Global, Regional, and National Burden of Female Infertility Attributable to Chlamydia Infections, 1990–2023: An Analysis Based on the Global Burden of Disease Study 2023

Female infertility refers to the inability to achieve pregnancy after 12 months or more of regular, unprotected sex or due to impaired reproductive function. 1 According to recent reports by the World Health Organization (WHO), approximately one-sixth of the global population has faced infertility at some point in their lives. 2 The global age-standardized prevalence rate(ASPR) of female infertility rose by an average of 0.68% per year from 1990 to 2021 3 The underlying causes of female infertility can be broadly classified into chromosomal abnormalities, ovarian factors, ovulation disorders, recurrent pregnancy losses, 4 endometriosis, 5 and tubal factors. 6 Infertility exerts a marked influence on women’s mental health, elevating their stress levels. 7 , 8 Female infertility is broadly categorized into two primary types: primary and secondary, distinguished by a woman’s history of clinical pregnancy. 1 According to recent GBD 2021 estimates, secondary infertility, with an ASPR roughly three times that of primary infertility, accounts for the larger part of the female infertility burden globally. 9 This burden is frequently associated with reproductive tract infections. 10–12 Among these, Chlamydia infection, a significant sexually transmitted bacterial infection, disproportionately affects women and can lead to a range of medical complications. 13 Notably, over 70% of chlamydia infections are asymptomatic. 14 Without treatment, the pathogen can ascend to the upper genital tract and cause pelvic inflammatory disease (PID). 15–18 Persistent tubal infection then triggers chronic inflammation, characterized by cytokine/chemokine release and iNOS-mediated nitric oxide production, leading to tissue remodeling and tubal scarring. 19 Immune sensitization to chlamydial heat shock protein 60 (cHSP60) 18 and activation of TLR/TGF-β/Smad signaling in tubal epithelial cells further promote fibrosis and epithelial-mesenchymal transition. 20 These processes ultimately result in tubal epithelial damage, adhesion formation, and luminal obstruction, causing tubal factor infertility and increasing the risk of ectopic pregnancy. 17 , 19 Previous research has primarily concentrated on the prevalence of chlamydia infections in infertile women. A study conducted in India, involving 477 infertile females, revealed a prevalence of chlamydia infection among infertile female patients of 15.7%. 21 In addition, a study in Australia, encompassing 1500 infertile women, reported a chlamydia infection rate of 12.4%. 22 At the global level, GBD 2021 data on STI-attributable infertility show that chlamydia accounts for the largest share of this burden, highlighting the pressing need to enhance chlamydia screening and related public health interventions. 23 , 24 However, despite the recognition of chlamydia as an important contributor to female infertility, no prior study has specifically quantified the global burden of chlamydia-attributable female infertility using standardized GBD methodology across all countries and time periods. The WHO’s 2025 report further emphasizes that untreated sexually transmitted infections remain a major preventable cause of infertility, underscoring the urgent need for such evidence. 25 To address this gap, this study provided a comprehensive assessment of the global, regional, and national burden of infertility due to chlamydia infection among women aged 15–49 years using GBD 2023 data, stratified by age and socio-demographic index (SDI) and covering 27 regions and 204 countries and territories from 1990 to 2023. Prevalence rates, years lived with disability (YLD), and trends were examined, and the analysis offers actionable recommendations for policy development and health system planning to prevent and manage infertility caused by chlamydia infections.

At global level, in 1990, there were 2.76 million prevalent cases of infertility among reproductive-aged women due to chlamydial infection, with an ASPR of 110.37 per 100,000 persons. By 2023, this number had significantly increased to 4.76 million cases, accompanied by an ASPR of 117.98 per 100,000 persons ( Table 1 ). Furthermore, over the past 30 years, there has been a consistent upward trend in the ASPRs for infertility, with an AAPC of 0.21 [95% UI: 0.19–0.23] ( Table 1 and Figure 1A ). Similarly, ASPRs for primary infertility and secondary infertility have also risen, with an AAPC of 0.18 (0.14–0.21) ( Table S1 and Figure 1B ), and an AAPC of 0.23 (0.20–0.25) ( Table S3 and Figure 1C ), respectively. Secondary infertility exhibited a greater prevalence and a pronounced surge than that observed in primary infertility ( Table S1 and S3 ). Figure 1 Age-standardized rates of prevalence and YLD among female of reproductive age (15 ~ 49 years) for infertility attributable to chlamydial infection by SDI during 1990 ~ 2023. ( A ) Prevalence of infertility; ( B ) Prevalence of primary infertility; ( C ) Prevalence of secondary infertility; ( D ) YLD of infertility; ( E ) YLD of primary infertility; ( F ) YLD of secondary infertility. The image A showing a multi-line graph. X-axis label: Year, range 1990 to 2023. Y-axis label: Infertility Age-standardized Rate (per 100,000), range 50 to 250. Legend lines: Global, High-middle SDI, High SDI, Low-middle SDI, Low SDI, Middle SDI. Trends: Low SDI is highest, declining from the early 1990s to around 2010 then rising slightly by 2020. Low-middle SDI is second highest, with a mild decline into the 2010s then a small rise by 2020. Global, High-middle SDI, Middle SDI and High SDI are lower and relatively flatter, with small gradual increases toward 2020. The image B showing a multi-line graph. X-axis label: Year, range 1990 to 2020. Y-axis label: Primary infertility Age-standardized Rate (per 100,000), range 10 to 45. Legend lines: Global, High-middle SDI, High SDI, Low-middle SDI, Low SDI, Middle SDI. Trends: Low SDI and Low-middle SDI are highest in the 1990s, both trending downward into the 2010s, then edging upward by 2020. High SDI shows a pronounced early peak in the 1990s before declining. Global and Middle SDI sit mid-range and drift slightly downward then stabilize. High- middle SDI is lowest and remains relatively flat with a slight decline. The image C showing a multi-line graph. X-axis label: Year, range 1990 to 2020. Y-axis label: Secondary infertility Age-standardized Rate (per 100,000), range 50 to 200. Legend lines: Global, High-middle SDI, High SDI, Low-middle SDI, Low SDI, Middle SDI. Trends: Low SDI is highest, falling steadily from the 1990s to around 2010 then increasing slightly by 2020. Low-middle SDI is next highest, dipping into the 2010s then rising modestly. Global, High-middle SDI, Middle SDI and High SDI are lower and show gentle upward movement toward 2020. The image D showing a multi-line