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

The study extracted global prevalence and disability-adjusted life years (DALYs) of infertility, along with their 95% uncertainty intervals (UIs) from the GBD database ( https://vizhub.healthdata.org/gbd-results/ ), spanning the period from 1990 to 2021 in the globe and SDI, and 1990 to 2023 in specific regions. Notably, because infertility is a non-fatal condition that does not directly result in premature mortality, the Years of Life Lost (YLL) is zero. Consequently, one DALY in this context represents the loss of one year of full health solely due to disability, meaning the DALYs reported in this study are comprised entirely of Years Lived with Disability (YLD). In line with the WHO standard and GBD 2021 and 2023 framework, infertility was defined as failure to achieve a clinical pregnancy after 12 months of regular unprotected intercourse, categorized into primary (no prior clinical pregnancy) and secondary (infertility after at least one previous pregnancy) subtypes. A unified age cut-off of 15–49 years (international reproductive-age standard) was applied to ensure comparability with existing literature; individuals outside this range were excluded. We included age/sex-stratified burden data and etiological data for congenital, endocrine, metabolic, and infectious causes. Infertility cases attributable to factors outside our scope were retained in overall burden estimates but excluded from etiological analyses. The SDI was employed as a metric to assess the socio-economic status of countries, with a higher score indicating more robust socio-economic development. Derived from national-level indicators encompassing per capita income, average educational attainment, and total fertility rate, the SDI assumes values ranging from 0 to 1. Countries were stratified into five quintiles based on the GBD studies: High SDI (> 0.81), High-middle SDI (0.70–0.81), Middle SDI (0.61–0.69), Low-middle SDI (0.46–0.60), and Low SDI (< 0.46) (Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021 2024 ; Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021 2024 ). To examine the correlation between SDI and the burden of infertility, locally estimated scatterplot smoothing (loess) models were applied, utilizing the geom_smooth function within the ggplot2 package. This analysis fitted the relationship across 21 regions, and 204 countries and territories. Furthermore, correlation analysis was conducted to quantify the strength and direction of the association between the burden of infertility and SDI 2023. In accordance with the recommendations of the World Health Organization, the SII and the CI were employed to assess absolute and relative income-related inequalities across nations (Organization WH 2023 ). The SII, an absolute measure of inequality, quantifies the difference in the estimated indicator values between the most and least privileged groups, taking into account all population subgroups. Its calculation involves proportionally weighting subgroups based on their population distribution (Global pattern, trend, and cross-country inequality of early musculoskeletal disorders from 1990 to 2019, with projection from 2020 to 2050 2024 ). And, the CI serves as a relative measure of inequality, reflecting the distribution of health indicators across socioeconomic status. It involves ranking the population by SDI, calculating the cumulative proportion of the population and the cumulative proportion of health outcomes for each group, and then plotting a Lorenz curve. The CI is twice the area between the Lorenz curve and the diagonal line (Ordunez et al. 2019 ). A positive CI indicates that the indicator is more concentrated among advantaged groups, whereas a negative value signifies concentration among disadvantaged groups. The bigger the absolute value of the CI, the higher the degree of inequality. To quantify the driving forces behind the variation in the number of patients with infertility, we estimated the relative contributions of aging, population, and epidemiological change. For this decomposition analysis, we employed the classical and widely used methodology developed by Das Gupta (Das 1978 ), which utilizes algebraic decomposition techniques to dissect the overall change into standardized impacts attributable to each factor, thereby identifying the contribution of each component. The ARIMA model is a common epidemiology technique for forecasting time-series data (Foreman et al. 2018 ). Specifically, the ARIMA model combines autoregressive (AR) and moving average (MA) elements with differencing (d) to stabilize the series. In an ARIMA (p, d, q) model, "p" represents the number of autoregressive terms, "d" denotes the order of differencing, and "q" signifies the number of moving average terms. The ASPR (age-standardized prevalence rate) and ASR of DALYs represent predicted values per 100,000 individuals in the population, including their 95% UI. All analytical procedures and graphical representations were executed using the statistical computing software R (version 4.4.1).

In 2021, the global prevalence of female infertility was estimated at 110,089,459 cases, with an ASPR of 2,764.62. For male infertility, the prevalence was 55,000,818 cases, corresponding to an ASPR of 1,354.76. Regarding DALYs, global female DALYs amounted to 601,134, and the ASR of DALYs was 15.12. Male DALYs totaled 317,614, and the ASR of DALYs of 7.84 (Table  1 , Fig.  1 ). From 1990, the global prevalence of female infertility was 59,690,000 cases, with an ASPR of 2,267.26 (Table  1 , Figure S1). Between 1990 and 2021, the ASPR increased by 0.22 (Table  1 , Figure S2). For male infertility, the prevalence was 31,490,382 cases, with an ASPR of 1,158.86, experiencing an increase of 0.17 over the same period (Table  1 , Fig.  1 ). In 1990, female infertility DALYs were 325,937, and the ASR of DALYs was 12.32. This ASR of DALYs increased by 0.18 from 1990 to 2021. For male infertility, DALYs were 181,869, and the ASR of DALYs was 6.65, experiencing an increase of 0.23 (Table  1 , Figure S1-2). Table 1 Prevalent cases, age-standardized prevalence rates, DALYs, and age-standardized rates of DALYs for infertility in 1990 and 2021 for both sexes and rate change of age-standardized rates by Global Burden of Disease. DALYs: Disability-adjusted life years 1990 2021 1990–2021 All-ages cases Age-standardized rates per 100,000 All-ages cases Age-standardized rates per 100,000 Rate change in age-standardized rates N (95%UI) N (95%UI) N (95%UI) Global Prevalence (female) 59,690,000 (32,625,584 to 104,614,493) 2267.26 (1219.63 to 3969.94) 110,089,459(58,608,815 to 195,025,585) 2764.62 (1476.33 to 4862.57) 0.22 (0.12 to 0.32) DALYs (female) 325,937 (114,823 to 807,747) 12.32 (4.39 to 30.93) 601,134 (213,158 to 1,468,475) 15.12 (5.35 to 36.88) 0.23 (0.13 to 0.34) Prevalence (male) 31,490,382 (18,725,068 to 50,165,061) 1158.86 (696.62 to 1858.35) 55,000,818 (32,611,257 to 88,727,953) 1354.76 (802.12 to 2174.77) 0.17 (0.09 to 0.25) DALYs (male) 181,869 (66,532 to 425,579) 6.65 (2.47 to 15.61) 317,614 (116,288 to 752,758) 7.84 (2.85 to 18.56) 0.18 (0.1 to 0.26) Socio-demographic Index (SDI)  High SDI Prevalence (female) 5,090,008 (2,095,085 to 10,270,333) 1049.61 (433.47 to 2114.52) 7,476,943 (2,888,374 to 14,892,481) 1415.8 (542.85 to 2854.67) 0.35 (0.18 to 0.5) DALYs (female) 28,320 (8576 to 75,480) 5.85 (1.77 to 15.46) 41,101 (11,612 to 110,625) 7.83 (2.2 to 21.41) 0.34 (0.17 to 0.5) Prevalence (male) 4,507,508 (2,671,002 to 7,483,432) 913.1 (540.97 to 1503.48) 5,890,821 (3,376,658 to 10,016,230) 1071.23 (617.22 to 1766.67) 0.17 (0.1 to 0.24) DALYs (male) 26,979 (10,068 to 64,671) 5.48 (2.05 