Global burden of female infertility attributable to sexually transmitted infections and maternal sepsis: 1990–2021 and projections to 2050

Abstract

Infectious diseases, such as sexually transmitted infections (STIs) and maternal sepsis, are major contributors to female infertility, creating a substantial burden on women of reproductive age. Based on Global Burden of Disease (GBD) 2021, this study analyzed the global trends and regional disparities in infection-related infertility for women aged 15–49 and projected future burdens. Our result showed that from 1990 to 2021, global age-standardized prevalence rate (ASPR) rose from 839.52 to 982.37 per 100,000 with estimated annual percentage change (EAPC) (0.26 [0.19 to 0.33]), and years lived with disability (YLDs) increasing from 62.81 to 106.69 thousand (EAPC 0.23 [0.16 to 0.31]), and was predicted to continue rising from 2022 to 2050. The disease burden showed significant regional disparities, low socio-demographic index (SDI) regions had the highest ASPR (1247.25 per 100,000 [1085.17 to 1443.57]) but also the fastest decline (EAPC -1.17 [-1.34 to -0.99]), and Western Sub-Saharan Africa (ASPR 1,925.52 [1655.35 to 2241.71] per 100,000) are the regions with highest burden. The disease burden increased with age, peaking at 40–44 years, and was inversely associated with SDI. These findings provide essential insights for policymakers to develop targeted strategies to prevent and control infection-related infertility, particularly in low-SDI regions.

Introduction

Infertility, especially infection-induced infertility, has become a critical issue in public health, significantly affecting family structure, marital stability, and social dynamics¹. In recent years, there has been an increase in the prevalence of infertility, with cases increasingly occurring at younger ages^2,3. Infectious diseases, particularly those affecting the female urogenital tract, are a major contributor to infertility^4–6. For example, many researches indicate that infections with Chlamydia trachomatis and Neisseria gonorrhoeae can lead to tubal factor infertility (TFI) and pelvic inflammatory disease (PID), serving as high-risk factors for female infertility⁷. Females are more prone to infections due to the structural characteristics of the urogenital anatomy and are influenced by many factors such as advanced age and lifestyle factors (e.g. excessive alcohol consumption, smoking)^8,9. Besides, studies have shown that intimate partner violence and post-traumatic stress disorder can also increase the risk of infection in women^10,11. These infections have a severe impact on quality of life and impose a substantial burden on female infertility, which have become an urgent social problem that needs to be addressed.

Most infections affecting the female urogenital tract are sexually transmitted, with common pathogens including Chlamydia trachomatis, Trichomonas vaginalis, Neisseria gonorrhoeae and Treponema pallidum. Sexually transmitted infections (STIs) spread more extensive and severe than generally recognized, with rates continuing to increase. In 2012, the World Health Organization (WHO) estimated that there were 357.4 million new patients of curable STIs globally annually¹², while in 2024, WHO reported over 100,000 new infections per day, among people aged 15–49¹³. According to the U.S. Centers for Disease Control and Prevention, the incidence of syphilis, gonorrhea, and chlamydia rose by nearly 30% from 2015 to 2019⁹. These data may underestimate true prevalence, particularly in regions with low income, due to asymptomatic early infections, limited screening, and underreporting.

STIs can ascend through the female urogenital tract, leading to complications such as tubal and pelvic inflammation, which significantly impact reproductive function and raise the risks of infertility, ectopic pregnancy, miscarriage, and other adverse pregnancy outcomes^14,15. TFI, predominantly caused by STIs, is the most leading cause of infertility¹⁶, accounting for 11% to 67% of infertility cases¹⁷. Previous clinical studies have confirmed that chronic Neisseria gonorrhoeae and Chlamydia trachomatis infections cause inflammation of oviduct epithelial surfaces, disrupting normal ovulation^18,19. TFI is secondary to PID in about 25% of diagnosed women²⁰, and C. trachomatis causes the majority of acute PID cases²¹. Beyond urogenital infections, maternal sepsis, a serious systemic infection and one of the major reasons for maternal deaths, has been linked to an elevated risk of secondary infertility^22,23. Numerous studies have explored how various pathogenic microbes affect female fertility, revealing that the mechanisms by which infections lead to infertility are complex, involving direct microbial effects, secondary infections, and interactions with the vaginal microbiota of the host^24,25.

Infection-induced infertility remains an under-recognized issue that warrants further research, with no comprehensive analysis available on its global burden. The 2021 Global Burden of Disease (GBD) offers a comprehensive collection of resources, including 371 injuries and diseases from 811 subnational, as well as regions 204 countries and territories²⁶. This research aimed to report the global impact and spatiotemporal patterns of infertility attributable to infections, analyzing data by age, socio-demographic index (SDI) region, and country to identify high-risk populations and inform strategies to protect female fertility.

Methods

Data sources

The data for this study were extracted from the latest GBD 2021, published in May 2024, which provides comprehensive information on disease burden across a wide range of conditions and publicly accessible. Over 11,500 collaborators from 164 countries contributed to data collection, review, and analysis from various sources. The GBD 2021 estimated disease burden and prevalence using the DisMod-MR 2.1²⁷ and classified all countries and regions into five categories based on SDI (low, low-middle, middle, high-middle, and high), which is a comprehensive indicator of social and economic development incorporating education, fertility, and economic data²⁸. GBD 2021 systematically reduced differences between global and local estimates through technological innovation in data integration, optimization of modeling algorithms, management of uncertainty, and collaborative mechanisms involving multiple parties.