graph. X-axis label: Year, range 1990 to 2020. Y-axis label: Infertility Age-standardized YLD Rate (per 100,000), range 0.4 to 1.3. Legend lines: Global, High-middle SDI, High SDI, Low-middle SDI, Low SDI, Middle SDI. Trends: Low SDI is highest, decreasing from the 1990s to around 2010 then rising slightly by 2020. Low-middle SDI is second highest with a similar dip then small rebound. The remaining groups cluster lower with mild increases over time. The image E showing a multi-line graph. X-axis label: Year, range 1990 to 2020. Y-axis label: Primary infertility Age-standardized YLD Rate (per 100,000), range 0.10 to 0.30. Legend lines: Global, High-middle SDI, High SDI, Low-middle SDI, Low SDI, Middle SDI. Trends: Low SDI and Low-middle SDI are highest in the 1990s, both declining into the 2010s and then rising slightly by 2020. Global and High SDI remain mid-range with small changes. High-middle SDI is lowest and stays relatively flat. The image F showing a multi-line graph. X-axis label: Year, range 1990 to 2020. Y-axis label: Secondary infertility Age-standardized YLD Rate (per 100,000), range 0.3 to 1.0. Legend lines: Global, High-middle SDI, High SDI, Low-middle SDI, Low SDI, Middle SDI. Trends: Low SDI is highest, dropping from the 1990s to around 2010 then increasing slightly by 2020. Low-middle SDI is next highest with a smaller dip and rebound. Global, High-middle SDI, Middle SDI and High SDI are lower and show gradual increases toward 2020. Six multi-line graphs showing age-standardized prevalence and YLD rates of infertility attributable to chlamydial infection among females of reproductive age (15–49 years), by SDI group, 1990–2023. Abbreviations: ASPR, age-standardized prevalence rate; YLD, years lived with disability; SDI, Sociodemographic index. Table 1 The Prevalence of Infertility Impairment Owing to Chlamydial Infection and Their AAPCs from 1990 to 2023 at the Global and Regional Levels 1990 2023 1990 ~ 2023 Prevalent Cases No. (95% UI) ASPR per 100,000 No. (95% UI) Prevalent Cases No. (95% UI) ASPR per 100,000 No. (95% UI) AAPC No. (95% CI) P value Global 2,758,535 (2021399–3560834) 110.37 (80.61–143.55) 4,761,445 (3926461–5834178) 117.98 (97.63–144.35) 0.21 (0.19–0.23) 0 Age   15-19 years 46,841 (28758–67425) 15.19 (9.33–21.87) 59,272 (35474–81724) 16.18 (9.68–22.31) 0.18 (0.05–0.31) 0.005837   20-24 years 153,568 (109668–215486) 49.07 (35.04–68.86) 211,672 (166236–270278) 56.21 (44.15–71.78) 0.42 (0.37–0.47) 0   25-29 years 338,394 (239295–448104) 116.72 (82.53–154.56) 498,853 (404060–612077) 130.14 (105.41–159.68) 0.35 (0.31–0.40) 0   30-34 years 541,917 (369147–732061) 208.71 (142.17–281.94) 895,405 (718752–1101723) 219.31 (176.04–269.84) 0.16 (0.12–0.19) 0   35-39 years 711,667 (510246–938117) 280.15 (200.86–369.29) 1,230,269 (1019888–1454299) 302.38 (250.68–357.45) 0.26 (0.20–0.32) 0   40-44 years 741,756 (548644–954256) 325.18 (240.52–418.34) 1,380,385 (1159323–1625892) 342.04 (287.27–402.88) 0.16 (0.10–0.21) 0   45-49 years 224,393 (68373–472333) 108.67 (33.11–228.75) 485,589 (151674–1010406) 113.57 (35.47–236.32) 0.13 (0.09–0.17) 0 Socio-demographic index   Low SDI 444,606 (331451–559352) 231.29 (172.82–291.13) 870,196 (749966–1024078) 181.99 (155.03–216.53) −0.17(−0.28 - −0.06) 0.00219   Low-middle SDI 724,386 (533000–926781) 150.3 (110.37–193.16) 1,396,245 (1159152–1684646) 142.24 (117.66–172.12) −0.76(−0.88 - −0.63) 0   Middle SDI 654,557 (475878–855683) 82.82 (59.64–110.46) 1,323,713 (1061241–1657937) 100.08 (80.6–124.33) 0.61 (0.59–0.63) 0   High-middle SDI 441,213 (327159–572409) 81.34 (59.78–106.2) 606,441 (485228–758954) 85.49 (69.46–105.67) 0.04 (−0.04 - 0.12) 0.310635   High SDI 491,335 (333876–671391) 101.11 (68.54–138.1) 561,767 (430905–714636) 102.27 (78.83–129.07) 0.37 (0.24–0.49) 0 Region   African Region 530,524 (393176–667826) 274.46 (202.85–346.3) 1,065,048 (908351–1266655) 210.66 (176.58–252.12) −0.86(−0.96 - −0.77) 0   Andean Latin America 22,782 (16525–29693) 137.21 (100.04–178.59) 59,471 (43602–72662) 166.89 (122.33–204.16) 0.75 (0.45–1.05) 0.000001   Australasia 23,696 (13280–36360) 208.58 (116.89–320.39) 34,364 (19917–50761) 216.21 (124.63–320.22) 0.13 (0.08–0.19) 0.000002   Caribbean 18,630 (14793–23011) 109.68 (86.63–135.91) 25,675 (22645–29274) 104.76 (92.75–119.24) −0.15(−0.18 - −0.12) 0   Central Asia 41,525 (33234–52128) 135.85 (107.51–170) 71,256 (60630–81858) 137.58 (117.18–158.25) 0.03 (−0.03 - 0.09) 0.340677   Central Europe 74,060 (57034–93072) 112.29 (86.66–141.11) 71,227 (60632–83861) 121.02 (103.49–141.63) 0.23 (0.14–0.32) 0   Central Latin America 72,560 (54293–92370) 98.78 (73.69–125.53) 144,874 (120611–171513) 103.96 (86.55–122.97) 0.16 (0.12–0.21) 0   Central Sub-Saharan Africa 43,720 (34243–55890) 212.56 (163.64–277.25) 106,295 (91154–124847) 189.79 (160.58–226.74) −0.39 (−0.66 - −0.13) 0.003876   East Asia 341,602 (237981–465053) 57.17 (38.91–79.41) 478,014 (356958–643975) 60.57 (46.47–79.22) 0.16 (−0.04 - 0.36) 0.124866   Eastern Europe 139,384 (99429–183501) 116.09 (83.26–153.23) 131,023 (104917–163398) 111.71 (89.89–139.07) −0.13 (−0.15 - −0.10) 0   Eastern Mediterranean Region 140,547 (105278–181822) 98.63 (73.44–128.59) 381,494 (318945–464409) 99.99 (82.96–122.56) 0.01 (−0.19 - 0.21) 0.907189   Eastern Sub-Saharan Africa 136,498 (103504–173123) 192.65 (145.97–243.19) 276,045 (237590–327281) 150.18 (127.82–180.34) −0.80(−0.90 - −0.70) 0   European Region 398,805 (299137–507933) 90.39 (67.73–115.13) 504,769 (415913–613727) 104.58 (86.65–126.27) 0.47 (0.38–0.57) 0   High-income Asia Pacific 180,730 (112549–253859) 186.46 (117.75–262.76) 183,334 (128439–242374) 206.89 (141.74–271.96) −0.73(−0.88 - −0.57) 0   High-income North America 138,905 (85951–195387) 85.19 (52.77–120.03) 123,454 (90544–157711) 68.61 (50.48–87.1) 0.15 (0.10–0.21) 0   North Africa and Middle East 108,452 (84833–135814) 81.6 (63.3–102.09) 271,349 (230318–324852) 82.31 (69.51–99.17) 0.05 (−0.01 - 0.11) 0.084651   Oceania 3327 (2521–4109) 126.8 (95.29–158.42) 6042 (5094–6808) 91.1 (76.46–102.77) −1.08(−1.13 - −1.03) 0   Region of the Americas 330,211 (238395–438792) 90.3 (65.23–120.07) 646,638 (531734–791468) 118.55 (97.51–144.83) 0.86 (0.72–0.99) 0   South Asia 765,039 (545637–996485) 166.23 (117.8–218.52) 1,449,646 (1159428–1787755) 149.55 (119.17–185.03) −0.28(−0.35 - −0.20) 0   Southeast Asia 95,724 (72068–122231) 44.96 (33.68–58.87) 168,361 (139097–202255) 43.96 (36.39–52.7) −0.35(−0.51 - −0.18) 0.000036   South-East Asia Region 774,010 (557409–1008269) 135.45 (96.75–177.62) 1,378,989 (1107219–1697953) 124.38 (99.78–153.45) −0.07(−0.11 - −0.03) 0.000178   Southern Latin America 38,660 (29571–51097) 158.8 (121.07–210.05) 56,624 (46993–68183) 153.4 (128.42–183.06) −0.10(−0.14 - −0.07) 0   Southern Sub-Saharan Africa 51,129 (36861–67313) 222.54 (159.62–293.02) 75,016 (61368–91891) 168.82 (137.83–207.07) −0.91(−1.10 - −0.72) 0   Tropical Latin America 41,507 (29436–54989) 56.43 (39.46–75.19) 239,186 (189903–302385) 181.99 (144.41–229.74) 