to 13.12) 34,878 (12,752 to 84,167) 6.4 (2.3 to 15.53) 0.17 (0.09 to 0.24)  High-middle SDI Prevalence (female) 16,546,621 (8,904,341 to 29,353,027) 2899.74 (1553.44 to 5158.24) 21,200,266 (10,465,956 to 38,450,758) 3180.18 (1643.03 to 5750.65) 0.1 (0 to 0.2) DALYs (female) 88,611 (30,730 to 229,796) 15.51 (5.41 to 40.19) 112,846 (38,219 to 282,874) 17.04 (5.87 to 41.71) 0.1 (0.01 to 0.21) Prevalence (male) 8,274,380 (4,805,665 to 13,829,973) 1402.44 (813.39 to 2341.64) 10,194,899 (5,795,901 to 17,173,215) 1472.79 (851.46 to 2414.28) 0.05 (−0.01 to 0.11) DALYs (male) 46,705 (16,702 to 115,887) 7.9 (2.88 to 19.66) 57,219 (21,039 to 141,093) 8.35 (3.02 to 20.74) 0.06 (−0.01 to 0.12)  Middle SDI Prevalence (female) 22,576,313 (12,416,219 to 39,052,724) 2664.97 (1427.1 to 4649.19) 39,038,802 (20,324,320 to 70,133,766) 3027.65 (1579.65 to 5404.99) 0.14 (0.02 to 0.26) DALYs (female) 121,994 (42,876 to 302,346) 14.3 (4.94 to 35.35) 211,708 (75,088 to 517,044) 16.47 (5.84 to 39.99) 0.15 (0.03 to 0.27) Prevalence (male) 10,643,923 (6,194,862 to 17,124,722) 1189.81 (698.93 to 1920.87) 18,151,666 (10,796,198 to 29,302,986) 1387.96 (819.52 to 2230.9) 0.17 (0.06 to 0.27) DALYs (male) 60,482 (21,611 to 143,641) 6.7 (2.43 to 16.14) 103,980 (38,249 to 249,703) 7.98 (2.9 to 19.24) 0.19 (0.08 to 0.31)  Low-middle SDI Prevalence (female) 10,739,460 (6,073,679 to 17,862,342) 2046.98 (1142.61 to 3550.73) 30,053,933 (16,629,265 to 51,679,485) 2940.52 (1623.86 to 5103.43) 0.44 (0.28 to 0.64) DALYs (female) 60,815 (21,169 to 143,024) 11.45 (4.01 to 27.23) 167,400 (58,563 to 403,460) 16.34 (5.7 to 39.57) 0.43 (0.27 to 0.62) Prevalence (male) 5,483,316 (3,304,295 to 8,526,906) 1019.46 (625.06 to 1572.81) 14,297,089 (8,370,702 to 22,875,418) 1395.96 (813.3 to 2252.12) 0.37 (0.23 to 0.53) DALYs (male) 32,734 (12,419 to 74,440) 6.01 (2.27 to 13.79) 84,065 (30,521 to 196,576) 8.18 (2.98 to 19.2) 0.36 (0.23 to 0.51)  Low SDI Prevalence (female) 4,687,801 (2,748,180 to 7,808,070) 2220.14 (1287.09 to 3716.05) 12,249,744 (6,801,478 to 20,619,052) 2333.95 (1299.03 to 3969.36) 0.05 (−0.04 to 0.15) DALYs (female) 25,922 (9533 to 58,929) 12.12 (4.52 to 27.6) 67,696 (24,767 to 161,485) 12.8 (4.73 to 31.1) 0.06 (−0.03 to 0.14) Prevalence (male) 2,553,100 (1,625,425 to 3,816,042) 1245.8 (798.69 to 1859.93) 6,427,824 (3,885,082 to 9,979,635) 1269.37 (770.19 to 1959.84) 0.02 (−0.06 to 0.1) DALYs (male) 14,805 (5551 to 33,573) 7.13 (2.73 to 16.32) 37,248 (13,729 to 85,517) 7.28 (2.7 to 16.88) 0.02 (−0.06 to 0.1) Fig. 1 Global distribution of infertility disease burden in 2021. A ASPR in males; B ASR of DALYs in males; C ASPR in females; D ASR of DALYs in females. ASPR: Age-standardized prevalence rates, ASR: Age-standardized rates, DALYs: Disability-adjusted life years Prevalent cases, age-standardized prevalence rates, DALYs, and age-standardized rates of DALYs for infertility in 1990 and 2021 for both sexes and rate change of age-standardized rates by Global Burden of Disease. DALYs: Disability-adjusted life years Global distribution of infertility disease burden in 2021. A ASPR in males; B ASR of DALYs in males; C ASPR in females; D ASR of DALYs in females. ASPR: Age-standardized prevalence rates, ASR: Age-standardized rates, DALYs: Disability-adjusted life years In 2021, at the SDI level, the highest ASPR for infertility was observed in the High-middle SDI category, with 3,180.18 among females and 1,472.79 among males (Table  1 , Fig. 1 ). Similar trends were observed in 1990, with the highest ASPR in the High-middle SDI category for both sexes: 2,899.74 among females and 1,402.44 among males (Table  1 , Figure S1). From 1990 to 2021, the fastest increase in ASPR was observed in the Low-middle SDI region, with a rise of 0.44 among females and 0.37 among males. The slowest increase was recorded in the Low SDI region, with 0.05 among females and 0.02 among males (Table  1 , Figure S2). Regarding the ASR of DALYs for infertility in 2021, the High-middle SDI category continued to exhibit the highest rates, with 17.04 among females and 8.35 among males (Table 1, Fig. 1 ). In 1990, the High-middle SDI category also had the highest ASR of DALYs (Table 1, Figure S1). From 1990 to 2021, the fastest growth in ASR of DALYs was recorded in the Low-middle SDI region, with a rise of 0.43 among females and 0.36 among males. The slowest growth was observed in the Low SDI region, with 0.06 among females and 0.02 among males (Table  1 , Figure S2). Geographically, in 2023 the highest ASPR for female infertility was recorded in East Asia, at 4132.12, followed by Eastern Europe and South Asia, with 3603.84 and 3498.98, respectively (Table  2 ). Among males, the three regions with the highest ASPRs were Eastern Europe with 2057.62, Western Sub-Saharan Africa with 1926.77, and East Asia with 1592.68 (Table  2 ). The top three regions with the highest ASPR for female infertility in 1990 were East Asia with 3,940.35, Eastern Europe with 3,322.64, and Southern Sub-Saharan Africa with 2,732.55. For male infertility, the top three regions were Eastern Europe with 2,048.71, Western Sub-Saharan Africa with 1,840.44, and East Asia with 1,505.44. Between 1990 and 2023, the most pronounced increase in ASPR for female infertility was observed in Andean Latin America, with a rise of 6.39, followed by Central Latin America with 1.16 and High-income North America with 0.8. Among males, the top three regions with increasing ASPRs were Andean Latin America with 0.66, Central Latin America with 0.55, and South Asia with 0.48. Table 2 Prevalent cases, age-standardized prevalence rates, DALYs, and age-standardized rates of DALYs for infertility in 1990 and 2023 of 21 regions for both sexes and rate change of age-standardized rates by Global Burden of Disease. DALYs: Disability-adjusted life years 1990 2023 1990–2023 All-ages cases Age-standardized rates per 100,000 All-ages cases Age-standardized rates per 100,000 Rate change in age-standardized rates N (95%UI) N (95%UI) N (95%UI) GBD Regions  Andean Latin America Prevalence (female) 11,645 (6577 to 25,547) 69.03 (38.32 to 148.11) 179,743 (18,640 to 650,348) 509.24 (52.66 to 1842.08) 6.39 (−0.06 to 22.5) DALYs (female) 64 (20 to 170) 0.38 (0.12 to 0.98) 957 (80 to 3577) 2.71 (0.23 to 10.14) 6.21 (−0.06 to 21.26) Prevalence (male) 66,689 (48,788 to 88,479) 396.61 (290.98 to 521.42) 228,461 (123,420 to 391,874) 659.52 (355.38 to 1133.84) 0.66 (0.07 to 1.64) DALYs (male) 382 (152 to 823) 2.26 (0.89 to 4.87) 1275 (445 to 3205) 3.68 (1.28 to 9.24) 0.63 (0.07 to 1.51)  Australasia Prevalence (female) 14,969 (3920 to 63,777) 131.95 (34.75 to 548.79) 25,817 (6272 to 104,555) 157.16 (39.83 to 603.48) 0.19 (−0.15 to 0.83) DALYs (female) 85 (14 to 364) 0.75 (0.12 to 3.24) 143 (22 to 542) 0.87 (0.14 to 3.36) 0.17 (−0.2 to 0.87) Prevalence (male) 66,017 (37,613 to 110,358) 588.59 (332.02 to 995.27) 98,068 (55,320 to 165,283) 625.79 (351.03 to 1063.26) 0.06 (−0.01 to 0.14) DALYs (male) 395 (146 to 979) 3.54 (1.29 to 8.71) 581 (217 to 1386) 3.74 (1.39 to 8.85) 0.06 (−0.03 to 0.16)  Caribbean Prevalence (female) 428,429 (267,614 to 698,029) 2384.28 (1481.38 to 3866.87) 602,891 (353,592 to 1,045,390) 2412.34 (1415.57 to 4191.63) 0.01 (−0.09 to 0.1) DALYs (female) 2394 (903 to 5819) 13.22 (5.08 to 32.55) 3296 (1293 to 8524) 13.2 (5.15 to 34.1) 0 (−0.11 to 0.08) Prevalence (male) 231,263 (145,912 to 352,736) 1330.56 (857.61 to 2009.98) 323,896 (199,670 to 504,715) 1331.95 (820.97 to 2072.82) 0 (−0.06 to 0.07) DALYs (male) 1377 (532 to 3136) 7.85 (3.02 to 17.75) 1867 (742 to 4203) 7.68 (3.05 to 17.27) −0.01 (−0.08 to 0.04)  Central Asia Prevalence (female) 515,912 (264,788 to 951,106) 1456 (731.59 to 2700.55) 811,081 (347,800 to 1,663,385) 1568.29 (699.61 to 3121.83) 0.08 (−0.08 to 0.22) DALYs (female) 2861 (964 to 7099) 8.03 (2.65 to 20.02) 4421 (1383 to 11,358) 8.59 (2.72 to 22.15) 0.07 (−0.09 to 0.22) Prevalence (male) 317,276 (189,426 to 515,684) 932.15 (558.25 to 1504.94) 490,002 (279,053 to 878,538) 943.56 (536.81 to 1649.62) 0.01 (−0.06 to 0.08) DALYs (male) 1869 (702 to 4282) 5.45 (2.09 to 12.22) 2825 (1039 to 6556) 5.47 (2.01 to 12.62) 0.01 (−0.07 to 0.08)  Central Europe Prevalence (female) 1,311,219 (598,614 to 2,598,281) 2054.38 (964.81 to 3963.58) 1,299,459 (588,593 to 2,427,450) 2533.68 (1205.55 to 4841.59) 0.23 (0.09 to 0.39) DALYs (female) 7097 (2214 to 18,258) 11.18 (3.56 to 28.09) 6971 (2274 to 18,313) 13.71 (4.3 to 34.61) 0.22 (0.09 to 0.36) Prevalence (male) 772,589 (413,731 to 1,338,292) 1192.22 (639.02 to 2009.25) 738,309 (402,724 to 1,363,443) 1377.66 (746.39 to 2397.11) 0.15 (0.06 to 0.26) DALYs (male) 4399 (1568 to 10,955) 6.83 (2.41 to 16.85) 4127 (1452 to 10,161) 7.79 (2.63 to 19.45) 0.14 (0.05 to 0.26)  Central Latin America Prevalence (female) 619,982 (225,562 to 1,276,674) 832.3 (309.93 to 1746.98) 2,565,569 (1,004,802 to 5,683,000) 1795.29 (702.27 to 3984.76) 1.16 (0.64 to 2.01) DALYs (female) 3368 (841 to 9450) 4.49 (1.13 to 12.67) 13,603 (3914 to 38,715) 9.53 (2.76 to 27.31) 1.14 (0.66 to 1.95) Prevalence (male) 536,999 (324,076 to 851,371) 723.65 (439.5 to 1145.16) 1,505,196 (847,551 to 2,612,113) 1119.26 (628.4 to 1951.22) 0.55 (0.32 to 0.75) DALYs (male) 3123 (1168 to 7315) 4.16 (1.57 to 9.81) 8444 (3144 to 20,575) 6.28 (2.33 to 15.29) 0.52 (0.31 to 0.73)  Central Sub-Saharan Africa Prevalence (female) 591,991 (313,522 to 1,069,334) 2674.03 (1356.24 to 4971.78) 1,792,912 (893,717 to 3,344,288) 2871.53 (1397.66 to 5380.37) 0.07 (−0.03 to 0.18) DALYs (female) 3163 (1051 to 7692) 14.13 (4.47 to 33.38) 9613 (3319 to 26,025) 15.26 (5.07 to 40.48) 0.08 (−0.02 to 0.17) Prevalence (male) 303,907 (178,728 to 485,298) 1408.9 (825.74 to 2239.33) 895,276 (490,540 to 1,508,363) 1420.73 (777.75 to 2470.25) 0.01 (−0.06 to 0.07) DALYs (male) 1706 (611 to 4003) 7.79 (2.8 to 18.83) 5013 (1716 to 12,852) 7.87 (2.85 to 19.68) 0.01 (−0.05 to 0.09)  East Asia Prevalence (female) 25,455,243 (13,651,646 to 44,268,551) 3940.35 (2027.52 to 6919.97) 29,978,669 (14,557,452 to 54,814,041) 4132.12 (2112.71 to 7284.14) 0.05 (−0.05 to 0.16) DALYs (female) 132,935 (44,100 to 341,116) 20.52 (6.83 to 53.23) 157,284 (52,419 to 426,436) 21.8 (7.57 to 59.63) 0.06 (−0.04 to 0.16) Prevalence (male) 10,509,539 (5,795,154 to 17,988,762) 1505.44 (828.85 to 2582.69) 12,205,064 (6,259,729 to 22,013,710) 1592.68 (855.72 to 2757.02) 0.06 (−0.02 to 0.15) DALYs (male) 56,532 (19,351 to 138,347) 8.07 (2.78 to 19.79) 65,604 (22,048 to 169,209) 8.63 (2.98 to 21.71) 0.08 (−0.01 to 0.17)  Eastern Europe Prevalence (female) 4,008,864 (2,013,408 to 7,351,356) 3322.64 (1695.06 to 5951.07) 3,620,465 (1,825,833 to 6,625,862) 3603.84 (1910.34 to 6403.58) 0.09 (−0.01 to 0.21) DALYs (female) 22,401 (7776 to 56,945) 18.69 (6.52 to 47.12) 19,980 (7010 to 50,377) 20.21 (7.02 to 49.03) 0.08 (−0.01 to 0.19) Prevalence (male) 2,436,821 (1,340,147 to 4,110,201) 2048.71 (1134.63 to 3451.39) 1,998,077 (1,135,423 to 3,298,923) 2057.62 (1148.06 to 3416.9) 0 (−0.06 to 0.05) DALYs (male) 14,342 (4988 to 36,044) 12.14 (4.22 to 30.2) 11,637 (4147 to 28,730) 12.19 (4.26 to 29.75) 0.01 (−0.05 to 0.05)  Eastern Sub-Saharan Africa Prevalence (female) 1,956,158 (1,312,452 to 2,936,820) 2486.78 (1666.91 to 3803.93) 5,877,983 (3,084,479 to 10,665,400) 2753.83 (1387.08 to 5107.05) 0.11 (−0.19 to 0.33) DALYs (female) 10,614 (4134 to 23,829) 13.32 (5.22 to 29.97) 31,966 (11,807 to 81,657) 14.83 (5.22 to 37.79) 0.11 (−0.17 to 0.33) Prevalence (male) 717,200 (457,300 to 1,082,606) 977.48 (625.39 to 1463.76) 2,002,350 (1,137,751 to 3,285,047) 990.06 (554.46 to 1676.56) 0.01 (−0.15 to 0.15) DALYs (male) 4081 (1517 to 9218) 5.49 (2.05 to 12.64) 11,383 (3785 to 28,338) 5.57 (1.92 to 13.75) 0.02 (−0.13 to 0.16)  High-income Asia Pacific Prevalence (female) 658,058 (58,320 to 1,978,968) 653.31 (61.92 to 1944.41) 538,085 (52,996 to 1,569,209) 612.47 (65.33 to 1816.55) −0.06 (−0.33 to 0.3) DALYs (female) 3524 (223 to 13,741) 3.51 (0.24 to 14.01) 2815 (192 to 10,648) 3.21 (0.24 to 11.01) −0.07 (−0.32 to 0.31) Prevalence (male) 939,652 (506,916 to 1,612,720) 954.64 (521.56 to 1618.01) 771,429 (426,199 to 1,476,867) 903.23 (512.86 to 1704.84) −0.05 (−0.12 to 0.02) DALYs (male) 5342 (1846 to 13,069) 5.46 (1.89 to 13.38) 4332 (1581 to 11,632) 5.16 (1.91 to 13.12) −0.05 (−0.12 to 0.02)  High-income North America Prevalence (female) 838,950 (80,704 to 2,240,173) 514.57 (50.56 to 1391.66) 1,621,413 (297,941 to 3,962,032) 927.57 (177.88 to 2187.25) 0.8 (0.35 to 2.75) DALYs (female) 4977 (394 to 15,754) 3.06 (0.24 to 9.6) 9310 (1274 to 27,295) 5.35 (0.77 to 15.66) 0.76 (0.35 to 2.64) Prevalence (male) 1,259,676 (681,361 to 2,083,776) 786.35 (428.27 to 1313.71) 1,797,135 (1,005,133 to 2,963,252) 1011.17 (558.03 to 1701.62) 0.29 (0.16 to 0.43) DALYs (male) 7922 (2749 to 19,766) 4.95 (1.71 to 12.43) 11,016 (3876 to 25,920) 6.23 (2.14 to 14.71) 0.27 (0.15 to 0.41)  North Africa and Middle East Prevalence (female) 1,927,243 (1,224,847 to 2,787,806) 1286.77 (839.19 to 1850.18) 6,289,460 (3,039,611 to 11,377,050) 1905.37 (920.92 to 3460.22) 0.48 (0.06 to 0.87) DALYs (female) 11,455 (4240 to 25,501) 7.54 (2.85 to 16.38) 35,422 (12,133 to 92,234) 10.76 (3.69 to 28.18) 0.43 (0.02 to 0.8) Prevalence (male) 1,461,619 (988,197 to 2,118,152) 903.37 (616.17 to 1278.62) 4,226,446 (2,500,552 to 6,761,741) 1150 (673.26 to 1849.59) 0.27 (0.02 to 0.51) DALYs (male) 9266 (3620 to 20,160) 5.65 (2.24 to 12.41) 25,344 (9363 to 56,690) 6.93 (2.54 to 15.44) 0.23 (0 to 0.45)  Oceania Prevalence (female) 48,370 (21,045 to 90,181) 1662.48 (712.57 to 3140.97) 79,118 (44,362 to 128,623) 1083.74 (602.68 to 1748.86) −0.35 (−0.53 to −0.01) DALYs (female) 267 (79 to 661) 9.09 (2.66 to 23.39) 436 (165 to 1056) 5.97 (2.26 to 14.5) −0.35 (−0.52 to 0) Prevalence (male) 28,943 (16,774 to 47,141) 940.62 (546.36 to 1505.52) 53,334 (36,954 to 75,101) 714.05 (495.27 to 1010.06) −0.24 (−0.43 to 0.01) DALYs (male) 166 (58 to 386) 5.36 (1.91 to 12.73) 305 (128 to 651) 4.07 (1.73 to 8.6) −0.24 (−0.41 to 0)  South Asia Prevalence (female) 11,114,297 (5,715,754 to 19,378,720) 2217.74 (1134.75 to 3927.32) 36,001,495 (20,809,434 to 62,792,381) 3498.98 (2025.56 to 6133.12) 0.58 (0.28 to 0.97) DALYs (female) 63,660 (19,959 to 148,994) 12.56 (3.93 to 30.53) 201,458 (73,925 to 484,520) 19.55 (7.23 to 46.83) 0.56 (0.3 to 0.91) Prevalence (male) 5,354,172 (3,009,881 to 8,820,631) 991.39 (567.54 to 1611.73) 15,512,983 (8,867,600 to 25,518,164) 1462.87 (848.72 to 2395.84) 0.48 (0.24 to 0.75) DALYs (male) 32,404 (11,819 to 74,722) 5.93 (2.14 to 13.93) 91,437 (33,043 to 204,211) 8.61 (3.13 to 19.29) 0.46 (0.24 to 0.71)  Southeast Asia Prevalence (female) 5,036,961 (2,626,029 to 8,899,881) 2186.16 (1157.11 to 3854.25) 11,664,053 (5,686,463 to 21,619,429) 3049.39 (1503.56 to 5676.1) 0.4 (0.22 to 0.57) DALYs (female) 28,085 (9537 to 69,716) 12.11 (4.2 to 30.16) 64,263 (22,471 to 176,089) 16.83 (5.84 to 45.78) 0.39 (0.22 to 0.57) Prevalence (male) 2,384,426 (1,376,796 to 3,855,373) 1048.85 (604.24 to 1714.31) 5,651,874 (3,237,983 to 9,281,977) 1446.16 (829.84 to 2365.92) 0.38 (0.23 to 0.52) DALYs (male) 14,074 (5053 to 32,607) 6.14 (2.17 to 14.34) 32,744 (11,938 to 79,368) 8.39 (3.06 to 20.43) 0.38 (0.24 to 0.51)  Southern Latin America Prevalence (female) 282,045 (78,216 to 599,780) 1150.19 (311.68 to 2468.19) 401,579 (92,259 to 945,038) 1051.65 (243.56 to 2477.27) −0.09 (−0.32 to 0.05) DALYs (female) 1582 (328 to 4683) 6.43 (1.31 to 19.04) 2223 (359 to 6599) 5.84 (0.94 to 