Suboptimal mid-luteal progesterone concentrations are associated with aberrant endometrial gene expression, potentially resulting in implantation failure

Abstract

Research question: What is the difference in endometrial transcriptomics between women with normal and with low mid-luteal progesterone during the implantation window?

Design: An endometrial biopsy and serum progesterone concentration were taken from participants during the mid-luteal phase (LH+7 to LH+9). A total of 12 participants were recruited and categorized into two groups based on their progesterone concentrations: normal progesterone (>15 ng/ml, n = 6) and low progesterone (<15 ng/ml, n = 6). Global endometrial gene expression between the two groups was compared by microarray techniques. Principal component analysis was used to display the gene's expression pattern. Pathway and gene ontology enrichment analysis were performed to determine the biological mechanism of progesterone on the endometrium.

Results: Several key genes related to endometrial receptivity were found to be regulated by progesterone. With regard to gene ontology and pathway analysis, progesterone was shown to be mainly involved in structure morphogenesis predominantly during a process of decidualization, extracellular matrix-receptor interaction and cell adhesion. Distinct differences were observed in the transcriptomic profiles between the two groups, indicating potential impairment of endometrial receptivity in women with suboptimal progesterone concentrations. There was a relatively similar pattern of gene expression between endometrial samples with progesterone concentrations approximately 10 ng/ml and >15 ng/ml. Thus, a progesterone concentration of between 10 and 15 ng/ml appears to be sufficient to induce endometrial receptivity.

Conclusions: Abnormally low progesterone below the threshold of 10-15 ng/ml during the implantation window results in aberrant endometrial gene expression that may affect implantation potential.

Keywords: Assisted reproductive technology; Endometrial gene expression; Endometrial receptivity; Microarray; Progesterone monitoring.