Dear editor,
The fertility rate has declined globally, and more than half of all countries and territories were below replacement level in 2021 [1]. Infertility is one of the major causes, leading to diminished quality of life, physical and mental health challenges, and increased economic burden [2]. However, comprehensive epidemiological estimates of infertility have not been fully reported [3]. This study utilized Global Burden of Disease (GBD) data to assess the trend and burden of infertility globally, regionally, and nationally from 1990 to 2021 to support policy-making and health planning.
The GBD 2021 study, conducted by the Institute for Health Metrics and Evaluation (IHME), involved a systematic evaluation of various data sources across 21 regions, 204 countries, and 811 subnational locations, as documented in prior publications [4]. The GBD 2021 data used in this study were sourced from the publicly available IHME database (https://www.healthdata.org). We focused on infertility, defined as the inability to conceive after 5 years of union without using contraceptives, among reproductive-aged individuals (15–49 years). Both prevalence and years lived with disability (YLD) data were extracted from 1990 to 2021, stratified by sex, type, and socio-demographic index (SDI).
Based on the world standard population in GBD 2021, we estimated age-standardized prevalence rate (ASPR) and YLD rate (ASYR) per 100,000 population with 95% confidence intervals (CI). Trends were assessed using the average annual percentage change (AAPC) via joinpoint regression to identify significant trend shifts. Loess regression was utilized for visualizing the potential nonlinear association of SDI with AAPC of corresponding age-standardized rates. Additionally, a Bayesian age-period-cohort (BAPC) model was employed to project future prevalence rates up to 2030. Analyses were performed using the R software and the Joinpoint Regression Program, with statistical significance set at P < 0.05.
Globally, the prevalent cases of infertility increased by 80.0% from 110.34 million in 1990 to 198.63 million in 2021 (Table S1). The ASPRs also were on the rise for both primary (AAPC 0.77) and secondary (AAPC 0.51) infertility. The prevalence in female infertility showed more cases and a sharper increase than that in male infertility (Table 1; Figure S1). As for the trend by five SDI quintiles, the ASPRs all displayed significant upward trends except for the low SDI region, and positive correlations were observed between their AAPCs and SDI (Table 1; Figure S2). For age-specific analyses, the prevalence consistently rose in each age group, with higher ASPR in the 20–29 and 30–44 age groups for primary and secondary infertility, respectively (Figure S3). In 2030, the prevalent cases were predicted to further increase to 231.33 million (Table S2; Figure S4).
Table 1.
Age-standardized prevalence and YLD rates of infertility globally from 1990 to 2021
| Categories | ASPR per 100,000 (95% CI) | AAPC (95% CI) | ASYR per 100,000 (95% CI) | AAPC (95% CI) | ||
|---|---|---|---|---|---|---|
| 1990 | 2021 | 1990 | 2021 | |||
| Global | 4236.68 (4235.88, 4237.48) | 5030.42 (5029.72, 5031.12) | 0.57 (0.55, 0.59)* | 23.93 (23.88, 23.99) | 28.54 (28.49, 28.60) | 0.58 (0.56, 0.60)* |
| Type | ||||||
| Primary | 921.60 (921.24, 921.96) | 1160.49 (1160.15, 1160.82) | 0.77 (0.74, 0.81)* | 6.90 (6.87, 6.93) | 8.68 (8.65, 8.71) | 0.77 (0.74, 0.81)* |
| Secondary | 3315.08 (3314.37, 3315.79) | 3869.93 (3869.32, 3870.54) | 0.51 (0.49, 0.53)* | 17.04 (16.99, 17.09) | 19.87 (19.82, 19.91) | 0.51 (0.49, 0.53)* |
| Sex | ||||||
| Female | 6142.50 (6141.13, 6143.87) | 7328.87 (7327.67, 7330.07) | 0.59 (0.57, 0.60)* | 34.25 (34.15, 34.36) | 41.04 (40.95, 41.13) | 0.60 (0.58, 0.62)* |
| Male | 2384.72 (2383.89, 2385.56) | 2779.52 (2778.79, 2780.25) | 0.51 (0.49, 0.52)* | 13.91(13.84, 13.97) | 16.31 (16.26, 16.37) | 0.52 (0.50, 0.54)* |
| Socio-demographic index | ||||||
