Aurora Test for Patients Treated With Recombinant Gonadotropins (AURORA-REC)

An Observational Cohort Study to Evaluate the Expression Profiles of Oocyte-potency-related Genes in Ovarian Cumulus Cells From Patients Treated by Intracytoplasmic Sperm Injection (ICSI) That Are Treated With Recombinant Gonadotropins

This is an observational study. The main aim is to determine the expression of potential biomarker genes in the cumulus cells isolated from individual oocytes in two patient cohorts: recombinant human Follicle Stimulating Hormone(hFSH) and recombinant hFSH:human Luteinizing Hormone(r-hLH) ratio 2:1. Algorithms from gene combinations will be identified that predict embryo quality and pregnancy outcomes.

Study Overview

• Status: Completed
• Conditions: Infertility
• Intervention / Treatment: Other: AURORA-Rec

• Study Type: Observational
• Enrollment (Actual): 137

Contacts and Locations

Study Locations

• Belgium
  • Jette, Belgium, 1090
    • Universitair Ziekenhuis Brussel

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 34 years (Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients for this study must be between 22-38 years of age, have a good ovarian reserve and response, and need to be naïve to IVF/ ICSI or have only one prior ICSI cycle. Only patients with 7-18 follicles at the end of ovarian stimulation will be allowed to enter the study on the day of decision of hCG injection (or the day before). Patients with fewer than 7 oocytes will be excluded from the study.

Description

Inclusion Criteria:

• Patients are between 22-38 years old
• BMI between 17-33
• provide written informed consent
• Patients undergoing a first or second ICSI treatment cycle.
• Patients will be treated by ICSI (intracytoplasmic sperm injection)
• Patients agree that the oocytes will be denuded for cumulus testing and agree to the single blastocyst transfer.
• Patients must be predicted good ovarian responders (AMH 1-4,7 ng/ml) with 7-18 follicles of minimum 10-11 mm on trigger day (oocyte retrieval minus 2 days (OR -2)) by ultrasound following ovarian stimulation with r-hFSH or r-hFSH with r-hLH in a Gonadotropin-releasing hormone (GnRH) antagonist protocol (starting dose recombinant Follicle Stimulating Hormone (rFSH) between 150-225 IU)
• HCG trigger after stimulation (r-hCG)

Exclusion Criteria:

• Women with less than 7 or more than 18 follicles at Day -2 or -3 measured by ultrasound
• Women with history of poor oocyte maturation or known maturation defect
• Irregular menstrual cycle (< 24 or > 35 days)
• BMI < 17 or > 33
• Smoking > 10 cigarettes per day.
• Known low ovarian response based on Bologna criteria
• Combined use of urinary and recombinant gonadotropins in the current cycle
• Patients with severe endometriosis ≥ III (AFS classification)
• Polycystic ovary syndrome (PCOS), defined by revised criteria American Society for Reproductive Medicine (ASRM) European Society of Human Reproduction and Embryology (ESHRE) 2018
• Patient included in any other study
• Patient scheduled for preimplantation genetic testing (PGT)
• Testicular sperm extraction (TESE) or extreme oligo-astheno-teratozoospermia (OAT) with sperm count below 100.000/ml.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
recombinant hFSH; Patient stimulated with recombinant hFSH	Other: AURORA-Rec; Explorative study of cumulus cells gene expression in relation to the patient treatment and oocyte competence.
recombinant hFSH : r-hLH; Patient stimulated with recombinant hFSH : r-hLH ratio 2:1	Other: AURORA-Rec; Explorative study of cumulus cells gene expression in relation to the patient treatment and oocyte competence.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Normalized messenger ribonucleic acid (mRNA) expression	Normalized mRNA levels of biomarker genes that are assessed in cumulus cells by reverse transcription quantitative Polymerase Chain Reaction (RT-qPCR) for each oocyte.	3 years after study start

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Meiosis II Oocyte rate	The number of meiosis II oocytes (nominator) divided by the total number of oocytes retrieved (denominator)	Day 0 of embryo collection
Normal fertilization rate	The number of fertilized oocytes on Day 1 (presence of 2 pronuclei (2PN) and the second polar body (2PB) assessed at 17 ± 1 h postinsemination, as a function of all cumulus-oocytes complexes (COCs) inseminated	Day 1 of embryo culture
Day 5 good-quality embryo rate	Defined as the proportion of 2PN zygotes which are good-quality blastocysts on Day 5	Day 5 of embryo culture
Embryo utilization rate	Defined as the number of embryos (or blastocysts) suitable for transfer or cryopreservation as a function of the number of normally fertilized (2PN) oocytes observed on Day 1	Day 5 of embryo culture
Biochemical pregnancy rate	A pregnancy diagnosed only by the detection of beta human chorionic gonadotropin (hCG) in serum or urine	Day 10 after embryo transfer
Fetal heart beat positive implantation rate	Rate refers to the proportion of fetal heartbeats detected relative to the number of embryos transferred	Week 5-6 after embryo transfer
Clinical pregnancy rate	Pregnancy diagnosed by ultrasonographic or clinical documentation of at least one fetus with a discernible heartbeat in gestational week 6 to 8	Week 5-6 after embryo transfer
Ongoing pregnancy rate	The presence of gestational sacs with fetal heart beat detected by transvaginal ultrasound examination in gestational week 10 to 11	Week 10-11 after embryo transfer
Miscarriage rate	The spontaneous loss of an intra-uterine pregnancy prior to 22 completed weeks of gestational age. In this study we capture spontaneous miscarriage till gestational week 12.	Week 12 after embryo transfer

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cumulative ongoing pregnancy rate	The accumulated ongoing pregnancy after fresh and frozen-warmed embryo transfers within one stimulation cycle. Pregnancy with detectable heart rate at ≥ 12 weeks gestation after the completion of the first transfer	3 years after study start
Live Birth rate	is defined as the birth of at least one newborn after 24 weeks gestation that exhibits any sign of live (twins will be a single count)	Week 24-42 after embryo transfer
Cumulative Live Birth rate	The number of deliveries with at least one live birth resulting from one initiated or aspirated artificial reproductive technologies (ART) cycle, including all cycles in which fresh and/or frozen embryos are transferred, until one delivery with a live birth occurs or until all embryos are used, whichever occurs first.	3 years after study start

Collaborators and Investigators

• Sponsor: Fertiga, Belgium
• Collaborators: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2021
• Primary Completion (Actual): December 31, 2023
• Study Completion (Actual): September 1, 2025

Study Registration Dates

• First Submitted: January 9, 2021
• First Submitted That Met QC Criteria: January 12, 2021
• First Posted (Actual): January 14, 2021

Study Record Updates

• Last Update Posted (Estimated): September 8, 2025
• Last Update Submitted That Met QC Criteria: September 2, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility
• Other Study ID Numbers: 2020.Aurora-Rec

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No