Infertility
Conditions
Brief summary
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.
Interventions
OTHERAURORA-Rec
Explorative study of cumulus cells gene expression in relation to the patient treatment and oocyte competence.
Sponsors
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Fertiga, Belgium
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
22 Years to 38 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Normalized messenger ribonucleic acid (mRNA) expression | 3 years after study start | Normalized mRNA levels of biomarker genes that are assessed in cumulus cells by reverse transcription quantitative Polymerase Chain Reaction (RT-qPCR) for each oocyte. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Embryo utilization rate | Day 5 of embryo culture | 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 |
| Clinical pregnancy rate | Week 5-6 after embryo transfer | Pregnancy diagnosed by ultrasonographic or clinical documentation of at least one fetus with a discernible heartbeat in gestational week 6 to 8 |
| Ongoing pregnancy rate | Week 10-11 after embryo transfer | The presence of gestational sacs with fetal heart beat detected by transvaginal ultrasound examination in gestational week 10 to 11 |
| Miscarriage rate | Week 12 after embryo transfer | 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. |
| Meiosis II Oocyte rate | Day 0 of embryo collection | The number of meiosis II oocytes (nominator) divided by the total number of oocytes retrieved (denominator) |
| Normal fertilization rate | Day 1 of embryo culture | 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 5 good-quality embryo rate | Day 5 of embryo culture | Defined as the proportion of 2PN zygotes which are good-quality blastocysts on Day 5 |
| Biochemical pregnancy rate | Day 10 after embryo transfer | A pregnancy diagnosed only by the detection of beta human chorionic gonadotropin (hCG) in serum or urine |
| Fetal heart beat positive implantation rate | Week 5-6 after embryo transfer | Rate refers to the proportion of fetal heartbeats detected relative to the number of embryos transferred |
Other
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Live Birth rate | 3 years after study start | 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. |
| Live Birth rate | Week 24-42 after embryo transfer | 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) |
| Cumulative ongoing pregnancy rate | 3 years after study start | 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 |
Countries
Belgium
Outcome results
None listed