China-East Asia comparison of male infertility burden and trend prediction: evidence from GBD 2023

Introduction

Infertility is a disease of the male or female reproductive system defined by the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse. Within the male reproductive system, the prevalent causes of infertility encompass semen discharge disorders, sperm insufficiency or low sperm concentration, along with abnormalities in sperm morphology and motility. Infertility can be categorized into primary and secondary types: primary infertility denotes a scenario where an individual has never achieved successful conception, whereas secondary infertility implies at least one previous pregnancy attempt (1). Male infertility represents a critical concern within the global reproductive health domain, significantly impacting both public health systems and societal structures. Data from the Global Burden of Disease (GBD) study reveal that the worldwide prevalence of male infertility approximated 55 million cases in 2021, with an age-standardized prevalence rate of 2,737.42 per 100,000 individuals, demonstrating a consistent upward trajectory since 1990 (2). The 2023 report by the World Health Organization (WHO) similarly highlights that approximately 17.5% of the global adult population is affected by infertility, with male factors contributing to 30–50% of these cases (3). Although infertility does not directly result in mortality, it exerts profound effects on individuals’ mental well-being, family stability, and demographic composition. Research indicates that male infertility patients are at heightened risk of depression, anxiety, and psychological distress. Treatment failures can evoke feelings of sorrow and inadequacy, while their avoidance coping strategies are strongly associated with diminished self-esteem, compromised relationship quality, and impaired sexual function (4). In nations with low fertility rates, the public health implications of male infertility are becoming increasingly pronounced. Some studies have indicated that infertile men exhibit a significantly elevated risk of cardiovascular disease, approximately 1.5 times higher (5). Moreover, they face a heightened risk of diabetes and hypertension, with increases ranging from 20% to 28% (6). Furthermore, infertility serves as an independent risk factor for certain cancers, particularly among individuals with severe spermatogenic dysfunction (e.g., azoospermia). Notably, azoospermic men have a nearly threefold higher risk of developing testicular cancer compared to the general male population (7). In most healthcare systems, male infertility is classified under reproductive medicine or urology, with an uneven distribution of diagnostic and treatment resources (8). While certain studies suggest an elevation in male infertility rates over the past few decades, the magnitude of this increase and the underlying etiologies remain contentious (9,10). Developed countries generally possess comprehensive infertility management systems, including semen analysis, hormone testing, genetic screening, and assisted reproductive technologies (e.g., in vitro fertilization, intracytoplasmic sperm injection). Nevertheless, in numerous low-and middle-income countries, screening and treatment resources for male infertility remain scarce, accompanied by lagging social awareness and policy support (11). The etiology of infertility encompasses not only physiological factors but also the socio-cultural context in which male partners are situated. Husbands frequently struggle to differentiate between infertility and notions of masculinity or sexual prowess (12).

In East Asia, shaped by traditional cultural and family value systems, procreation is considered a substantial family and social obligation. As a result, infertility problems frequently encounter substantial societal pressure (13). In recent years, with economic progress and evolving social perspectives, the rates of infertility consultations have increased in multiple East Asian countries, and assisted reproductive technologies have witnessed rapid development (14). Some countries have included infertility care in public health priorities, providing partial insurance coverage or policy backing (15).

As a highly populous nation in East Asia, China also focuses on male infertility issues. Nevertheless, public awareness of male infertility is still characterized by biases, with relatively low rates of medical consultations and screenings, and an uneven distribution of medical resources across regions (16).

In predictive analysis, it was primarily observed that the temporal framework for predicting changes in the GBD database is influenced by multiple factors, including disease-specific attributes, data quality and accessibility, prediction methods, sociodemographic elements, and the expected impact of public health interventions. All these factors contribute to the complexity of forecasting disease burden over different time spans (17,18). The number of infertility patients seeking medical assistance fluctuates, and due to public health interventions, the infertility population demonstrates significant short-term improvements. Therefore, predictions of infertility disease burden tend to utilize short-term projections to capture these variations (19).