17.42) −0.09 (−0.35 to 0.05) Prevalence (male) 242,928 (136,166 to 415,118) 1016.39 (575.35 to 1727.87) 376,271 (207,520 to 646,741) 1017.36 (556.55 to 1774.3) 0 (−0.06 to 0.07) DALYs (male) 1442 (517 to 3588) 6.02 (2.13 to 14.96) 2219 (831 to 5219) 6.02 (2.26 to 14.39) 0.01 (−0.07 to 0.08)  Southern Sub-Saharan Africa Prevalence (female) 691,791 (339,581 to 1,243,466) 2732.55 (1346.85 to 4937.82) 1,549,583 (731,015 to 2,867,143) 3004.7 (1428.88 to 5556.74) 0.1 (−0.03 to 0.22) DALYs (female) 3810 (1345 to 9669) 14.9 (5.34 to 37.97) 8408 (2817 to 22,417) 16.32 (5.5 to 43.55) 0.09 (−0.03 to 0.21) Prevalence (male) 242,946 (138,827 to 396,823) 1023.78 (592.99 to 1704.41) 554,778 (299,933 to 971,537) 1113.99 (602.09 to 1941.78) 0.09 (−0.03 to 0.21) DALYs (male) 1409 (509 to 3474) 5.88 (2.16 to 14.62) 3161 (1127 to 7983) 6.35 (2.26 to 16) 0.08 (−0.02 to 0.21)  Tropical Latin America Prevalence (female) 1,042,453 (543,526 to 1,869,616) 1341.42 (708.43 to 2412.64) 2,113,714 (900,941 to 4,403,735) 1703.05 (734.32 to 3515.95) 0.27 (−0.03 to 0.52) DALYs (female) 5989 (2095 to 15,567) 7.66 (2.7 to 20.06) 11,584 (3662 to 34,312) 9.39 (2.97 to 27.1) 0.23 (−0.06 to 0.46) Prevalence (male) 616,956 (342,574 to 1,048,655) 811.64 (467.99 to 1334.73) 1,304,951 (731,882 to 2,159,859) 1113.55 (633.51 to 1884.19) 0.37 (0.22 to 0.56) DALYs (male) 3770 (1378 to 9099) 4.92 (1.82 to 11.86) 7604 (2870 to 18,504) 6.52 (2.48 to 15.81) 0.33 (0.19 to 0.52)  Western Europe Prevalence (female) 1,725,906 (765,757 to 3,309,948) 857.31 (379.43 to 1654.61) 2,570,192 (775,631 to 5,537,151) 1236.64 (362.02 to 2703.28) 0.44 (−0.05 to 0.72) DALYs (female) 9963 (3055 to 24,796) 4.95 (1.51 to 12.37) 14,442 (3412 to 37,421) 7.02 (1.67 to 18.59) 0.42 (−0.05 to 0.71) Prevalence (male) 1,548,472 (985,968 to 2,357,811) 759.86 (482.71 to 1159.86) 1,960,016 (1,097,348 to 3,260,641) 975.71 (545.12 to 1591.85) 0.28 (0.07 to 0.44) DALYs (male) 9633 (3653 to 22,178) 4.73 (1.79 to 11.01) 11,903 (4444 to 27,670) 5.99 (2.24 to 13.96) 0.28 (0.05 to 0.45)  Western Sub-Saharan Africa Prevalence (female) 1,409,512 (720,926 to 2,539,665) 1725.65 (884.55 to 3165.94) 4,893,512 (2,154,908 to 9,693,113) 2047.57 (854.8 to 4105.46) 0.19 (−0.14 to 0.42) DALYs (female) 7643 (2645 to 18,891) 9.21 (3.12 to 22.65) 26,412 (8512 to 73,804) 10.94 (3.17 to 30.54) 0.19 (−0.12 to 0.4) Prevalence (male) 1,452,293 (995,233 to 2,071,791) 1840.44 (1266.65 to 2640.41) 4,206,910 (2,469,887 to 6,671,436) 1926.77 (1124.57 to 3174.28) 0.05 (−0.12 to 0.21) DALYs (male) 8232 (3105 to 18,390) 10.32 (3.93 to 23.31) 23,823 (8906 to 55,040) 10.79 (4.06 to 24.9) 0.05 (−0.11 to 0.2) Prevalent cases, age-standardized prevalence rates, DALYs, and age-standardized rates of DALYs for infertility in 1990 and 2023 of 21 regions for both sexes and rate change of age-standardized rates by Global Burden of Disease. DALYs: Disability-adjusted life years In 2023, the top three regions with the highest ASR of DALYs for female infertility were East Asia with 21.8, Eastern Europe with 20.21, and South Asia with 19.55. Among males, the top three regions were Eastern Europe with 12.19, Western Sub-Saharan Africa with 10.79, and South Asia with 8.63. Geographically, the top three regions with the highest ASR of DALYs for female infertility in 1990 were East Asia, Eastern Europe, and Southern Sub-Saharan Africa, while for males, they were Eastern Europe, Western Sub-Saharan Africa, and East Asia (Table  2 ). From 1990 to 2023, the fastest growth in ASR of DALYs was recorded in Andean Latin America with 6.21, followed by Central Latin America with 1.14 and High-income North America with 0.76 among females. The top three regions with increasing ASPRs were Andean Latin America with 0.63, Central Latin America with 0.52, and South Asia with 0.46 among males. In 2023, the top three countries with the highest prevalence of female infertility were India with 29,691,696, China with 29,181,468, and Indonesia with 6,499,566. For males, the top three were India with 12,708,601, China with 11,898,432, and Indonesia with 3,231,121 (Table S1). Regarding the ASPR of female infertility, the top three countries were the Central African Republic with 5,696.71, Djibouti with 5,270.79, and Gabon with 5,034.29 (Table  2 , Table S2). For males, the top three were Cameroon with 3,257.57, the Central African Republic with 2812.11, and Liberia with 2786.67(Table S2). In 1990, both female and male infertility prevalence was highest in China, India, and the Russian Federation. For ASPR of female infertility, Djibouti, Gabon, and Maldives topped the list, while for males, Cameroon, Guinea, and Niger were the highest (Tables S3 and S4). From 1990 to 2023, the countries with the fastest increase in female infertility ASPR were Peru with 14.54, Colombia with 5.41, and Ecuador with 3.71. For males, the fastest increases were observed in Peru with 1.05, Colombia with 1, and Finland with 0.97 (Table S5). In 2023, India, China, and Indonesia had the highest DALYs for both sexes. For females, the values were 164,748, 153,113, and 35,433, respectively. For males, the values were 74,325, 63,958, and 18,512, respectively (Table S2). Among females, the top three countries with the highest ASR of DALYs were the Central African Republic with 31.4, Djibouti with 28.4, and Gabon with 26.99. For males, the top three were Cameroon with 18.96, Central African Republic with 16, and Mauritania with 15.59 (Table S2). In 1990, the top three countries for both female and male infertility DALYs were consistent with the prevalence rankings, namely China, India, and the Russian Federation (Table S3). The ASR of DALYs also mirrored this trend, with Djibouti, Maldives, and Gabon topping the list for females, and Cameroon, Guinea, and Niger for males (Table S4). From 1990 to 2023, Peru showed the largest increase in ASR of DALYs for females with 14.17, followed by Colombia with 5.15 and Ecuador with 3.52. For males, Peru led with 1, followed by Colombia with 0.93, and Finland with 0.92. (Table S5). In 2021, the global prevalence and DALYs for both females and males aged 35–39 years peaked in both number and rate (Fig.  2 A-D). This trend was consistent in 1990 (Fig.  2 E-H). Across all ages, females exhibited higher prevalence and DALYs in both number and rate compared to males in 2021 and 1990, except for the 15–19 and 45–49 age groups where males marginally surpassed females in number and rate (Fig.  2 ). Fig. 2 Sex- and age-structured analysis of infertility disease global burden in 2021 and 1990. A Prevalence cases in 2021; B DALYs cases in 2021; C Prevalence rates in 2021; D DALYs rates in 2021; E Prevalence cases in 1990; F DALYs cases in 1990; G Prevalence rates in 1990; (H) DALYs rates in 1990. DALYs: Disability-adjusted life years Sex- and age-structured analysis of infertility disease global burden in 2021 and 1990. A Prevalence cases in 2021; B DALYs cases in 2021; C Prevalence rates in 2021; D DALYs rates in 2021; E Prevalence cases in 1990; F DALYs cases in 1990; G Prevalence rates in 1990; (H) DALYs rates in 1990. DALYs: Disability-adjusted life years From 1990 to 2021, the global prevalence and DALYs for both female and male cases across all ages demonstrated an overall upward trend. The ASPR and ASR of DALYs for both sexes fluctuated until 2010, followed by a consistent increase thereafter (Fig.  3 A, B). Specifically, among the 15–19 age group, the prevalence and DALYs in males showed a fluctuating increase, while females experienced a slight decline until 2010, followed by an increase. Regarding rates, females displayed a slight increase from 1990–1995, followed by a notable decline until 2010, and then an increase. Males, on the other hand, experienced a