Reversal of tubo‐ovarian atypical epithelial patterns after cessation of ovarian stimulation by letrozole

Summary Letrozole (LTZ), one of the ovulation induction medications, is increasingly prescribed in various gynaecological conditions. Previous studies have demonstrated its potential hazardous effect on the ovarian surface epithelium (OSE) as well as on tubal epithelial cells (TEC). However, it is n...

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Bibliographic Details
Published in:International journal of experimental pathology 2016-08, Vol.97 (4), p.329-336
Main Authors: Abdel‐Hamid, Ahmed A.M., Mesbah, Yaser, Soliman, Mona F.M.
Format: Article
Language:English
Subjects:
Animals
Aromatase Inhibitors - pharmacology
Cell Proliferation - drug effects
Chemokine CCL2 - blood
cytokines
Cytokines - metabolism
epithelial atypia reversal
Epithelial Cells - drug effects
Epithelial Cells - metabolism
Epithelial Cells - pathology
Epithelium - drug effects
Epithelium - metabolism
Epithelium - pathology
Fallopian Tubes - drug effects
Fallopian Tubes - metabolism
Fallopian Tubes - pathology
Female
interleukins
Ki67 proliferation index
letrozole cessation
Nitriles - pharmacology
Original
Ovary - drug effects
Ovary - metabolism
Ovary - pathology
Ovulation Induction - methods
Pharmacopathology
Rats, Sprague-Dawley
Triazoles - pharmacology
Withholding Treatment
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Summary:Summary Letrozole (LTZ), one of the ovulation induction medications, is increasingly prescribed in various gynaecological conditions. Previous studies have demonstrated its potential hazardous effect on the ovarian surface epithelium (OSE) as well as on tubal epithelial cells (TEC). However, it is not clear whether this effect could be reversed by LTZ cessation. Therefore, the objective of our study was to investigate the effect of stoppage of LTZ on these cells after 12 cycles of ovarian stimulation. A total of 54 Sprague Dawley rats were used in this study, divided equally into control, LTZ12 and CES12 groups (received saline, 12 cycles of LTZ and 12 cycles of cessation post‐LTZ12 respectively). Samples from the ovaries as well as fallopian tubes (FTs) were studied histologically for the changes associated with LTZ12 and CES12 respectively. There was evident increase in the proliferative activity and Ki67 immunoexpression in the OSE of LTZ12. The OSE was hyperchromatic, and abnormally frequent deep invaginations, micropapillae and cortical cysts. Their TEC showed frequent multilayering, papillary projections and loss of cilia. Almost all these changes disappeared 12 cycles after LTZ cessation. While the tubal IL‐1β, IL‐6, TNF‐α and serum MCP‐1 levels significantly increased in the LTZ12 group compared with the control group, their levels decreased in the CES12 group compared with those of the control. Therefore, the abnormal tubo‐ovarian epithelial patterns may completely regress after cessation of LTZ stimulation for a reasonable duration. This is a potentially good omen and a positive indicator of the relatively safe use of LTZ after its intake has been stopped.
ISSN:0959-9673
1365-2613
DOI:10.1111/iep.12196