Volume 173, February 2026, 104833Author links open overlay panel, , , Highlights•

FGTB disrupts STAT3/VEGF→implantation via endometrial granuloma formation.

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Taurine↓ + TLR8 SNP predict IVF failure in latent FGTB.

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DHEA rescues oocytes; intrauterine VEGF↑ implantation.

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TB-FertiScore + CRISPR-POC enable risk-adapted ART in TB-endemic zones.

Abstract

Female genital tuberculosis (FGTB) is a major cause of infertility in regions where it is common, causing permanent damage to the reproductive tract. It mainly causes fibrosis and blockage of the fallopian tubes, directly hindering gamete movement. Meanwhile, FGTB leads to a decline in ovarian reserve and function by disrupting folliculogenesis in the ovaries, resulting in decreased levels of anti-Müllerian hormone (AMH). Mycobacterium tuberculosis also affects endometrial receptivity by inhibiting the STAT3/VEGF pathway and the imbalance of Th1/Th2 immune responses. This review explains these mechanisms and offers a multi-omics approach for early detection, identifying taurine deficiency in endometrial fluid and the TLR8 rs3764880 polymorphism as potential predictive markers. Importantly, we point out that first-line anti-tuberculosis therapy (ATT) may worsen ovarian damage by causing mitochondrial dysfunction in oocytes. For treatment, we propose the TB-FertiScore to assist personalized management: patients with a high risk (score ≥7) and severe tubo-ovarian damage should receive ATT combined with IVF, while those with less severe disease might benefit from ovulation induction along with intrauterine VEGF treatment. This comprehensive approach allows for precise, risk-based fertility preservation in areas heavily affected by the disease.

Section snippetsBackground

The impact of tuberculosis (TB) on women's reproductive health is particularly pronounced, with female genital tuberculosis (FGTB) accounting for 5 %–10 % of infertility cases in endemic regions (WHO, 2024, Bagchi et al., 2019). Approximately 25 %–30 % of extrapulmonary TB cases involve the genital tract (Silveira-Mattos et al., 2020), often presenting as latent or mildly symptomatic infections that may nonetheless lead to irreversible tissue damage (Gerald et al., 2010). Despite treatment with

Pathogenic mechanism linking TB and female infertility (Table 1, Fig. 1A-B)

Table 1, Table 2, Table 3, Table 4Genital tuberculosis (GTB) is one of the common types of extrapulmonary tuberculosis (EPTB), which mostly affects young adults. Due to the variation in clinical presentations (including asymptomatic infertility, atypical pelvic pain, and menstrual irregularities), lack of clear diagnostic procedures, slow detection speed, and low detection rates with traditional methods (encompassing acid-fast bacilli (AFB) smear, histopathology, and Lowenstein-Jensen culture),

Genomics in the elucidation of pathological processes (Fig. 2 A)

Genomics, defined as the study of an organism’s complete genome, has evolved from mere association analyses to providing molecular mechanisms underlying the pathogenesis of FGTB and associated infertility. By identifying key genetic variants regulating innate and adaptive immunity, genomics has elucidated the molecular basis of disease susceptibility and progression, thereby revealing potential host-directed therapeutic targets (Abdellaoui et al., 2023, Liu et al., 2016). Genomic analyses have

Drug reproductive toxicology reveals ATT damage to germ cells (Fig. 1 C, Table 3)

The use of anti-tuberculosis drugs may cause damage to reproductive cells (Rao et al., 2020, Akhigbe et al., 2021). The quantity and quality of oocytes are considered important factors that affect the outcome of assisted reproductive technologies. Studies have shown a significant association between tuberculosis infection and oocytes, suggesting that it may affect the outcome of assisted reproduction (Jirge et al., 2018, Sharma et al., 2018). Compared with the control group, patients in the

Clinical translation and challenges (Table 4)

FGTB-induced infertility represents a hidden epidemic of immunological origin, and multi-omics-guided fertility-sparing immunotherapies could alleviate disparities in high-TB-burden regions. Multi-omics techniques hold great potential for the early diagnosis of diseases, including tuberculosis. By integrating genomic, transcriptomic, proteomic, and metabolomic immune-omics data, it is possible to identify biomarkers that are specific to the early stages of the disease. These biomarkers can be

The efficacy of early diagnosis and treatment in preventing FGTB

The damage caused by FGTB to fertility is largely irreversible, making prevention far more effective than treating subsequent sequelae (Sharma et al., 2020). Early diagnosis and timely treatment of active pulmonary or EPTB constitute the cornerstone for preventing FGTB and its consequent lifelong infertility.

Interrupting hematogenous dissemination: FGTB typically originates from tuberculous foci in other parts of the body—most commonly the lungs—and spreads hematogenously to reproductive organs

The management of FGTB

The management of FGTB is a prolonged and challenging process, with objectives extending far beyond mere microbiological cure (Sharma et al., 2020). Conceptually, this process can be divided into two consecutive and distinct phases: (WHO, 2024) clearance of active infection, and (Bagchi et al., 2019) management of sequelae and restoration of fertility (Sharma, 2015).

Conclusions

FGTB is a major cause of irreversible infertility in endemic regions. This review synthesizes existing evidence, identifying immune-metabolic dysfunction as the core pathophysiological mechanism underlying FGTB-related infertility. We delineate a convergent pathogenic cascade: genetic susceptibility (e.g., TLR8 and VDR single nucleotide polymorphisms) triggers chronic inflammation and metabolic reprogramming, directly impairing endometrial receptivity (via suppression of LIF/VEGF/STAT3

Ethics approval and consent to participate

Not applicable.

Funding

Supported by the Key Research and Development program of Ningxia (2022CMG02028), the Central Guidance for Local Science and Technology Development (2024FRD05140), and the Sichuan Provincial Natural Science Foundation Project (2024NSFSC1675) for data fee (scientific research informed consent), paper modification, and publication fee.

CRediT authorship contribution statement

Rong Hu: Writing – review & editing, Visualization, Supervision, Funding acquisition, Conceptualization. Linlin Song: Supervision, Investigation. Yunxing Fu: Project administration, Funding acquisition, Conceptualization. Guiyi Ji: Writing – review & editing, Writing – original draft, Visualization, Supervision, Project administration, Methodology, Investigation, Conceptualization.

Declaration of Competing Interest

The authors declare no conflict of interest.

Acknowledgments

Not applicable.

Consent for publication

Not applicable.

Authors’ Contributions

All authors have approved the manuscript that is enclosed. G.J. and Y.F. contributed equally to this work. The authors’ contributions are detailed: Conceptualization: G.J. and R.H.; Methodology: Y.F.; Formal analysis and investigation: L.S.; Writing - original draft preparation: G.J.; Writing - review and editing: Y.F.; Funding acquisition: R.H.; Resources: R.H.; Supervision: R.H.

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