For infertility, GBD 2021 incorporated 43 new data sources and included three new countries compared to previous versions²⁶. Infertility data for women of reproductive age (WRA) extracted from sources such as World Fertility Surveys, Demographic, the Family and Fertility Survey, Health Surveys and Health Surveys Reproductive. GBD 2021 identified nine causes of female infertility: endometriosis; PID due to STIs, including chlamydial infection and gonococcal infections; maternal sepsis; congenital Klinefelter syndrome; congenital Turner syndrome and polycystic ovarian syndrome and congenital urogenital anomalies. The GBD 2021 study applied specific inclusion/exclusion criteria to ensure data quality and relevance during data collection and processing, the following data were excluded: 1. Studies without raw data; 2. studies not representing the nation’s population; 3. studies without data on the gender responsible for the couple’s infertility 4. studies with only estimated data; 5. samples sizes of less than 50 or case studies; 6. studies conducted prior to 1970²⁶. For missing data, the study uses statistical models to estimate values based on available data from similar populations or regions. We used the GBD results tool (https://vizhub.healthdata.org/gbdresults/) to obtain numbers and rates of the prevalence and years lived with disability (YLDs), and make an analysis of trends and burdens by SDI and age, specifically, we made infertility as the impairment and included all infectious diseases as causes.

Variable definitions

This study focused on all infection-related causes in GBD 2021, the following are detailed descriptions of disease types and subcategories, represented by the latest international classification of diseases (ICD) codes: chlamydial infection (ICD-10 A55-A56.8, K67.0, N74.4), gonococcal infection (ICD-10 A54-A54.9, K67.1, M73.0, N74.3), other STIs (ICD-10 A57-A58, A63-A64.0, B63, N70-N71.9, N73-N74, N74.2, N74.8), and maternal sepsis and other maternal infections (MSMI) (ICD-10 O23-O23.93, O41.1-O41.93, O85-O86.89, O91-O91.23), infectious diseases and the detailed subcategories included are listed in Table S1. Notably, the research subjects in this study are female infertility. Due to limitations in data availability and quality in the original GBD data sources, other infections that may affect infertility were not included in this study. Infertility impairments from chlamydial infection, gonococcal infection, and other STIs included both primary and secondary infertility, while maternal sepsis was associated with secondary infertility. In GBD definitions, primary infertility applies to couples with no live births who desire a child, have been in a union for at least five years, and are not using contraception. Secondary infertility applies to couples whose last live birth was over five years ago, with similar criteria for union and contraceptive use. The study focused on women aged 15–49, in line with the WHO’s definition of WRA²⁹.

Statistical analysis

We used age-standardized rates (ASR) to allow for comparisons across different populations by adjusting for the age structure of the population. The age-standardized prevalence rate (ASPR) and age-standardized YLD rate (ASYR) were calculated, and trends in burden were assessed by estimated annual percentage change (EAPC) in ASPR and ASYR from 1990 to 2021, following methodologies from previous studies^30,31. Specific calculations are as follows:

The EAPC was calculated using a linear regression model based on the natural logarithm of the ASR. The model assumes that the natural logarithm of ASR follows a linear relationship with the calendar year:

where is the natural logarithm of the ASR, represents the calendar year, and is the error term. The slope coefficient from the regression model is then used to compute the EAPC:

The EAPC represents the average annual percentage change in ASR over the study period, with its associated 95% confidence interval (CI). Trends were classified based on the EAPC and its 95% CI: a positive EAPC with CI above 0 represents an upward trend, a negative EAPC with CI below 0 represents a downward trend, and a CI encompassing 0 suggests no significant trend.

We applied the Locally Estimated Scatterplot Smoothing (LOESS) method to explore trends in the relationship between SDI and EAPC, ASPR and ASYR. The degree of smoothing is controlled by the span parameter, which defines the fraction of data points considered for each local fit. In our analysis, a span of 0.5 was chosen to balance data fitting and avoid overfitting. The LOESS smoothing curve was visualized alongside the data points, with the shaded area representing the 95% CI of the estimated smoothed values. Residual analysis was performed to validate the model’s suitability. The R code used for generating the figures is available in the supplementary file 1.

A model for assessing the impact of infections on infertility was developed, leveraging data from the 1990–2021 GBD data, to derive the ASPR for infertility cases linked to infections, specifically for the future timeframe of 2022 to 2050. The Bayesian age-period-cohort (BAPC) techniques and Integrated Nested Laplace Approximation (INLA) software packages were deployed to predict the burden of infertility related to infections worldwide. The model is specified as follows:

where is the outcome (ASPR) for age group in period , , , and represent the age, period, and cohort effects, respectively, and ​ is the error term.

Implemented within a Bayesian framework, the BAPC model uses normal priors for the parameters, assuming a normal distribution with a mean of zero and large variance. Model validation was performed using posterior predictive checks, and forecasts were compared with actual data from previous years to assess predictive performance. The model was implemented using the BAPC R package and INLA method for efficient Bayesian inference, with uncertainty intervals applied to explore potential trends. The R code used for BAPC model is available in the supplementary file 2.

All data were processed and visualized using R software (version 4.4.1), the differences were considered statistically significant when the P value was below 0.05.

Result

Global burden of infertility attributable to infections

The global number of prevalent infertility cases attributable to infections rose from 11,274,462 to 19,145,047 from 1990 to 2021. During this period, the ASPR increased from 839.52 to 982.37 per 100,000 population, and YLDs rose from 62.81 (24.53 to 132.90) thousand to 106.69 (42.35 to 221.01) thousand. The calculated EAPC showed that both the global ASPR (0.26 [0.19 to 0.33]) and ASYR (0.23 [0.16 to 0.31]) for infertility attributable to infections demonstrated a significant upward trend over these years. Notably, there were 2 turning points in ASPR and ASYR, in 2005 and 2010, during which the burden of infertility attributable to infections decreased and then continued to increase. (Table 1, Fig. 1).

Table 1.

The prevalence and YLDs of infertility impairment attributable to infections and their EAPCs from 1990 to 2021 at the global and regional levels.

