Alfonso Bermejo1, María Cerrillo1, María Ruiz-Alonso2, David Blesa3, Carlos Simón3, Antonio Pellicer4, Juan A Garcia-Velasco5. 1. IVI Madrid, Madrid, Spain. 2. IVIOMICS SL, Paterna, Spain. 3. Fundación IVI, Valencia University INCLIVA, Valencia, Spain. 4. IVI Valencia, Valencia University, Valencia, Spain. 5. IVI Madrid, Madrid, Spain; Rey Juan Carlos University, Madrid, Spain. Electronic address: juan.garcia.velasco@ivi.es.
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.
RCT Entities:
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.