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Effect of GnRH-antagonist, mifepristone and letrozole on preventing ovarian hyperstimulation syndrome in rat model
Reproductive BioMedicine Online ( IF 4 ) Pub Date : 2020-10-14 , DOI: 10.1016/j.rbmo.2020.10.006
Jin Luo 1 , Qianrong Qi 1 , Yinmei Chen 1 , Yaqin Wang 1 , Qingzhen Xie 1
Affiliation  

Research question

Can luteolysis-targeted drugs, gonadotrophin-releasing hormone antagonist (GnRH-ant), mifepristone and letrozole, administered separately or in combination, prevent the progression of ovarian hyperstimulation syndrome (OHSS) in a rat model?

Design

Thirty-six female Wistar rats were randomly divided into six groups, including control group (OHSS group, ovarian hyperstimulation-induced OHSS); GnRH-ant group (OHSS with GnRH-ant treatment); mifepristone group (OHSS with mifepristone treatment); letrozole group (OHSS with letrozole treatment); combination group (OHSS with GnRH-ant, mifepristone and letrozole treatment in combination). The main outcomes were the alterations in OHSS-related indices, including ovarian weight, vascular permeability, serum oestradiol and progesterone levels, corpus luteum proportion and diameter, ovarian vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), caspase-3 and cleaved caspase-3 levels.

Results

No significant difference was found in body weight gain among the six groups. Compared with the control group, the OHSS group showed significant increases in all OHSS-related indices. GnRH-ant treatment showed decreases in vascular permeability, serum oestradiol level, corpus luteum diameter, ovarian VEGF /IL-6 mRNA levels, and increases in ovarian caspase-3 and cleaved caspase-3 levels. Mifepristone treatment demonstrated reduction in serum progesterone level and corpus luteum diameter, and elevation in ovarian caspase-3 and cleaved caspase-3 levels. Letrozole treatment displayed a decline in serum oestradiol level and corpus luteum diameter, and up-regulation in ovarian caspase-3 and cleaved caspase-3 levels. The combination treatment by GnRH-ant, mifepristone and letrozole showed enhanced synergistic effect on reducing OHSS-related indices.

Conclusions

GnRH-ant, mifepristone and letrozole are beneficial in preventing the progression of OHSS through different luteolytic mechanisms. Cocktail style treatment shows enhanced synergistic effect on preventing the progression of OHSS.



中文翻译:

GnRH拮抗剂米非司酮和来曲唑对大鼠模型卵巢过度刺激综合征的预防作用

研究问题

黄体溶解靶向药物、促性腺激素释放激素拮抗剂 (GnRH-ant)、米非司酮和来曲唑单独或联合给药能否预防大鼠模型中卵巢过度刺激综合征 (OHSS) 的进展?

设计

36只雌性Wistar大鼠随机分为6组,包括对照组(OHSS组,卵巢过度刺激引起的OHSS);GnRH-ant组(OHSS用GnRH-ant处理);米非司酮组(OHSS 与米非司酮治疗);来曲唑组(OHSS 来曲唑治疗);联合组(OHSS 与 GnRH-ant、米非司酮和来曲唑联合治疗)。主要结果是 OHSS 相关指标的变化,包括卵巢重量、血管通透性、血清雌二醇和孕酮水平、黄体比例和直径、卵巢血管内皮生长因子 (VEGF)、白细胞介素 6 (IL-6)、半胱天冬酶- 3 和裂解的 caspase-3 水平。

结果

六组间体重增加无显着差异。与对照组相比,OHSS 组的所有 OHSS 相关指标均显着增加。GnRH-ant 治疗显示血管通透性、血清雌二醇水平、黄体直径、卵巢 VEGF/IL-6 mRNA 水平降低,以及卵巢 caspase-3 和 cleaved caspase-3 水平增加。米非司酮治疗表明血清孕酮水平和黄体直径降低,卵巢 caspase-3 和 cleaved caspase-3 水平升高。来曲唑治疗显示血清雌二醇水平和黄体直径下降,卵巢 caspase-3 和 cleaved caspase-3 水平上调。GnRH-ant、米非司酮和来曲唑的联合治疗对降低 OHSS 相关指标显示出增强的协同作用。

结论

GnRH-ant、米非司酮和来曲唑通过不同的黄体溶解机制有助于预防 OHSS 的进展。鸡尾酒式治疗在预防 OHSS 进展方面显示出增强的协同作用。

更新日期:2020-10-14
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