Given that East Asia stands as one of the most densely populated regions worldwide, confronting persistently declining fertility rates (20), a swiftly aging social demographic (21), and severe environmental pollution, notably air pollution (22)—all factors that may exert profound influences on male reproductive health—comprehending the epidemiological features of male infertility in East Asia assumes paramount practical significance. Nevertheless, systematic epidemiological investigations into male infertility within East Asia remain notably scarce. For example, certain studies suggest that China and Japan exhibit the highest reported incidences of male infertility across East Asia (23,24). However, these conclusions are easily constrained by differences in healthcare seeking behaviors and diagnostic standards across regions, thus lacking a unified survey standard. Based on the above situation, this study will provide a comprehensive and systematic analysis of the prevalence and changing trends of male infertility in East Asia using the GBD database. We present this article in accordance with the GATHER reporting checklist (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0288/rc).

Methods

Data sources

The principal data source for this research is the GBD 2023 database, a comprehensive and systematic data repository that offers global disease burden estimations across multiple dimensions, including age, gender, and geographical region. These estimations are accompanied by 95% confidence intervals (CIs) (16). By means of these metrics, researchers and policymakers can carry out comparative analyses across national, regional, and temporal dimensions, facilitating the effective monitoring of health trends, the evaluation of health intervention outcomes, and the optimization of resource allocation. Relevant data can be retrieved from the GBD 2023 database through the Global Health Data Exchange (GHDx) query tool (https://www.healthdata.org/data-tools-practices/interactive-visuals/gbd-results) (25). The database encompasses disease burden data from 288 causes of death, 371 diseases and injuries, and 88 risk factors across 204 countries and regions (21 regions and 7 super-regions) and 5 Socio-demographic Index (SDI) categories, covering epidemiological data and disease burden indicators such as years lived with disability (YLD), years of life lost (YLL), YLDs (years of life lost due to disability), disability-adjusted life years (DALY), and health-adjusted life expectancy (HALE) (26). In this study, the significance of YLDs in the assessment of male infertility lies in its ability to transcend the single clinical outcome of “fertility capability” and quantify the comprehensive health burden caused by the disease on society and individuals from a broader public health perspective. The specific parameter settings in this paper are provided in Appendix 1. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Joinpoint regression analysis

Joinpoint regression is a statistical approach utilized for the analysis of trend change points in time-series data. It partitions the overall trend into multiple local linear segments with distinct slopes to depict temporal patterns. This method applies a grid search method (GSM), Monte Carlo permutation testing, and Bonferroni multiple comparison correction for model optimization (27). The output of the analysis encompasses the quantity of connection points, their temporal locations, the annual percentage change (APC) of each segment along with its 95% CI, and the average annual percentage change (AAPC) for the entire study period. APC reflects the trend of disease standardized rate variations within a specific time interval, whereas AAPC reflects the overall trend of disease standardized rate changes throughout the entire analysis period. If both APC/AAPC and the lower limit of its 95% CI are greater than 0, it signifies a significant upward trend; if both APC/AAPC and the upper limit of its 95% CI are less than 0, it indicates a significant downward trend; if the 95% CI contains 0, the trend is stable (28).

Predictive analysis

The Autoregressive Integrated Moving Average (ARIMA) model is a widely used univariate statistical method for time series forecasting. It assumes that the series can be transformed into a stationary process through differencing and utilizes autoregressive and moving average terms to jointly characterize the dynamic dependency structure of the series. In this study, the auto.arima() function in the forecast package was used to automatically identify the optimal model order. Modeling was based on historical data of age-standardized prevalence rate (ASPR) in East Asia from 1990 to 2023, and extrapolation predictions were made for the trend during the period from 2022 to 2051. The prediction results provided multi-level CIs, including 80%, 85%, 90%, and 95%, to reflect the uncertainty of future trends. Although the ARIMA model does not explicitly incorporate covariate structures such as age, period, or cohort, its characteristic of relying on the series’ own historical information for extrapolation makes it still have good practicality and interpretability in short- to medium-term predictions. The ARIMA model is a classic time series forecasting method proposed by Box and Jenkins (29). It has been widely applied in disease burden forecasting in the field of epidemiology, including cancer mortality, infectious disease incidence rate, and reproductive health-related disease burden (30,31), and is a commonly used tool for epidemiological time series forecasting.

This study employs the ARIMA model for prediction, primarily based on the following considerations: (I) the ARIMA model is a mature method for epidemiological time series prediction and has been widely applied to long-term trend prediction of disease burden; (II) the GBD database provides continuous annual data on the prevalence of male infertility from 1990 to 2021, providing sufficient historical information for model fitting; (II) previous studies have shown that the ARIMA model is robust in capturing long-term trends and performs better than complex mechanism models in data-driven scenario predictions (32). It should be noted that the main limitation of the ARIMA model is that the reliability of long-term predictions decreases as the prediction period extends (33). Therefore, the prediction results of this study should be understood as scenario simulations of future burden assuming the current trend continues unchanged, rather than deterministic and precise prophecies.

