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.

IF 2.6 4区医学 Q2 OBSTETRICS & GYNECOLOGY

International Journal of Women's Health Pub Date : 2025-09-05 eCollection Date: 2025-01-01 DOI:10.2147/IJWH.S543096

Yuan Zhou, Dan Peng

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引用次数: 0

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_FDR = 1.24×10^-5), elevated waist-to-hip ratio (WHR) (IVW OR, 1.12; 95% CI, 1.04-1.20; P_FDR = 3.26×10^-3), and neuroticism (IVW OR, 1.10; 95% CI, 1.04-1.15; P_FDR = 1.25×10^-3) as significant risk factors, whereas higher educational attainment (IVW OR, 0.95; 95% CI, 0.93-0.97; P_FDR = 3.26×10^-4), greater body fat percentage (IVW OR, 0.67; 95% CI, 0.52-0.85; P_FDR = 4.10×10^-3) and napping (IVW OR, 0.63; 95% CI, 0.45-0.89; P_FDR = 1.94×10^-2) 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.

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女性不孕症的全球时空趋势和可改变的危险因素：使用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

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，为女性不孕症的预防和管理提供有针对性的流行病学见解。方法：根据GBD 2021研究的见解，我们分析了全球各地区1990-2021年女性不孕症的年龄标准化患病率（ASPR）和社会人口指数（SDI）类别。我们使用估计的年百分比变化（EAPC）和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，通过双样本孟德尔随机化（MR）和中介分析，评估了16种可改变的危险因素、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岁达到高峰。MR分析确定一般健康状况不佳（IVW OR, 1.94; 95% CI, 1.49-2.52; PFDR = 1.24×10-5）、腰臀比升高（IVW OR, 1.12; 95% CI, 1.04-1.20; PFDR = 3.26×10-3）和神经过敏（IVW OR, 1.10; 95% CI, 1.04-1.15; PFDR = 1.25×10-3）是显著的危险因素，而较高的受教育程度（IVW OR, 0.95; 95% CI, 0.93-0.97; PFDR = 3.26×10-4）、较高的体脂率（IVW OR, 0.67; 95% CI, 0.52-0.85; PFDR = 4.10×10-3）和午睡(IVW OR, 0.63; 95% CI, 0.45-0.89；PFDR = 1.94×10-2)有保护作用。中介分析表明，HbA1c和甘油三酯（TG）在WHR与不孕之间的关系中起部分中介作用，而TG在受教育程度对女性不孕的影响中起中介作用。结论：年龄-时期-队列模型表明，生育年龄模式、环境暴露和队列特定风险概况的变化是观察到的差异的关键因素。有针对性的公共卫生干预措施，包括教育推广、生活方式改变和常规代谢筛查，对于减轻未来几十年不断上升的不孕症负担至关重要。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

International Journal of Women's Health OBSTETRICS & GYNECOLOGY-

CiteScore

3.70

自引率

0.00%

发文量

194

审稿时长

16 weeks

期刊介绍： International Journal of Women''s Health is an international, peer-reviewed, open access, online journal. Publishing original research, reports, editorials, reviews and commentaries on all aspects of women''s healthcare including gynecology, obstetrics, and breast cancer. Subject areas include: Chronic conditions including cancers of various organs specific and not specific to women Migraine, headaches, arthritis, osteoporosis Endocrine and autoimmune syndromes - asthma, multiple sclerosis, lupus, diabetes Sexual and reproductive health including fertility patterns and emerging technologies to address infertility Infectious disease with chronic sequelae including HIV/AIDS, HPV, PID, and other STDs Psychological and psychosocial conditions - depression across the life span, substance abuse, domestic violence Health maintenance among aging females - factors affecting the quality of life including physical, social and mental issues Avenues for health promotion and disease prevention across the life span Male vs female incidence comparisons for conditions that affect both genders.