Risk of Mortality in Family Members of Men Seeking Fertility Assessment

Journal Article · Tue Jul 15 00:00:00 EDT 2025 · Fertility and Sterility

DOI:https://doi.org/10.1016/j.fertnstert.2025.07.016· OSTI ID:2575347

Ramsay, Joemy M. ^[1]; Shonnard, Cameron ^[2]; Hanson, Heidi A. ^[3]; Horns, Joshua J. ^[1]; Emery, Benjamin R. ^[1]; Aston, Kenneth I. ^[1]; Stern, Joshua M. ^[4]; Hotaling, James M. ^[1]

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1. Univ. of Utah, Salt Lake City, UT (United States)
2. Univ. of Nevada, Reno, NV (United States)
3. Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
4. Intermountain Urologic Institute, Salt Lake City, UT (United States)

Objective: To assess mortality in family members of men seeking fertility assessment. Subfertility serves as a biomarker for overall somatic health, and poor semen quality is associated with increased risk of hospitalization and mortality from chronic conditions. However, it is unclear if these risks extend to family members of men with low sperm count. Design: Retrospective cohort study. Subjects: Family members, up to third-degree relatives, of men in the Subfertility, Health and Assisted Reproduction and the Environment cohort who underwent a semen analysis as part of a fertility assessment 1996–2017. Relatives of men with a recorded total sperm count who lived in Utah for ≥1 year 1904–2017 were included in the analysis (N = 22,280 families). Exposure: Individuals were classified by family membership. Families were classified as relatives of azoospermic (0M), oligozoospermic (<39M), or normozoospermic (≥39M) men. The average total sperm count of the proband (male relative) with fertility assessment was also included as a continuous exposure measure. Main Outcome Measures: The main outcomes were all-cause and cause-specific mortality risk by sex, age, and degree of relation: first-, second-, and third-degree. Cox proportional hazard models were used to test the association between fertility classification and mortality, controlling for sex, race/ethnicity, and birth year. Results: A total of 666,437 relatives of men with fertility assessment (N_deaths = 183,974) were included in the analysis. Relative to normozoospermia families, all-cause mortality risk increased in oligozoospermia families (hazard ratio [HR]_{oligozoospermia}, 1.03; 95% confidence interval [CI], 1.01–1.05). Close relatives, first- (HR_{oligozoospermia}, 1.17; 95% CI, 1.07–1.28) and second-degree relatives (HR_azoospermia, 1.11; 95% CI, 1.04–1.20; HR_{oligozoospermia}, 1.05; 95% CI,1.01–1.09), of azoospermic and oligozoospermic men had the highest all-cause and cause-specific mortality risk, including death attributed to cardiovascular disease or congenital birth conditions. Conclusion: Our results suggest that familial all-cause and cause-specific mortality risk differ by fertility phenotype. Families of azoospermic and oligozoospermic men showed significantly increased risk, particularly for close relatives. This study provides further evidence that shared genetic and/or environmental factors could influence both fertility and somatic health.

• Research Organization: Oak Ridge National Laboratory (ORNL), Oak Ridge, TN (United States)
• Sponsoring Organization: National Cancer Institute's SEER Program; National Institutes of Health (NIH); US Centers for Disease Control and Prevention (CDC); USDOE
• Grant/Contract Number: AC05-00OR22725
• OSTI ID: 2575347
• Journal Information: Fertility and Sterility, Journal Name: Fertility and Sterility; ISSN 0015-0282
• Publisher: Elsevier
• Country of Publication: United States
• Language: English

Related Subjects

Male fertility
familial mortality risk
mortality risk patterns