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

Abstract Research Question What is the difference of endometrial transcriptomics between women with normal and low mid-luteal progesterone during the implantation window? Design An endometrial biopsy and serum progesterone level were taken from participants during the mid-luteal phase (LH+7 to LH+9). A total of 12 participants were recruited. The participants were categorised into two groups based on their progesterone levels: normal progesterone (>15 ng/ml, n=6) and low progesterone ( 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 decidualisation, extracellular matrix-receptor interaction, and cell adhesion. Distinct differences in the transcriptomic profiles between the two groups were observed indicating potential impairment of endometrial receptivity in women with suboptimal progesterone levels. There was a relatively similar pattern of gene expression between endometrial samples with progesterone levels approximately 10 ng/ml and >15 ng/ml. Thus, a progesterone level of between 10-15 ng/ml seems 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. Trial registration This trial was registered at clinicaltrials.gov as NCT04323683