Characteristics	Prevalence					YLDs
	Number of cases, million, 1990 (95% UI)	ASR per 100,000 population, 1990 (95% UI)	Number of cases, million, 2021 (95% UI)	ASR per 100,000 population, 2021 (95% UI)	EAPC, 1990–2021 (95% UI)	Number of cases, thousand, 1990 (95% UI)	ASR per 100,000 population, 1990 (95% UI)	Number of cases, thousand, 2021 (95% UI)		ASR per 100,000 population, 2021 (95% UI)	EAPC, 1990–2021 (95% UI)
Global	11.23(8.54–14.47)	839.52 (638.45–1082.25)	19.15(15.98–23.24)	982.37 (820.15–1192.44)	0.26 (0.19–0.33)	62.81(24.53–132.90)	4.7 (1.83–9.94)	106.69(42.35–221.01)	5.47 (2.17–11.34)		0.23 (0.16–0.31)
Causes
Chlamydial infection	2.76(2.02–3.56)	206.27 (151.15–266.26)	4.76(3.93–5.83)	244.32 (201.48–299.36)	0.32 (0.24–0.39)	15.44(6.38–32.19)	1.15 (0.48–2.41)	26.58(11.05–55.22)	1.36 (0.57–2.83)		0.29 (0.21–0.37)
Gonococcal infection	0.73(0.54–0.96)	54.56 (40.61–72.03)	1.03(0.85–1.25)	52.63 (43.87–64.36)	-0.41 (-0.52–0.3)	4.11(1.60–9.06)	0.31 (0.12–0.68)	5.73(2.15–12.37)	0.29 (0.11–0.63)		-0.45 (-0.56–0.34)
Maternal sepsis and other maternal infections	0.52(0.44–0.60)	38.53 (32.79–44.82)	0.73(0.64–0.83)	37.52 (33.03–42.43)	-0.3 (-0.42–0.18)	2.63(0.98–5.51)	0.20 (0.07–0.41)	3.73(1.42–7.98)	0.19 (0.07–0.41)		-0.3 (-0.42–0.18)
Other sexually transmitted infections	7.22(5.54–9.35)	540.17 (413.90–699.15)	12.63(10.56–15.32)	647.91 (541.77–786.29)	0.33 (0.26–0.4)	40.64(15.56–86.15)	3.04 (1.16–6.44)	70.65(27.73–145.44)	3.63 (1.42–7.46)		0.31 (0.23–0.38)
Sociodemographic index
Low	1.76(1.39–2.17)	1572.1 (1240.85–1942.66)	3.42(2.98–3.96)	1247.25 (1085.17–1443.57)	-1.17 (-1.34–0.99)	9.67(3.80–20.19)	8.66 (3.4–18.08)	18.86(7.54–38.62)	6.87 (2.75–14.08)		-1.17 (-1.35–1)
Low-middle	2.89(2.23–3.70)	1058.13 (815.32–1355.85)	5.44(4.58–6.52)	1075.06 (905.49–1288.17)	-0.27 (-0.39–0.14)	16.23(6.35–34.04)	5.95 (2.33–12.47)	30.64(12.26–62.86)	6.05 (2.42–12.42)		-0.27 (-0.39–0.15)
Middle	2.82(2.09–3.72)	629.76 (467.93–833.16)	5.39(4.37–6.69)	872.27 (706.53–1081)	0.95 (0.86–1.05)	15.62(6.02–33.17)	3.49 (1.35–7.42)	30.01(11.96–63.04)	4.85 (1.93–10.19)		0.95 (0.85–1.05)
High-middle	1.82(1.37–2.40)	653.83 (492.09–864.68)	2.53(2.02–3.21)	828.46 (661.59–1050.51)	0.68 (0.63–0.74)	10.08(3.89–21.44)	3.63 (1.4–7.72)	13.86(5.44–29.52)	4.54 (1.78–9.67)		0.64 (0.59–0.69)
High	1.94(1.40–2.64)	857.05 (615.41–1163.04)	2.35(1.84–2.92)	964.98 (754.96–1201.03)	0.04 (-0.07–0.16)	11.16(4.28–24.07)	4.92 (1.89–10.62)	13.25(5.29–28.36)	5.45 (2.17–11.66)		-0.03 (-0.16–0.09)
GBD regions
Andean Latin America	0.09(0.07–0.11)	908.36 (686.08–1156.73)	0.22(0.16–0.27)	1266.91 (930.98–1524.16)	1.75 (1.48–2.02)	0.48(0.19–1.05)	5.09 (1.95–11.07)	1.22(0.47–2.62)	6.97 (2.67–14.99)		1.65 (1.4–1.9)
Australasia	0.07(0.04–0.10)	1230.26 (696.03–1870.28)	0.10(0.06–0.14)	1325.15 (763.58–1926.45)	0.27 (0.21–0.32)	0.38(0.13–0.90)	7.04 (2.48–16.69)	0.54(0.19–1.27)	7.51 (2.68–17.62)		0.25 (0.2–0.3)
Caribbean	0.07(0.06–0.09)	765.7 (625.97–925.24)	0.10(0.09–0.11)	824.37 (730.34–943.96)	0.12 (-0.09–0.34)	0.41(0.16–0.83)	4.38 (1.76–8.95)	0.56(0.22–1.13)	4.62 (1.85–9.39)		0.09 (-0.13–0.31)
Central Asia	0.15(0.13–0.19)	919.76 (747.38–1131.91)	0.27(0.23–0.30)	1096.61 (953.15–1248.88)	0.21 (0.07–0.34)	0.86(0.35–1.78)	5.14 (2.09–10.61)	1.47(0.59–3.01)	6.04 (2.42–12.41)		0.16 (0.03–0.3)
Central Europe	0.27(0.21–0.34)	878.27 (694.67–1094.59)	0.26(0.22–0.30)	1000.62 (859.72–1172.37)	0.57 (0.43–0.71)	1.49(0.58–3.09)	4.85 (1.9–10.06)	1.41(0.56–2.91)	5.47 (2.17–11.31)		0.54 (0.4–0.68)
