Aurora Test for Patients Treated With Recombinant Gonadotropins

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Infertility

Intervention / Treatment
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* Other: AURORA-Rec


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 22 Years
Maximum Age: 38 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

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

What is the study measuring?
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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 |