The Impact of Luteal Phase Support on Gene Expression of Extracellular Matrix Protein and Adhesion Molecules in the Human Endometrium During the Window of Implantation Following Controlled Ovarian Stimulation with a GnRH Antagonist Protocol

Objective: To evaluate the impact of two different luteal phase support protocols on gene expression of extracellular matrix (ECM) proteins and adhesion molecules in the human endometrium.

Design: Eighty-four ECM protein and adhesion molecule genes were analyzed using array-based reverse-transcription polymerase chain reaction.

Setting: Academic hospital.

Patient(s): Nine oocyte donors.

Intervention(s): Endometrial biopsies were obtained on the day of oocyte retrieval (group I) and 3-5 days later (group II) after randomization into 3 groups. Group IIa had no luteal phase support, group IIb had luteal support with micronized progesterone, and group IIc had luteal support with progesterone plus 17β-estradiol.

Main Outcome Measure(s): Gene expression profiles in relation to different types of luteal phase support protocols.

Result(s): Compared with the day of retrieval (group I), 24 genes were significantly up-regulated (4 in group IIa, 14 in group IIb, 22 in group IIc) and 14 genes were down-regulated (5 in group IIa, 2 in group IIb, 10 in group IIc) on day 3-5 (P<.05). In the luteal support group, up- regulation occurred predominantly in genes encoding for matrix metallopeptidases (MMP10, MMP3, MMP9), integrins (ITGA3, ITGA5, ITGB3, ITGB4), and laminin (LAMB3). In contrast, the most significant suppression was documented in genes encoding for catenin-D2, collagen-11A1, and the laminins (LAMA1 and LAMA3). Significant changes between groups IIb and IIc were also observed in 9 genes.

Conclusion(s): Luteal phase support following controlled ovarian stimulation has a profound impact on the ECM pathway targeted genes.