He Zhuqiang, Guo Na, Yao Yangcheng, Zhou Jie, Deng Taoran, Du Yaoyao, Li Yufeng, Yin Li
Department of Neurosurgery, Wuhan First Hospital, Wuhan, China.
Department of Gynecology and Obstetrics, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
J Assist Reprod Genet. 2025 May 10. doi: 10.1007/s10815-025-03495-5.
Endometrial receptivity is a critical determinant of successful embryo implantation and pregnancy. Gonadotropin-releasing hormone (GnRH) analogues are widely used in in vitro fertilization (IVF) but their effects on endometrial receptivity remain incompletely understood. This study aims to investigate the impact of GnRH analogues on endometrial receptivity through various in vitro models.
Endometrial samples were collected across various stages of the menstrual cycle. The expression of the gonadotropin-releasing hormone receptor (GnRHR) was analyzed and quantified. A 3D endometrial model was constructed, and effects of GnRH analogues on trophoblast adhesion, as well as on the expression of markers related to endometrial receptivity, were assessed.
The results indicate that GnRHR expression is higher in epithelium in the secretory phase. However, no significant difference in the adhesion of trophoblast cell spheres to endometrial cells across different GnRH analogue concentrations was observed. GnRH analogues did not affect gene mRNAs expressions or protein levels either. Proteomic analysis revealed a downregulation of ITGAE in the antagonist regimen and an upregulation of FAAH2 in the agonist regimen.
This study suggests that GnRH analogues at different physiological concentrations used in IVF protocols do not significantly impact primary markers of endometrial receptivity. However, the use of antagonist may have an adverse effect on endometrial receptivity. Further research is required to elucidate indirect mechanisms by which GnRH analogues might affect endometrial receptivity and IVF outcomes.
子宫内膜容受性是胚胎成功着床和妊娠的关键决定因素。促性腺激素释放激素（GnRH）类似物在体外受精（IVF）中广泛应用，但其对子宫内膜容受性的影响仍不完全清楚。本研究旨在通过各种体外模型研究GnRH类似物对子宫内膜容受性的影响。
在月经周期的各个阶段收集子宫内膜样本。分析并定量促性腺激素释放激素受体（GnRHR）的表达。构建三维子宫内膜模型，评估GnRH类似物对滋养层细胞黏附以及与子宫内膜容受性相关标志物表达的影响。
结果表明，分泌期上皮细胞中GnRHR表达较高。然而，在不同GnRH类似物浓度下，未观察到滋养层细胞球与子宫内膜细胞黏附的显著差异。GnRH类似物也未影响基因mRNA表达或蛋白质水平。蛋白质组学分析显示，拮抗剂方案中ITGAE下调，激动剂方案中FAAH2上调。
本研究表明，IVF方案中使用的不同生理浓度的GnRH类似物对子宫内膜容受性的主要标志物没有显著影响。然而，拮抗剂的使用可能对子宫内膜容受性产生不利影响。需要进一步研究以阐明GnRH类似物可能影响子宫内膜容受性和IVF结局的间接机制。
