Effects of Low Luteinizing Hormone During Ovarian Stimulation on Endometrial Gene Expression and Function - Transcriptome Analysis During the Implantation Window.

This study explored the impact of low luteinizing hormone (LH) levels during ovarian stimulation on endometrial function. Based on previous studies by us and others, we divided the patients into low (< 4 IU/L), medium (4-10 IU/L), and high (> 10 IU/L) LH groups. The study utilized a comparison control group design with three groups of 10 patients. Gene set enrichment analysis (GSEA) was applied for functional annotation. By analyzing the exon differentially expressed genes in the endometrium of these three patient groups during the embryo implantation window, we found that when compared to the medium LH group, low LH downregulated endometrial cell metabolism, including mitochondrial-nicotinamide adenine dinucleotide (Normalized Enrichment Scores, NES =  - 1.53) and glycolytic metabolism (NES =  - 1.22), immune regulation, and autophagy (NES =  - 1.58). Transcription factors were the main regulators of cell function. We found that MCM2 was probably involved in regulating the endometrial function induced by low LH. MCM2 target genes were enriched in low LH group, NES =  - 1.54. Low LH, but not high LH, altered the endometrial receptivity assay gene expression in comparison to the medium LH. Our results indicated that low LH impacted the endometrial cell function, with a greater effect than high LH. This research provides timely and necessary data on the involvement of LH in important endometrial cellular processes and these data support further clinical development of endometrial receptivity.