Central Latin America	0.27(0.21–0.35)	654.62 (506.22–832.76)	0.54(0.46–0.63)	787.36 (667.24–922.7)	0.34 (0.26–0.43)	1.55(0.60–3.23)	3.69 (1.43–7.7)	2.97(1.20–6.09)	4.36 (1.76–8.93)		0.3 (0.22–0.38)
Central Sub-Saharan Africa	0.18(0.15–0.22)	1460.75 (1191.14–1798.5)	0.44(0.38–0.51)	1346.61 (1163.29–1565.73)	-0.55 (-0.65–0.46)	0.98(0.38–2.08)	7.94 (3.07–16.79)	2.38(0.94–5.02)	7.3 (2.88–15.38)		-0.56 (-0.66–0.46)
East Asia	1.74(1.23–2.41)	522.65 (369.37–723.81)	2.45(1.82–3.32)	741.08 (550.11–1002.03)	1.07 (0.95–1.18)	9.27(3.48–19.63)	2.78 (1.04–5.89)	13.03(4.96–27.96)	3.94 (1.5–8.45)		1.05 (0.93–1.17)
Eastern Europe	0.52(0.37–0.69)	938.21 (677.55–1256.84)	0.49(0.39–0.61)	1008.25 (810.93–1266.32)	-0.08 (-0.19–0.03)	2.95(1.13–6.31)	5.33 (2.04–11.4)	2.74(1.08–5.70)	5.67 (2.24–11.81)		-0.13 (-0.24–0.02)
Eastern Sub-Saharan Africa	0.55(0.44–0.69)	1279.04 (1012.65–1602.17)	1.10(0.96–1.28)	1030.96 (895.87–1193.37)	-1.13 (-1.31–0.96)	3.03(1.18–6.37)	7.01 (2.74–14.76)	6.02(2.41–12.42)	5.62 (2.25–11.59)		-1.16 (-1.33–0.99)
High-income Asia Pacific	0.66(0.43–0.90)	1439.72 (949.01–1977.12)	0.65(0.45–0.84)	1700.34 (1170.92–2204.14)	0.8 (0.7–0.9)	3.62(1.31–8.01)	7.91 (2.85–17.5)	3.53(1.30–7.76)	9.27 (3.43–20.39)		0.77 (0.66–0.87)
High-income North America	0.69(0.47–0.95)	932.7 (629.79–1281.85)	0.81(0.62–1.02)	964.68 (734.42–1219.08)	-0.67 (-0.97–0.38)	4.17(1.53–9.31)	5.61 (2.05–12.52)	4.75(1.88–10.16)	5.65 (2.24–12.09)		-0.76 (-1.06–0.46)
North Africa and Middle East	0.41(0.33–0.51)	527.84 (427.91–652.29)	1.05(0.89–1.26)	658.46 (560.77–788.12)	0.79 (0.73–0.85)	2.44(1.00–4.94)	3.13 (1.28–6.32)	5.97(2.36–12.31)	3.75 (1.48–7.72)		0.69 (0.63–0.76)
Oceania	0.02(0.01–0.02)	1043.1 (809.32–1271.78)	0.03(0.03–0.03)	866.85 (752.01–989.08)	-0.64 (-0.86–0.42)	0.09(0.03–0.18)	5.71 (2.12–11.8)	0.17(0.07–0.35)	4.79 (1.94–10.09)		-0.61 (-0.82–0.39)
South Asia	3.06(2.28–4.01)	1198.75 (894.9–1573.72)	5.61(4.58–6.84)	1134.38 (927.02–1385.06)	-0.51 (-0.65–0.37)	17.26(6.69–36.55)	6.77 (2.62–14.34)	32.00(12.81–66.50)	6.47 (2.59–13.46)		-0.5 (-0.64–0.35)
Southeast Asia	0.43(0.33–0.54)	357.11 (278.53–452.23)	0.74(0.63–0.89)	406.35 (341.62–485.49)	0.43 (0.38–0.48)	2.43(0.95–5.00)	2.02 (0.79–4.16)	4.17(1.65–8.56)	2.27 (0.9–4.67)		0.38 (0.33–0.43)
Southern Latin America	0.15(0.12–0.19)	1183.31 (942.14–1504.06)	0.21(0.18–0.25)	1219.58 (1026.09–1450.6)	0 (-0.1–0.09)	0.83(0.33–1.75)	6.69 (2.62–14.09)	1.20(0.47–2.50)	6.88 (2.71–14.31)		-0.01 (-0.1–0.08)
Southern Sub-Saharan Africa	0.21(0.16–0.27)	1576.89 (1183.14–2067.39)	0.31(0.26–0.37)	1419.56 (1178.38–1702.51)	-1.08 (-1.47–0.68)	1.16(0.45–2.53)	8.76 (3.35–19.03)	1.70(0.68–3.55)	7.82 (3.15–16.33)		-1.12 (-1.53–0.72)
Tropical Latin America	0.17(0.12–0.22)	415.32 (306.03–549.59)	0.88(0.72–1.09)	1456.22 (1182.69–1792.86)	4.6 (3.42–5.79)	0.97(0.38–2.05)	2.43 (0.95–5.15)	5.02(2.03–10.35)	8.27 (3.34–17.08)		4.53 (3.35–5.72)
Western Europe	0.39(0.28–0.52)	406.32 (293.44–540.35)	0.59(0.46–0.73)	630.41 (495.74–782.68)	1.15 (0.82–1.48)	2.27(0.88–4.89)	2.38 (0.92–5.11)	3.35(1.33–7.16)	3.6 (1.43–7.68)		1.07 (0.75–1.39)
Western Sub-Saharan Africa	1.14(0.86–1.41)	2605.61 (1983.62–3222.33)	2.31(1.98–2.69)	1925.52 (1655.35–2241.71)	-1.52 (-1.75–1.28)	6.18(2.39–12.94)	14.18 (5.48–29.68)	12.52(5.01–26.22)	10.44 (4.18–21.87)		-1.53 (-1.77–1.29)