In terms of model selection, this study relies on auto.arima to automatically identify models and estimate parameters, in order to avoid biases caused by subjective settings. The predictive performance of the model is evaluated using goodness-of-fit metrics (such as AIC) to ensure its superiority over simple trend extrapolation or naive prediction methods. Although no formal prediction tests were conducted, the model’s fitted curve to historical data exhibited good consistency with observed values. All prediction results in this report are accompanied by multi-level uncertainty intervals (UIs), which are derived from quantile estimates of the model’s predictive distribution and reflect the range of prediction variation under the combined effects of parameter estimation and random error.

Statistical analysis

This study utilized Excel software to statistically describe and analyze the distribution of morbidity indicators across different years, age groups, and subgroups of infertility-related diseases associated with male infertility from 1990 to 2023 globally. The primary metrics included the number of cases, prevalence rate, and YLD rate. The Joinpoint (version 5.4.0) software was employed to calculate the AAPC and APC, with a significance level of α=0.05. All analyses were set at P<0.05 to determine statistical significance, in accordance with standard practices in epidemiological and public health research, particularly those conducted by the GBD study. Data processing, analysis, and graphical presentation were performed using the R software package “dplyr”, “ggplot2”, “reshape2”, and “readxl”.

Results

Comparison of the prevalence of infertility-related diseases associated with male infertility in East Asian countries

Based on the 2023 statistical data from the GBD, the estimated number of infertility-related diseases associated with male infertility in East Asia in 2023 was 12,827,353 cases. Among them, China accounted for nearly 92.8% (11,898,432 cases; 95% UI: 6,092,547–21,530,761). The prevalence rate of infertility-related diseases associated with male infertility in China was 1,608.6 cases per 100,000 population (95% UI: 864.16–2,780.15; Table 1). By integrating the data on infertility, primary infertility, and secondary infertility in 2023, China ranked first in terms of prevalence, followed by North Korea (1,164.1/100,000; age-standardized rate), Japan (1,046.2/100,000), Mongolia (1,035.2/100,000), and South Korea (665.8/100,000; Figure 1 and Table 1). Notably, Mongolia (AAPC, 0.28%) witnessed the most significant increase in infertility-related diseases associated with male infertility among all countries, while China (AAPC, 0.01%) maintained a stable state.

Figure 1 Comparison of infertility prevalence rates related to male infertility among five East Asian countries in 2023.

As presented in Table 2, the prevalence rate of primary infertility associated with male infertility in China in 2023 was 242.9 cases per 100,000 population, showing a significant increase compared to 1990 (AAPC, 0.33). In North Korea, the trend of primary infertility remained stable (AAPC, −0.01%), while Japan showed a declining trend (AAPC, −0.03%), Mongolia presented a significant upward trend (AAPC, 0.38%), and South Korea remained stable (AAPC, −0.01%). Additionally, Table 3 shows the data related to secondary infertility associated with male infertility. China showed a declining trend (AAPC, −0.04%), North Korea exhibited a significant upward trend (AAPC, 0.05%), Japan (AAPC, −0.07%) showed a declining trend, Mongolia demonstrated a significant upward trend (AAPC, 0.24%), and South Korea exhibited a significant declining trend (AAPC, −0.16%).

In conclusion, male-related infertility poses a substantial burden and presents diverse patterns in East Asia. The total number of cases in China is considerable, and the prevalence of primary infertility shows a significant upward trend, which continuously challenges the reproductive health service system. The growth trend of age-standardized prevalence rate (ASPR) (especially primary infertility) in Mongolia is the most prominent and deserves attention. In contrast, the overall ASPR burden in Japan and South Korea shows a stable or declining trend, which may reflect their more mature diagnostic, treatment, and health management systems. These differences imply that health policies in different countries need to formulate differentiated strategies for early screening, standardized diagnosis and treatment, and long-term management based on their specific disease burden trends.

