Impact of final oocyte maturation using gonadotropin-releasing hormone agonist triggering and different luteal support protocols on endometrial gene expression

Abstract

Objective: To use microarray technology to analyze endometrial gene expression after gonadotropin-releasing hormone agonist (GnRH-a) triggering with four different protocols of luteal support in comparison with results obtained after a human chorionic gonadotropin (hCG) trigger.

Design: Prospective, randomized, controlled trial.

Setting: University-affiliated private assisted-reproduction center.

Patient(s): 25 healthy oocyte donors undergoing controlled ovarian stimulation.

Intervention(s): On day of final oocyte maturation, randomization to [1] GnRH-agonist triggering and luteal support with oral estradiol (2 mg/8 hours) and vaginal progesterone (200 mg/12 hours), [2] GnRH-a and a daily dose of 150 IU of recombinant LH from oocyte pickup, [3] GnRH-a and a single bolus of 60 μg of recombinant hCG on oocyte pickup, [4] GnRH-a and three doses of 20 μg of recombinant hCG separated by 48 hours, or [5] 250 μg of recombinant hCG for trigger and standard luteal support; with endometrial biopsy samples collected 7 days after triggering.

Main outcome measure(s): Gene expression using the Endometrial Receptivity Array (ERA) and pathway and network analysis of study groups 1-4 compared with controls (group 5).

Result(s): The 56 genes in group 1 (25 up-regulated and 31 down-regulated) exhibited altered expression compared with the 36 genes from group 2 (13 up-regulated and 23 down-regulated), 44 from group 3 (28 up-regulated and 16 down-regulated), and 30 (20 up-regulated and 10 down-regulated) from group 4.

Conclusion(s): Differences were seen in endometrial gene expression related to the type of ovulation trigger and luteal support. However, gene expression after the GnRH-a trigger and modified luteal support adding LH/hCG activity more closely resembles the pattern seen in the hCG group.

Clinical trial registration number: EudraCT 2011-003250-34.

Keywords: Endometrial receptivity; GnRH agonist; gene expression; ovarian stimulation.