Global estimates of infertility burden and contributions of congenital, endocrine, metabolic and infectious factors

Infertility is a critical global public health issue imposing a heavy burden on health systems. This study aimed to estimate the global burden of infertility and analyze trends attributable to congenital, endocrine, metabolic, and infectious factors, to inform evidence-based policy and clinical care. We retrieved global data from the Global Burden of Disease (GBD) Study 2021 and 2023. Epidemiological metrics, including prevalence and disability-adjusted life years (DALYs). Correlation, inequality indices (slope index of inequality, SII; concentration index, CI), decomposition analysis, and autoregressive integrated moving average (ARIMA) modeling were applied to examine burden patterns, drivers, and future trends. In 2021, female infertility prevalence was 110,089,459 (DALYs: 601,134), and male prevalence was 55,000,818 (DALYs: 317,614). Age-standardized prevalence/DALYs per 100,000 were 2764.62/15.12 (female) and 1354.76/7.84 (male). Compared with 1990, annual percentage changes in prevalence and DALYs rates increased by 0.22 and 0.18 in females, and by 0.17 and 0.23 in males, respectively. Gender and age-specific analysis revealed females and the 35–39 age group had the highest burden. Higher age-standardized prevalence and DALYs rates were observed in low, middle, and high-middle socio-demographic index (SDI) regions. Inequality analysis showed a negative SII in 2021, with minimal changes in the CI. Population growth accounted for the majority of the increase in prevalence and DALYs globally from 1990 to 2021, contributing both 61.37% in females and 67.27% and 67.28% in males. Polycystic ovary syndrome was the leading cause of primary and secondary infertility among females, while chlamydia infection-related infertility increased with age and regional variation. For males, Klinefelter syndrome was the main cause of primary infertility. Projections for the next 15 years indicate age-standardized prevalence and DALYs rates of 2967.98 and 16.02 per 100,000 females, and 1442.29 and 7.83 per 100,000 males, respectively. Global infertility burden has risen, disproportionately affecting females, adults aged 35–39, and less developed regions. Targeted prevention and policy interventions are urgently needed to address congenital, endocrine, metabolic, and infectious drivers of infertility worldwide.