3.89 (3.33–4.46) 0   Western Europe 122,976 (87140–164482) 60.88 (42.93–81.33) 187,905 (146353–238397) 88.91 (70.16–111.4) 1.22 (1.13–1.32) 0   Western Pacific Region 574,344 (406205–778200) 75.66 (52.99–103.21) 772,642 (583762–1019073) 76.74 (59.31–98.86) 0.04 (0.00–0.07) 0.034033   Western Sub-Saharan Africa 297,631 (216059–376985) 412.91 (298.46–523.52) 602,283 (507523–715354) 294.34 (245.54–351.68) −1.08(−1.19 - −0.96) 0 Abbreviations : ASPR, age-standardized prevalence rate; AAPC, average annual percentage change; UI, uncertainty interval; SDI, Socio-demographic index. Age-standardized rates of prevalence and YLD among female of reproductive age (15 ~ 49 years) for infertility attributable to chlamydial infection by SDI during 1990 ~ 2023. ( A ) Prevalence of infertility; ( B ) Prevalence of primary infertility; ( C ) Prevalence of secondary infertility; ( D ) YLD of infertility; ( E ) YLD of primary infertility; ( F ) YLD of secondary infertility. The Prevalence of Infertility Impairment Owing to Chlamydial Infection and Their AAPCs from 1990 to 2023 at the Global and Regional Levels Abbreviations : ASPR, age-standardized prevalence rate; AAPC, average annual percentage change; UI, uncertainty interval; SDI, Socio-demographic index. Globally, between 1990 and 2023, the YLDs associated with infertility caused by chlamydial infection surged by 72.2%, from 15.44 thousand to 26.58 thousand ( Table 2 ). Specifically, there was a 62.2% rise in the YLDs associated with primary infertility, increasing from 4.45 thousand to 7.22 thousand ( Table S2 ). Meanwhile, the YLDs for secondary infertility witnessed a 76.3% growth, climbing from 10.98 thousand to 19.36 thousand ( Table S4 ). The global age-standardized rates of YLD for infertility, primary infertility, and secondary infertility each exhibited an upward trend. Specifically, the AAPC for infertility was 0.22 (0.19–0.26) ( Table 2 and Figure 1D ). Similarly, the AAPC for primary infertility was 0.18 (0.14–0.23) ( Table S2 and Figure 1E ), and for secondary infertility, it was 0.24 (0.21–0.26) ( Table S4 and Figure 1F ). It is noteworthy that the global prevalence rate of infertility attributable to chlamydial infection remained relatively stable until 2011. However, a notable upward trend in prevalence has emerged since that time ( Figure 1 ). Table 2 The YLD of Infertility Impairment Owing to Chlamydial Infection and Their AAPCs from 1990 to 2023 at the Global and Regional Levels 1990 2023 1990 ~ 2023 YLD No. (95% UI) Age-Standardized YLD per 100,000 No. (95% UI) YLD No. (95% UI) Age-Standardized YLD per 100,000 No. (95% UI) AAPC No. (95% CI) P value Global 15,436 (6378–32186) 0.62 (0.25–1.28) 26,579 (11049–55222) 0.66 (0.27–1.36) 0.22 (0.19–0.26) 0 Age   15-19 years 298 (109–647) 0.1 (0.04–0.21) 365 (124–810) 0.1 (0.03–0.22) 0.10 (−0.01 - 0.21) 0.088533   20-24 years 962 (386–1886) 0.31 (0.12–0.6) 1293 (514–2603) 0.34 (0.14–0.69) 0.35 (0.29–0.42) 0   25-29 years 2016 (800–4025) 0.7 (0.28–1.39) 2939 (1217–5757) 0.77 (0.32–1.5) 0.31 (0.27–0.36) 0   30-34 years 3031 (1227–6328) 1.17 (0.47–2.44) 4980 (2026–10236) 1.22 (0.5–2.51) 0.12 (0.08–0.17) 0   35-39 years 3859 (1579–7981) 1.52 (0.62–3.14) 6700 (2737–14001) 1.65 (0.67–3.44) 0.27 (0.22–0.31) 0   40-44 years 4038 (1656–8460) 1.77 (0.73–3.71) 7597 (3139–15556) 1.88 (0.78–3.85) 0.19 (0.11–0.27) 0.000005   45-49 years 1233 (312–3251) 0.6 (0.15–1.57) 2705 (684–7229) 0.63 (0.16–1.69) 0.18 (0.13–0.22) 0 Socio-demographic index   Low SDI 2449 (1030–5263) 1.27 (0.52–2.77) 4810 (1994–9710) 1 (0.41–2.05) −0.15 (−0.25 - −0.05) 0.002398   Low-middle SDI 4086 (1739–8536) 0.84 (0.36–1.76) 7880 (3336–16215) 0.8 (0.34–1.66) −0.73 −0.86 - −0.61) 0   Middle SDI 3639 (1502–7731) 0.46 (0.19–0.98) 7376 (3081–15406) 0.56 (0.23–1.16) 0.64 (0.61–0.67) 0   High-middle SDI 2445 (1004–5186) 0.45 (0.18–0.96) 3336 (1353–7045) 0.47 (0.19–0.99) 0.00 (−0.05 - 0.06) 0.870969   High SDI 2804 (1125–5925) 0.58 (0.23–1.22) 3160 (1273–6900) 0.58 (0.23–1.25) 0.36 (0.28–0.44) 0 Region   African Region 2892 (1198–6225) 1.49 (0.61–3.27) 5804 (2389–12175) 1.14 (0.47–2.43) −0.86 −0.94 - −0.77) 0   Andean Latin America 127 (50–281) 0.76 (0.31–1.69) 328 (126–713) 0.92 (0.35–2) 0.69 (0.41–0.97) 0.000001   Australasia 136 (51–311) 1.2 (0.45–2.74) 195 (71–448) 1.23 (0.44–2.84) 0.13 (0.03–0.22) 0.008071   Caribbean 106 (45–212) 0.62 (0.26–1.25) 144 (58–291) 0.59 (0.24–1.18) −0.19 (−0.24 - −0.13) 0   Central Asia 231 (100–468) 0.75 (0.33–1.51) 393 (158–821) 0.76 (0.31–1.58) 0.01 (−0.03 - 0.05) 0.4712   Central Europe 407 (170–830) 0.62 (0.26–1.26) 389 (157–784) 0.66 (0.27–1.34) 0.21 (0.16–0.27) 0   Central Latin America 408 (166–849) 0.55 (0.22–1.16) 801 (332–1635) 0.57 (0.24–1.17) 0.12 (0.07–0.17) 0.000001   Central Sub-Saharan Africa 238 (96–482) 1.15 (0.46–2.37) 579 (233–1211) 1.03 (0.41–2.18) −0.34 (−0.51 - −0.18) 0.000035   East Asia 1799 (721–3930) 0.3 (0.12–0.66) 2529 (1024–5531) 0.32 (0.13–0.7) 0.19 (0.14–0.24) 0   Eastern Europe 786 (330–1664) 0.66 (0.28–1.39) 733 (305–1501) 0.63 (0.26–1.27) −0.14(−0.16 - −0.11) 0   Eastern Mediterranean Region 819 (349–1680) 0.57 (0.24–1.17) 2224 (928–4521) 0.58 (0.24–1.19) 0.05 (−0.14 - 0.23) 0.625775   Eastern Sub-Saharan Africa 748 (314–1606) 1.05 (0.44–2.27) 1510 (620–3071) 0.82 (0.33–1.69) −0.79 (−0.91 - −0.68) 0   European Region 2271 (942–4745) 0.52 (0.21–1.08) 2836 (1159–5820) 0.59 (0.24–1.2) 0.44 (0.35–0.53) 0   High-income Asia Pacific 992 (382–2138) 1.03 (0.4–2.22) 1001 (380–2230) 1.14 (0.43–2.59) −0.80(−0.95 - −0.64) 0   High-income North America 831 (335–1745) 0.51 (0.21–1.07) 723 (293–1504) 0.4 (0.16–0.83) 0.15 (0.10–0.20) 0   North Africa and Middle East 643 (280–1266) 0.48 (0.21–0.96) 1549 (621–3128) 0.47 (0.19–0.96) −0.05 (−0.11 - 0.02) 0.17078   Oceania 18 (7–37) 0.69 (0.27–1.42) 34 (14–71) 0.51 (0.21–1.06) −1.02 (−1.12 - −0.93) 0   Region of the Americas 1919 (788–3985) 0.52 (0.21–1.09) 3657 (1521–7475) 0.67 (0.28–1.37) 0.79 (0.67–0.92) 0   South Asia 4346 (1835–9138) 0.94 (0.39–1.96) 8289 (3509–17097) 0.86 (0.36–1.76) −0.26 (−0.34 - −0.18) 0   Southeast Asia 543 (223–1091) 0.25 (0.1–0.52) 948 (389–1934) 0.25 (0.1–0.5) −0.30 (−0.44 - −0.17) 0.000013   South-East Asia Region 4394 (1850–9233) 0.76 (0.32–1.59) 7828 (3328–16136) 0.71 (0.3–1.46) −0.08 (−0.13 - −0.03) 0.001506   Southern Latin America 218 (89–441) 0.9 (0.36–1.81) 321 (126–667) 0.87 (0.34–1.81) −0.08 (−0.13 - −0.03) 0.00296   Southern Sub-Saharan Africa 284 (119–613) 1.23 (0.52–2.68) 415 (175–855) 0.93 (0.4–1.94) −0.94 (−1.13 - −0.76) 0   Tropical Latin America 244 (102–500) 0.33 (0.14–0.69) 1355 (575–2769) 1.03 (0.44–2.1) 3.79 (3.22–4.37) 0   Western Europe 720 (286–1504) 0.36 (0.14–0.74) 1076 (436–2301) 0.51 (0.21–1.08) 1.18 (1.11–1.24) 0   Western Pacific Region 3087 (1223–6564) 0.41 (0.16–0.87) 4165 (1650–9231) 0.42 (0.17–0.9) 0.06 (0.03–0.10) 0.000208   Western Sub-Saharan Africa 1611 (655–3442) 2.22 (0.9–4.84) 3269 (1337–6987) 1.59 (0.65–3.43) −1.08 (−1.15 - −1.01) 0 Abbreviations : YLD, years