mild decline until 2000, followed by a gradual increase (Fig.  3 C, D). For the 20–24 age group, both the number and rate of prevalence and DALYs in both sexes exhibited slight fluctuations until 2000, followed by an overall upward trend (Fig.  3 E, F). In the 25–29 age group, the number of prevalence and DALYs followed a similar pattern to the 20–24 group, with a slight initial rise and subsequent decline before 2000, followed by an overall increase. However, after 2015, the number remained stable. The rate for females declined slightly in 2000, while the male rate remained relatively flat. Post-2000, both sexes showed an overall increase in rate (Fig.  3 G, H). Among the 30–34 age group, the number of prevalence and DALYs fluctuated upwards until 2005, declined from 2005–2009, and then rose again. The rate for both sexes remained relatively stable until 2010 when it began to increase (Fig.  3 I, J). For the 35–39 age group, the number of prevalence and DALYs declined in 1996, while the rate decreased before 1997. Subsequently, the number increased steadily, and the rate fluctuated upwards (Fig.  3 K, L). In the 40–44 age group, females' number of prevalence and DALYs rose until 1997, declined from 1998–2000, and then increased. The rate remained stable until 1996, declined significantly from 1997–2007, and then increased gradually. Males showed a gradual increase in both number and rate (Fig.  3 M, N). In the 45–49 age group, males surpassed females in both the number and rate of prevalence and DALYs. The number increased until 2001, declined until 2005, and then rose steadily. The rate fluctuated significantly, rising until 2000, declining until 2008, remaining stable until 2015, rising markedly from 2015 to 2019, declining in 2020, and rising again in 2021. Females' numbers increased until 2000, declined until 2005, rose until 2012, declined until 2015, and then increased from 2016 to 2019. A notable decline was observed in 2020, followed by an increase in 2021. The rate followed a similar pattern to the number (Fig.  3 O, P). Fig. 3 Overall temporal trends analysis in all age groups of the infertility disease burden in the globe, 1990–2021. A Prevalence number in all ages and ASPR; B DALYs number in all ages and age-standardized DALYs rates; C Prevalence number and rates in 15–19 years; D DALYs number and rates in 15–19 years; E Prevalence number and rates in 20–24 years; F DALYs number and rates in 20–24 years; G Prevalence number and rates in 25–29 years; H DALYs number and rates in 25–29 years; I Prevalence number and rates in 30–34 years; J DALYs number and rates in 30–34 years; K Prevalence number and rates in 35–39 years; L DALYs number and rates in 35–39 years; M Prevalence number and rates in 40–45 years; N DALYs number and rates in 40–44 years; O Prevalence number and rates in 45–49 years; P DALYs number and rates in 45–49 years. ASPR: age-standardized prevalence rates; DALYs: Disability-adjusted life years Overall temporal trends analysis in all age groups of the infertility disease burden in the globe, 1990–2021. A Prevalence number in all ages and ASPR; B DALYs number in all ages and age-standardized DALYs rates; C Prevalence number and rates in 15–19 years; D DALYs number and rates in 15–19 years; E Prevalence number and rates in 20–24 years; F DALYs number and rates in 20–24 years; G Prevalence number and rates in 25–29 years; H DALYs number and rates in 25–29 years; I Prevalence number and rates in 30–34 years; J DALYs number and rates in 30–34 years; K Prevalence number and rates in 35–39 years; L DALYs number and rates in 35–39 years; M Prevalence number and rates in 40–45 years; N DALYs number and rates in 40–44 years; O Prevalence number and rates in 45–49 years; P DALYs number and rates in 45–49 years. ASPR: age-standardized prevalence rates; DALYs: Disability-adjusted life years From 1990 to 2023, across the 21 regional contexts, the ASPR and ASR of DALYs for both female and male infertility were relatively higher in the High-middle SDI, Middle SDI, and Low SDI regions. In the low SDI, a declining SDI was associated with an increasing trend in ASPR and ASR of DALYs. Conversely, in regions with high SDI, an increasing SDI was associated with a decrease in these rates (Figure S3 A-D). Similar patterns were observed in the relationship between SDI and ASR for female infertility across different countries and territories in 2023 (Figure S3  E, F). For male infertility, the overall association between SDI and ASPR and ASR of DALYs mirrored that of females, albeit with a slight initial rise followed by a decline in Low SDI regions as SDI increased, yet remaining consistently higher than in other SDI regions (Figure S3 G, H). Fig. 4 Multi-disease attribution analysis of primary and secondary infertility among females in 21 regions in 2023. A Prevalence attribution for primary infertility; B Prevalence attribution for secondary infertility; C DALYs attribution for primary infertility; D DALYs attribution for secondary infertility. DALYs: Disability-adjusted life years Multi-disease attribution analysis of primary and secondary infertility among females in 21 regions in 2023. A Prevalence attribution for primary infertility; B Prevalence attribution for secondary infertility; C DALYs attribution for primary infertility; D DALYs attribution for secondary infertility. DALYs: Disability-adjusted life years Between 1990 and 2023, health inequality metrics revealed a persistent and intensifying concentration of the infertility burden in underdeveloped regions. For female infertility, absolute inequality widened significantly, with the SII for prevalence declining sharply from −157.07 in 1990 to −607.51 in 2023, and the SII for DALYs decreasing from −0.63 to −3.11 (Figure S4 A, B). These distinctly negative values directly indicate that the absolute burden of female infertility is disproportionately concentrated in less-developed, wealth-deprived nations. Meanwhile, the CI for female prevalence and DALYs remained highly stable, shifting only marginally from −0.15 to −0.12 and −0.15 to −0.13, respectively (Figure S4 C, D). This stable negative CI, juxtaposed with the rising overall prevalence, explicitly confirms a critical trend: while the absolute 'volume' of the global female infertility problem is growing, its disproportionate distribution remains stubbornly fixed among marginalized populations. Crucially, a dynamic shift in disease concentration relative to national wealth was observed for male infertility over the past three decades. In 1990, male infertility exhibited a positive SII for both prevalence (98.48) and DALYs (0.74), suggesting a historically higher diagnosed burden in higher-developed regions. However, by 2023, both metrics dynamically inverted to firmly negative values (prevalence SII: −92.29; DALYs SII: −0.35). Concurrently, the CI for male prevalence and DALYs shifted further into the negative spectrum (from −0.07 to −0.08 and −0.06 to −0.08, respectively). This striking inversion illustrates a global epidemiological transition: the burden of male infertility is no longer predominantly a 'high-income' issue but has decisively shifted to become overwhelmingly concentrated in lower-developed populations. The primary cause of both primary and secondary female infertility in 2023 is polycystic ovary syndrome (PCOS). However, in Central and Eastern Europe, Central Asia, and Tropical Latin America, the burden of primary and secondary infertility caused by chlamydia infection is heavier. Additionally, in Low SDI regions and Central, Eastern, Southern, and Western Sub-Saharan Africa, the burden of secondary infertility due to chlamydia infection is similar to or higher than that