Foeniculum vulgare and metformin combination improve ovarian function in a rat model of polycystic ovary syndrome: targeting AMH imbalances, folliculogenesis disruption, fibrosis, and abnormal vascular density.

Polycystic ovary syndrome (PCOS), a major cause of female infertility, is accompanied by elevated anti-Mullerian hormone (AMH), ovarian hypervascularity, and excessive collagen deposition. While metformin is a well-established treatment, no study has yet explored whether Foeniculum vulgare (Fennel)-a medicinal plant with documented anti-PCOS benefits, administered alone or in combination-can attenuate these hormonal and structural abnormalities; this study provides the first integrated evaluation of both agents on ovarian damage in rats. Thirty-three female Wistar adult rats were divided into control and letrozole-induced PCOS groups. PCOS rats received saline (1 ml/kg/day; PCOS-Veh), fennel extract (500 mg/kg/day), metformin (300 mg/kg/day), or both for 21 days (n = 5/group). Body and ovarian weights were recorded, and blood samples were analyzed for AMH levels. Ovarian folliculogenesis, fibrosis, and vessel density were assessed by hematoxylin and eosin, and Masson's trichrome staining, and ovarian AMH expression by Western blot. PCOS rats exhibited fewer corpus luteum and pre-ovulatory follicles, more ovarian cysts, and increased fibrosis, vascularity, and AMH levels compared to the control. Fennel and metformin, particularly in combination, ameliorated ovarian histopathology by improving follicular abnormalities, increasing corpus luteum and pre-ovulatory follicles, and reducing cysts, fibrosis, hypervascularity, and ovarian dimensions. They also significantly lowered serum and ovarian AMH, with combination therapy being the most effective. These findings position fennel-particularly as an adjunct to metformin-as a dual modulator of both hormonal (AMH) and structural (vascular and fibrotic) ovarian alterations in a rat model of PCOS, although clinical trials remain essential before application in women with PCOS.