lived with disability; AAPC, average annual percentage change; UI, uncertainty interval; SDI, Socio-demographic index. The YLD of Infertility Impairment Owing to Chlamydial Infection and Their AAPCs from 1990 to 2023 at the Global and Regional Levels Abbreviations : YLD, years lived with disability; AAPC, average annual percentage change; UI, uncertainty interval; SDI, Socio-demographic index. A notable increase in prevalence rate of total infertility and secondary infertility was observed across nearly all age groups from 1990 to 2023 ( Table 1 and Table S3 ). Notably, primary infertility shows a unique trend with declines in the 15–19 and 30–34 age groups but increases in other groups, peaking in the 40–44 age groups ( Table S1 ). The aforementioned results provide further evidence that secondary infertility may have a more significant impact on overall infertility than primary infertility. Additionally, there was an increase in the YLD rate in each age group for infertility and secondary infertility ( Table 2 and Table S4 ), and the age distribution of the YLD for primary infertility was the similar to the age distribution of the prevalence Table S2 ). Globally, the age distribution of prevalent cases and rates for infertility, as well as secondary infertility, remained largely consistent among women of reproductive age ( Figure 2A ). The analysis of data from 2023 reveals an upward trend in the prevalence related to infertility and secondary infertility with advancing age, peaking at the 40–44 age group. However, upon reaching 44 years of age, both the prevalence associated with infertility underwent a swift decline ( Figure 2A ). In addition, primary infertility shows a very different trend: it remains at a relatively low and stable level before 35–39 age groups, then reaching a small peak at 40–45 years of age. A comparable decline was also observed in the 45–49 age group with regard to primary infertility ( Figure 2A ). The age distribution of YLD exhibited a similar pattern to that observed in the prevalencenumbers and rates in 2023 ( Figure 2B ). Figure 2 The cross-sectional (2023) and longitudinal trends (1990~2023) of prevalence and YLD rate of female infertility attributable to chlamydial infection throughout women of child-bearing age (15~49 years). Numbers and rates of prevalent cases ( A ) and YLD ( B ) of female infertility. Percentage changes of prevalence ( C ) and YLD rate ( D ) of female infertility. The image A showing a stacked bar and line graph for age groups 15 to 19 years, 20 to 24 years, 25 to 29 years, 30 to 34 years, 35 to 39 years, 40 to 44 years, 45 to 49 years. X axis label: age group (years). Primary y axis label: Number of prevalent cases in 2023 (times 100,000), range 0 to 30. Secondary y axis label: Rate of prevalence in 2023, range 0 to 600. Three line series with markers: Infertility, Primary infertility, Secondary infertility. Stacked bars are segmented by the same three categories. Trend: all three lines rise from 15 to 19 years to 40 to 44 years, then drop at 45 to 49 years; infertility is highest, secondary infertility is next, primary infertility is lowest. The image B showing a stacked bar and line graph for the same age groups. X axis label: age group (years). Primary y axis label: Number of YLD in 2023 (times 1,000), range 0 to 20. Secondary y axis label: Rate of YLD in 2023, range 0 to 4. Three line series with markers: Infertility, Primary infertility, Secondary infertility. Stacked bars are segmented by the same three categories. Trend: lines increase to a peak at 40 to 44 years and decline at 45 to 49 years; infertility is highest, secondary infertility is next, primary infertility is lowest. The image C showing a line graph. X axis label: age group (years). Y axis label: Percentage change of prevalence rate (1990 to 2023), range negative 10 to 40, with a dotted baseline at 0. Three line series with markers: Infertility, Primary infertility, Secondary infertility. Trend: infertility and secondary infertility are positive across all age groups, rising to their highest values around 40 to 44 years and then falling at 45 to 49 years; primary infertility is near 0 at younger ages, dips below 0 around 30 to 34 years, then rises sharply to a peak around 40 to 44 years and declines at 45 to 49 years. The image D showing a line graph. X axis label: age group (years). Y axis label: Percentage change of YLD rate (1990 to 2023), range negative 0.05 to 0.20, with a dotted baseline at 0. Three line series with markers: Infertility, Primary infertility, Secondary infertility. Trend: infertility and secondary infertility rise to their highest values around 35 to 39 years, then decline; primary infertility is near 0 at younger ages, dips below 0 around 30 to 34 years, then rises to a peak around 40 to 44 years and declines at 45 to 49 years. Relationship across graphs: A and B show 2023 levels for prevalence and YLD by age group, while C and D show percentage changes from 1990 to 2023 for prevalence rate and YLD rate by age group, using the same three infertility categories. A four graph figure of infertility, primary infertility and secondary infertility by age group. Abbreviation: YLD, years lived with disability. The cross-sectional (2023) and longitudinal trends (1990~2023) of prevalence and YLD rate of female infertility attributable to chlamydial infection throughout women of child-bearing age (15~49 years). Numbers and rates of prevalent cases ( A ) and YLD ( B ) of female infertility. Percentage changes of prevalence ( C ) and YLD rate ( D ) of female infertility. The percentage changes in the burdens of infertility and secondary infertility between 1990 and 2023 exhibited an upward trend, peaking in the 35–39 age group and maintaining high levels among individuals aged 40–45 ( Figure 2C ). In primary infertility, the percentage changes remained stable before age 29, and reached their lowest point in the 30–34 age group, subsequently experiencing a rapid increase to peak in the 40–44 age group ( Figure 2C ). Moreover, there has been a notable decline in the percentage change for both infertility and its subtypes in the 45–49 age range ( Figure 2C ). It is noteworthy that the percentage change in primary infertility was higher than that of secondary infertility among individuals aged 40–45 ( Figure 2C ). Therefore, despite the significantly lower number of cases, the impact of primary infertility on overall infertility in 40–45 age group cannot be underestimated. Similar patterns were observed in the percentage changes of YLD from 1990 to 2023 ( Figure 2D ). In comparison to the data from 1990, the low SDI region demonstrated a decline in the ASPR, with an AAPC of −0.17 (95% CI: −0.28 to −0.06) in 2023. Moreover, the low-middle SDI region exhibited a sharper decline, with an AAPC of −0.76 (95% CI: −0.88 to −0.63) during the same period ( Table 1 ). In addition, the ASPR in the middle-SDI regions in 2023 showed a significant