P-677 Letrozole inhibits ovulation via reducing responsiveness to luteinizing hormone in in vitro-grown mouse follicles

Abstract Study question Does letrozole reduce responsiveness to luteinizing hormone (LH) in vitro-grown mouse follicles? Summary answer We found that reduced LH via reducing of hormone/chorionic gonadotropin receptor (Lhcgr) transcription vitro. What is known already The continuous dosing letrozole, the third-generation aromatase inhibitor, used for controlled ovarian stimulation (COS) fertility preservation cycles women with hormone-sensitive breast cancer prevent transient rise serum estrogen levels. Recently, lower oocyte maturation rates and higher abnormal fertilization COS compared standard have been reported. studies using knockout mice beta showed intra-follicular essential granulosa cells. However, whether reduces follicles remains unknown. design, size, duration evaluated effect on vitro follicle culture system. Preantral (150-200 µm) a small number stromal cells were isolated from 3 weeks old C57BL/6jjcl ovaries cultured presence letrozole. analyzed ovulation ability, expression levels ovulation-related genes clarify follicles. Participants/materials, setting, methods (0.01µM, 0.1µM, or 1µM) vehicle (0.1% DMSO) 5 days followed by IU/ml hCG ng/ml hEGF as induction. diameter survival rate assessed. After16 hours after induction, we assessed measured Lhcgr, Ptgs2, Runx1 Actb (internal control) RT-qPCR. conducted collateral experiment estradiol. Main results role chance growth did not change was addition dose-dependent manner (Cochran-Armitage trend test, P < 0.0001): 41.2% 0.01µM treated group (n = 23), 10.5% 0.1µM treated-group 17), no 1µM 19) 69.6% vehicle-group 18). Exogenous restored ability letrozole-treated same group. RT-qPCR revealed 0.1 µM significantly Lhcgr (P 0.0027), 0.0124), Ptgs2 0.0067) vehicle-treated these observed also positive correlation between (R 0.55, 0.0003), 0.71, 0.0001), 0.77, 0.0001). Our suggested impaired due dysregulation its downstream cascade caused deficiency. Limitations, reasons caution This an model. Further research needed determine our findings are applicable humans. Wider implications imply may disadvantages only ovulation, but subsequent reproductive processes affected effectiveness surge, such maturation, fertilization, preimplantation embryo development. When evaluating cryopreservation preservation, it be necessary consider protocol. Trial registration Not