Global, regional, and national prevalence and years lived with disability due to infertility, 1990-2021: Results from the Global Burden of Disease Study 2021.

Infertility is defined as the failure to achieve pregnancy after one year or more of regular and unprotected sexual intercourse. The direct causes of infertility vary widely. In addition to reproductive hormone imbalances caused by endocrine disorders, specific causes in women include fallopian tube obstruction, uterine inflammation, and polycystic ovary syndrome (PCOS). For men, causes include obstruction due to reproductive tract injury or infection, low sperm count, and abnormal sperm function or quality. [ 1 ] In the context of declining fertility intentions, infertility further reduces the birth rate and intensifies social aging. Meanwhile, infertility negatively affects a couple’s quality of life and increases the risk of early onset chronic diseases in the reproductive-age labor force, such as cardiovascular diseases, diabetes mellitus, and ovarian and colorectal cancers. [ 2 – 5 ] This, in turn, significantly increases the long-term burden of chronic diseases on society. Furthermore, infertility may influence the psychological well-being of the affected couples, potentially leading to intimate partner violence and other social issues. [ 6 ] In 1994, the International Conference on Population and Development first recognized the right to sexual and reproductive health and outlined a program of action integrating fertility control with the prevention and treatment of infertility. [ 7 ] However, countries worldwide have made limited progress in promoting sexual and reproductive health and rights. Assisted reproductive treatments, for example, still benefit only a small portion of the population. [ 8 ] In contexts with competing public health priorities, such as those with a high maternal mortality burden, allocating resources for costly fertility treatments is challenging for policymakers. Therefore, reliable estimates of the infertility burden and regular updates will enable policymakers to obtain the accurate information required for informed policy formulation. In this study, we used data from the Global Burden of Disease (GBD) 2021 study to describe the disease burden of infertility and its current trends at the global, regional, and national levels from 1990 to 2021. We assessed its relationship with the level of development.

This work was supported by grants from the China National Key Research & Development (R&D) Plan (No. 2021YFC2700600) and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (No. 82221005).

This study used GBD 2021 data to perform a comprehensive analysis of the global infertility burden. The disease burden was assessed based on the prevalence and years lived with disability (YLDs), which were identical to the disability-adjusted life-years since no deaths were directly attributed to infertility. Additionally, we examined the relationship between infertility burden and the sociodemographic index (SDI), which ranged from 0 to 1, with low values representing a low sociodemographic status. GBD 2021 incorporates disease-related data from various sources, such as disease registries, epidemiological surveillance, and household survey data, across multiple countries and regions worldwide. Following the methods used for the GBD 2019, estimates of disease burden indicators for 371 diseases and injuries were produced by age, sex, location, and year, along with a 95% uncertainty interval (UI). Moreover, 95% of the UIs were estimated based on the 25th to 975th values of the ordered 1000 draw-level estimates. A comprehensive description of the analytical methods for GBD 2021 was provided in a previously published paper. [ 9 ] In this study, we used data on infertility prevalence and YLDs related to infertility and age-standardized rates (per 100,000) for men and women from 1990 to 2021. Ethical approval was not sought for this study because open data sources were used. The SDI is a holistic indicator that estimates the level of development of a country or region based on data such as fertility rates, education levels, and per capita income. Details of the SDI calculations are available in previous GBD publications. [ 10 , 11 ] The SDI ranges from 0 to 1, with higher values indicating more advanced socioeconomic and demographic development in the region. In this study, country-level estimates of the SDI for 2021 were used to determine quintile cut-off values, and countries and regions were categorized into five SDI regions (low, low–middle, middle, high–middle, and high) to explore the relationship between the burden of infertility disease and socioeconomic development. Due to sex differences in the distribution of infertility, all analyses were performed independently for men and women. The main indicators used to evaluate the disease burden of infertility in each region or country were the number of cases and the YLDs. We applied age-standardized prevalence rates (ASPR) and YLDs rates (ASYR) for a more accurate comparison between populations from different regions or age groups (15–19, 20–24, 25–29, 30–34, 35–39, and 40–44 years). [ 12 ] To understand the temporal trends in the disease burden of infertility from 1990 to 2021, we calculated the estimated annual percentage change (EAPC) and its 95% confidence interval (CI). [ 13 ] If both the EAPC and upper limit of the 95% CI were negative, the corresponding age-standardized rates were indicated to decrease. However, if both the EAPC and the lower limit of the 95% CI were positive, the rates were indicated to increase. In all other cases, the rates remained stable. We employed the locally estimated scatterplot smoothing method to model the relationship between SDI and the age-standardized rates of infertility burden. This analysis used GBD estimates from all national locations for each year from 1990 to 2021. [ 14 ] All statistical analyses were performed using R Studio, version 4.4.1 (R Foundation, Vienna, Austria). All P -values were two-sided, and P -values less than 0.05 were considered statistically significant.

