Majid Shabbir

STUDY QUESTION: Can a core outcome set be developed through a global consensus to standardize outcome selection, collection, comparison, and reporting in future male infertility trials? SUMMARY ANSWER: A minimum dataset, known as a ‘core outcome set’, has been developed for randomized controlled trials (RCTs) and systematic reviews evaluating potential interventions for male infertility. WHAT IS KNOWN ALREADY: 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). PARTICIPANTS/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 Organization 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 work was funded by The Urology Foundation, Small Project Fund awarded to Michael P Rimmer at the University of Edinburgh, UK. RTM was supported by a United Kingdom Research and Innovation (UKRI) Future Leaders Fellowship (MR/Y011783/1). C.L.R.B. is the co-editor in chief of Human Reproduction and 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. R.P.B. receives royalties from Flow diagnósticos. M.L.E. is an advisor to the companies Hannah, Illumicell, Next, Legacy, Doveras, Vseat and received a consultancy fee for this. B.W.M. is a paid consultant for Norgine and Organon and has received research funding from Ferring and Merck, he also receives consultancy and travel support from Merck. R.R.H. received royalties from Elsevier for a book, consultancy fees from Glyciome, and presentation fees from GryNumber Health and Aytu Bioscience. 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. has been an associate editor with Human Reproduction Open. K.Mc.E. received funding to attend Fertility 2025 by the British Fertility Society and is the Chair of the British Fertility Society. He is a member of the HFEA’s Scientific and Clinical Advances Advisory Committee and a Committee Member of the NICE Fertility Problems Guideline Group. M.H.V.L. receives consultation fees for the WHO Manual Spanish translation, and travel expenses for the ESHRE MRHI meeting in Budapest. She is a member of the editorial board for Fertility & Sterility, F&S Science, Human Reproduction, and Frontiers in Endocrinology. She is also a panel member of the World Health Organization (WHO) Human Reproduction Programme (HRP) Research Project Review Panel. R.S.M. is a member of the NICE Guideline Committee on Fertility and former chair of the British Fertility Society. A. Perheentupa receives an honoraria for lecturing from Merck for the Tackling Infertility manifest, Gedeon Richter & Ferring. A. Perheentupa declares lecture honoraria from Merck, Gideon Richter, and Ferring; and payment from Merck for the Tackling Infertility manifesto. A. Pacey receives consultancy fees for Carrot Fertility and Cryos International as well as lecturing for IBSA Institut Biochimique SA and Mealis Group—all fees paid to The University of Manchester. He is also a Trustee of Progress Educational. Trust (Charity Number 1139856) and Chairman of UKNEQAS Reproductive Sciences Advisory Committee. F.T. is the recipient...

Objectives: This study aimed to assess current international clinician practices, attitudes and barriers related to testicular prosthesis implantation in patients with testicular cancer at the time of radical inguinal orchidectomy.Methods: An international online survey of urologists who perform radical orchidectomy for testicular cancer was developed. The recruitment process used social media and the emailing lists of national urological societies. Responses were collected between 10 February 2021 and 31 May 2021. The primary outcome was the proportion of urologists who always offered testicular prosthesis implantation to patients undergoing radical orchidectomy. Secondary outcomes included the reasons for not offering testicular prosthesis implantation.Results: A total of 393 respondents took part in the online survey; of these, the majority were from the UK (66%), with the remaining international respondents (34%) from six different continents. Urologists (53%) reported they always offer testicular prosthesis implantation. Of those that offered testicular prosthesis implantation, 28% did so as a secondary procedure after radical orchidectomy, rather than the time of radical orchidectomy (72%). The most frequently selected reasons for not offering testicular prosthesis implantation included concerns about delaying chemotherapy (41%), infection (33%), impaired cosmesis (17%) and lack of availability (17%).Conclusion: Despite evidence confirming the safety and the psychological benefit of testicular prosthesis implantation during radical orchidectomy, current international practice suggests just over half of urologists always offer this to their patients. Increased clinician awareness of the low risk of complications and high patient satisfaction may act to reduce the perceived barriers in offering testicular prosthesis implantation.

Objective: To determine the success rate of oncological microdissection testicular sperm extraction (onco‐microTESE) in patients with testicular cancer (TC) with azoospermia and severe oligoasthenoteratozoospermia (OAT; ex vivo microTESE of the affected testis). Those with unsuccessful surgical sperm retrieval (SSR) from the affected testis underwent contemporaneous contralateral microTESE, if no contraindication was present. The primary outcome was successful SSR from the affected testicle sufficient for assisted reproductive techniques. Secondary outcomes included contralateral microTESE success, the time from referral to procedure, and the total successful fertility preservation rate. Results: Initial onco‐microTESE was successful in 19 of 31 patients (61%) with azoospermia. Contralateral microTESE was successful in a further two of eight patients with azoospermia with failed onco‐microTESE. Overall, 22/31 patients with azoospermia (71%) had successful fertility preservation in this series. In addition, six of seven patients with severe OAT had further sperm harvested by onco‐microTESE to maximise their fertility preservation. All surgery was performed within median (interquartile range) of 7 (5–13) days from presentation. Conclusions: Onco‐microTESE represents an effective method of fertility preservation for sub‐fertile patients with TC without delaying oncological treatment. Knowledge of the fertility status at first presentation is essential to allow for such additional options for optimal fertility preservation in TC.

