Semen quality, infertility and mortality in the USA

Michael L Eisenberg; Shufeng Li; Barry Behr; Mark R Cullen; Deron Galusha; Dolores J Lamb; Larry I Lipshultz

doi:10.1093/humrep/deu106

Semen quality, infertility and mortality in the USA

Eisenberg ML, Li S, Behr B, Cullen MR, Galusha D, Lamb DJ, Lipshultz LI

Published July 2014 Human reproduction (Oxford, England)

DOI 10.1093/humrep/deu106 PMID 24838701 PMC PMC4059337

RRM Academy Synopsis

Men with abnormal semen at an infertility visit had higher death risk

In a cohort of 11,935 US men evaluated for infertility, men with two or more abnormal semen measures had 2.3 times the death risk of men with normal semen. That figure adjusts for current health. Overall, the cohort had fewer deaths than the general population: 69 observed against 176.7 expected.

Key Findings

69 of 11,935 men died (0.58%) over 92,104 person years of follow-up. Average age at evaluation was 36.6 years, and mean follow-up was 7.7 years.
Compared with the general population, the cohort had 69 observed deaths against 176.7 expected, a standardized mortality rate of 0.39 (95% CI 0.30-0.49).
Lower semen volume, concentration, motility, total count and total motile count each went with a higher risk of death. Abnormal morphology showed no association (unadjusted hazard ratio 0.89, 95% CI 0.40-2.00).
After accounting for baseline comorbidity scores, the link between death and each single abnormal semen measure was lost. Comorbidity data covered the California cohort only.
Men with two or more abnormal measures (volume, concentration, motility) still had an elevated risk of death versus men with normal semen: hazard ratio 2.29, 95% CI 1.12-4.65.

Interpretation

Researchers linked semen results from two infertility centers, one at Stanford and one at Baylor, to national death records. The design is a retrospective cohort of men aged 20 to 50. Once baseline health entered the models, single abnormal measures lost their link to death. The authors suggest current health may mediate the relationship and that semen quality may provide a marker of health. They also note that men who seek infertility care tend to have higher socioeconomic status, so the results may not extend to men in the general population.

RRM Context

Restorative reproductive medicine treats infertility as a sign of an underlying condition and evaluates both partners. The semen analysis belongs to that couple-level assessment. A man's semen result may reflect his whole-body health. The authors note that less is understood about what a diagnosis of impaired fertility means for the health of the man himself.

Our editorial summary of this paper, not the article's abstract.

Abstract

Study Question

What is the relationship between semen parameters and mortality in men evaluated for infertility?

Summary Answer

Among men undergoing an infertility evaluation, those with abnormal semen parameters have a higher risk of death, suggesting a possible common etiology between infertility and mortality.

What Is Known Already

Conflicting data exist that suggest either an inverse relationship or no relationship between semen quality and mortality.

Study Design, Size, Duration

A study cohort was identified from two centers, each specializing in infertility care. In California, we identified men with data from 1994 to 2011 in the Stanford Reproductive Endocrinology and Infertility semen database. In Texas, we identified men with data from 1989 to 2009 contained in the andrology database at the Baylor College of Medicine Special Procedures Laboratory who were evaluated for infertility. Mortality was determined by data linkage to the National Death Index or Social Security Death Index. Comorbidity was estimated based on calculation of the Charlson Comorbidity Index or Centers for Medicare & Medicaid Services-Hierarchical Condition Categories Model.

Participants/Materials, Setting, Methods

In all, 11,935 men were evaluated for infertility from 1989 to 2011. During 92 104 person years of follow-up, 69 of 11,935 men died (0.58%). The mean age at infertility evaluation was 36.6 years with a mean follow-up of 7.7 years.

Main Results and the Role of Chance

Compared with the general population, men evaluated for infertility had a lower risk of death with 69 deaths observed compared with 176.7 expected (Standardized mortality rate 0.39, 95% CI 0.30-0.49). When stratified by semen parameters, however, men with impaired semen parameters (i.e. male factor infertility) had significantly higher mortality rates compared with men with normal parameters (i.e. no male factor infertility). Low semen volume, sperm concentration, sperm motility, total sperm count and total motile sperm count were all associated with higher risk of death. In contrast, abnormal sperm morphology was not associated with mortality. While adjusting for current health status attenuated the association between semen parameters and mortality, men with two or more abnormal semen parameters still had a 2.3-fold higher risk of death compared with men with normal semen (95% CI 1.12-4.65).

Limitations, Reasons for Caution

Our cohort represents infertile men, which may limit generalizability. As comorbidity relied on administrative data, granular information on each man regarding infertility diagnosis and lifestyle factors was unavailable.

Wider Implications of the Findings

Men with impaired semen parameters have an increased mortality rate in the years following an infertility evaluation suggesting semen quality may provide a marker of health.

Study Funding/Competing Interests

This study is supported in part by P01HD36289 from the Eunice Kennedy Shriver National Institute for Child Health and Human Development, National Institutes of Health (to D.J.L. and L.I.L.). The project was also partially supported by an NIH CTSA award number UL1 RR025744. None of the authors has any conflict of interest to declare.

Michael L Eisenberg, Shufeng Li, Barry Behr, Mark R Cullen, Deron Galusha, Dolores J Lamb, Larry I Lipshultz

Mike Eisenberg, M Eisenberg, S Li, B Behr, M Cullen, D Galusha, D Lamb, Lawrence Lipshultz, Laurence Lipshultz, L Lipshultz

PMID 24838701 24838701 DOI 10.1093/humrep/deu106 10.1093/humrep/deu106 Eisenberg et al. 2014, Eisenberg 2014

Semen quality, infertility and mortality in the USA

Men with abnormal semen at an infertility visit had higher death risk

Key Findings

Interpretation

RRM Context

Abstract

By this author

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