| High SDI | 2928.95 (2927.41, 2930.49) | 3556.28 (3554.66, 3557.90) | 0.64 (0.61, 0.67)* | 17.24 (17.12, 17.36) | 20.77 (20.65, 20.89) | 0.61 (0.58, 0.64)* |
| High-middle SDI | 4976.21 (4974.36, 4978.06) | 5421.55 (5419.77, 5423.33) | 0.28 (0.27, 0.29)* | 27.60 (27.46, 27.74) | 30.12 (29.99, 30.26) | 0.28 (0.27, 0.29)* |
| Middle SDI | 4536.15 (4534.70, 4537.61) | 5306.36 (5305.09, 5307.62) | 0.50 (0.49, 0.51)* | 25.22 (25.11, 25.33) | 29.91 (29.82, 30.01) | 0.55 (0.53, 0.56)* |
| Low-middle SDI | 3940.81 (3939.06, 3942.55) | 5254.97 (5253.54, 5256.39) | 0.96 (0.91, 1.02)* | 22.81 (22.68, 22.94) | 30.24 (30.14, 30.35) | 0.95 (0.89, 1.01)* |
| Low SDI | 4684.66 (4681.60, 4687.72) | 4645.72 (4643.79, 4647.64) | 0.00 (− 0.03, 0.06) | 26.46 (26.23, 26.69) | 26.30 (26.16, 26.45) | 0.01 (− 0.03, 0.07) |
| Region | ||||||
| Andean Latin America | 1360.47 (1354.77, 1366.20) | 2365.45 (2360.33, 2370.58) | 1.99 (1.67, 2.36)* | 7.72 (7.30, 8.16) | 13.18 (12.80, 13.56) | 1.91 (1.62, 2.23)* |
| Australasia | 1845.84 (1837.82, 1853.89) | 1997.33 (1990.18, 2004.50) | 0.26 (0.25, 0.27)* | 10.95 (10.34, 11.59) | 11.80 (11.26, 12.37) | 0.25 (0.24, 0.26)* |
| Caribbean | 4541.98 (4531.77, 4552.20) | 4562.15 (4553.57, 4570.75) | 0.01 (− 0.01, 0.03) | 26.26 (25.49, 27.04) | 26.03 (25.39, 26.69) | − 0.03 (− 0.05, − 0.01)* |
| Central Asia | 3095.98 (3089.83, 3102.14) | 3186.10 (3181.18, 3191.02) | 0.11 (0.08, 0.16)* | 17.68 (17.22, 18.15) | 18.09 (17.72, 18.46) | 0.09 (0.06, 0.13)* |
| Central Europe | 3786.30 (3781.50, 3791.10) | 4464.49 (4458.74, 4470.24) | 0.54 (0.52, 0.56)* | 21.33 (20.97, 21.70) | 24.85 (24.43, 25.29) | 0.50 (0.48, 0.52)* |
| Central Latin America | 2480.21 (2476.54, 2483.89) | 3731.79 (3728.49, 3735.10) | 1.27 (1.24, 1.32)* | 14.09 (13.82, 14.37) | 20.79 (20.55, 21.04) | 1.22 (1.18, 1.27)* |
| Central Sub-Saharan Africa | 5322.53 (5312.35, 5332.72) | 5399.48 (5393.38, 5405.58) | 0.12 (− 0.08, 0.37) | 29.33 (28.58, 30.09) | 29.83 (29.38, 30.28) | 0.12 (− 0.07, 0.37) |
| East Asia | 5998.33 (5996.43, 6000.23) | 6370.90 (6369.06, 6372.74) | 0.17 (0.14, 0.20)* | 32.02 (31.88, 32.15) | 34.30 (34.16, 34.43) | 0.20 (0.17, 0.22)* |
| Eastern Europe | 6016.27 (6011.83, 6020.72) | 6292.32 (6287.26, 6297.38) | 0.16 (0.14, 0.17)* | 35.12 (34.78, 35.46) | 36.51 (36.12, 36.90) | 0.14 (0.12, 0.15)* |
| Eastern Sub-Saharan Africa | 4609.71 (4604.64, 4614.78) | 3666.08 (3663.29, 3668.87) | − 0.65 (− 0.72, − 0.53)* | 25.60 (25.22, 25.98) | 20.35 (20.14, 20.55) | − 0.65 (− 0.73, − 0.54)* |
| High-income Asia Pacific | 3052.65 (3049.13, 3056.18) | 3004.92 (3001.19, 3008.65) | 0.02 (− 0.03, 0.06) | 17.23 (16.97, 17.50) | 16.94 (16.66, 17.22) | 0.00 (− 0.03, 0.04) |
| High-income North America | 2289.56 (2287.19, 2291.93) | 3024.23 (3021.62, 3026.84) | 0.91 (0.84, 0.97)* | 14.21 (14.03, 14.40) | 18.41 (18.21, 18.62) | 0.84 (0.77, 0.91)* |
| North Africa and Middle East | 2895.68 (2892.91, 2898.46) | 3844.51 (3842.43, 3846.60) | 1.02 (0.93, 1.12)* | 17.73 (17.51, 17.94) | 22.82 (22.66, 22.98) | 0.91 (0.83, 1.01)* |
| Oceania | 3573.66 (3551.49, 3595.95) | 2658.82 (2646.58, 2671.11) | − 0.98 (− 1.02, − 0.95)* | 20.11 (18.49, 21.86) | 15.09 (14.18, 16.05) | − 0.92 (− 0.96, − 0.89)* |
| South Asia | 4066.98 (4065.19, 4068.76) | 5876.91 (5875.40, 5878.41) | 1.21 (1.13, 1.29)* | 23.78 (23.64, 23.91) | 34.10 (33.99, 34.22) | 1.17 (1.09, 1.24)* |
| Southeast Asia | 3893.62 (3890.99, 3896.26) | 5160.52 (5158.21, 5162.83) | 0.95 (0.92, 0.99)* | 22.36 (22.16, 22.56) | 29.51 (29.33, 29.68) | 0.93 (0.89, 0.98)* |
| Southern Latin America | 3113.44 (3106.31, 3120.58) | 3099.20 (3093.39, 3105.02) | − 0.00 (− 0.02, 0.02) | 18.15 (17.61, 18.70) | 18.11 (17.67, 18.56) | 0.01 (− 0.01, 0.02) |
| Southern Sub-Saharan Africa | 5096.70 (5087.42, 5105.99) | 3472.54 (3467.02, 3478.07) | − 1.23 (− 1.35, − 1.13)* | 28.75 (28.06, 29.45) | 19.49 (19.07, 19.90) | − 1.25 (− 1.36, − 1.14)* |
| Tropical Latin America | 2597.62 (2593.92, 2601.31) | 3738.74 (3735.34, 3742.13) | 1.21 (1.13, 1.28)* | 15.52 (15.23, 15.81) | 21.62 (21.37, 21.88) | 1.12 (1.05, 1.21)* |