Comparison of male infertility-related infertility in China across different years

Age stratification analysis indicates that the problem of male infertility in China presents distinct age-specific distribution and temporal variation trends (Figure 2). During the reproductive years (15–49 years), overall infertility, primary infertility, and secondary infertility demonstrate different age-related patterns, with certain disparities observed between 2023 and 2013.

Figure 2 Age distribution and temporal changes of infertility related to male infertility in China [2013–2023]. (A) Comparison of infertility. (B) Comparison of primary infertility. (C) Comparison of secondary infertility.

From the aspect of overall infertility, the incidence rate follows a trend of initially increasing and subsequently decreasing with age, reaching its peak in the 35–39 years age group. In comparison to 2013, the overall infertility rate in most age groups remained stable or slightly decreased in 2023. However, the incidence rates in the 30–34 and 35–39 years age groups remained at relatively high levels. For example, in the 35–39 years age group, the overall infertility rate rose from 6,745.82 per 100,000 in 2013 to 6,810.16 per 100,000 in 2023.

Further subtype comparisons revealed that, when compared to primary infertility, the incidence rates in most age groups in 2023 were slightly decreased or largely unchanged compared to 2013. For instance, in the 20–24 years age group, the rate declined from 841.77 per 100,000 to 837.03 per 100,000, indicating that this type of infertility did not increase significantly over the years. This may be associated with the increasing emphasis on the diagnosis and treatment of infertility within the Chinese population in recent years.

Conversely, secondary infertility exhibited a clear age-and time-dependent upward trend, especially after the age of 30. In the 30–34 years age group, the incidence rate increased from 4,581.60 per 100,000 in 2013 to 4,668.48 per 100,000 in 2023, becoming the primary type contributing to the overall burden of infertility.

Notably, all types of infertility showed a sharp decline after the age of 45–49 years, and no case reports were collected in the age group above 50 years, which is consistent with the natural decline in male fertility. Moreover, secondary infertility imposes the greatest burden in middle age (30–44 years), and it showed an upward trend across multiple age groups in 2023 compared to 2013. This suggests that the cumulative effects of reproductive history, environmental, or behavioral factors may play a significant role in this type of infertility.

Temporal trends in the prevalence of male infertility-related disorders across East Asian countries

A joinpoint regression analysis of infertility prevalence data from five Northeast Asian countries spanning the period from 1990 to 2023 (Figure 3) unveiled distinct disparities and commonalities in the overall trends of infertility, along with alterations in primary and secondary infertility across these nations.

Figure 3 Trends in ASPR by cancer site and gender in (A) China, (B) Japan, (C) Republic of Korea, (D) Mongolia and (E) Democratic People’s Republic of Korea. The data used to generate this figure were from the GBD database. APC, annual percent change; ASPR, age-standardized prevalence rate; GBD, Global Burden of Disease.

Regarding the overall infertility rates, South Korea demonstrated the most fluctuating trend, undergoing a decline, an increase, another decline, and subsequent stabilization, followed by a substantial upsurge from 2016 to 2020 (APC =1.67*), and then achieving stability after 2020. Japan’s trend closely paralleled that of South Korea, indicating comparable influences from social and fertility-policy factors in both countries. China witnessed a remarkable increase from 1990 to 1994, succeeded by a protracted gradual decline, with a slight resurgence after 2020. Mongolia experienced a notable ascent from 2010 to 2015 (APC =1.68*), remaining relatively stable during other intervals. North Korea exhibited minor fluctuations overall, with a slight increment after 2011.

In the case of primary infertility, China encountered a sharp rise in the early 1990s (APC =9.40* from 1990 to 1993), followed by a long-term gradual decline. South Korea and Japan displayed minor fluctuations across multiple phases, with South Korea showing an upward trend after 2018. Mongolia experienced a significant increase from 2011 to 2014 (APC =2.72*). The overall variation in the primary infertility rate in North Korea was moderate, without a significant sustained upward or downward tendency.

Concerning secondary infertility, South Korea and Japan also presented similar fluctuation patterns, with significant increases between 2016 and 2020 (South Korea APC =2.51*, Japan APC =2.35*), followed by a gradual leveling off. China’s secondary infertility rate has been gradually declining since 1994, with a slight rebound after 2020. In contrast, Mongolia witnessed a significant rise between 2010 and 2015, followed by a deceleration in growth.

