Our projects are designed to answer clinically important questions, address evidence gaps and support better decision-making for women, families, clinicians and health systems.
Full title: EfficAcy of In-vitro Fertilisation add-ons in improvINg reproductive outcomes of couples with inferTilitY
Health area: Fertility and IVF
Study type: Adaptive RCT development programme – Bayesian multi-stage multi-arm adaptive randomised controlled trial
Funder and grant value: NIHR Efficacy and Mechanism Evaluation (EME) Programme, £159,630.14
Chief investigator: Dr Bassel H. Al Wattar (ARU)
Many IVF clinics offer patients additional 'add-on' treatments – from endometrial scratching to immune therapies and nutritional supplements – which are sold alongside standard IVF. Most of these interventions lack robust evidence of benefit, yet they are widely used, at significant cost to patients.
AFFINITY is developing the scientific infrastructure – including systematic evidence review, patient and clinician priority-setting, and an innovative adaptive trial design – to rigorously evaluate which IVF add-ons genuinely improve pregnancy outcomes and which do not. The programme will lay the groundwork for a future definitive adaptive RCT that can efficiently test multiple interventions simultaneously.
The HFEA currently flags many IVF add-ons as having 'red' or 'amber' evidence status. Patients and clinicians deserve reliable comparative data to support informed decision-making. AFFINITY will produce the evidence framework needed to rigorously and efficiently answer this question.
The Fertility Alliance is a charity partner, ensuring patient priorities shape the trial design. Verity is engaged for any overlap with fertility in PMOS/PCOS.
Full title: Effectiveness of ClOmipheNe CitRate for the management of mEn wiTh infErtility
Health area: Male infertility and reproductive medicine
Study type: Randomised, double-blind, placebo-controlled trial
Funder and grant value: NIHR Efficacy and Mechanism Evaluation (EME) Programme, £2,123,307.33
Chief investigator: Dr Bassel H. Al Wattar (ARU)
Male factor infertility contributes to approximately 40–50% of all cases of infertility, yet evidence-based treatment options are extremely limited. Clomiphene citrate is an oral medication that stimulates the production of reproductive hormones and is widely used in fertility clinics for men with certain types of infertility – but it has never been properly tested in a large, well-designed clinical trial.
CONCRETE is the first large-scale, double-blind, placebo-controlled RCT to evaluate whether clomiphene citrate genuinely improves sperm quality and, ultimately, the chances of couples conceiving and having a healthy baby. Live birth is the primary outcome – the most meaningful measure for couples undergoing fertility treatment.
Without a definitive trial, clinicians are prescribing clomiphene to men based on limited evidence, and many couples may be receiving ineffective treatment during precious time. CONCRETE will produce the first reliable answer to the question: does clomiphene citrate work for men with infertility? The result will directly inform clinical practice and NICE guidance.
The Fertility Alliance and Progress Educational Trust (PET) are engaged as patient/public partners to ensure the trial reflects the priorities of those with lived experience of infertility.
Full title: Treatment options for women with heavy menstrual bleeding: comprehensive systematic review, network meta-analyses and health economic assessment
Health area: Heavy menstrual bleeding (HMB) and gynaecology
Study type: Comprehensive systematic review, network meta-analysis and health economic evaluation
Funder and grant value: NIHR Evidence Synthesis Programme, £225,992.79
Chief investigator: Dr Bassel H. Al Wattar (ARU)
Co-investigators: Dr Ewelina Rogozinska (MRC Clinical Trials Unit, University College London) and collaborators
Heavy menstrual bleeding (HMB) affects approximately one in four women of reproductive age and is one of the most common reasons for gynaecology outpatient referral. Women with HMB have access to a range of treatments – from hormonal medicines and the Mirena coil, to endometrial ablation and hysterectomy – but the comparative effectiveness and cost-effectiveness of these options has never been comprehensively evaluated in a single analysis.
This study is conducting the most comprehensive synthesis of HMB treatment evidence to date, combining a systematic review with a network meta-analysis (which allows simultaneous comparison of all treatments against each other) and a full health economic assessment.
Current clinical guidance for HMB is based on limited and sometimes conflicting evidence. This NMA will establish a clear comparative hierarchy of treatments – by effectiveness, safety and cost-effectiveness – providing the most reliable evidence base yet available for this common and impactful condition. The results will directly inform NICE clinical guidelines and help clinicians and women make better-informed treatment decisions.
Al Wattar, B. H. et al. (2025) 'Treatment options for women with heavy menstrual bleeding: protocol for a comprehensive systematic review, network meta-analyses and health economic assessment', BMJ Open, 15(4), e085292. Available at: https://doi.org/10.1136/bmjopen-2024-085292
This protocol paper outlines the methodology for EVIE's landmark NIHR-funded network meta-analysis of all available treatments for heavy menstrual bleeding – the most comprehensive comparative effectiveness synthesis in this area to date.
Fibroid Forum UK contributed patient and public perspectives to outcome selection and the research protocol.
Full title: Blood transfusion and management of acute heavy menstrual bleeding
Health area: Acute heavy menstrual bleeding and emergency gynaecology
Study type: Retrospective observational study and cost analysis service evaluation
Chief investigator: Dr Bassel H. Al Wattar (ARU)
Women presenting to hospital with acute heavy menstrual bleeding – a sudden and often frightening episode of very heavy or uncontrolled bleeding – represent a significant proportion of emergency gynaecology presentations. Decisions about whether to give a blood transfusion and how to manage these episodes vary widely between hospitals.
BROWNIE examined real-world patterns of blood transfusion use and resource utilisation in acute HMB management across UK NHS settings, identifying significant variation in practice and substantial opportunities to improve both patient outcomes and the cost-effectiveness of care. The findings provide an important evidence base for future clinical guideline work and service improvement.
Acute HMB is distressing and potentially life-threatening. Despite its frequency, there are no standardised pathways for its management. BROWNIE is the first study to systematically examine patterns of blood transfusion in acute HMB, and its findings inform both clinical practice and future prospective research in this area.
Al Wattar, B. H. et al. (2025) 'Blood transfusion and management of acute heavy menstrual bleeding', Lancet Obstetrics, Gynaecology and Women's Health, 2(2), e140–e148. Available at: https://doi.org/10.1016/j.lanogw.2025.09.017
First systematic examination of real-world patterns of blood transfusion and resource use in acute HMB management, identifying significant practice variation and opportunities for cost-effective care improvement.
Full title: Feasibility of Body Identical Progesterone for the management of endometriosis-associated pain
Health area: Endometriosis and pain management
Study type: Feasibility study
Funder and grant value: NIHR Research for Patient Benefit (RfPB), £313,094
Co-applicant: Dr Bassel H. Al Wattar (ARU)
Body identical progesterone (also known as micronised progesterone or Utrogestan) is a naturally-derived hormone that mimics the progesterone produced by the body. There is growing interest in its use for the management of endometriosis-associated pain, particularly as an alternative or complement to existing hormonal treatments.
BIP-4 is a feasibility study assessing whether a definitive randomised trial of body identical progesterone for endometriosis pain is feasible – examining recruitment, retention, acceptability to patients, and the appropriate outcome measures for a future trial. The study will also explore whether body identical progesterone is acceptable to women who have not tolerated other hormonal treatments.