increase compared to 1990, with an APPC of 0.61 (95% CI: 0.59–0.63) ( Table 1 ). Furthermore, a markedly higher ASPR was observed in the low SDI region compared with the other four SDI regions. ( Figure 1A ). Although the regions categorized as low SDI and low-middle SDI have generally seen a decline in infertility linked to chlamydia infections, it is Intriguing that there has been a notable increase in both regions over the past five years or so ( Figure 1A ). These rates of increase exceed those seen over the past decades, necessitating greater vigilance and attention. Additionally, the ASPR of middle-SDI has maintained a steady increase from 1990 to 2023 ( Figure 1A ). Comparable trends were observed in cases of primary and secondary infertility due to chlamydia infection ( Figure 1B and C ; Tables S1 and S3 ). The age-standardized YLD rate in the five SDI regions resembled the ASPR pattern ( Figure 1D–F ; Figure 2 ). More details are shown in Table 2 , Tables S2 and S4 . In addition, a weak and positive correlation between SDI and the ASPR of total infertility, primary infertility, and secondary infertility attributable to chlamydia infections was observed in 27 regions (R = 0.10, 0.09, and 0.11, respectively; all P < 0.05, Figure 3A–C ). Specifically, the ASPR did not follow a linear gradient; it was highest at low SDI values, declined to a nadir at intermediate SDI values, and then showed a modest increase at high SDI values ( Figure 3 ). Similar pattern can be observed between the YLD of total infertility, primary infertility, and secondary infertility and SDI(R=0.10,0.09,0.12, respectively, all P<0.05, Figure 3D and F ). Figure 3 The correlation between age-standardized rates and SDI globally and for 21 GBD regions for female infertility attributable to chlamydial infection from 1990 to 2023. ( A ) Prevalence of infertility. ( B ) Prevalence of primary infertility. ( C ) Prevalence of secondary infertility. ( D ) YLD of infertility. ( E ) YLD of primary infertility. ( F ) YLD of secondary infertility. Colored lines show global and region values for age-standardized burden estimates rates. Each point in a line represents 1 year starting at 1990 and ending at 2023. The black line represents the average expected relationship between SDI and burden estimates rates for infertility based on values from each region in the 1990–2023 estimation period. The images show scatter plots of infertility metrics against SDI (0.3 to 0.9). Image A: Infertility ASPR (50-250) decreases from 190 at SDI 0.33 to 95 at 0.50, then increases to 160 at 0.90 (R=0.10, P=0.01). Image B: Primary infertility ASPR (0-60) drops from 50 at SDI 0.33 to 22 at 0.50, then rises to 32 at 0.90 (R=0.09, P=0.03). Image C: Secondary infertility ASPR (0-150) falls from 135 at SDI 0.33 to 70 at 0.50, then climbs to 120 at 0.90 (R=0.11, P=0.00). Image D: Infertility age-standardized YLD rate (0.5-1.5) decreases from 1.2 at SDI 0.33 to 0.65 at 0.50, then rises to 0.95 at 0.90 (R=0.10, P=0.02). Image E: Primary infertility age-standardized YLD rate (0.0-0.4) drops from 0.35 at SDI 0.33 to 0.15 at 0.50, then increases to 0.23 at 0.90 (R=0.09, P=0.02). Image F: Secondary infertility age-standardized YLD rate (0.25-0.75) decreases from 0.70 at SDI 0.33 to 0.35 at 0.50, then rises to 0.60 at 0.90 (R=0.12, P=0.00). Legend: Global regions include Asia, Europe, Americas, etc. A set of six scatter plots showing infertility measures versus socio demographic index across regions. Abbreviations: GBD, global burden of diseases; ASPR, age-standardized prevalence rate; YLD, years lived with disability; SDI, socio-demographic index. The correlation between age-standardized rates and SDI globally and for 21 GBD regions for female infertility attributable to chlamydial infection from 1990 to 2023. ( A ) Prevalence of infertility. ( B ) Prevalence of primary infertility. ( C ) Prevalence of secondary infertility. ( D ) YLD of infertility. ( E ) YLD of primary infertility. ( F ) YLD of secondary infertility. Colored lines show global and region values for age-standardized burden estimates rates. Each point in a line represents 1 year starting at 1990 and ending at 2023. The black line represents the average expected relationship between SDI and burden estimates rates for infertility based on values from each region in the 1990–2023 estimation period. In 2023, the majority of prevalent cases were concentrated in the low-middle and middle SDI regions, with the highest numbers reported in the South Asia (Prevalent cases = 1,449,646, 95% UI: [1,159,428 - 1,787,755]), Southeast Asia (Prevalent cases = 1,378,989, 95% UI:[1,107,219 - 1,697,953]) and African region (Prevalent cases = 1,065,048, 95% UI:[908,351 - 1,266,655]) ( Table 1 , Figure 4A ). Furthermore, the regions with the highest ASPRs in 2023 were Western Sub-Saharan Africa (ASPR = 294.34; 95% CI:[245.54-351.68]), Australasia (ASPR = 216.21; 95% CI:[124.63-320.22]), and the African Region (ASPR = 210.66; 95% CI:[176.58-252.12]) ( Table 1 ). Conversely, the lowest ASPRs were recorded in Southeast Asia (ASPR = 43.96; 95% CI:[36.39-52.7]), East Asia (ASPR = 60.57; 95% CI:[46.47-79.22]), and High-income North America (ASPR = 68.61; 95% CI:[50.48-87.1])( Table 1 ). Regarding annual percentage changes in ASPRs, the most significant increases were observed in Tropical Latin America (AAPC = 3.89; 95% CI:[3.33-4.46]), Western Europe (AAPC = 1.22; 95% CI:[1.13-1.32]), and the Region of the Americas (AAPC = 0.86; 95% CI:[0.72-0.99]). In contrast, the most notable decreases in ASPRs were noted in Western Sub-Saharan Africa (AAPC = −1.08; 95% CI:[−1.19 to −0.96]), Oceania (AAPC = −1.08; 95% CI:[−1.13 to −1.03]), and Southern Sub-Saharan Africa (AAPC = −0.91; 95% CI:[−1.10 to −0.72]) ( Table 1 ). Notably, despite the high ASPRs observed in Western Sub-Saharan Africa in 2023, the region’s ASPRs have declined substantially over the last 30 years. Further details may be found in Table 1 , Tables S1 and S3 . Figure 4 Numbers and proportions of prevalent cases and YLD contributed by GBD regions and SDI, for female infertility attributable to chlamydial infection, in 2023. Numbers of prevalent cases ( A ) and YLD ( B ) of women infertility. Image A displays a horizontal bar graph comparing infertility types globally, across SDI groups, health systems and GBD regions. The legend includes Infertility, Primary infertility and Secondary infertility. The X-axis shows prevalent cases in 2023 (x 100,000) with tick labels 25, 0, 25 and a top scale of 0, 25, 50, 75. Y-axis categories include Global, various SDI levels, health systems and regions like Western Europe, South Asia and African Region. Bars extend from 0, with Limited Health System reaching near 75. Image B features a similar graph with the same legend and Y-axis categories. The X-axis indicates YLD in 2023 (x 1,000) with tick labels 20, 0, 20 and a top scale of 0, 20, 40. Again, Limited Health System has the largest extent, nearing 40. A grouped