Predictive analysis of the prevalence of infertility diseases related to male infertility in China

The prediction of prevalence trends reveals notable heterogeneity in the disease burden of male infertility in China (Figure 4). The age-standardized prevalence rate (ASPR) of overall infertility is anticipated to remain relatively stable throughout the prediction period. However, the cumulative effect of the population base will result in a continuous increase in the cumulative number of cases. It is noteworthy that modern research indicates that the disease factors contributing to the increasing burden of infertility primarily focus on several types of etiologies closely related to contemporary lifestyles, such as environmental pollution (22), metabolic and endocrine system diseases (34), as well as psychological disorders and sexual dysfunction (4). These diseases collectively exacerbate the burden of infertility through different pathological pathways, and due to chronicity, comorbidity, and psychological impacts, they severely impair the overall quality of life of patients.

Figure 4 Prediction of infertility related to China and male infertility (based on data from 1990 to 2023, projected to 2051). (A) Prevalence rate. (B) Prevalence number of cases. ASR.

The projection of the overall infertility burden suggests that the ASPR is expected to decline from approximately 1,608.61 per 100,000 in 2023 to 1,585.42 per 100,000 (95% CI: 1,395.67–1,775.17) in 2051, with an estimated prevalence of 10,759,438.45 cases (95% CI: 8,288,123.91–13,230,752.98). The subtype-specific projections further disclose distinct trends for primary and secondary infertility. Primary infertility shows the most stable trend in ASPR, with the rate projected to decrease marginally from 242.95 per 100,000 in 2023 to 239.18 per 100,000 (95% CI: 180.45–297.91) in 2051, featuring minimal annual variation and an estimated prevalence of 1,152,383.63 cases (95% CI: 741,929.64–1,562,837.62). In contrast, the ASPR for secondary infertility demonstrates a more prominent and gradual decline. The predicted value will decrease from 1365.66 per 100,000 in 2023 to 1,344.65 (95% CI: 1,167.22–1,522.08) per 100,000 in 2051, with an estimated number of cases of 9,602,476.93 (95% CI: 7,428,875.72–11,776,078.14).

Changes and comparisons in the burden of infertility-related diseases associated with male infertility across East Asian countries

Based on the analysis of years lived with disability (YLDs) data of male infertility in China, Japan, South Korea, North Korea, and Mongolia from 1990 to 2023, the variations in disease burden among different countries exhibited significant regional heterogeneity (Figure 5).

Figure 5 Rank changes in DALYs attributable to cancers and percentage change in all age and age-standardized DALY rates in China, Japan, Republic of Korea, Mongolia and Democratic People’s Republic of Korea from 1990 to 2023. (A) Infertility. (B) Primary infertility. (C) Secondary infertility. DALYs, disability-adjusted life years; YLDs, years of life lost due to disability.

Changes in the YLDs burden of overall infertility: In 2023, the age-standardized YLDs rates ranked as follows: China (8.85/100,000), North Korea (6.38/100,000), Mongolia (6.06/100,000), Japan (6.05/100,000), and South Korea (3.89/100,000). Between 1990 and 2023, the trends varied significantly across the five countries: Mongolia saw the largest increase, with its age-standardized YLDs rate rising by 8.9% (from 5.57 to 6.06/100,000), while the full-age rate surged by 21.3% (from 5.22 to 6.33/100,000). North Korea and Japan experienced slight increases of 3.3% and decreases of 1.8% (age-standardized rates), respectively. Although China’s age-standardized rate rose by 7.7% (from 8.22 to 8.85/100,000), its full-age rate declined by 3.5% (from 9.19 to 8.87/100,000), indicating that population aging has a push effect on standardized rates. Notably, South Korea saw the most significant decline among all countries, with its age-standardized YLDs rate decreasing by 3.4% (from 4.03 to 3.89/100,000).

Changes in the YLDs burden of primary infertility: In 2023, the age-standardized YLDs rates ranked as follows: Japan (2.08/100,000), Mongolia (2.33/100,000), China (1.81/100,000), South Korea (1.39/100,000), and North Korea (1.22/100,000). Between 1990 and 2023, Mongolia and Japan saw increases of 11.7% and decreases of 0.7%, respectively, while China, South Korea, and North Korea all showed a downward trend, with China experiencing the largest decline, where the age-standardized rate dropped by 38.0% (from 3.06 to 1.81/100,000), and the full-age rate decreased by 23.8% (from 2.18 to 1.58/100,000). South Korea’s age-standardized rate rose slightly by 1.8%, but its full-age rate fell by 24.0% (from 1.73 to 1.31/100,000), indicating a slight increase in the age-standardized risk of primary infertility in South Korea, but an actual reduction in the overall population burden due to demographic changes.

