Immuno-metabolic dysregulation in female genital tuberculosis: Multi-omics insights into infertility mechanisms and therapeutic targets.

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.