女性不孕症的全球时空趋势及可改变的风险因素：基于2021年全球疾病负担研究和孟德尔随机化分析的年龄-时期-队列研究

Global Spatiotemporal Trends and Modifiable Risk Factors for Female Infertility: An Age-Period-Cohort Using Global Burden of Disease Study 2021 and Mendelian Randomization Analysis.

作者信息

Zhou Yuan, Peng Dan

机构信息

Department of Medical Genetics, Changde Hospital, Xiangya School of Medicine, Central South University (The First People's Hospital of Changde City), Changde, Hunan, 415000, People's Republic of China.

出版信息

Int J Womens Health. 2025 Sep 5;17:2929-2945. doi: 10.2147/IJWH.S543096. eCollection 2025.

DOI:10.2147/IJWH.S543096

PMID:40933848

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12419219/

Abstract

BACKGROUND

This study aims to describe the global burden of female infertility, analyze its spatial and temporal trends, and offer targeted epidemiological insights to support the prevention and management of female infertility.

METHODS

Drawing on insights from the GBD 2021 study, we analyzed age-standardized prevalence rates (ASPR) of female infertility (1990-2021) across global regions and Socio-Demographic Index (SDI) categories. We quantified temporal trends using estimated annual percentage change (EAPC) and Age-Period-Cohort analyses across age groups and geographic regions. Furthermore, the causal relationships between 16 modifiable risk factors, 10 serum biomarkers, and female infertility were assessed by two-sample Mendelian randomization (MR) and mediation analysis.

RESULTS

Globally, the ASPR of female infertility exhibited an increasing trend over the study period. Across all SDI regions, infertility prevalence peaked at ages 35-40. MR analysis identified poor general health (IVW OR, 1.94; 95% CI, 1.49-2.52; P = 1.24×10), elevated waist-to-hip ratio (WHR) (IVW OR, 1.12; 95% CI, 1.04-1.20; P = 3.26×10), and neuroticism (IVW OR, 1.10; 95% CI, 1.04-1.15; P = 1.25×10) as significant risk factors, whereas higher educational attainment (IVW OR, 0.95; 95% CI, 0.93-0.97; P = 3.26×10), greater body fat percentage (IVW OR, 0.67; 95% CI, 0.52-0.85; P = 4.10×10) and napping (IVW OR, 0.63; 95% CI, 0.45-0.89; P = 1.94×10) had protective effects. Mediation analysis demonstrated that HbA1c and triglycerides (TG) partially mediated the relationship between WHR and infertility, while TG mediated the effect of educational attainment on female infertility.

CONCLUSION

Age-Period-Cohort modeling suggests that shifts in reproductive age patterns, environmental exposures, and cohort-specific risk profiles are key contributors to observed disparities. Targeted public health interventions, including educational promotion, lifestyle modifications, and routine metabolic screening, are essential to mitigate the rising infertility burden in the coming decades.

摘要

背景

本研究旨在描述全球女性不孕症负担，分析其时空趋势，并提供有针对性的流行病学见解，以支持女性不孕症的预防和管理。

方法

借鉴全球疾病负担（GBD）2021研究的见解，我们分析了全球各地区和社会人口指数（SDI）类别中女性不孕症（1990 - 2021年）的年龄标准化患病率（ASPR）。我们使用估计年百分比变化（EAPC）以及跨年龄组和地理区域的年龄 - 时期 - 队列分析来量化时间趋势。此外，通过两样本孟德尔随机化（MR）和中介分析评估了16种可改变的风险因素、10种血清生物标志物与女性不孕症之间的因果关系。

结果

在全球范围内，女性不孕症的ASPR在研究期间呈上升趋势。在所有SDI区域，不孕症患病率在35 - 40岁达到峰值。MR分析确定一般健康状况差（IVW比值比，1.94；95%置信区间，1.49 - 2.52；P = 1.24×10）、腰臀比（WHR）升高（IVW比值比，1.12；95%置信区间，1.04 - 1.20；P = 3.26×10）和神经质（IVW比值比，1.10；95%置信区间，1.04 - 1.15；P = 1.25×10）为显著风险因素，而较高的教育程度（IVW比值比，0.95；95%置信区间，0.93 - 0.97；P = 3.26×10）、较高的体脂百分比（IVW比值比，0.67；95%置信区间，0.52 - 0.85；P = 4.10×10）和午睡（IVW比值比，0.63；95%置信区间，0.45 - 0.89；P = 1.94×10）具有保护作用。中介分析表明，糖化血红蛋白（HbA1c）和甘油三酯（TG）部分介导了WHR与不孕症之间的关系，而TG介导了教育程度对女性不孕症的影响。