Cited by 730Sperm and Testicular FunctionMale Reproductive Health StudiesHypothalamic control of reproductive hormones

Temporal trends in sperm count: a systematic review and meta-regression analysis of samples collected globally in the 20th and 21st centuries

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Levine, Hagai, Jørgensen, Niels, Martino-Andrade, Anderson, Mendiola, Jaime, Weksler-Derri, Dan, Jolles, Maya, Pinotti, Rachel, Swan, Shanna H·2023·Human Reproduction Update

Abstract

BACKGROUND: Numerous studies have reported declines in semen quality and other markers of male reproductive health. Our previous meta-analysis reported a significant decrease in sperm concentration (SC) and total sperm count (TSC) among men from North America–Europe–Australia (NEA) based on studies published during 1981–2013. At that time, there were too few studies with data from South/Central America–Asia–Africa (SAA) to reliably estimate trends among men from these continents. OBJECTIVE AND RATIONALE: The aim of this study was to examine trends in sperm count among men from all continents. The broader implications of a global decline in sperm count, the knowledge gaps left unfilled by our prior analysis and the controversies surrounding this issue warranted an up-to-date meta-analysis. SEARCH METHODS: We searched PubMed/MEDLINE and EMBASE to identify studies of human SC and TSC published during 2014–2019. After review of 2936 abstracts and 868 full articles, 44 estimates of SC and TSC from 38 studies met the protocol criteria. Data were extracted on semen parameters (SC, TSC, semen volume), collection year and covariates. Combining these new data with data from our previous meta-analysis, the current meta-analysis includes results from 223 studies, yielding 288 estimates based on semen samples collected 1973–2018. Slopes of SC and TSC were estimated as functions of sample collection year using simple linear regression as well as weighted meta-regression. The latter models were adjusted for predetermined covariates and examined for modification by fertility status (unselected by fertility versus fertile), and by two groups of continents: NEA and SAA. These analyses were repeated for data collected post-2000. Multiple sensitivity analyses were conducted to examine assumptions, including linearity. OUTCOMES: Overall, SC declined appreciably between 1973 and 2018 (slope in the simple linear model: –0.87 million/ml/year, 95% CI: –0.89 to –0.86; P < 0.001). In an adjusted meta-regression model, which included two interaction terms [time × fertility group (P = 0.012) and time × continents (P = 0.058)], declines were seen among unselected men from NEA (–1.27; –1.78 to –0.77; P < 0.001) and unselected men from SAA (–0.65; –1.29 to –0.01; P = 0.045) and fertile men from NEA (–0.50; –1.00 to –0.01; P = 0.046). Among unselected men from all continents, the mean SC declined by 51.6% between 1973 and 2018 (–1.17: –1.66 to –0.68; P < 0.001). The slope for SC among unselected men was steeper in a model restricted to post-2000 data (–1.73: –3.23 to –0.24; P = 0.024) and the percent decline per year doubled, increasing from 1.16% post-1972 to 2.64% post-2000. Results were similar for TSC, with a 62.3% overall decline among unselected men (–4.70 million/year; –6.56 to –2.83; P < 0.001) in the adjusted meta-regression model. All results changed only minimally in multiple sensitivity analyses. WIDER IMPLICATIONS: This analysis is the first to report a decline in sperm count among unselected men from South/Central America–Asia–Africa, in contrast to our previous meta-analysis that was underpowered to examine those continents. Furthermore, data suggest that this world-wide decline is continuing in the 21st century at an accelerated pace. Research on the causes of this continuing decline and actions to prevent further disruption of male reproductive health are urgently needed.

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  • Some evidence suggests that decreased male fertility is due to an annual decline of 1.4% in sperm concentration and 1.6% in total sperm count, although the impact on TFR is yet unknown.

    “Some evidence suggests that decreased male fertility is due to an annual decline of 1.4% in sperm concentration and 1.6% in total sperm count, although the impact on TRF is yet unknown (Levine et al., 2017; Jørgensen et al., 2021; Levine et al., 2023).”

