Comparative Histological and Immunohistochemical Study on Rat Ovarian and Endometrial Responses to Letrozole versus Clomiphene Citrate

Aim of the Work: To compare the effects of letrozole and clomiphene citrate on ovarian stimulation and endometrial response in rats. Materials and Methods: Thirty adult virgin female albino rats (20 weeks of age) were equally divided into 3 groups. The first group received saline orally and served as control. Second group was given letrozole (Femara) at dose: 5mg/ Kg daily orally and third group received clomiphene citrate (Clomid) at a dose: 100 μg/Kg daily orally. Treatment was given during the diestrus phase of 2 consecutive cycles, then animals were sacrificed at the estrus phase. The ovaries and uteri were dissected. The ovarian sections were subjected to Hematoxylin and Eosin staining and Proliferating Cell Nuclear Antigen (PCNA) immunostaining. Uterine sections were stained with Hematoxylin and Eosin and immnuohistochemically stained with Vascular Endothelial Growth Factor (VEGF ) and integrin β-1 (CD 29) antibodies. Follicular counting was done in PCNA-immunostained sections. Image analysis was done for optical density for VEGF immunostaining. Semiquantitative scoring system was done for integrin expression. Results were statistically compared. Results: Multiple follicular development was induced by both drugs. The number of small and medium sized follicles as well as corpora lutea was significantly higher in clomiphene citrate group compared to letrozole group. Large follicles were significantly increased in letrozole group compared to clomiphene citrate group. The optical density of endometrial VEGF expression was statistically increased in letrozole group compared to clomiphene citrate group. With reference to control sections, integrin immunostaining was markedly reduced in clomiphene citrate group while it was more intense in letrozole group. Conclusion: It could be concluded that, clomiphene citrate was more effective than letrozole in ovulation induction but letrozole had better effect on endometrial vasculature and endometrial, receptivity.