Changes in the YLDs burden of secondary infertility: In 2023, the age-standardized YLDs rates ranked as follows: China (7.04/100,000), Japan (3.96/100,000), Mongolia (3.73/100,000), North Korea (5.15/100,000), and South Korea (2.49/100,000). From 1990 to 2023, only China and Japan showed an upward trend. China’s age-standardized rate increased slightly by 1.9% (from 6.91 to 7.04/100,000), while the overall age-standardized rate decreased by 4.3% (from 7.62 to 7.29/100,000). Japan’s age-standardized rate dropped by 2.4% (from 4.06 to 3.96/100,000), and the overall age-standardized rate plummeted by 24.0% (from 4.80 to 3.65/100,000). Both Mongolia and North Korea showed a downward trend, with North Korea experiencing the steepest decline, where the age-standardized rate fell by 21.4% (from 6.56 to 5.15/100,000), and the overall age-standardized rate dropped by 24.9% (from 7.70 to 5.79/100,000). South Korea’s burden of secondary infertility continued to ease, with the age-standardized rate decreasing by 6.1% (from 2.65 to 2.49/100,000).

Discussion

The international community has increasingly acknowledged that infertility has emerged as a significant determinant influencing marital harmony, with numerous infertile couples encountering both physiological and psychological challenges (35). The burden of infertility-related diseases associated with male infertility exerts a substantial burden on individual patients, society, and the healthcare economic system (36). Nevertheless, at present, there is a dearth of systematic evaluation grounded in comprehensive and authoritative databases concerning the burden of infertility-related diseases associated with male infertility, especially regarding detailed incidence rates and long-term trends. To address this gap, this study systematically analyzed the incidence trends and correlations of infertility-related diseases associated with male infertility in East Asia based on global disease burden data spanning from 1990 to 2023.

The 2023 age-distribution data regarding male infertility in five East Asian countries indicated that the overall prevalence of infertility and YLDs rates presented a unimodal distribution pattern. Specifically, they initially increased and then declined with the advancement of age, reaching a peak within the 30–44 years age group. Throughout the disease progression, infertility predominantly affects men of reproductive age. The burden of infertility becomes evident from 15–19 years of age, experiences a rapid increase after 20–24 years, reaches its apex at 30–39 years, then gradually decreases from 40–44 years, and shows a sharp decline after 45 years in both prevalence and YLDs rates. This distribution pattern is consistent with the physiological process of the natural decline in male reproductive function and sperm quality with age. Simultaneously, it reflects the influence of social fertility behaviors (e.g., concentrated child-bearing plans between 20 and 40 years) on disease diagnosis. Subtype analysis demonstrated that the peak of primary infertility occurred at 25–34 years, while the peak of secondary infertility shifted significantly to 35–44 years. This disparity implies that primary infertility is frequently associated with congenital or early-acquired reproductive system abnormalities, thereby constituting a major burden during the younger reproductive years. In contrast, secondary infertility is more commonly caused by cumulative acquired factors (e.g., environmental exposure, reproductive tract infections, lifestyle, etc.), and its effects are more prominent in older men of reproductive age. In the 35–39 years age group, the prevalence of secondary infertility was significantly higher than that of primary infertility, emerging as the primary contributor to overall infertility. Nevertheless, in the 40–44 years age group, the burden of infertility remained high in Japan and South Korea, especially for secondary infertility. This indicates that the social phenomenon of late marriage and child-bearing may postpone the peak age of infertility. In light of the substantial burden of infertility among males aged 25–44 years, special attention ought to be directed towards the high-risk population of secondary infertility within the 35–44 years age group. It is advisable to enhance reproductive health management for men of reproductive age, advocate for premarital and preconception reproductive health screenings, execute targeted surveillance for high-risk occupational cohorts (e.g., those with long-term exposure to environmental contaminants), and carry out early interventions aimed at the major risk factors for secondary infertility (e.g., smoking, obesity, reproductive tract infections).A robust body of research underpins the necessity for risk monitoring and early intervention in high-risk groups, including elderly individuals and those exposed to occupational hazards. Elderly fathers are not only confronted with risks such as declining sperm quality, heightened DNA fragmentation, and the accumulation of de novo mutations, but also face a significantly elevated risk of their offspring developing neurodevelopmental disorders, congenital malformations, and other related conditions (37). With regard to occupational exposure, factors such as heavy metals, pesticides, solvents, heat stress, and shift work have been definitively linked to a deterioration in semen quality (38). In terms of intervention, moderate exercise, antioxidant therapy, and nutritional interventions have been demonstrated to enhance fertility in elderly men (39); moreover, the collaborative interview model between occupational medicine and reproductive medicine has proven effective in bolstering protective awareness and facilitating behavioral changes among exposed populations (38).