horizontal bar graph showing infertility prevalent cases and YLD by SDI and region in 2023. Abbreviations: YLD, years lived with disability; SDI, Socio-demographic index. Numbers and proportions of prevalent cases and YLD contributed by GBD regions and SDI, for female infertility attributable to chlamydial infection, in 2023. Numbers of prevalent cases ( A ) and YLD ( B ) of women infertility. The distribution of YLD across different regions is same to the distribution of prevalent cases ( Figure 4B ). Additionally, the age-standardized YLD rates of the 27 regions exhibited a comparable trend to that observed for ASPR. The regions exhibiting the highest and lowest age-standardized YLD rates are identical to those observed for the ASPR. Similarly, the regions with the highest and lowest annual increase rates are also consistent with those observed for the ASPR ( Table 2 ). Further details may be found in Table 2 and Tables S2 and S4 . The national ASPR of infertility attributed to chlamydia infection ranged from 25.4 to 336 per 100,000 individuals in 2023. Cabo Verde (336), Cameroon (332.6), and Liberia (329.3) reported the highest rates of infertility attributed to chlamydia infection, whereas Iceland (25.4), Cyprus (28.2), and Malta (29.1) had the lowest estimates ( Figure 5 and Table S5 ). When considering infertility subtypes, the distribution across different countries of primary infertility differs from that of secondary infertility and total infertility. The countries with the highest national ASPR of primary infertility are New Zealand (63.4), the United Kingdom (57.6), and Cameroon (54.3). Conversely, Taiwan (Province of China) (4.3), the Democratic People’s Republic of Korea (4.8), and China (5.3) have the lowest ASPR ( Figure S1 and Table S6 ). Cabo Verde boasts the highest ASPR for secondary infertility at 301.1, closely followed by Sierra Leone at 300.1 and Liberia at 295.7. In contrast, Iceland (18), Denmark (19.5), and Cyprus (19.7) show the lowest ASPR ( Figure S2 and Table S7 ). The annual changes in the ASPR of infertility exhibited the most rapid growth from 1990 to 2023 in Brazil (AAPC = 3.99), followed by Spain (AAPC = 2.17) and Italy (AAPC = 2). Conversely, the steepest annual declines in the ASPR were observed in Mali (AAPC=−2.32), Burkina Faso (AAPC = −1.53), and Bangladesh (AAPC = −1.51) ( Figure 5 and Table S8 ). Over the same period, the ASPR for primary infertility has been most significant in Brazil (AAPC=3.03), Italy (AAPC=1.92) and the United Kingdom (AAPC=1.46). Conversely, the largest annual decreases in the ASPR for primary infertility have been observed in Burkina Faso(AAPC=−2.46), Mali (AAPC=−2.11), and Thailand (AAPC=−1.82)( Figure S1 and Table S9 ). Additionally, Brazil (AAPC=4.38), Spain (AAPC=2.79),and Italy (AAPC=2.03) have the greatest annual increase in rates of ASPR secondary infertility, with Mali (AAPC=−2.35), Papua New Guinea (AAPC=−1.63), and Bangladesh (AAPC=−1.53) having the largest annual decreases Figure S2 and Table S10 ). Figure 5 Global map of 2023 age-standardized rates and corresponding average annual percentage changes from 1990 to 2023 for female infertility attributable to chlamydial infection. ( A ) The ASPR of infertility attributable to chlamydial infection in 2023. ( B ) The AAPC of ASPR from 1990 to 2023. ( C ) The age-standardized YLD rate of infertility attributable to PCOS in 2023. ( D ) The AAPC of age-standardized YLD rate from 1990 to 2023. A) The map shows age-standardized rates (ASR) per 100,000 population for female infertility in 2023. Rates range from 0.0 to 30+, with higher values in parts of Africa and South America. B) The map displays average annual percentage change (AAPC) in ASR from 1990 to 2023. Values range from -3.0 to 3.0+, with rapid growth in South America and parts of Europe. C) The map illustrates years lived with disability (YLD) rates per 100,000 population for female infertility in 2023. Rates range from 0.0 to 1.50+, with higher values in South America and Africa. D) The map shows AAPC in YLD rates from 1990 to 2023, ranging from -3.0 to 3.0+, with significant increases in South America and parts of Africa. Each map uses a gradient to represent different rate categories, highlighting regional variations. Four world maps showing ASR, AAPC and YLD rates per 100,000 population for female infertility in 2023. Abbreviations: ASPR, age-standardized prevalence rate; AAPC, average annual percentage change; YLD, years lived with disability. Global map of 2023 age-standardized rates and corresponding average annual percentage changes from 1990 to 2023 for female infertility attributable to chlamydial infection. ( A ) The ASPR of infertility attributable to chlamydial infection in 2023. ( B ) The AAPC of ASPR from 1990 to 2023. ( C ) The age-standardized YLD rate of infertility attributable to PCOS in 2023. ( D ) The AAPC of age-standardized YLD rate from 1990 to 2023. In 2023, the national age-standardized YLD of infertility attributed to chlamydia infection ranged from 0.1 to 1.8 per 100,000. The countries with the highest age-standardized YLD of infertility were Mauritania (1.8), Liberia (1.8), and Gambia (1.8), whereas the lowest age-standardized YLD were observed in Iceland (0.1), Cambodia (0.2), and Myanmar (0.2) ( Figure 5 and Table S11 ). Subsequently, an examination of the age-standardized YLD for the subtypes of infertility was conducted. New Zealand (0.47), United Kingdom (0.43), and Cameroon (0.4) had the highest age-standardized YLD of primary infertility, with Taiwan (Province of China) (0.03), China (0.04), and Democratic People’s Republic of Korea (0.04) having the lowest estimates ( Figure S1 and Table S12 ). Moreover, the highest age-standardized YLD of secondary infertility were observed in Cabo Verde (1.54), followed by Sierra Leone (1.53) and Liberia (1.5). Conversely, the lowest age-standardized YLD were observed in Iceland (0.09), Cyprus (0.1), and Denmark (0.1) ( Figure S2 and Table S13 ). From 1990 to 2023, the annual growth rate of age-standardized YLDs due to infertility exhibited the most rapid increase in Brazil (AAPC=3.88), followed by Spain (AAPC=2.06) and Italy (AAPC=1.93), whereas Mali (AAPC=−2.29), Burkina Faso (AAPC=−1.56), and Ethiopia (AAPC=−1.51) having the steepest annual declines ( Figure 5 and Table S14 ). Furthermore, for primary infertility, the largest increases of annual growth rate of age-standardized YLDs occurred in Brazil (AAPC=3.03), Italy (AAPC=1.91), and United Kingdom (AAPC=1.47). In contrast, Burkina Faso (AAPC=−2.44), Mali (AAPC=−2.08), and Thailand (AAPC=−1.8) had the largest declines ( Figure S1 and Table S15 ). In addition, Brazil (AAPC=4.39) also had the highest increase in the annual change in the age-standardized YLDs for secondary infertility, followed by Spain (AAPC=2.71), and Italy (AAPC=2.03), with Mali (AAPC=−2.33), Papua New Guinea (AAPC=−1.62), and Bangladesh (AAPC=−1.48) having the largest reductions ( Figure S2 and Table S16 ).

