Association between Particulate Matter (PM₂.₅), Nitrogen Dioxide (NO₂), Bisphenol A (BPA), and Phthalates and Infertility Outcomes: A Systematic Review and Meta-Analysis.
Level 3 - non-randomized controlled study
Systematic review and meta-analysis of observational studies
PubMed 41649762 · doi:10.1007/s43032-026-02055-1
What was done
Authors conducted a systematic review and random-effects meta-analysis following PRISMA 2020 guidelines (PROSPERO CRD420251066799). They searched PubMed, Scopus, Web of Science, and Embase from January 2008 to December 2024 for studies evaluating human exposure to particulate matter (PM2.5), nitrogen dioxide (NO2), bisphenol A (BPA), and phthalates via ambient monitoring or biomarkers, in relation to reproductive outcomes. Study quality was evaluated using the Newcastle-Ottawa Scale and the ROBINS-I V2 tool.
What was found
Thirty-eight studies comprising 55,620 participants met inclusion criteria. PM2.5 exposure (per 10 µg/m³) was associated with a 5.5 million/mL reduction in sperm concentration (95% CI: -6.05 to -5.11, P < 0.001, I² = 72%) and reduced oocyte yield (SMD: -0.33, 95% CI: -0.38 to -0.28, P < 0.001, I² = 62%). NO2 exposure (per 10 ppb) was associated with a 4.3 percentage-point decrease in sperm motility (95% CI: -4.52 to -4.11, P < 0.001, I² = 65%). BPA exposure was associated with lower anti-Müllerian hormone (SMD: -0.42, 95% CI: -0.46 to -0.37, P < 0.001, I² = 69%) and lower clinical pregnancy rates (OR: 0.83, 95% CI: 0.81 to 0.85, P = 0.001, I² = 58%). Phthalates were associated with lower antral follicle counts (SMD: -0.38, 95% CI: -0.42 to -0.33, P < 0.001, I² = 67%). Time to pregnancy was not significantly altered (SMD: 0.10, 95% CI: -0.09 to 0.29, P = 0.30, I² = 85%).
Why it matters
This review synthesizes quantitative evidence demonstrating that exposure to common environmental air pollutants and endocrine-disrupting chemicals is consistently associated with measurable decrements in male and female fertility parameters. The findings provide an empirical basis to consider environmental pollutant reduction as a modifiable factor in reproductive health.
Limits
All included studies were observational, which inherently limits causal inference and leaves room for residual confounding by unmeasured lifestyle or co-exposure factors. Most pooled analyses exhibited moderate-to-high statistical heterogeneity (I² from 58% to 85%), driven in part by regional differences and exposure duration definitions. Furthermore, many outcomes were evaluated in assisted reproductive technology cohorts, which may not generalize to natural conception in the broader population.
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