In 2021, there were 143,261,562 (95% UI, 91,398,431–228,211,228) female infertility cases worldwide [Table 1 ]. It has increased by 82% (95% UI, 0.74–0.93) since 1990. The ASPR also increased, with an EAPC of 0.59% (95% CI, 0.45–0.72%). The number of male infertility cases was 55,481,380 (95% UI, 33,085,672–89,190,209) [Table 2 ], which increased by 74% (95% UI, 0.64–0.84) since 1990. The EAPC for the ASPR of male infertility was 0.50% (95% CI, 0.36–0.63%). Before 2010, the ASPR of infertility for both females and males remained relatively stable but exhibited a rapid upward trend after 2010 [Figure 1 A and B]. The highest infertility prevalence rate was observed in the 35–39 years age group during the entire observation period [Supplementary Figure 1A and B, http://links.lww.com/CM9/C633 ]. In 2021, the infertility prevalence rate in the 35–39 age group was 13,684 per 100,000 women and 4722 per 100,000 men. Prevalence of female infertility in 1990 and 2021, and the corresponding change from 1990 to 2021 at the global and regional level. EAPC is calculated based on ASPR and presented as the point estimate with its 95% CI. ASPR: Age-standardized prevalence rate; CI: Confidence interval; EAPC: Estimated annual percentage change; SDI: Sociodemographic index; UI: Uncertainty interval. Prevalence of male infertility in 1990 and 2021, and the corresponding change from 1990 to 2021 at the global and regional level. EAPC is calculated based on ASPR and presented as the point estimate with its 95% CI. ASPR: Age-standardized prevalence rate; CI: Confidence interval; EAPC: Estimated annual percentage change; SDI: Sociodemographic index; UI: Uncertainty interval. Trends of infertility prevalence and years lived with disability (YLDs) from infertility by sex globally and across five sociodemographic index (SDI) regions from 1990 to 2021. (A) Trends in age-standardized prevalence rate (ASPR) of female infertility. (B) Trends in ASPR of male infertility. (C) Trends in age-standardized YLD rate (ASYR) of female infertility. (D) Trends in ASYR of male infertility. In 2021, the number of YLDs related to female infertility worldwide was 801,995 (95% UI, 312,683–1,904,064) [Supplementary Table 1, http://links.lww.com/CM9/C633 ]. It has increased by 82% (95% UI, 0.73–0.92) since 1990. The EAPC for the ASYR of female infertility was 0.59% (95% CI, 0.45–0.72%). The YLDs related to male infertility were 325,681 (95% UI, 118,921–775,247) [Supplementary Table 2, http://links.lww.com/CM9/C633 ], increasing by 74% (95% UI, 0.64–0.84) since 1990. The EAPC for the ASYR of male infertility was 0.50% (95% CI, 0.37–0.64%). The ASYR trend was consistent with that of the ASPR [Figure 1 C and D]. The 35–39 years age group had the highest YLDs rate of infertility [Supplementary Figure 1C and D, http://links.lww.com/CM9/C633 ]. In 2021, the YLDs rate of infertility in the 35–39 years age group was 74 per 100,000 for women and 26 per 100,000 for men. Middle SDI regions had the highest number of infertility cases, whereas high and low SDI regions had the lowest [Tables 1 and 2 ]. However, the low-SDI and low–middle-SDI regions showed the largest relative increase, with the number of both female and male infertility cases rising approximately 1.5 times from 1990 to 2021. Examining the ASPR for infertility in 2021, the middle-, low–middle, and high–middle SDI regions recorded the highest values, whereas the low- and high-SDI regions recorded the lowest values. The prevalence of infertility has increased across all regions since 1990, but the changing patterns are slightly different [Figure 1 A and B]. In the middle, high-middle, and high SDI regions, the ASPR of infertility increased steadily during the entire observation period (EAPC: 0.33–0.85% for females; 0.13–0.62% for males). In contrast, in the low- and low–middle SDI regions, the ASPR for infertility declined from 1990 to 2010 and began to rise thereafter. The regional distribution and temporal trends of YLDs and ASYR related to infertility were largely consistent with those of prevalence. Middle-SDI regions had the highest number of infertility-related YLDs, whereas high-SDI and low-SDI regions had the lowest numbers [Supplementary Tables 1 and 2, http://links.lww.com/CM9/C633 ]. However, the low-SDI and low-middle-SDI regions demonstrated the largest