A 32-year-old woman with secondary infertility presents with a history of pelvic tuberculosis confirmed on endometrial biopsy and culture. She has tubal blockage and endometrial damage on hysterosalpingography. What is the drug of choice for managing the underlying infection before considering assisted reproductive techniques?

## Tuberculosis-Related Female Infertility: Pharmacologic Management ### Clinical Context: Genital TB & Infertility **Key Point:** Genital tuberculosis (TB) is a major cause of secondary infertility in endemic regions (India, Southeast Asia). It causes: - Endometrial damage and fibrosis - Tubal strictures and blockage - Ovarian involvement (less common) - Asherman's syndrome (intrauterine adhesions) ### First-Line Antituberculous Therapy (ATT) **Standard Regimen:** - **Intensive phase (2 months):** Isoniazid (INH) + Rifampicin (RIF) + Pyrazinamide (PZA) + Ethambutol (EMB) - **Continuation phase (4 months):** INH + RIF - **Total duration:** 6 months (Category I TB) ### Dosing (WHO/Indian Guidelines) | Drug | Dose | Remarks | |------|------|----------| | Isoniazid | 5 mg/kg/day | Vitamin B6 supplementation to prevent neuropathy | | Rifampicin | 10 mg/kg/day | Reduces oral contraceptive efficacy; may affect fertility drugs | | Pyrazinamide | 25 mg/kg/day | Hyperuricemia; avoid if gout history | | Ethambutol | 15–25 mg/kg/day | Optic neuritis monitoring required | ### Why This Regimen? 1. **Bactericidal efficacy:** Combination therapy prevents resistance and ensures mycobacterial eradication 2. **Tissue penetration:** All four drugs achieve adequate endometrial and tubal concentrations 3. **Duration:** 6 months is standard for non-CNS TB; longer courses do not improve fertility outcomes 4. **Guideline-endorsed:** WHO, CDC, Indian TB Programme, and FOGSI all recommend this regimen ### Fertility Considerations During ATT **High-Yield:** - Conception should be **avoided during ATT** (teratogenic risk, especially PZA in first trimester) - Rifampicin reduces oral contraceptive efficacy; use barrier methods or alternative contraception - Ovulation induction or ART should be deferred until **completion of ATT + 3–6 month consolidation** - Endometrial biopsy may be repeated post-ATT to assess healing ### Post-ATT Fertility Outcomes **Clinical Pearl:** Even with complete ATT, fertility restoration is limited due to irreversible endometrial fibrosis and tubal damage. Pregnancy rates after ATT alone are ~10–20%; most patients require IVF-ET if conception is desired. **Mnemonic:** **IRPE** = Isoniazid, Rifampicin, Pyrazinamide, Ethambutol (the four-drug intensive phase) ### Why Not Monotherapy or Shorter Courses? - **Monotherapy (e.g., ciprofloxacin):** Inadequate mycobacterial kill, risk of resistance, poor tissue penetration in genital TB - **Shorter courses (< 6 months):** Incomplete eradication, relapse risk, persistent endometrial inflammation - **Fluoroquinolones alone:** Not recommended as monotherapy for TB; reserved as adjuncts in drug-resistant TB [cite:WHO TB Treatment Guidelines 2023; Indian TB Programme; FOGSI Guidelines on TB and Infertility]