This study examined data pertaining to infertility linked to chlamydia infection, sourced from GBD 2023. The GBD 2023 produced estimates for 371 diseases and injuries across 204 countries and territories, grouped into 27 regions, including 21 countries with subnational locations, and both females, males, and both sexes combined, spanning the years 1990–2023. 26 The SDI is an aggregate indicator of social and economic development that affects the health outcomes of each nation. In accordance with the SDI scores recorded for each country in 2023, the 204 countries and territories were classified into five distinct SDI quintiles: low, low-middle, middle, high-middle, and high. The SDI is calculated on a scale of 0 to 1, utilizing three key variables: the average years of education for individuals over the age of 15, the total fertility rate for those under the age of 25, and the lagged income per capita. Regions with more advanced socioeconomic and demographic progress are characterized by higher SDI values. 26 In the GBD 2023 study, the case definition for chlamydia infection is genital infections caused by the bacterium Chlamydia trachomatis . 26 Chlamydia trachomatis is one of the most frequently identified pathogens associated with PID. 16 Notably, PID has been considered to be a risk factor for infertility. 16 The burden of female infertility and its subtypes (primary and secondary infertility) was estimated in this study. Primary infertility was used to describe a woman who previously had not been pregnant, whereas secondary infertility was used to describe a woman who had previously given birth and was unable to do so subsequently. 27 According to the GBD 2023 cause list, a few primary causes of female infertility were identified, encompassing PID due to chlamydia, gonorrhoea, and other STIs, endometriosis, maternal sepsis, polycystic ovary syndrome, congenital Turner syndrome, and congenital urogenital anomalies. DisMod-MR 2.1 is a Bayesian meta-regression tool used in the GBD framework to integrate data from multiple sources and generate internally consistent estimates of disease parameters. In the GBD 2023 methodology, data are extracted from population-based surveys and processed using DisMod-MR 2.1 models. The prevalence of total, primary, and secondary infertility is estimated by sex and cause, employing four distinct DisMod-MR 2.1 models. Data on the prevalence, YLD, and ASPR due to chlamydia-induced female infertility were obtained directly from the GBD 2023 results database. Age-standardized rates (ASRs) were calculated per 100,000 population using the following formula: \documentclass[12pt]{minimal} \usepackage{wasysym} \usepackage[substack]{amsmath} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage[mathscr]{eucal} \usepackage{mathrsfs} \DeclareFontFamily{T1}{linotext}{} \DeclareFontShape{T1}{linotext}{m}{n} {linotext }{} \DeclareSymbolFont{linotext}{T1}{linotext}{m}{n} \DeclareSymbolFontAlphabet{\mathLINOTEXT}{linotext} \begin{document}$$ASR = {{\mathop \sum \nolimits_{i = 1}^A {a_i}{w_i}} \over {\mathop \sum \nolimits_{i = 1}^A {a_i}}} \times 100,000 $$\end{document} (a i : the age-specific rate in i th the age group; \documentclass[12pt]{minimal} \usepackage{wasysym} \usepackage[substack]{amsmath} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage[mathscr]{eucal} \usepackage{mathrsfs} \DeclareFontFamily{T1}{linotext}{} \DeclareFontShape{T1}{linotext}{m}{n} {linotext }{} \DeclareSymbolFont{linotext}{T1}{linotext}{m}{n} \DeclareSymbolFontAlphabet{\mathLINOTEXT}{linotext} \begin{document}${w_i}$\end{document} : the number of people in the corresponding i th age group among the standard population; A : the number of age groups). The ASR was directly standardized and the GBD global age-standard population was used as the reference population to standardize these rates. 28 Disability-adjusted life years (DALYs) are the sum of YLDs and years of life lost (YLLs); YLDs are generated by multiplying prevalence by disability weights (0.008 for primary infertility and 0.005 for secondary infertility). Because chlamydia-attributable female infertility is non-fatal, YLLs were zero, and therefore DALYs equaled YLDs. 26 The 95% uncertainty intervals (UIs) were derived from the 2.5 th and 97.5 th percentiles of 1000 draws from the posterior distribution. This study adhered to the Guidelines for Accurate and Transparent Health Estimates Reporting, which specifically tailored for cross-sectional studies. As the data set did not contain any personal information and was publicly accessible, ethical approval was not required. Prevalent cases, YLDs, and corresponding ASRs were obtained directly from GBD 2023. The analysis was restricted to female infertility attributable to Chlamydia trachomatis infection among women aged 15–49 years, divided into seven 5-year age groups. Trends in female infertility attributable to Chlamydia trachomatis infection from 1990 to 2023 were assessed using the Joinpoint Regression program, which identifies significant changes in time-series data. For each segment, the model estimates the annual percentage change (APC) with 95% confidence intervals (CIs), and the average annual percentage change (AAPC) is calculated as a weighted average of the segment-specific APCs. Statistical significance was determined using the Monte Carlo Permutation method. The analytical models can either account for the estimated variability of individual data points or employ a Poisson distribution to represent variability. The AAPC was computed using the following formula: \documentclass[12pt]{minimal} \usepackage{wasysym} \usepackage[substack]{amsmath} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage[mathscr]{eucal} \usepackage{mathrsfs} \DeclareFontFamily{T1}{linotext}{} \DeclareFontShape{T1}{linotext}{m}{n} {linotext }{} \DeclareSymbolFont{linotext}{T1}{linotext}{m}{n} \DeclareSymbolFontAlphabet{\mathLINOTEXT}{linotext} \begin{document}$$AAPC = \left \{ {exp\left({{{\mathop \sum {w_i}{b_i}} \over {\mathop \sum {w_i}}}} \right) - 1} \right\}$$\end{document} In this formula, \documentclass[12pt]{minimal} \usepackage{wasysym} \usepackage[substack]{amsmath} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage[mathscr]{eucal} \usepackage{mathrsfs} \DeclareFontFamily{T1}{linotext}{} \DeclareFontShape{T1}{linotext}{m}{n} {linotext }{} \DeclareSymbolFont{linotext}{T1}{linotext}{m}{n} \DeclareSymbolFontAlphabet{\mathLINOTEXT}{linotext} \begin{document}${w_i}$\end{document} denotes the length of each time segment in years, and \documentclass[12pt]{minimal} \usepackage{wasysym} \usepackage[substack]{amsmath} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage[mathscr]{eucal} \usepackage{mathrsfs} \DeclareFontFamily{T1}{linotext}{} \DeclareFontShape{T1}{linotext}{m}{n} {linotext }{} \DeclareSymbolFont{linotext}{T1}{linotext}{m}{n} \DeclareSymbolFontAlphabet{\mathLINOTEXT}{linotext} \begin{document}${b_i}$\end{document} represents the slope coefficient for the corresponding segment. 29 A trend was considered increasing when both the AAPC and the lower bound of its 95% CI were greater than zero, decreasing when both the AAPC and the upper bound of its 95% CI were less than zero, and stable when the 95% CI contained zero. In addition, global trends of age groups were also estimated in this study. Considering the disparity in SDI values across countries between 1990 and 2023, the distribution of ASPR and YLD rates by SDI was summarized for 27 regions. The association between SDI and ASPR/YLD rates was assessed using Spearman correlation analysis. A further analysis was conducted of the distribution of age-standardized prevalence/YLD, as well as their respective AAPC across 204 countries. R software (version 4.0.5), and Joinpoint Regression Program (version 4.9.1.0, Surveillance Research Program, National Cancer Institute, Calverton, MD, USA, https://www.r-project.org/ ) were employed in this study. The p-value was deemed statistically significant if it was less than 0.05.