ASR, Age-standardized rate; YLD, years lived with disability; EAPC, estimated annual percentage change; UI, uncertainty interval.

Fig. 1.

Trends in age-standardized rates of prevalence and YLDs for infertility attributable to infectious causes in women of child-bearing age from 1990 to 2021, by SDI. (A) Prevalence of overall infections, (B) YLDs of overall infections, (C) Prevalence of chlamydial infections, (D) YLDs of chlamydial infections, (E) Prevalence of gonococcal infections, (F) YLDs of gonococcal infections, (G) Prevalence of other STIs, (H) YLDs of other STIs, (I) Prevalence of MSMI, (J) YLDs of MSMI. YLDs, years lived with disability; SDI, socio-demographic index; STIs, other sexually transmitted infections; MSMI, maternal sepsis and other maternal infections.

Among the four infection-related causes of infertility identified in GBD 2021 (chlamydial infection, gonococcal infection, other STIs, and MSMI), the highest prevalence was attributable to other STIs, with an estimated 12,626,805 new cases (65.95%) and an ASPR of 647.91 per 100,000 (541.77 to 786.29) population in 2021. This category also had the fastest increase, with EAPCs of 0.33 (0.26 to 0.40) for ASPR and 0.31 (0.23 to 0.38) for ASYR. Chlamydial infection was the second most prevalent cause, with 4,761,445 new cases (24.87%) and an ASPR of 244.32 per 100,000 in 2021. Both ASPR (EAPC 0.32 [0.24 to 0.39]) and ASYR (EAPC 0.29 [0.21 to 0.37]) for infertility attributable to chlamydial infection showed significant increases since 1990. In contrast, gonococcal infection and MSMI had relatively lower prevalence rates in 2021, with estimated new cases of 729,666 (3.82%) and 515,275 (6.59%), and ASPRs of 52.63 (43.87 to 64.36) and 37.52 (33.03–42.43) per 100,000, respectively. Infertility attributable to gonococcal infection and MSMI decreased slightly compared to 1990, with EAPCs of –0.41 (–0.52 to –0.30) and –0.30 (–0.42 to –0.18) for ASPR, and –0.45 (–0.56 to –0.34) and –0.30 (–0.42 to –0.18) for ASYR (Table 1).

The burden of infertility attributable to infections by SDI, region and nation

In SDI regions, low SDI regions exhibited the highest ASPR at 1,247.25 per 100,000 population and ASYR at 6.87 per 100,000 population (Table 1, Fig. 1A-B). However, these regions also showed the fastest decline in ASPR (EAPC –1.17 [–1.34 to –0.99]) and ASYR (EAPC –1.17 [–1.35 to –1.00]). Regions with high-middle SDI recorded the lowest ASPR (828.46 [661.59 to 1050.51] per 100,000) and ASYR (4.54 [1.78 to 9.67] per 100,000). From 1990 to 2021, ASPR and ASYR generally decreased in low and low-middle SDI regions but slightly increased over the last decade. With initially lower burdens, middle and high-middle SDI regions modestly rose in ASPR and ASYR, while high SDI regions remained stable (Fig. 1A,B). Low SDI regions carried the greatest burden of infertility attributable to chlamydial infection, gonococcal infection, other STIs, and MSMI in 2021(Fig. 1C–J). High SDI regions ranked second in ASPR and ASYR for gonococcal infection-related infertility, following low SDI regions (Fig. 1E,F). Notably, secondary infertility attributable to MSMI showed marked regional disparities, with ASPR in low and low-middle SDI regions approximately 6–7 times higher than in high and high-middle SDI regions (Fig. 1G,H).

Regarding the 21 GBD regions, eight showed declines in ASPR and ASYR for infertility attributable to infections from 1990 to 2021. the fastest decline region was Western Sub-Saharan Africa which still had the highest ASPR (1,925.52 [1655.35 to 2241.71] per 100,000) and ASYR (10.44 [4.18 to 21.87] per 100,000) in 2021. In contrast, Southern Asia had the lowest ASPR (406.35 [341.62 to 485.49] per 100,000) and ASYR (2.27 [0.9 to 4.67] per 100,000) in the same year (Table 1, Fig. 2A). In contrast, 11 regions experienced increases in burden, with Tropical Latin America exhibiting the fastest growth in ASPR (EAPC 4.6 [3.42 to 5.79]) and ASYR (EAPC 4.53 [3.35 to 5.72]). Southern Latin America and the Caribbean maintained stable trends throughout this period (Fig. 2B, Table S2).

Fig. 2.

Age-standardized rates of prevalence and YLDs in 2021, with their trends in estimated annual percentage changes for infertility attributable to infectious causes across global and regional levels, from 1990 to 2021. (A) Prevalence and YLDs, (B) EAPC for prevalence and YLDs. Overall infections include Chlamydia infections, Gonococcal infections, STIs, and MSMI. YLDs, years lived with disability; EAPC, estimated annual percentage change; STIs, other sexually transmitted infections; MSMI, maternal sepsis and other maternal infections.

At the national level in 2021, Cabo Verde, Togo, and Ghana had the highest ASPR and ASYR for infection-related infertility, while Belarus had the lowest burden. From 1990 to 2021, 111 countries experienced increases in ASPR and ASYR for infertility attributable to infections, with Brazil, Spain, and Greece showing the most substantial growth. Conversely, 57 countries experienced declines, led by Mali, Ethiopia, and Burkina Faso, while 36 countries maintained stable trends (Fig. 3, Table S3).

Fig. 3.

National-level age-standardized rates of prevalence and YLDs in 2021 and their trends in estimated annual percentage changes for infertility attributable to infections from 1990 to 2021. World maps show prevalence (A) and YLDs (B) by country in 2021. (C) and (D) show EAPC in prevalence and YLDs, respectively. Overall infections include Chlamydia infections, Gonococcal infections, STIs, and MSMI. YLDs, years lived with disability; EAPC, estimated annual percentage change; STIs, other sexually transmitted infections; MSMI, maternal sepsis and other maternal infections.

