Effects of high progesterone level on the day of human chorionic gonadotrophin administration in in vitro fertilization cycles on epigenetic modification of endometrium in the peri-implantation period

Objective: To investigate the effects of high P level on the day of hCG administration in IVF cycles on epigenetic modifications of endometrium in the peri-implantation period. Design: Retrospective study. Setting: University assisted reproductive unit. Patient(s): Forty patients were recruited: 20 women with high P levels were compared with 20 women with normal P levels. Intervention(s): Endometrial tissues were collected 7 days after hCG administration in women with normal or high P levels on the day of hCG administration. Immunohistochemical staining of DNA methylation (5-methylcytosine, 5-mC), histone methylation (H3K4me2/3, H3K9me2, H3K27me3), and histone acetylation (H3K4ac, H3K9ac) was performed. Main Outcome Measure(s): A semiquantitative analysis was performed in the luminal epithelium, glandular epithelium, and stroma, separately. Correlations between P, estrogen levels, and epigenetic markers were compared. Result(s): In luminal epithelium, the expression of H3K9me2 in the high P group was significantly higher than that in the normal P group. In glandular epithelium, the expression of 5-mC, H3K9me2, and H3K9ac in the high P group was significantly higher than that in the normal P group. In stroma, the expression of H3K27me3 in the high P group was significantly higher than that in the normal P group. Expression of 5-mC in glandular epithelium, H3k9me2 in glandular and luminal epithelium, and H3K27me3 in stroma was significantly correlated with P levels. H3k9me2 in glandular epithelium was significantly correlated with estrogen levels. Conclusion(s): High P level on the day of hCG administration in IVF cycles affects epigenetic modifications in three compartments of endometrium in the peri-implantation period. The epigenetic markers' expression was mainly correlated with P level. The altered epigenetic modification status in the endometrium may disrupt the endometrial receptivity in women with high P on the day of hCG administration. (C) 2017 by American Society for Reproductive Medicine.