    From Declining global fertility rates and the implications for family planning and family building: an IFFS consensus document based on a narrative review of the literature (2024) · cites this paper as Levine et al., 2023

    The Meta-regression models for SC and TSC sections (pages unavailable) report declining sperm measures among unselected men, and Other issues links those measures to chances of conception. But the reported annual declines are 1.16% for sperm concentration and 1.40% for total sperm count—not 1.4% and 1.6%, respectively. The paper does not establish that the sperm-count decline caused decreased male fertility or assess its impact on the total fertility rate. (LLM, conf=0.91)

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  • Biological sterility in industrialized economies is increasing among both women and men due to environmental factors.

    “There are strong indications that biological sterility in industrialized economies is increasing among both women and men due to environmental factors (for a survey, see Skakkebæk et al. 2022, Levine et al. 2023).”

    From Fertility in High-Income Countries: Trends, Patterns, Determinants, and Consequences (2024) · cites this paper as Levine et al. 2023

    The Conclusion and wider implications (page unavailable) reports declining sperm counts among men in North America, Europe and Australia, and the Introduction links sperm count to infertility. It does not establish increasing biological sterility in women or show that environmental factors caused the decline; the conclusion calls for research into its causes. (LLM, conf=0.88)

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Research works printed but not linked: 6

  1. Ahmed FK, Memon AS, Khan AM, Burney I, Bano K. Effect of BMI on semen parameters in male infertility in tertiary care hospital of Karachi. Natl Editor Advis Board 2019;30:104.
  2. Azad N, Nazarian H, Nazari L, Novin MG, Piryaei A, Heidari MH, Farahani RM, Sadjadpour SS. Evaluation of PAWP and PLCf ex- pression in infertile men with previous ICSI fertilization failure. Urol J 2018;15:38-43.
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  4. Kumar K, Venkatesh S, Sharma PR, Tiwari PK, Dada R DAZL 260A > G and MTHFR 677C > T variants in sperm DNA of infertile Indian men. Indian J Biochem Biophys 2011;48:422-426.
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Authors
Levine, H., Jørgensen, N., Martino-Andrade, A., Mendiola, J., Weksler-Derri, D., Jolles, M., Pinotti, R., & Swan, S. H.
Affiliations
  • Hebrew University of Jerusalem (IL)
  • University of Copenhagen (DK)
  • Department of Physiology, Federal University of Parana , Curitiba, Brazil
  • Instituto Murciano de Investigación Biosanitaria (ES)
  • Ben-Gurion University of the Negev (IL)
  • Icahn School of Medicine at Mount Sinai (US)
Corresponding author
Levine, Hagai
Venue
Human Reproduction Update
Published
2022-11-15
Volume
29
Issue
2
Pages
157-176
ISSN
  • 1355-4786 (ISSN-L)
  • 1460-2369
OpenAlex
W4309099580
Cited by
728
References
245
Citations by year
2026: 206 · 2025: 205 · 2024: 183 · 2023: 130 · 2022: 3 · 2020: 1
FWCI
21.07
Type
journal article
Language
en
Open access
Locations
  • Human Reproduction Update (publishedVersion)
  • PubMed (publishedVersion)
  • Hispana (publishedVersion)
Funders
  • The Grantham Foundation for the Protection of the Environment
  • National Council for Scientific and Technological Development
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Sperm and Testicular Function
  • Health Sciences › Health Professions › General Health Professions › Male Reproductive Health Studies
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
sperm count, total sperm count, semen quality, male reproductive health, temporal trends, fertility status, semen volume, sperm concentration, meta-regression, Central and South America, Asia and Africa, 20th-21st century, lifestyle factors, reproductive toxicants
MeSH terms
Humans, Male, Regression Analysis, Semen, Sperm Count, Sperm Motility, Spermatozoa, Semen Analysis

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