Significant variations appeared in ASPR and ASYR across regions and nations for each type of infection-related infertility. In 2021, Western Sub-Saharan Africa reported the highest ASPR for both chlamydial infections (502.36 [423.32 to 596.68] per 100,000) and other STIs (1230.23 [1065.04 to 1424.91] per 100,000). Australasia had the highest ASPR for gonococcal infections (153.33 [86.21 to 224.76] per 100,000), while Southern Sub-Saharan Africa exhibited the highest ASPR for MSMI (118.89 [105.69 to 133.39] per 100,000) (Fig. 2A). Nationally, Ghana had the highest ASPR of Gonococcal infections (161.88 per 100,000), while Pakistan had the highest prevalence of MSMI (168.67 per 100,000). Cabo Verde reported the highest rates for both chlamydial infection (673.90 [568.56 to 790.55] per 100,000) and other STIs (1,656.60 [1445.89 to 1917.67] per 100,000). Between 1990 and 2021, ASPRs and YLDs for infertility attributable to Chlamydial infection, Gonococcal infections, MSMI, and other STIs rose in 15, 6, 11, and 14 regions, respectively. Tropical Latin America showed the most substantial increases in ASPR and ASYR for infertility related to chlamydial infection, gonococcal infection, and other STIs, while Eastern Europe saw the largest rise for MSMI. Conversely, Western Sub-Saharan Africa recorded the fastest declines in ASPR and ASYR for infertility from chlamydial infection, gonococcal infections, and other STIs, while the High-income Asia Pacific region showed the most substantial decrease for MSMI (Fig. 2B).

The burden of infertility attributable to infections by age

To analyze the global burden of infection-induced infertility in WRA at specific ages, we divided this population (ages 15–49) into specific age groups. The results revealed a consistent age-related pattern for the prevalence and YLDs of infection-related infertility in 2021. Overall, both the prevalence and YLDs rose with age, peaking at 40–44 years and then declining in the 45–49 age group (Fig. 4A,B). Specifically, the age distribution for infertility attributable to chlamydial infection, gonococcal infection and other STIs was similar to the overall trend. However, secondary infertility attributable to MSMI showed a continuous increase from ages 15–29, maintaining a high level from ages 25–49. Across all age groups, other STIs were the leading infection type associated with the highest prevalence and YLDs of infertility, followed by chlamydial infection, gonococcal infection, and MSMI (Fig. 4A,B).

Fig. 4.

Cross-sectional and longitudinal trends of prevalence and YLDs in 2021 for Infertility attributable to infections across reproductive age groups. (A) the number and incidence rates of prevalent cases in 2021, (B) the number and rates of YLDs for the same year. (C) percentage changes in prevalence rates from 1990 to 2021. (D) percentage changes in YLDs rates from 1990 to 2021. Overall infections include Chlamydia infections, Gonococcal infections, STIs, and MSMI. YLDs, years lived with disability; STIs, other sexually transmitted infections; MSMI, maternal sepsis and other maternal infections.

From 1990 to 2021, the 40–44 age group consistently had the highest burden of infection-related infertility, while the 20–24 age group showed the most significant increases (Figure S3, Fig. 4C,D). Infertility attributable to other STIs and chlamydial infection increased across all age groups, with the fastest growth observed among younger women, especially in the 25–29 and 20–24 age groups. In contrast, all age groups demonstrated a declining trend in infertility attributable to gonococcal infection and MSMI, with the sharpest reduction in the 45–49 age group (Fig. 4C,D).

The Relevance of SDI and Burden of infertility attributable to infections

The analysis of the relationship between SDI and infection-related infertility, found that the burden showed a general decline as SDI increased. The global ASPR and ASYR for infertility attributable to infections among WRA decreased as SDI increased, reaching their lowest at around an SDI of 0.5, followed by a slight upward trend (Fig. 5A,B). A similar trend was noted for the burden of infertility attributable to chlamydial infection, gonococcal infection, and other STIs (Figures S1-S2). For infertility attributable to MSMI, ASPR and ASYR decreased significantly with higher SDI levels (Figure S1-S2). In addition, the analysis of the EAPC in 204 countries demonstrated a positive correlation between the SDI and EAPC from 1990 to 2021, higher-SDI countries experienced more rapid increases in infection-related infertility prevalence and YLDs, peaking around an SDI of 0.75, whereas low and lower-middle SDI countries showed a declining trend (Fig. 5C,D).

Fig. 5.

Correlation between SDI in 2021 and prevalence and YLDs for infertility attributable to overall infections. (A) Age-standardized rates of prevalence, globally and for 21 GBD regions. (B) Age-standardized rates of YLDs, globally and for 21 GBD regions. (C) EAPCs of prevalence for 204 counties. (D) EAPCs of YLDs for 204 counties. Expected values with 95% CI, based on SDI and disease rates in all locations, are shown as a solid line and shaded area. Points are plotted for each region and show the observed age-standardized incidence or YLDs rates for each year from 1990 to 2021. Overall infections include Chlamydia infections, Gonococcal infections, STIs, and MSMI. YLDs, years lived with disability; GBD, Global Burden of Diseases, Injuries and Risk Factors Study; STIs, other sexually transmitted infections; MSMI, maternal sepsis and other maternal infections; SDI, socio-demographic index.

Forecasts of the burden of infertility attributable to infection from 2022 to 2050

Based on data from 1990 to 2021, we constructed a BAPC model to predict trends in the global burden of infertility attributable to infections by 2050, and validated the reliability of the model by comparing it with the existing GBD data from 1990–2021 (Figure S4, Table S4-S8). Our results showed that the overall burden for infertility attributable to all infections fluctuated between years from 2022 to 2050, with an overall slightly increasing trend (Fig. 6A), with the ASPR for WRA increasing to 1339.60 per 100,000 by 2050. Of all age groups, the 40–44 group remains predicted to suffer the highest burden of disease, and also the fastest growing (Fig. 6B–H). Analyzed by type of infection, the burden of infertility attributable to chlamydial infection, gonococcal infection, and other STIs will increase, and further age subgroup analyses showed that women in the 40–44 age group would continue to have the highest burden. While the highest burden of infertility due to MSMI will change from the 35–39 group in 2021 to the 40–44 age group by 2050 (Figure S5-S8).

Fig. 6.

