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General health outcomes in subfertile men: a UK register-based cohort study

Chief investigator: Alastair Sutcliffe
Research establishment: University College London
Year of approval: 2023

Lay summary

The use of assisted reproductive technology (ART) has steadily increased, and individuals requiring ART to conceive are a growing group in the UK. Male subfertility (defined as the inability of a sexually active couple to achieve pregnancy within one year) alone is estimated to account for approximately 20% of couples experiencing difficulty conceiving, and often remains underdiagnosed as many at-risk men may not seek medical help or may not be referred for evaluation. Although ART substantially increases the chances for the affected men to become fathers, the effects of the underlying fertility problems on the health of these men remains unclear. Male subfertility may be an early and identifiable risk factor for the development of diseases later in life and more research into the long-term health effects associated with fertility problems is essential to improve diagnosis and treatment.

Therefore, our research team at The Great Ormond Street Institute of Child Health, University College of London have designed a national population-based record-linkage study to examine the impact of subfertility on the short and long-term cancer and other health outcomes of men. We will use the Human Fertilization & Embryology Authority (HFEA) register to identify all subfertile men who underwent fertility treatment in the UK between August 1991 and September 2009, and match them with men of a similar age who have not sought ART for the conception of a child. We will then then use NHS medical records (cancer registration records and hospital records of care) to compare the risk of cancer, chronic conditions (e.g., cardiovascular disease), and early death between these two groups of men. Using routine NHS data has several important methodological strengths, including national coverage, large sample size, robust markers of (sub)fertility, robust control group from the general male population, longitudinal follow-up of health and mortality outcomes in males throughout their lifespan.

Public benefit statement

Individuals needing ART to conceive are a growing group, with approximately 1 in 7 couples in the UK being affected by it. Subfertility is associated with significant medical, social, economic and demographic consequences, and is considered a major public health problem by the World Health Organization with approximately 50 million couples experiencing infertility globally in 2010. A growing body of literature (from the US and the Scandinavian countries) suggests that the reproductive health of men may reflect their somatic health and, more importantly, may be considered an early and identifiable risk factor for the development of disease and early death. However, despite the prevalence of male subfertility, research in the UK on the long-term health of the affected men remains limited. Therefore, the findings of this study will provide critical insight into the sequelae of subfertility, help develop targeted interventions, advance current diagnosis and treatment methodologies, and improve our understanding of its impact on our society and the economy.

Data linkages

  • Cancer registration data (National Cancer Registration and Analysis Service)
  • Hospital care data [Personal Demographics Service, Hospital Episode Statistics (HES) Accident and Emergency, HES Admitted Patient Care, HES Critical Care, HES Outpatients datasets]
  • Civil Registration of Death

Review date: 2 May 2026