relative increase, with the number of YLDs related to infertility rising by approximately 1.5 times for both females and males from 1990 to 2021. The ranking of regions by ASYR related to infertility mirrored the infertility prevalence rate, with middle-, low–middle-, and high–middle-SDI regions being higher, and low- and high-SDI regions being lower. The patterns and magnitudes of the increase in the ASYR of infertility during 1990–2021 were similar to those of prevalence [Figures 1 C and D]. Among the 21 geographically classified regions, South Asia had the highest number of infertility cases, with 43,795,883 (95% UI, 28,273,758–68,531,616) female cases and 15,346,753 (95% UI, 8,793,192–25,113,836) male cases. In contrast, Oceania had the lowest number of cases, with 131,913 (95% UI, 101,466–173,067) female cases and 51,554 (95% UI, 36,053–73,321) male cases [Tables 1 and 2 ]. The number of infertility cases increased from 1990 to 2021 in most regions, except for the number of both female and male cases in the high-income Asia Pacific region and the number of male cases in Eastern Europe. Examining the ASPR of infertility in 2021, East Asia had the highest prevalence of female infertility and Eastern Europe had the highest prevalence of male infertility [Figure 2 A and B]. The ASPR of infertility increased in almost all regions between 1990 and 2021, and the increase in Andean Latin America was the fastest, with the EAPC of ASPR being 2.47% (95% CI, 2.07–2.86%) for females and 2.08% (95% CI, 1.72–2.45%) for males. Eastern Sub-Saharan Africa, Oceania, Southern Sub-Saharan Africa, Western Sub-Saharan Africa, and the high-income Asia Pacific experienced a decline during this period. Coevolution of age-standardized burden estimates of infertility by sex with sociodemographic index (SDI) globally and for 21 GBD regions, 1990–2021. (A) Age-standardized prevalence rate (ASPR) of female infertility. (B) ASPR of male infertility. (C) Age-standardized years lived with disability rate (ASYR) of female infertility. (D) ASYR of male infertility. Colored lines show global and regional values for age-standardized burden estimates rates. Each point in a line represents 1 year, starting at 1990 and ending at 2021. The average expected relationship between SDI and burden estimates rates of infertility was shown as the black line. The number of YLDs related to infertility was highest in South Asia, with 251,436 (95% UI, 96,492–583,241) in females and 92,534 (95% UI, 33,029–214,188) in males in 2021. Oceania had the lowest number of metrics: 742 (95% UI, 296–1660) in females and 302 (95% UI, 116–698) in males [Supplementary Tables 1 and 2, http://links.lww.com/CM9/C633 ]. As with prevalence, the number of infertility-related YLDs increased in almost all regions from 1990 to 2021, except for female and male infertility in the high-income Asia Pacific and male infertility in Eastern Europe. For ASYR-related infertility, East Asia and Eastern Europe had the highest metrics for females and males, respectively [Figure 2 C and D]. Andean Latin America had the fastest increase, with the EAPC for ASYR of infertility being 2.36% (95% CI, 1.99–2.73%) for females and 1.99% (95% CI, 1.65–2.32%) for males. We further analyzed the data from 204 countries and territories. In 2021, India had the highest number of infertility cases, with 35,625,971 (95% UI, 22,772,548–55,715,301) and 12,449,381 (95% UI, 7,187,309–20,371,265) cases in women and men, respectively [Supplementary Tables 3 and 4, http://links.lww.com/CM9/C633 ]. From 1990 to 2021, the number of female and male cases increased in 152 and 143 countries, respectively. Qatar had the largest relative increase, with female and male cases rising 6.84 and 6.95 times, respectively. Examining the ASPR for infertility in 2021, the Central African Republic demonstrated the highest prevalence of female infertility, whereas Cameroon showed the highest male infertility prevalence. The ASPR for female and male infertility increased in 135 and 72 countries, respectively. The highest increase rate was observed in the Philippines, with the EAPC for the ASPR of infertility being 5.40% (95% CI, 3.30–7.54%) for females and 5.27% (95% CI, 3.23–7.34%) for males. The number of infertility-related YLDs was the highest in India, with 202,647 (95% UI, 76,155–470,921) in