Objective: The study aims to assess current international clinician attitudes, practices and barriers towards fertility assessment and preservation in patients undergoing radical inguinal orchidectomy (RIO) for testicular cancer.Materials and methods: An international online survey of urologists and urologists in training who perform RIO for testicular cancer was developed by the British Association of Urological Surgeons (BAUS) Sections of Andrology and Oncology and the British Urology Researchers in Surgical Training (BURST). The recruitment process used social media and the emailing lists of national urological societies. Responses were collected between 10/02/2021 and 31/05/2021 and stored using password‐protected Research Electronic Data Capture (REDCap) database software. The primary outcome was the proportion of urologists who routinely offer semen cryopreservation prior to RIO. The study was reported according to the Checklist for Reporting Results of Internet E‐Surveys platform.Results: A total of 393 respondents took part in the online survey; of these, the majority were from the United Kingdom (65.9%), with the remaining international respondents (34.1%) from six different continents, which included 45 different countries. Of the respondents, 57.1% reported that they would routinely offer semen cryopreservation to all patients undergoing RIO for testicular cancer. In addition, 36.0% of urologists routinely performed pre‐operative semen analysis, and 22.1% routinely performed pre‐operative testicular serum hormone profile. Of the respondents, 14.4% performed expedited RIO within 48 h; 31.2% of respondents reported that they considered no delay to RIO to allow for semen cryopreservation to be acceptable.Conclusions: A significant proportion of international urologists do not offer pre‐operative fertility assessment and preservation in men undergoing RIO for testicular cancer. Surgery is performed in an expedited fashion within 1 week in the majority of patients. Urologists perceive there to be a lack of access and availability to fertility services, and that delay to RIO to allow for fertility preservation is often not acceptable.

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 www.comet-initiative.org/Studies/Details/1586. N/A. N/A.

Objectives: To develop and validate the Urethroplasty Training and Assessment Tool ( UTAT ) using Healthcare Failure Mode and Effect Analysis ( HFMEA ) for training and assessment of urology trainees learning this urethral reconstruction technique, as urethroplasty is the ‘gold standard’ treatment for long and recurrent urethral strictures and with a variety of techniques and a lack of standardised reconstructive curricula, there is a need for procedure‐specific training tools to improve surgeon training and patient safety. Materials and Methods: This international observational study was performed over an 11‐month period. The HFMEA was used to identify and evaluate hazardous stages of urethroplasty to develop the UTAT . Hazard scores were calculated for the included steps of urethroplasty. Content validation was performed by 12 expert surgeons and multidisciplinary teams from international tertiary centres. Results: The HFMEA process resulted in an internationally validated UTAT . Hazard scores ≥4 and single point weaknesses were included to implement actions and outcome measures. Content validation was achieved by circulating the process map, hazard analysis table, and developed tools. Changes were implemented based on the feedback received from expert surgeons. The content validated dorsal onlay buccal mucosa graft bulbar UTAT contained five phases, 10 processes and 23 sub‐processes. Conclusions: The modular UTAT offers a comprehensive validated training tool developed via a detailed HFMEA protocol. This may be utilised to standardise the training and assessment of urology trainees.

Objectives: The aim of the present paper was to determine the impact of testicular cancer ( TC ) and its treatments on fertility and to review the current management options for the infertile patient with TC , both before diagnosis and after treatment, with the aim of providing practical recommendations to update contemporary guidelines and standardize clinical practice. Patients and Methods: Searches were conducted for relevant articles on Pubmed and Google Scholar between 2000 and 2017, with additional articles sourced from reference lists of included publications. Results: At time of diagnosis, 6–24% of patients with TC were reported to be azoospermic and 50% oligozoospermic. Without conducting semen analysis at diagnosis, these patients cannot be identified and may be at further risk of subfertility. Gonadotoxic therapies cause an overall decrease in male fertility by 30% and there is currently no method to predict which patients will become azoospermic after treatment. Patients with larger, more invasive tumours, however, are at greater risk of infertility from local tumour effects, and are also more likely to undergo several different type of therapy, which has further detrimental effects on conception rates. Most treatment‐induced infertility recovers 2 years post‐treatment, but paternity can be delayed during a couple's peak reproductive years. Semen cryopreservation remains the procedure of choice in preserving fertility, but the service is underused, with only 24% of patients banking sperm. Microdissection testicular sperm extraction (micro TESE ) at the time of orchidectomy (onco‐micro TESE ) is a successful infertility treatment option for those found to be azoospermic or severely oligozoospermic at diagnosis, while micro TESE may still retrieve sperm in azoospermic patients after chemotherapy. Conclusion: The underutilisation of semen analysis and sperm cryopreservation results in the failure to identify the azoospermic or severely oligozoospermic patient at diagnosis who may benefit from fertility‐preserving procedures, for example, onco‐micro TESE at the time of orchidectomy. Fertility preservation and counselling needs to be broached earlier in the TC treatment pathway and made a greater priority. Given the advances in treatment, more patients with TC are surviving and looking to return to a normal life. Preserving their future fertility plays an important role in achieving this.