Simultaneously, attention should be given to the tendency of delayed childbearing and the shifting peak ages of infertility in late-childbearing nations such as Japan and South Korea. Predictions should be made and adjustments to the allocation of reproductive health service resources should be carried out to cope with the evolving patterns of disease burden. These findings suggest that the alterations in the prevalence of male infertility in East Asia from 1990 to 2023 mirror the dual impacts of modernization: on one hand, economic development and medical progress contribute to burden mitigation; on the other hand, environmental deterioration and significant lifestyle changes may counterbalance or even reverse these positive effects (40,41).

This disparity is closely associated with the demographic structure, economic development level, healthcare resources, lifestyle, and environmental factors of different countries. Relevant research has substantiated that sperm quality declines with advancing age (42). On the other hand, studies investigating the effects of environmental exposure on male reproductive health have revealed a significant correlation between exposure to air pollutants (e.g., PM2.5 and NO₂) and a reduction in sperm quality (43), while smoking can reduce sperm production by 30–40% (44). These factors are particularly prominent in some industrialized and highly polluted regions of China, partially accounting for its higher burden of secondary infertility. Meanwhile, the significant influence of socioeconomic status and healthcare investment on reproductive health is also confirmed in this study. Japan and South Korea, with their advanced economies and abundant medical resources, bear a lighter and decreasing burden. In contrast, Mongolia and North Korea, which are in the process of development or face economic constraints, confront an increasing burden.

As the most populous country in East Asia, China has experienced a cumulative increase in the burden of infertility due to delayed childbearing, persistent environmental pollution (especially air pollution), and persistently high male smoking rates (16,45,46). Despite facing severe population aging, Japan and South Korea have effectively controlled the disease burden through their advanced reproductive medical technologies and comprehensive environmental governance systems (15). As a developing country, Mongolia has the most pronounced upward trend in its burden because of environmental degradation during rapid urbanization and relatively scarce medical resources. In North Korea, due to insufficient economic and medical investment, basic reproductive health services are limited. Although the burden is at a moderate level, it is on the rise. In the absence of basic reproductive health services, the actual incidence of infertility is often underestimated. However, its potential risks (such as secondary infertility caused by infections) are inevitably increasing with inadequate medical investment (47).

The unequal distribution of the disease burden associated with male infertility across East Asian countries reflects substantial disparities in socioeconomic development, environmental policies, and medical resource allocation. Each country should formulate targeted prevention and control strategies according to its own characteristics. Specifically, China should enhance environmental governance and tobacco-control measures while improving the accessibility of diagnosis and treatment for secondary infertility. Japan and South Korea should concentrate on the reproductive health requirements of the late-childbearing population. Mongolia should increase investment in primary reproductive health services, and North Korea should seek international cooperation to improve basic medical conditions.

Applying the ARIMA model to predict the number of male infertility cases in China from 2023 to 2051, the results indicate that by 2051, the total number of male infertility cases in China is projected to remain at a substantial scale of 10.759 million (95% CI: 8.288–13.231 million). Among them, secondary infertility cases will be the majority, reaching 9.602 million (95% CI: 7.429–11.776 million), while primary infertility cases will be 1.152 million (95% CI: 742,000–1.563 million). Although the age-standardized prevalence rate (ASPR) shows a gradual downward trend during the prediction period, the absolute number of cases will remain at a high level for an extended period. This prediction suggests that in the coming decades, the pressure exerted by male infertility in China on the healthcare system, socioeconomic conditions, and family well-being will persist and cannot be overlooked. In particular, the burden of secondary infertility is heavy, as it is closely associated with acquired factors such as environmental pollution, lifestyle changes, and reproductive tract infections (43,44,48). As the world’s most populous country, China confronts multiple challenges, including a delayed childbearing age, cumulative environmental exposure, and high smoking rates, resulting in a severe situation in infertility prevention and control (16). Therefore, it is essential to conduct an in-depth analysis of the key factors driving the disease burden and develop targeted public health strategies, with an emphasis on strengthening early intervention for secondary infertility and improving the accessibility of reproductive health services to address the persistent infertility burden.