females and 74,379 (95% UI, 26,619–172,676) in males [Supplementary Tables 5 and 6, http://links.lww.com/CM9/C633 ]. Qatar had the largest relative increase in YLDs from 1990 to 2021, with the number of YLDs related to infertility rising by 6.74 times (95% UI, 5.71–7.95) for females and 6.88 times (95% UI, 6.02–7.80) for males. For the ASYR of infertility, the Central African Republic had the highest value for females, whereas Cameroon had the highest value for males. The Philippines had the highest increase rate in ASYR, with an EAPC of 5.31% (95% CI, 3.29–7.37%) for females and 5.19% (95% CI, 3.24–7.17%) for males. We observed a horizontal S-shaped association between the SDI and ASPR and ASYR of infertility in 21 regions spanning the period from 1990 to 2021. When the SDI was less than 0.5, the expected values decreased with increasing SDI. For SDI values between 0.50 and 0.70, especially within the 0.65–0.70 range, an increasing trend was observed. However, when the SDI values exceeded 0.7, the burden estimates of infertility declined as the SDI increased [Figure 2 ]. At the national level, a clear decline was observed in the burden estimates of infertility when the SDI values were greater than 0.8 in 2021 [Supplementary Figure 2, http://links.lww.com/CM9/C633 ].

This study showed that the global burden of female and male infertility, as measured by prevalence and YLDs, exhibited an upward trend between 1990 and 2021. The burden estimates for women were consistently higher than those for men, with a higher rate of increase. Certain regions, such as East Asia, have particularly high infertility burdens, with the ASPR and ASYR of female infertility being the highest globally, whereas Eastern Europe has the highest male infertility burden. The infertility burden was correlated with the SDI. We observed that as the SDI increased from lower levels, the ASPR and ASYR of infertility initially declined and then increased. However, when the SDI was >0.7, the burden estimates decreased as the SDI continued rising. The prevalence and YLDs of female infertility were consistently higher than those of male infertility, and this sex difference persisted across regions. Similar results have been observed in cross-sectional studies conducted in other countries. [ 15 , 16 ] Two possible reasons exists for this observation. In contrast, several factors contribute to infertility in women. Based on the latest health statistics released by the World Health Organization, approximately 50% of global infertility cases can be attributed to female factors, whereas only approximately 30% are related to male factors. [ 17 ] In women, conditions such as diminished ovarian reserve, PCOS, blocked fallopian tubes, endometriosis, and cervicitis can all lead to infertility. In addition to physiological causes, obesity is an important risk factor for female fertility, [ 18 ] and its prevalence among women has increased recently. By 2022, 18.5% of adult women globally were obese, [ 19 ] with the rate of increase in developing countries outpacing that in developed countries. [ 20 ] Another important reason is the traditional perception that women are often blamed for infertility, leading to higher detection rates for female infertility than for male causes. Even if male infertility is detected in some regions, it may go unreported, particularly in patriarchal countries. [ 21 ] We observed that for both men and women, the 35–39 years age group had the highest prevalence and YLD rates for infertility. A study based on the 2009–2010 Canadian Community Health Survey showed that women aged 35–44 years were more likely to be infertile than those aged 18–34 years. [ 22 ] A cross-sectional study conducted in the Chinese population documented that infertility prevalence increased with age before 45 years. [ 23 ] Previous studies have shown that the later the age at marriage, the higher the likelihood of infertility. [ 24 ] As men age, their sperm count decreases and quality deteriorates, [ 25 ] whereas the number of oocytes in women declines and errors during meiosis become more frequent. [ 26 , 27 ] In addition, compared with people under 30 years, older age groups may face greater work pressure and engage in unhealthy lifestyles, such as sedentary behavior and staying up late, which may affect reproductive