Molecular–immunological mechanisms of the impact of chronic vulvovaginal and cervical infections on women’s reproductive function: optimization of pathogenetic therapy using ozone therapy

Infertility associated with chronic vulvovaginal and cervical infections is accompanied by dysbiosis, persistent biofilms, and chronic inflammation, which collectively impair fertility.The objective: to analyze molecular–immunological alterations in chronic lower genital tract infections and to assess the effectiveness of ozone therapy as a pathogenetically grounded adjuvant to comprehensive infertility treatment.Materials and methods. This prospective study (2022–2025) enrolled 180 women, stratified into three groups of 60: I – vulvovaginal, II – cervical, III – combined infections. Each group was subdivided into subgroup A (standard therapy + local ozone therapy) and subgroup B (standard therapy alone). Ozone therapy consisted of vaginal instillations of ozonated solution (5–10 mg/L), 50–100 mL, 10–15 minutes, 8–10 procedures per course. Outcomes: IL-6, IL-8, TNF-α, CD4+/CD8+, vaginal microbiocenosis (CFU/mL), 6-month relapse rate, and clinical pregnancy rate.Results. Compared with subgroup B, subgroup A showed significant post-treatment reductions in pro-inflammatory cytokines: IL-6 – 8.5 ± 2.1 vs 15.2 ± 3.4 pg/mL (p < 0,01), IL-8 – 12.3 ± 2. vs 20.5 ± 3.7 pg/mL (p < 0,01), TNF-α – 10.1 ± 1.8 vs 16.7 ± 3.1 pg/mL (p < 0,01). The CD8+fraction increased to 29.0 ± 3.0% vs 21.0 ± 2.8% (p < 0,01), with a decrease in the CD4+/CD8+index to 1.43 (p < 0,05). Microbiocenosis normalized: Lactobacillus 4.6×105 vs 3.1×105 CFU/mL (p < 0,05), Gardnerella vaginalis 1.5×104 vs 3.9×104 CFU/mL (p < 0,05). Six-month relapse rates were 10% in subgroup A vs 28% in B (RR ≈ 0.36; NNT ≈ 6). The clinical pregnancy rate reached 70% in subgroup A vs 45% in B (p < 0,05). The greatest benefit was observed in women with isolated vulvovaginal infections and baseline IL-6 < 12 pg/mL.Conclusions. Adding local ozone therapy to standard treatment provides a pronounced anti-inflammatory and anti-biofilm effect, promotes restoration of mucosal immunity and vaginal microbiocenosis, and is associated with a higher clinical pregnancy rate.Keywords: infertility, ozone therapy, vulvovaginal infections, cervicitis, cytokines, CD8+, microbiocenosis, vaginal microbiota, biofilm, NF‑κB; Nrf2