Abstract
GnRH antagonist negatively affects endometrial receptivity in in vitro fertilization (IVF) cycles, however, its underlying mechanism remains unclear. To explore its target molecules, we studied endometria in the window phase of fixed GnRH antagonist, low-dose flexible GnRH antagonist, GnRH agonist long protocol, and untreated control groups. There were 384 differentially expressed genes (DEGs) in the fixed antagonist group with greater than twofold expression change compared with the control group and 197 DEGs between the fixed antagonist and agonist groups, the majority of which were associated with the natural killer (NK) cell-mediated cytotoxicity pathway. We then analysed the PRF1 and FASLG protein levels. The perforin level were significantly higher in both the antagonist groups than in other two groups, and was higher in the fixed antagonist group. Similarly, the uNK cell numbers were higher in the antagonist groups, and the highest uNK cell number occurred in the fixed group (p < 0.05). No significant differences existed in the Fas ligand levels and apoptosis rates among the three treatment groups, but were higher in the treatment groups than the control group. Together, these data indicate that GnRH antagonist may increase the uNK cell numbers and perforin expression, and this effect may be dose-dependent.
Highlights
Age Weight Body mass index Stimulation duration Total Gn used (IU) Average serum oestradiol values on human chorionic gonadotropin day Total Cetrotide used Duration of Cetrotide used Average serum progesterone values on hCG day Average serum LH values on hCG day (U/L) Number of oocytes retrieved Endometrial thickness on biopsy day
Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis showed that the majority of these differentially expressed genes (DEGs) were associated with the NK cell-mediated cytotoxicity pathway in the antagonist group but only few of the DEGs in the agonist group were associated with this pathway
The Gonadotropin-releasing hormone (GnRH) antagonist protocol has significantly improved the flexibility and security of clinical applications compared with the GnRH agonist long protocol, and this antagonist protocol has been widely used in IVF cycles
Summary
Age (years) Weight (kg) Body mass index Stimulation duration (day) Total Gn used (IU) Average serum oestradiol values on human chorionic gonadotropin (hCG) day (pmol/L) Total Cetrotide used (mg) Duration of Cetrotide used (day) Average serum progesterone values on hCG day (ng/L) Average serum LH values on hCG day (U/L) Number of oocytes retrieved Endometrial thickness on biopsy day (cm). HOXA10, were significantly decreased in endometrial stromal cells[15]. The key factors involved in this process remain unclear. We explored the factors by which GnRH antagonist affects the endometrial receptivity, so as to provide theoretical support for the underlying mechanisms of this phenomenon and to optimize its application in ovarian stimulation in IVF in the future
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