caused by PCOS (Fig.  4 ). Furthermore, the burden of infertility caused by chlamydia infection increases with age (Figure S5). For male primary infertility, the main cause is Klinefelter syndrome. There is no significant regional variation in this burden, except in Australasia, Eastern Sub-Saharan Africa, and Tropical Latin America, where urogenital congenital anomalies account for a relatively high proportion (Fig.  5 ). Additionally, the proportion of urogenital congenital anomalies decreases with age (Figure S6). The different age groups and regions corresponding to primary and secondary infertility for each disease are detailed in Table S6-59. Fig. 5 Multi-disease attribution analysis of primary infertility among males in the 21 regions in 2023. A Prevalence attribution for primary infertility; B DALYs attribution for primary infertility. DALYs: disability-adjusted life years Multi-disease attribution analysis of primary infertility among males in the 21 regions in 2023. A Prevalence attribution for primary infertility; B DALYs attribution for primary infertility. DALYs: disability-adjusted life years From 1990 to 2021, population growth was the primary contributor to changes in prevalence and DALYs for both female and male infertility globally, accounting for 61.37% and 67.27% of prevalence changes, respectively, and 61.37% and 67.28% of DALYs changes. Aging contributed the least, with 5.58% and 4.55% for females and 4.08% and 2.74% for males, respectively (Fig.  6 A, B, and Table S6). In High SDI regions, epidemiological change emerged as the primary driver of prevalence and DALYs changes for both sexes, while aging remained the least influential factor (Fig.  6 C, D and Table S6). In High-middle SDI regions, population growth and epidemiological change contributed equally to prevalence and DALYs changes among female infertility, with aging contributing the least but more significantly than in other regions. For male infertility in High-middle SDI and both sexes in Middle SDI, Low-middle SDI, and Low SDI, population growth was the primary driver of prevalence and DALYs changes, with aging contributing the least (Fig.  6 E-L and Table S60). Fig. 6 Changes in prevalence and DALYs for both sexes according to population-level determinants of population growth, aging, and epidemiological change from 1990 to 2021 in the globe and SDI regions. A Changes in prevalence at the global level; B Changes in DALYs at the global level; C Changes in prevalence at the high SDI regions; D Changes in DALYs at the high SDI regions; E Changes in prevalence at the high-middle SDI regions; F Changes in DALYs at the high-middle SDI regions; G Changes in prevalence at the middle SDI regions; H Changes in DALYs at the middle SDI regions; I Changes in prevalence at the low-middle SDI regions; J Changes in DALYs at the low-middle SDI regions; K Changes in prevalence at the low SDI regions; L Changes in DALYs at the low SDI regions. SDI: Socio-demographic index; DALYs, Disability-adjusted life years Changes in prevalence and DALYs for both sexes according to population-level determinants of population growth, aging, and epidemiological change from 1990 to 2021 in the globe and SDI regions. A Changes in prevalence at the global level; B Changes in DALYs at the global level; C Changes in prevalence at the high SDI regions; D Changes in DALYs at the high SDI regions; E Changes in prevalence at the high-middle SDI regions; F Changes in DALYs at the high-middle SDI regions; G Changes in prevalence at the middle SDI regions; H Changes in DALYs at the middle SDI regions; I Changes in prevalence at the low-middle SDI regions; J Changes in DALYs at the low-middle SDI regions; K Changes in prevalence at the low SDI regions; L Changes in DALYs at the low SDI regions. SDI: Socio-demographic index; DALYs, Disability-adjusted life years Using the ARIMA forecasting model, we projected trends for the period 2022–2036 based on infertility. From 1990 to 2021, the ASPR for females rose from 2267.26 to 2764.62 during the same period and is anticipated to reach 2,967.98 by 2036. The ASPR for males increased from 1158.86 to 1354.76 and is projected to reach 1,442.29 by 2036. Additionally, the ASR of DALYs for females decreased from 12.32 to 15.12 during this period but is projected to increase to 16.02 by 2036. The ASR of DALYs for males increased from 6.65 to 7.83 between 1990 and 2021 and is projected to be 8.29 by 2036 (Fig.  7 , Table S61). Fig. 7 Prediction trends of infertility in the globe over 15 years in males and females in the globe (2022–2036). A Prediction trends of ASPR in males; B Prediction trends of ASPR in females; C Prediction trends of ASR of DALYs in males; D Prediction trends of ASR of DALYs in females. ASPR: age-standardized prevalence rates, ASR: age-standardized prevalence rate, DALYs: Disability-adjusted life years Prediction trends of infertility in the globe over 15 years in males and females in the globe (2022–2036). A Prediction trends of ASPR in males; B Prediction trends of ASPR in females; C Prediction trends of ASR of DALYs in males; D Prediction trends of ASR of DALYs in females. ASPR: age-standardized prevalence rates, ASR: age-standardized prevalence rate, DALYs: Disability-adjusted life years

Infertility poses a significant public health challenge globally, with its disease burden eliciting substantial research and attention. This study comprehensively estimates the prevalence and DALYs of infertility across regions, countries, and territories, stratified by sex and age groups, providing a detailed portrayal of the disease burden. The key findings are as follows: Firstly, in 2021, the global prevalence of female infertility was 110,089,459 with 601,134 DALYs. For males, the prevalence was 55,000,818 and 317,614 DALYs (Table  1 ). In 2023, South Asia and India had the highest prevalence and DALYs for both sexes (Table  2 and Table S1). The global ASPR for female infertility in 2021 was 2,764.62, with an ASR of DALYs of 15.12. For females, ASPR and ASR of DALYs both were highest in East Asia and the Central African Republic in 2023. For males, the global ASPR was 1,354.76, and the ASR of DALYs was 7.84 in 2021, with Eastern Europe and Cameroon having the highest values in 2023 (Table  1 , Table  2 , Table S2). From 1990 to 2021, both global ASPR and DALYs for female and male infertility showed an overall increasing trend (Table  1 , Figure S2). Secondly, in 2021, the global burden of female infertility was generally higher than that of males across all age groups, except for 15–19 and 45–49 years. The peak prevalence, DALYs, and DALYs rate were observed in the 35–39 age group (Fig.  2 ). Between 1990 and 2021, an upward trend was observed across all age groups, with 2000 and 2010, along with their proximate years, marking pivotal points. The physiological dimension suggests that risk factors for female infertility may be more prevalent than in males. The multi-disease attribution analysis presented in this study further highlights the substantial burden of both primary and secondary infertility among women (Figs.  4  and  5 , and Figures S5-6). The primary causes of female infertility encompass a range of conditions including chlamydial infection, endometriosis, gonococcal infection, and PCOS. Similarly, secondary infertility is attributed to chlamydial infection, endometriosis, gonococcal infection, maternal sepsis and other maternal infections, as well as PCOS. For instance, PCOS, a common gynecological endocrine disorder, affects 7% to 15% of women of reproductive age (Collée et al. 2021 ). Endometriosis has a prevalence of 6% to 10% (Chapron et al. 2019 ), and the estimated global prevalence of chlamydial