

DO - 10.1093/humrep/deaf039

M3 - Article

C2 - 40233940

SN - 0268-1161

VL - 40

SP - 865

EP - 875

JO - Human Reproduction

JF - Human Reproduction

IS - 5

ER -

A core outcome set for future male infertility research: development of an international consensus

Abstract

Keywords / Materials (for Non-textual outputs)

Access to Document

Fingerprint

Projects

Protecting spermatogonial stem cells from chemotherapy-induced damage for fertility preservation in childhood cancer

Cite this