BAPC model projections of age-standardized rates of infertility attributable to overall infections from 2022 to 2050, by age groups. (A) Predicted age-standardized incidence of infertility attributable to infections in age 15–49. (B) Predicted age-standardized incidence in age group 15–19 years. (C) Predicted age-standardized incidence in age group 20–24 years. (D) Predicted age-standardized incidence in age group 25–29 years. (E) Predicted age-standardized incidence in age group 30–34 years. (E) Predicted age-standardized incidence in age group 35–39 years. (E) Predicted age-standardized incidence in age group 40–44 years. (E) Predicted age-standardized incidence in age group 45–49 years. Agestd, age standard.

Discussion

Infertility has become a global health issue, impacting not only reproductive function but also overall health¹⁷. Based on the latest GBD 2021 data, our research presents a detailed analysis of the burden of infection-related infertility, examining time trends at national, regional and global levels. From 1990 to 2021, global ASPR and ASYR for infection-related infertility increased. Significant geographic differences emerged, with low SDI regions bearing the highest burden but showing improvements over time. In contrast, middle and high-middle SDI regions, which had the lowest initial burden, showed rising ASPR and YLDs and experienced increasing ASPR and ASYR. Overall, the burden of infection-related infertility, particularly for MSMI, correlated negatively with SDI.

Our results showed that the global burden of infertility attributable to infections is predominantly driven by other STIs and chlamydia infections, which were also the main factors in the increasing burden. The increased burden may be related to more comprehensive and specific testing and screening policies, especially in high and high-middle SDI regions³². In contrast, infertility attributable to gonococcal infections and MSMI remained lower and showed a decline since 1990. This decline correlates with effective prevention and treatment of related infections, for instance, in 2017, WHO developed a consensus definition of maternal sepsis and provided guidance on the prevention, early diagnosis, and clinical management and then America, British and Australia issued their own consensus on screening and treatment^33,34. A GBD 2019-based study reported a global decline in chlamydial infection and gonococcal infection prevalence³⁵. However, our study revealed an increasing burden of female infertility attributable to chlamydial infection. This variation may partly stem from advancements in testing technologies and related policies³⁶ and lifestyle changes among WRA in these regions. Increased participation in career and educational pursuits has led to delayed reproduction, and it is the delay in childbearing that increases the risk of infertility due to advanced age^3,37,38. Additionally, although the overall burden of infertility attributable to gonococcal infections has decreased since 1990, the past decade has shown a resurgence. This trend is likely linked to rising antimicrobial resistance in Neisseria gonorrhoeae. Currently, gonococcal resistance has been documented in multiple antimicrobial classes, including sulfonamides, penicillins, tetracyclines, and fluoroquinolones^39–41. Moreover, the occurrence of multidrug-resistant Neisseria gonorrhoeae has risen significantly in the last ten years⁴², compounding treatment challenges and worsening infertility outcomes. To combat these challenges, the WHO and several countries have implemented strategies such as dual antimicrobial therapy and the development of new antimicrobials³⁹. Meanwhile, vaccine development against Neisseria gonorrhoeae and Chlamydia trachomatis has also been recognized as a vital and sustainable approach to control these infections⁴³.

Both clinical and laboratory researches have shown that STIs, such as chlamydia and gonococcal can result in female infertility. C. trachomatis, the most common STI in America⁴⁴, often causes asymptomatic infections that can lead to tubal damage and TFI. The pathogen’s heat shock protein 60 induces inflammation, resulting in scarring and tubal occlusion²⁴. Moreover, the autoimmune response can impair embryo development and implantation⁴⁵. N. gonorrhoeae also attacks the epithelial cells of the fallopian tube, increasing the risk of infertility and ectopic pregnancy⁴⁶. For women of advanced age, the damage caused by such infections can further increase the risk of infertility. Studies have shown that 40–44 years is the age stage with the heaviest burden of female infertility³, and our results also found that the burden of infection-related infertility rose with age, peaking in the 40–44 age group and then declining. This trend may be attributed to two factors: the general increase in infertility risk with age^47,48, and a reduced incidence of STIs among women aged 45–49³⁵.

Our results indicated that Western Sub-Saharan Africa faced the most significant burden of infection-related infertility, while Tropical Latin America has shown the fastest growth. This pattern is partly attributable to limited economic and healthcare resources, such as inadequate screening for sexually transmitted infections and difficulty in accessing antibiotics. Additionally, social factors related to health, such as insufficient sexual health education and the cultural stigma surrounding infertility, also aggravate the situation^49,50. Several high-income countries have introduced control strategies for asymptomatic infections in STIs, while clinicians in low- and middle-income countries (LMICs) often rely on syndromic management to address and manage the diseases follow the WHO’s strategy⁵¹. However, as many STIs are asymptomatic⁵², which may result in misdiagnosis in 20%-70% of cases⁵³. STIs remain a major public health threat, especially in LMICs where the majority of the global STI impairment occurs^54,55. Encouragingly, current health policies have shown positive effects in these regions, contributing to a rapid decline in the burden of infertility attributable to infections.

Additionally, we also reported the global epidemiologic status and trends of secondary infertility attributable to MSMI for the first time. Limited studies have identified secondary infertility as a complication of maternal sepsis^21,56. Severe infections from maternal sepsis cause inflammatory damage to the oviducts and endometrium, impairing reproductive function. Subsequent treatments, such as dilation and curettage or abscess drainage, can also lead to iatrogenic injury of reproductive organs^57–59. However, robust clinical evidence remains limited, and the exact mechanisms of this association are not yet fully understood, further studies are necessary to prove this association. Previous studies based on GBD 2019 have documented a steady decline in global prevalence, mortality, and disability-adjusted life-years of MSMI, with low SDI regions experiencing the heaviest burden but showing the most significant decreases⁶⁰. Our findings aligned with these trends and underscored marked disparities in infertility attributable to MSMI across SDI regions. According to our results, Southern Sub-Saharan Africa suffered the heaviest burden of infertility attributable to MSMI, it closely related to the low-quality medications, economic challenges, and limited educational resources in the region^61–63. Fortunately, the low SDI region, especially South Asia, has shown the most significant downward trend in the burden of infertility attributable to MSMI, this decline may be due to their effective screening and postnatal visit policies⁶⁴. However, maternal sepsis diagnosis and treatment often receive inadequate attention, the latest Surviving Sepsis Campaign guidelines lack protocols specific to pregnant or postpartum populations⁶⁵. Consequently, the WHO recommends adapted sepsis protocols for maternal sepsis treatment tailored to local obstetric patients⁶⁶. However, guideline adherence still needs to progress, for example, in sub-Saharan Africa, only 1.5% of hospitals surveyed adhered to clinical sepsis guidelines, which means that efforts are still necessary to prevent and treat maternal sepsis in these high-burden areas, with effective strategies such as vaccination programs, quality control of medicines, and regionally tailored interventions⁶⁷. Moreover, future research should prioritize the development of standardized diagnostic criteria and treatment protocols for maternal sepsis. Additionally, policymakers should focus on improving healthcare infrastructure and access, particularly in low-income regions, to ensure timely and effective management of infections.