| Western Europe | 2436.21 (2434.03, 2438.39) | 3223.36 (3220.83, 3225.89) | 0.91 (0.88, 0.95)* | 14.87 (14.70, 15.04) | 19.45 (19.25, 19.64) | 0.87 (0.84, 0.90)* |
| Western Sub-Saharan Africa | 5412.55 (5407.21, 5417.89) | 5499.71 (5496.43, 5502.99) | 0.05 (0.01, 0.10)* | 30.02 (29.62, 30.42) | 30.45 (30.20, 30.69) | 0.05 (0.00, 0.10)* |
Abbreviations: YLD years lived with disability, ASPR age-standardized prevalence rate, ASYR age-standardized YLD rate, AAPC average annual percentage change, CI confidence interval, SDI socio-demographic index
*Statistical significance of AAPC (P < 0.05)
Regionally, 14 regions showed upward trends in ASPRs of infertility. The greatest AAPCs from 1990 to 2021 were observed in Andean Latin America (1.99), Central Latin America (1.27), Tropical Latin America (1.21), and South Asia (1.21). Conversely, Southern Sub-Saharan Africa (− 1.23), Oceania (− 0.98), and Eastern Sub-Saharan Africa (− 0.65) experienced significant decreases. Four regions like Caribbean exhibited little to no change (Table 1).
Nationally, the highest ASPRs of infertility in 2021 were recorded in Cameroon, Central African Republic, and Gabon, while Burundi, Colombia, and Denmark had the lowest ASPRs. We observed increasing, decreasing, and stable trends in 136, 42, and 26 countries and territories, respectively. The highest AAPCs occurred in Peru (2.83), Turkey (2.21), and Dominican Republic (2.21), while Malawi (− 4.23), Uganda (− 2.50), and Armenia (− 2.41) had the lowest AAPCs (Fig. 1).
Fig. 1.
The global disease burden of infertility across 204 countries/territories. The left panel shows AAPC of age-standardized rates of infertility prevalence (A) and YLD (B) from 1990 to 2021. The right panel shows age-standardized rates of infertility prevalence (C) and YLD (D) in 2021. AAPC, average annual percentage change; YLD, years lived with disability
The YLDs and ASYRs of infertility followed a similar trend with prevalent cases and ASPRs. The details are presented in Table 1, Tables S1, and Figure S5–S7.
The present study reveals a continuously rising global burden of infertility and demonstrates its discrepancies across gender, type, age, SDI categories, and different regions and nations. This systematic overview emphasizes the need to provide equitable access to infertility treatment and also address risk factors for its prevention.
A major strength of our study is the use of GBD 2021 data to provide the latest estimates. However, the findings are limited by the lack of specific causes of infertility [5], the inconsistent diagnostic standards from World Health Organization [3], and the reliance on predictive models where data were incomplete among resource-limited areas [6]. Despite efforts to minimize bias, some inaccuracies remain, and future research should address these gaps. In addition, the BAPC model assumes that historical trends will continue. However, it does not account for potential shifts due to unforeseen factors, which may alter the trajectory of infertility prevalence and affect the validity of future projections. Given the rising burden of infertility, various interventions at individual, societal, and healthcare system levels should be considered, including expanding access to fertility care for counseling and treatment, promoting public health campaigns to reduce modifiable risk factors, and investing in research to better understand the causes for prevention.
Supplementary Information
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Funding
This study was funded by the National Natural Science Foundation of China (82260315), Natural Science Foundation of Jiangxi Province (20242BAB25446, 20224BAB216025), and Wenzhou Key Laboratory of Reproduction and Genetics (2022HZSY0051).
Declarations
Competing interests
The authors declare no competing interests.
Footnotes
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Contributor Information
Haisheng Wu, Email: haisheng@connect.hku.hk.
Yan Zhao, Email: zhaoyan1967_jx@126.com.
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