infection among women is 3.8% (Hocking et al. 2023 ). Furthermore, the significant regional variations in Chlamydia-related secondary infertility are intrinsically linked to disparities in healthcare infrastructure and public health policies. In high-developed regions, the widespread implementation of systematic, asymptomatic screening programs enables the early detection and antibiotic treatment of Chlamydia trachomatis before irreversible tubal damage occurs (LeFevre 2014 ). Conversely, low-developed countries predominantly rely on syndromic management due to limited diagnostic resources (Gupta and Sharma 2019 ). Given that up to 80% of female chlamydial infections remain asymptomatic, this lack of routine screening allows infections to progress unchecked into pelvic inflammatory disease (PID), thereby disproportionately driving up the rates of infection-induced secondary infertility in marginalized regions (LeFevre 2014 ; Gupta and Sharma 2019 ). On the other hand, the primary risk factor for male primary infertility is Klinefelter syndrome, which is defined by the presence of an extra X chromosome (47, XXY) resulting from errors in chromosome segregation during parental gametogenesis (Chen et al. 2024 ). Despite being the most common genetic cause of human male infertility (Chen et al. 2024 ; Lanfranco et al. 2004 ), its incidence is relatively low, occurring in approximately 1 in 650 newborn males (approximately 0.15%) (Kanakis and Nieschlag 2018 ). Furthermore, male infertility is primarily manifested as reduced sperm count and quality (Carson and Kallen 2021 ), with declining trends documented since the twentieth century (Rolland et al. 1989 ; Levine et al. 2023 ; Carlsen et al. 1992 ), but it lacks specific quantification of risk factors of secondary infertility, which is a limitation of database inclusion. Socially, male infertility is often underreported, especially in countries with cultural and patriarchal barriers to accurate data collection (Sun et al. 2019 ), and infertility is often blamed on women, particularly in low-income countries, where childless women face stigma, isolation, exclusion, inheritance denial, and neglect (Inhorn and Patrizio 2015 ; Hammarberg and Kirkman 2013 ). This societal burden exacerbates the psychological and mental stress on women, likely potentially impacting endocrine function and exacerbating infertility. Age-wise, the rising prevalence among 15–19-year-olds underscores the need for educational programs to promote family planning and prevent infertility. Recommendations and knowledge gaps are identified to inform professionals, the public, and policymakers on child-friendly policies (Fauser et al. 2024 ). The peak age of 35–39 aligns with studies indicating a notable rise in infertility incidence post-mid-30 s (Roode et al. 2015 ), with declining pregnancy rates after age 30 (Farquhar et al. 2019 ). Age-related fertility decline accelerates after 37, and women are more prone to uterine fibroids or endometriosis, which will compromise fertility (Carson and Kallen 2021 ). Numerous studies have documented a global trend towards delayed parenthood, likely influenced by advocacy for later marriages and childbirth, career pursuits, and societal pressures leading to postponed union formation or childbearing decisions. To mitigate this expanding demographic challenge, public health frameworks must shift from passive observation to proactive intervention. Healthcare systems should implement robust fertility preservation education programs to enhance reproductive health literacy, informing the public about age-related physiological declines and the clinical feasibility of proactive options, such as oocyte cryopreservation. Furthermore, from a clinical standpoint, diagnostic protocols should be optimized for earlier intervention; for individuals aged 35 years and older, the traditional 12-month evaluation window should be truncated to 6 months of unprotected intercourse, thereby accelerating referrals to specialist reproductive care and minimizing the therapeutic delays that compound age-related fertility loss. Analysis focusing on the years 2000 and 2010, including a systematic review and meta-regression of globally collected samples spanning the twentieth and twenty-first centuries, suggests that the decline in sperm counts has intensified post-2000 (Levine et al. 2023 ). Similarly, estimates of infertility in the United States have revealed an increase from 5.8% in 2006–2010 to 8.1% in 2017–2019 across nearly all subgroups (Snow et al. 1995 ). Furthermore, the generalized upward trend in global infertility prevalence and DALYs must be systematically interpreted through the lens of evolving medical landscapes and epidemiological shifts over the past three decades. First, updates and standardization in diagnostic criteria have broadened the clinical identification of infertile couples who might have previously gone unrecorded. Second, the rapid advancement and popularization of ART, coupled with significant improvements in general medical accessibility and healthcare infrastructure globally, have fundamentally changed help-seeking behaviors. The higher success rates of these treatments and the reduction of social stigma have encouraged more individuals to undergo screening and diagnosis, which paradoxically contributes to the statistical increase in reported prevalence. Lastly, undeniable changes in population health status have organically contributed to the declining reproductive capacities in both sexes, driving the actual incidence rates upward alongside diagnostic artifacts. Thirdly, from 1990 to 2023, the ASPR and ASR of DALYs for infertility exhibited a pattern of high values in low, middle, and high-middle SDI areas, with lower values in high-SDI areas (Figure S3 A-D). In 2023, the relationship between ASPR/ASR of DALYs and SDI was similar but with a more moderate trend (Figure S3 E–G). Inequality analysis revealed that lower-SDI countries and territories bore a higher absolute burden of infertility, as indicated by the SII for both sexes from 1990 to 2023 (Figure S4 A, B, E, F). The CI for females showed a slight decrease in relative inequality, whereas it increased slightly for males (Figure S4 C, D, G, H). Regionally, the lower prevalence and DALYs in high-SDI regions partly stem from total fertility rates being a factor in SDI assessments. Furthermore, educational attainment, socioeconomic status, health behaviors, access to quality infertility services, and help-seeking behaviors contribute to these regional variations (Sun et al. 2019 ). Concurrent research underscores education, women's empowerment, and economic prosperity as the most effective solutions to infertility-related challenges (Pennings et al. 2009 ). In developing countries, both local healthcare providers and international organizations exhibit limited engagement with this issue (Ombelet 2008 ), exacerbated by a lack of medical resources from high-income nations (Hammarberg and Kirkman 2013 ). Moreover, ART remains inaccessible in many parts of the world, particularly in sub-Saharan Africa, where most countries lack in vitro fertilization clinics (Inhorn and Patrizio 2015 ). High SDI regions boast more comprehensive infertility healthcare policies, often mitigating cost-induced disengagement. For instance, 19 US states have enacted laws mandating insurance coverage for fertility treatments (Carson and Kallen 2021 ). Dietary factors also significantly impact infertility, with consumption of folate, low-pesticide fruits and vegetables, whole grains, seafood, dairy products, and soy linked to improved fertility outcomes (Gaskins et al. 2019 ). However, female obesity is notably associated