A comprehensive assessment of the burden of infertility among women of reproductive age, attributable to chlamydia infection, has been conducted at global, regional, and national levels from 1990 to 2023. The results revealed a gradual increase in both the prevalence and YLDs due to chlamydia-related infertility worldwide over the past three decades. In addition, the prevalence of infertility due to chlamydia infection is highest among people aged 35–44. Over the past three decades, the trends in infertility prevalence and YLD attributable to chlamydia infection have exhibited variability across different SDI levels. However, a consistent upward trajectory has emerged over the past five years across the majority of SDI categories, with the exception of the high-middle regions. In light of these findings, regions and countries with a substantial burden of infertility due to chlamydia infection urgently require tailored and effective prevention and treatment strategies. A notable upward trend has revealed in the prevalence and YLD linked to infertility caused by chlamydia infections, especially between 1990 and 2023. Previous study observed a consistent rise in the global number of reported infertility cases from 1990 to 2017. 30 Notably, the annual number of reported chlamydia cases continues to climb, underscoring the expanding impact of this infection on global health. 31 Given the 50%–70% asymptomatic presentation of chlamydial infections, the increase in reported cases is plausibly a reflection of enhanced screening activities, which have effectively identified a greater number of previously unrecognized infections. 31 , 32 In addition, the “immune arrest” hypothesis suggests that antimicrobial treatment for chlamydia may suppress the immune response, rendering individuals more susceptible to rapid reinfection, thereby elevating their risk of recurrent chlamydia infections. 32 Frequent chlamydia reinfections, in turn, lead to repeated inflammatory responses that cause repetitive tissue damage and promote tissue scarring, ultimately contributing to the development of infertility. 15 , 33 Furthermore, a standardized screening protocol is currently lacking, and current antibiotic treatments have been ineffective in halting the rise in incidence. 31 , 34 A notable decline in condom use may also have contributed to the escalation of reported cases. 30 Our study demonstrates that women aged 40 to 44 years exhibit a relatively high prevalence of infertility attributed to Chlamydia infection, consistent with previous research. 35 Notably, Chlamydia infections frequently present as asymptomatic in women, resulting in frequent oversight, undertreatment, and underreporting of these cases. 36 Therefore, women who delay seeking medical care for such asymptomatic infections face an elevated risk of infertility and other reproductive health complications. 36 A previous study revealed that the prevalence of chlamydia infection among individuals aged 10 to 24 years was higher compared with other age groups from 1990 to 2023. 37 Considering that tubal damage induced by Chlamydia infections may only become evident years later through unsuccessful pregnancy attempts, the adverse outcomes of infertility may not be recognized until well after the infection has occurred. 38 Moreover, the reduced frequency and incidence of sexual activity among women aged 45 to 49 years may be a contributing factor to the lower prevalence of infertility due to Chlamydia infection observed in this age group compared with others. 39 Regions with low and low-middle SDI exhibited markedly higher age-standardized prevalence and YLD rates of chlamydia-attributable infertility than other SDI regions. However, the correlation between SDI and chlamydia-attributable infertility burden, although statistically significant, was very weak, indicating that SDI alone is a poor predictor. This discrepancy suggests that SDI, as a composite indicator, may mask the effects of more specific determinants. The higher burden in low and low-middle SDI regions likely reflects a combination of factors. Limited public awareness of the reproductive consequences of untreated chlamydia may delay health-seeking behavior and reduce screening uptake. 40 , 41 Inadequate funding and constrained access to assisted reproductive technologies may further amplify the observed infertility burden. 42 , 43 At the same time, the recent growth in reported prevalence over the past five years may partly reflect improved detection. Following the WHO Global STI Strategy 2016–2021, many low- and middle-income countries expanded chlamydia screening and diagnostic testing, 44 however, investment remains insufficient, as Sub-Saharan Africa, bearing 40% of curable STI burdens, accounts for 44% of global service needs but only 30% of costs. 44 Conversely, some high-SDI regions also showed elevated prevalence and YLD rates. This likely reflects improved case detection rather than a true increase in burden, given the advanced healthcare infrastructure and wider availability of nucleic acid amplification tests (NAATs) in high-resource settings. 45 Collectively, these findings indicate that SDI is not a strong predictor of chlamydia-related infertility burden, and that more specific factors—including public awareness, healthcare access and detection capacity—likely play a greater role in shaping the observed burden. A surprisingly high prevalence of infertility attributed to chlamydia infections was observed in Western Sub-Saharan Africa, Australasia, and across the African Region. According to the WHO, approximately 50 million women globally are newly infected with Chlamydia trachomatis each year, with a staggering 34 million of these cases occurring in Sub-Saharan Africa and South/Southeast Asia. 46 In addition to the limited availability of ART in Sub-Saharan Africa, detrimental cultural practices, female illiteracy, and inadequate access to screening services for pregnant women are also reasons hindering the mitigation of Chlamydia trachomatis in the region. 41 , 42 It is intriguing to note that the African region has witnessed the most substantial decrease in infertility attributed to chlamydial infections in 2023, when compared to 1990. A separate study documented a notable decline in the ASPR of STIs in southern sub-Saharan Africa. 37 In addition, among the 204 countries reviewed, Brazil stands out with the fastest-growing prevalence of infertility linked to chlamydia over the past 30 years. The underlying burden of chlamydia infection in Brazil is substantial; a 2022 national study among pregnant women reported a chlamydia prevalence of 9.9%, with the highest rates among women aged 15–24 years. 47 In parallel, the Brazilian public health system has progressively expanded molecular testing for chlamydia since 2018, with the establishment of a national molecular detection network in 2019. 48 This expansion of NAAT-based testing is likely to have improved case detection, contributing to the observed increase in estimated prevalence and YLD rates. Italy has also seen one of the highest averaged annual growth rates in infertility due to chlamydia infections over the past 30 years. Similarly, a prior global study placed Italy among the countries with the highest estimated annual increase in the burden of PID worldwide from 1990 to 2019. 49 Notably, PID may serve as an intermediary process leading to infertility caused by chlamydia infections. 16 National sentinel surveillance data from Italy show that between 2005 and 2016, the reported incidence of genital Chlamydia trachomatis infection in women rose from 2.9 to 7.1 cases per 100,000 population, with the highest burden among women aged 20–24, 50 suggesting that the infection may have increased. This upward trend may have continued in recent years: one report indicates that the incidence of STI among people aged 15–24 in Italy increased significantly over the past decade. 51 However, due to inadequate surveillance coverage, reported prevalence likely underestimates the true burden of infection. For example, a single-center study from 2022–2023 showed that only 42.4% of pregnant women underwent chlamydia testing; 52 between 2007 and 2012, only 4% of confirmed chlamydia cases in Italy were included in the surveillance system. 53 These findings suggest that the observed increase in chlamydia-attributable infertility in Italy likely reflects a true rise in infection burden, while inadequate surveillance may still obscure the full magnitude of the problem. Strengthening screening and surveillance systems is therefore essential to accurately assess and address this burden. In addition, an unexpected finding was the highest ASPR of primary infertility in New Zealand, despite its high SDI. Several factors may contribute to this pattern. Chlamydia testing in New Zealand is markedly lower among men than among women, 54 which may allow undetected infections to persist in the community and contribute to ongoing transmission. Additionally, deficiencies in the delivery of best-practice STI management have been documented, including low and inequitable rates of retesting after treatment. 55 Inadequate retesting may increase the risk of reinfection and subsequent reproductive complications. Furthermore, national surveillance data have shown substantial increases in reported chlamydial infections and associated complications, particularly among young women aged 15–24 years. 56 Because primary infertility is closely linked to prior upper genital tract infection, the historically high burden of chlamydia in young women may translate into elevated primary infertility rates in later reproductive years. Moreover, disparities in sexual health service access and quality, particularly affecting Māori populations, may further contribute to the observed burden. 55 Taken together, these findings suggest that even in high-income settings, gaps in sexual health service delivery, gender disparities in testing, and suboptimal partner notification and retesting can sustain a high burden of chlamydia-attributable reproductive morbidity. Strengthening equitable access to testing, retesting, and partner management may be essential to reduce this burden in New Zealand. Our study has several strengths. First, it is the first comprehensive study to focus on the global, regional and national burden of infertility and its subtypes due to chlamydia infection. This effort provides unique insights into the complex interplay between chlamydia-related infertility and health service delivery. However, there are also several limitations in our study. Notably, data availability in certain countries is constrained, potentially leading to an underestimation of the actual burden of infertility linked to chlamydia infection in those regions. Furthermore, Ascertainment bias in diagnosis may affect our findings. Physicians may be more likely to test for chlamydia in women with a history of infection and lower abdominal pain or diagnose PID in those with positive chlamydia tests. Regional differences in medical conditions could lead to variations and biases in test results. Additionally, as chlamydia is frequently asymptomatic at any site of infection, the diagnosis data for chlamydia may underestimate the true prevalence within the population.

In summary, this study found that the global burden of female infertility attributable to chlamydia infection increased from 1990 to 2023. The highest age-standardized prevalence rate was observed among women aged 40–44 years, and the burden was disproportionately higher in low and low-middle SDI regions. Marked increases were also observed in some countries, including Brazil and Italy. Notably, New Zealand showed the highest ASPR of primary infertility. These findings highlight the need for targeted public health interventions, including health education to raise awareness of the reproductive consequences of untreated chlamydia infection, and enhanced screening and treatment programs in high-burden regions and age groups, to curb the rising burden of chlamydia-induced infertility.