The WHO report emphasized that early prevention, diagnosis, and treatment of STIs, along with managing maternal sepsis complications, are essential for reducing infertility, especially in LMICs^7,68, where the assisted reproductive technologies are limited. In 2022, WHO introduced the Global Health Sector Strategies for human immunodeficiency virus(HIV), viral hepatitis, and STIs for 2022–2030, aiming to reduce new cases of syphilis and Gonorrhea by 90% and Chlamydia and trichomoniasis by 50% by 2030, with 2020 as the baseline⁶⁹. In 2023, WHO incorporated STI prevention and control into its Universal Health Coverage strategy to reduce the global STI burden by expanding screening, increasing treatment access, and promoting health education⁷⁰. Achieving these goals requires coordinated efforts among organizations, governments, and public health institutions to strengthen health systems, optimize resource allocation, and enhance preventive strategies.

There are some limitations in this research. First, this study relies on GBD data, which inevitably has the raw data quality issues, such as possible underreporting or methodological flaws in collection. The quality and completeness of GBD data can vary across countries due to differences in healthcare infrastructure and data collection systems, and the reporting standards and diagnostic criteria for infertility and infections may differ across regions, which may be subject to reporting bias. Particularly in LMICs, face challenges in providing adequate primary data attributable to limited resources, underdeveloped health systems, and insufficient data collection and reporting mechanisms. Besides, infertility is often stigmatized in these regions, leading women to avoid seeking medical care or disclosing their condition. In conclusion, underreporting likely underestimates the true global burden of infection-related infertility, particularly in regions with high stigma (e.g., Western Sub-Saharan Africa) or inadequate healthcare (e.g., Southern Asia)^71–73. Second, although the SDI is a widely used descriptive measure of socio-economic status, it also has limitations that it does not reflect local disparities in healthcare access or cultural factors influencing reproductive health outcomes, suggesting incorporating mixed-methods approaches to address these gaps in future research. Third, our study suggests there is an association between maternal sepsis and secondary infertility, but there is limited clinical and laboratory evidence, which will require more studies in the future to prove the association. Finally, infections that may be associated with female reproductive health, such as HIV and Human Papillomavirus (HPV) infections, are not included due to unavailable data in GBD 2021, we acknowledge that the exclusion of these conditions may have underestimated the true burden of infertility attributable to infections, particularly in high-prevalence regions. However, the majority of the evidence for HIV and HPV impairment of fertility focuses on male infertility, while the evidence for causing female infertility is limited⁷⁴. This study included all the infection types related to female infertility available in GBD 2021, which also are infection types with the strongest evidence, thus the conclusion remains credible. Meanwhile, it is necessary for future studies to include a broader range of infectious and analyze more completely the influence of infections on female reproductive health, to develop more targeted and effective intervention strategies.

Despite these limitations, GBD data remains a valuable resource for understanding global health trends and informing public health policies. Our projections indicate an increasing trend in infertility attributable to infections by 2050. Policymakers and healthcare providers should use these projections to design prevention and treatment strategies tailored to local needs, effectively reducing the burden of infection-related infertility in WRA. Effective strategies include increasing access to STI screening and treatment services⁷⁵, implementing comprehensive sex education programs⁷⁶, and promoting condom use to reduce the spread of infections^77,78. Additionally, the rising trends in infertility could place additional pressure on healthcare systems, particularly in LMICs where resources are already stretched thin. Addressing these challenges requires a multifaceted approach, including strengthening healthcare infrastructure, training healthcare providers, expanding assisted reproductive technology services and raising public awareness about the importance of reproductive health⁷⁹. Vaccination programs are vital in preventing infections that lead to infertility. HPV vaccine is a successful example⁸⁰, studies and observational data suggested that the gonorrhea vaccine can reduce disease prevalence, and current clinical trials are ongoing⁸¹. However, Chlamydia vaccine development has been challenging, with no effective vaccine found after numerous trials⁹. Future efforts should focus on advancing vaccine research and ensuring widespread implementation to improve the current situation. Overall, a multifaceted approach involving prevention, treatment, and education is necessary to decrease the burden of infertility attributable to infections and improve reproductive health worldwide.

In conclusion, infectious diseases are a major cause of infertility and a significant threat to the health of women of reproductive age worldwide. This study offers detailed insights into the geographic distribution, age patterns, and temporal trends of infection-related infertility, highlighting the urgent need for targeted global and regional strategies to address infection-related infertility, especially in low-SDI regions. The findings provide essential scientific evidence for policymakers to prioritize investment in STIs prevention, screening, and treatment.

Author contributions

Conception and design: JW, LF. Data collection: JW, HH. Analysis and interpretation of data: HH. Manuscript writing: JW, LF, HH. All authors were involved in the editing and approval of the final manuscript.

Data availability

All data used in this study for analysis are available through the Global Burden of Diseases, Injuries, and Risk Factors Study 2021（https://vizhub.healthdata.org/gbd-results/).

Declarations

Competing interests

The authors declare no competing interests.

Supplementary Information

The online version contains supplementary material available at 10.1038/s41598-025-94259-9.