health. [ 28 , 29 ] However, the extent to which these risk factors contribute to infertility remains unclear. Given the high cost of infertility treatment, many countries prioritize younger couples for publicly funded treatment, leaving older couples with less access to treatment. [ 30 ] This study showed a nonlinear relationship between the SDI, ASPR, and ASYR for infertility. When the SDI was below 0.5, the burden decreased, whereas between 0.5 and 0.7, it increased. Subsequently, it declined again above 0.7. In regions with medium levels of development, rapid changes in the social environment, particularly industrial growth, can lead to greater exposure to harmful environmental pollutants. Social development has promoted the availability of medical tests and increased the infertility detection rate. Hence, we observed an increase in the disease burden. With further development, better socioeconomic and ecological conditions, and healthcare, along with access to fertility treatments, will help reduce the infertility burden. Furthermore, infertility is only identified when a couple desires to conceive but faces difficulties. [ 31 ] With higher levels of social development, women tend to pursue higher education and have higher economic status, allowing them to focus more on education and work, potentially lowering their desire for childbirth. At the regional level, the highest burden of female infertility was in East Asia, whereas that of male infertility was in Eastern Europe. The infertility burden in African regions was high, particularly in Western and Central Sub-Saharan Africa. Previous studies have identified this distributional pattern. [ 21 , 31 ] Several factors influence the distribution of infertility, such as in countries like the Philippines, where religious doctrines and policies prohibit female contraception and abortion. This increases the risk of unintended pregnancies and unsafe abortions, leading to a higher risk of secondary infertility. [ 32 ] In African regions, infections such as chlamydia and gonorrhea have a high prevalence of infertility. [ 33 , 34 ] However, in recent years, under the initiatives of international organizations, more fertility clinics have been established across Africa to provide necessary fertility treatments. [ 35 ] International agencies have organized campaigns to educate people about the causes, treatments, and prevention of infertility, all of which have led to a downward trend in infertility prevalence and YLDs rates in African regions. This underscores the importance of global health cooperation in achieving health equity. This study examined the complex relationship between infertility burden and SDI. However, these limitations merit attention when interpreting the results. First, the GBD data are model-based and subject to uncertainty. Second, GBD data are subjectively provided by each country, and data sparsity in undeveloped countries may lead to an underestimation of infertility burden. However, the true burden in these areas may be higher than that reported previously. Future studies incorporating more diverse data sources may provide more precise estimates. In addition, infertility subtypes, including primary and secondary infertility, were not further stratified, as the study analysis focused on the burden and trends of infertility in terms of sex, age, and region. In conclusion, this study observed that the global infertility burden has increased over the past few decades, based on the newly released GBD 2021 data. Moreover, it highlights the significant regional heterogeneity. The burden is greater in regions with lower levels of development. These findings serve as a warning to global policymakers that infertility healthcare should be prioritized and preventive and clinical interventions should be implemented to address the rising burden of infertility. Given the complexity of the causes of infertility, this requires collaboration across multiple sectors, such as departments of environmental health, to improve ecological governance, and policymakers to ensure women’s rights to sexual and reproductive health. There is an urgent need for culturally sensitive awareness campaigns to reduce the stigma of infertility and promote the generation of accurate data on the infertility burden for scientific research.

None.