with compromised spontaneous fertility and adverse pregnancy outcomes (Sermondade et al. 2019 ), while male heavy consumption of alcohol, caffeine, and processed meats negatively affects their partners' pregnancy chances or fertilization rates (Salas-Huetos et al. 2017 ), emphasizing the criticality of maintaining healthy weights and lifestyles. Fourthly, decomposition analysis reveals that population growth predominantly drove changes in prevalence and DALYs for infertility from 1990 to 2021 in most regions (excepting high-SDI and high-middle SDI female infertility) (Fig.  6 ). This finding aligns with a systematic analysis of 277 health surveys, which highlights the substantial impact of population growth, with the absolute number of infertile couples rising from 42 million in 1990 to 48.5 million in 2010 (Mascarenhas et al. 2012 ). This population-driven amplification of the absolute disease burden demands a strategic tailoring of resource allocation, particularly in low-SDI settings. Because these regions face an expanding baseline population with limited access to expensive advanced reproductive technologies, public health investments should prioritize high-yield, cost-effective preventative strategies. Specifically, global and local health authorities must focus on reducing secondary infertility by scaling up screening and early treatment for sexually transmitted infections (STIs, such as chlamydia and gonorrhea) and decisively investing in maternal health infrastructure to ensure safe obstetric care, thereby eliminating postpartum infections and maternal sepsis, which remain major yet entirely preventable drivers of tubal-factor infertility in developing nations. Fifthly, ARIMA model projections for the next fifteen years suggest an overall increasing trend in ASPR and ASR of DALYs for both sexes, implying a potential further aggravation of the infertility burden (Fig.  7 ). The study has its limitations. Firstly, the GBD database primarily aggregates data from national and regional reports and publications, rather than direct national reports, potentially compromising data integrity, timeliness, and quality, especially in low-income settings where access to raw data may be limited. Secondly, differences in disease management, including diagnosis, recording, and reporting practices across countries and regions, may affect the results. Thirdly, the GBD database exhibits inherent constraints in comprehensively capturing the etiology of male infertility. While explicit genetic or anatomical anomalies (such as Klinefelter syndrome) are accurately recorded, a substantial proportion (up to 30–50%) of male infertility cases globally are considered idiopathic (Agarwal et al. 2021 ). These cases are heavily driven by complex, overlapping factors—including exposure to environmental endocrine disruptors, occupational hazards, lifestyle shifts, and psychological stress—which currently lack standardized quantification and coding within macroscopic global epidemiological models, potentially leading to an under-characterization of male etiological drivers in our analysis. Notably, the UI for infertility in the GBD database is relatively wide, and temporal variations in diagnostic and testing protocols may undermine result comparability and data accuracy. Lastly, the unprecedented disruptions caused by the COVID-19 pandemic introduced potential data volatility during the 2020–2021 period. Global lockdowns, the severe reallocation of healthcare resources, and the widespread suspension of routine reproductive clinics and STI screening programs may have temporarily skewed reporting rates and interrupted longitudinal diagnosis trends. This exogenous shock introduces a degree of uncertainty into the prevalence and DALY estimates for these specific years, and long-term surveillance is required to fully decouple pandemic artifacts from true epidemiological trends.

Infertility is defined as the inability to conceive after 12 months of regular unprotected sexual intercourse (Carson and Kallen 2021 ). Clinically, it is broadly classified into two categories: primary infertility, defined as the inability to achieve a clinical pregnancy without any prior pregnancies, and secondary infertility, which refers to the inability to conceive following at least one previous successful pregnancy (Carson and Kallen 2021 ; WHO 2025 ). Furthermore, infertility is a pervasive global health challenge with profound public health implications. According to comprehensive estimates by the WHO, approximately 1 in 6 individuals worldwide experience infertility during their reproductive lifetimes, underscoring its widespread nature (WHO 2025 ; 2023 ). It stands as a global public health concern and a prominent clinical challenge (Salas-Huetos et al. 2017 ), impacting not only the quality of life but also contributing to significant physical distress, stigma, and economic hardship, thereby elevating the risks of mental disorders and psychological distress such as anxiety, dysthymia, and panic disorder (Liu et al. 2024 ; Klemetti et al. 2010 ). Infertility is influenced by a complex interplay of risk factors, including reproductive tract infections, genetic predispositions, modern lifestyle changes, and ubiquitous environmental pollution (WHO 2025 ; Fauser et al. 2024 ; Silva et al. 2023 ; Bala et al. 2021 ). Furthermore, the burden of infertility is significantly exacerbated in less-developed nations. In these regions, limited access to advanced medical resources, inadequate sanitation leading to higher rates of untreated infections, and a general lack of reproductive health awareness compound the demographic and psychological toll of infertility (Mutumba Nakalembe and Janes 2025 ; Gedef et al. 2025 ). The cost of infertility treatment often poses an unaffordable burden for many patients (Fauser et al. 2024 ), as evidenced by a French study estimating an economic toll of approximately €70 million imposed on approximately 10,000 women aged 18 to 50 years due to infertility (Bourrion et al. 2022 ). The United States also witnesses numerous campaigns advocating for financial assistance to cover infertility care expenses, highlighting substantial unmet economic burdens (Lai et al. 2021 ). Moreover, infertility is suspected to precede poor health outcomes, as both men and women with infertility exhibit increased risks of endocrine disorders, cardiovascular diseases, cancer, and mortality (Carson and Kallen 2021 ; Dougherty et al. 2023 ). The current analysis aims to characterize the global, regional, and country-specific trends in prevalence and DALYs related to infertility, encompassing data on gender, age groups, and the SDI. This endeavor intends to inform health policies, allocate medical resources more effectively, and optimize patient management plans. Leveraging the 2021 and 2023 GBD comprehensive assessment of 371 health conditions and injuries, 288 causes of death, and life expectancy decomposition across 204 countries and territories, supported by over 11,500 collaborators from 164 nations, this study systematically evaluates global health status and disease burden through extensive data sourcing, review, and analysis (Global incidence, prevalence, years lived with disability (YLDs), disability-adjusted life-years (DALYs), and healthy life expectancy (HALE) for 371 diseases and injuries in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021 2024 ; Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021 2024 ; Sun et al. 2024 ; Tuo et al. 2024 ; Yang et al. 2024 ). Hence, the GBD serves as a reliable instrument for understanding and assessing the current burden of infertility.

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