Sacubitril/Valsartan: Breaking barriers in uterine adhesion and boosting pregnancy outcomes by suppressing inflammation and fibrosis.

OBJECTIVES: Intrauterine adhesion (IUA) enhances infertility and is primarily driven by inflammation and fibrosis. Sacubitril/Valsartan (Sac/Val), an angiotensin receptor-neprilysin inhibitor, exhibits anti-inflammatory and anti-fibrotic properties; however, its effects on IUA and reproductive outcomes have not been previously studied. MATERIALS AND METHODS: A rat model of IUA was established by mechanical endometrial injury. Animals were treated orally with Sac/Val (100 mg/kg/day) for 10 days. Inflammatory cytokine expression, oxidative stress markers, histological changes, and fibrotic indices were evaluated. Endometrial regeneration, embryonic development, pregnancy outcomes, and extra-uterine adhesion formation were also assessed. RESULTS: Sac/Val treatment significantly reduced uterine inflammation, oxidative stress, and collagen deposition, as evidenced by decreased expression of pro-inflammatory cytokines and pro-fibrotic markers. Histological analysis demonstrated improved endometrial regeneration, including increased gland numbers and endometrial thickness. In addition, Sac/Val enhanced embryonic development, improved pregnancy rates, increased the number of live offspring, shortened time to conception, and reduced extra-uterine adhesion formation. CONCLUSION: Sac/Val enhances regeneration of endometrium and pregnancy outcomes in a rat model of IUA, primarily through suppression of inflammation and fibrosis. Further preclinical and clinical studies are needed to determine the protective functions of Sac/Val for IUA treatment.