{"title":"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","authors":"Yuan Zhou, Dan Peng","doi":"10.2147/IJWH.S543096","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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<sub>FDR</sub> = 1.24×10<sup>-5</sup>), elevated waist-to-hip ratio (WHR) (IVW OR, 1.12; 95% CI, 1.04-1.20; P<sub>FDR</sub> = 3.26×10<sup>-3</sup>), and neuroticism (IVW OR, 1.10; 95% CI, 1.04-1.15; P<sub>FDR</sub> = 1.25×10<sup>-3</sup>) as significant risk factors, whereas higher educational attainment (IVW OR, 0.95; 95% CI, 0.93-0.97; P<sub>FDR</sub> = 3.26×10<sup>-4</sup>), greater body fat percentage (IVW OR, 0.67; 95% CI, 0.52-0.85; P<sub>FDR</sub> = 4.10×10<sup>-3</sup>) and napping (IVW OR, 0.63; 95% CI, 0.45-0.89; P<sub>FDR</sub> = 1.94×10<sup>-2</sup>) 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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":14356,"journal":{"name":"International Journal of Women's Health","volume":"17 ","pages":"2929-2945"},"PeriodicalIF":2.6000,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419219/pdf/","citationCount":"0","resultStr":"{\"title\":\"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.\",\"authors\":\"Yuan Zhou, Dan Peng\",\"doi\":\"10.2147/IJWH.S543096\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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<sub>FDR</sub> = 1.24×10<sup>-5</sup>), elevated waist-to-hip ratio (WHR) (IVW OR, 1.12; 95% CI, 1.04-1.20; P<sub>FDR</sub> = 3.26×10<sup>-3</sup>), and neuroticism (IVW OR, 1.10; 95% CI, 1.04-1.15; P<sub>FDR</sub> = 1.25×10<sup>-3</sup>) as significant risk factors, whereas higher educational attainment (IVW OR, 0.95; 95% CI, 0.93-0.97; P<sub>FDR</sub> = 3.26×10<sup>-4</sup>), greater body fat percentage (IVW OR, 0.67; 95% CI, 0.52-0.85; P<sub>FDR</sub> = 4.10×10<sup>-3</sup>) and napping (IVW OR, 0.63; 95% CI, 0.45-0.89; P<sub>FDR</sub> = 1.94×10<sup>-2</sup>) 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.</p><p><strong>Conclusion: </strong>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.</p>\",\"PeriodicalId\":14356,\"journal\":{\"name\":\"International Journal of Women's Health\",\"volume\":\"17 \",\"pages\":\"2929-2945\"},\"PeriodicalIF\":2.6000,\"publicationDate\":\"2025-09-05\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12419219/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Women's Health\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.2147/IJWH.S543096\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/1/1 0:00:00\",\"PubModel\":\"eCollection\",\"JCR\":\"Q2\",\"JCRName\":\"OBSTETRICS & GYNECOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Women's Health","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2147/IJWH.S543096","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"OBSTETRICS & GYNECOLOGY","Score":null,"Total":0}
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.
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; PFDR = 1.24×10-5), elevated waist-to-hip ratio (WHR) (IVW OR, 1.12; 95% CI, 1.04-1.20; PFDR = 3.26×10-3), and neuroticism (IVW OR, 1.10; 95% CI, 1.04-1.15; PFDR = 1.25×10-3) as significant risk factors, whereas higher educational attainment (IVW OR, 0.95; 95% CI, 0.93-0.97; PFDR = 3.26×10-4), greater body fat percentage (IVW OR, 0.67; 95% CI, 0.52-0.85; PFDR = 4.10×10-3) and napping (IVW OR, 0.63; 95% CI, 0.45-0.89; PFDR = 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.
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.
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