The predictive findings of this study can be juxtaposed with prior investigations into the burden of male infertility, which were also grounded in the GBD database. Several studies utilizing GBD data have revealed that the estimated global prevalence of male infertility stood at 56.53 million cases in 2019, marking a 76.9% surge from the figures recorded in 1990, with East Asia emerging as one of the regions shouldering the heaviest disease burden (49). An analysis predicated on GBD 2021 further underscored that China contributed to over one-fifth of the global prevalence and DALYs attributable to male infertility, with the age-standardized rate in China significantly surpassing the global mean (16). Collectively, these studies attest to the fact that the disease burden of male infertility in China ranks high on a global scale, aligning with the substantial case count observed in the present study. On a regional front, other research endeavors focusing on male infertility among Asian men aged 20–49 have discerned that East Asia bears the brunt of the disease burden, and the projected upward trajectory is anticipated to persist (50). This study, which centers on China, arrives at conclusions that are largely congruent with the assessments made in these regional-level studies, thereby reinforcing the gravity of the male infertility prevention and control landscape in China, a densely populated nation in East Asia.

Nevertheless, this study has certain limitations. Firstly, the completeness and quality of the GBD data are limitations. Although the GBD research team has made great efforts to collect and integrate global health data, the diversity of data sources and regional disparities have led to variations in data completeness and quality across different regions, diseases, and time periods. Such data gaps or quality issues may affect the accuracy and generalizability of research findings, especially when conducting in-depth analyses of specific diseases or populations. If the original data is biased, analyses based on these data may inherit and amplify such biases. Secondly, the complexity of models and attribution in the GBD database comorbidity data is another significant challenge. Disease comorbidity is a common phenomenon, but GBD studies typically employ complex statistical models to estimate disease burden rather than direct measurements. These models may be based on certain assumptions, and if these assumptions do not conform to reality, they may lead to biased results. Additionally, the data sources relied on by GBD (e.g., medical records, death certificates) themselves may carry risks of misclassification. The ARIMA prediction model provides a baseline forecast for future disease burden based on historical trends. However, future disease trajectories may be significantly influenced by numerous nonlinear factors that are not incorporated into current models. For example, breakthrough therapies in assisted reproductive technology, along with the extensive implementation of more stringent tobacco-control and air-pollution management policies, could fundamentally change the incidence and prognosis of male infertility-related conditions. Therefore, our predictions should be regarded as a warning rather than a definite future.

Conclusions

This research systematically examined the burden of infertility-related diseases associated with male infertility in East Asia from 1990 to 2023, along with its trends over the past three decades. Generally speaking, the disease burden of male-related infertility in East Asia demonstrates significant national heterogeneity and phased evolution. Among these countries, South Korea and Japan exhibit highly synchronized trends, especially with a remarkable recent increase in secondary infertility. China, after an initial rise, entered a long-term phase of slow decline. However, since 2020, all three types of infertility have shown signs of resurgence. The internal burden is mainly concentrated among men aged 30 to 44 in the middle of their reproductive years, with secondary infertility being predominant, which reflects the substantial influence of acquired factors. In contrast, Mongolia witnessed a general increase in various infertility rates between 2010 and 2015, potentially related to rapid urbanization and environmental deterioration. Meanwhile, North Korea experienced relatively stable changes in various infertility rates. These regional disparities profoundly mirror the comprehensive impacts of socioeconomic development, fertility policies, medical standards, and behavioral changes among the reproductive-age population in each country (49,51). They also offer crucial references for China to formulate precise reproductive health intervention strategies.

Acknowledgments

The authors thank the collaborators of the Global Burden of Disease (GBD) Study 2023 for their work and thank all the individuals who contributed to the GBD 2023 for their extensive support in finding, cataloguing and analysing data and facilitating communications.

Footnote

Reporting Checklist: The authors have completed the GATHER reporting checklist. Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0288/rc

Peer Review File: Available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0288/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tau.amegroups.com/article/view/10.21037/tau-2026-0288/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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