Infertility
Conditions
Brief summary
This is a randomized observational study. The main aim is to determine potential oocyte competence predictive mRNA expression profiles in the cumulus cells isolated form individual oocytes. In 2 patient cohorts: 1)GnRH Antagonist & hr-FSH with GnRH Agonist trigger, 2) Progesterone & hr-FSH with GnRH Agonist trigger.
Interventions
OTHERAURORA-Donor
Explorative study of cumulus cells gene expression in relation to the oocyte competence for good quality blastocyst formation and predictive for clinical pregnancy.
Sponsors
Fertilab
Ferring Pharmaceuticals
Fertiga, Belgium
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
Donor: * Patients are 18 to 35 years old * BMI between 17-30 * Regular menstrual cycles * AFC \> 8 * Patient profile in compliance with SEF (Sociedad Española de Fertilidad) directives for egg donation (medical, psychological and genetic screening, informed consent) * Patients' stimulation: GnRH Antagonist & hr-FSH with GnRH Agonist trigger or Progesterone & hr-FSH with GnRH Agonist trigger * Patients agree that the oocytes will be denuded for cumulus testing and provide written informed consent for participation to the study
Exclusion criteria
Donor: * BMI \< 17 or \> 30 * Extreme irregular menstrual cycles (\<20 days or \>40 days) * AFC \< 8 * \<8 MII on previous egg retrieval * Women with history of poor oocyte maturation or known maturation defect or unexplained failure in previous treatments * Patients that fail to comply with SEF (Sociedad Española de Fertilidad) directives for egg donation (medical, psychological and genetic screening, informed consent) Inclusion Criteria Recipient: * Patients applying for ART egg donation with fresh/frozen sperm from the partner or frozen donor sperm. With eSB-FET in modified natural cycle or an HRT cycle. * Patients are from 18 to 50 years old. * Patients will be treated by ICSI (intracytoplasmic sperm injection) and eSB-FET (elective Single Blastocyst Frozen Embryo Transfer) * Recipient patients agree that the donors' oocytes will be denuded for cumulus testing and provide written informed consent for participation to the study
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Expression profile: blastocyst formation | 2.5 years after study start | The expression profiles of cumulus of oocyte leading to a blastocyst and the expression profiles of cumulus of oocyte not leading to a blastocyst has been determined using RNA-Seq. |
| Clinical evaluation: number of Follicles | During ovarian stimulation (max 3 weeks) | The number of follicles at time of trigger (oocyte-pick-up day-2) |
| Clinical evaluation: number of cumulus-oocyte complex | Day 1 of embryo culture | The number of cumulus-oocyte complex at time of pick-up |
| Clinical evaluation: Meiosis II oocytes | Day 1 of embryo culture | The number of meiosis II oocytes (nominator) divided by the total number of oocytes retrieved (denominator) |
| Clinical evaluation: Abnormal fertilization | Day 1 of embryo culture | The number of abnormal fertilized oocytes on day 1 at 17+1h post insemination, as a function of all COC's inseminated |
| Clinical evaluation: Normal Fertilization | Day 1 of embryo culture | The number of fertilized oocytes on day 1 (presence of 2PN and 2PB assessed at 17 + 1h post-insemination), as a function of all COC's inseminate |
| Clinical evaluation: Day 3 embryo evaluation | Day 3 of embryo culture | Day 3 embryo morphology evaluation according to the standard of care of the ART clinic |
| Clinical evaluation: Day 5/6 embryo evaluation | Day 6 of embryo culture | Day 5/6 embryo evaluation based on the criteria of Gardner and Schoolcraft (Gardner and Schoolcraft 1999) |
| Clinical evaluation: Day5/6 good quality blastocyst rate | Day 6 of embryo culture | Defined as the proportion of 2PN zygotes which are good-quality blastocyst on Day 5/6 (116 +-2h and 140 +-2h post-insemination) (ESHRE Special Interest Group of Embryology and Alpha Scientists in Reproductive Medicine 2017) |
| Clinical evaluation: Embryo utilization | Day 6 of embryo culture | Defined as the number of blastocyst suitable for cryopreservation and transfer as a function of the number of normally fertilized (2PN) oocytes observed on day 1 (ESHRE Special Interest Group Alpha Scientists 2017) |
| Basic clinical donor patient and stimulation characteristics: P4 | During ovarian stimulation (max 3 weeks) | Serum values for P4 (ng/ml) |
| Basic clinical donor patient and stimulation characteristics: E2 | During ovarian stimulation (max 3 weeks) | Serum values for E2 (ng/L) |
| Basic clinical donor patient and stimulation characteristics: Gonadotropin type and dose | During ovarian stimulation (max 3 weeks) | Gonadotropin type and dose (IU) used for stimulation |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Biochemical pregnancy | Day 10 after embryo transfer | A pregnancy diagnosed only by the detection of beta human chorionic gonadotropin (hCG) in serum or urine |
| Expression profile: pregnancy prediction | 2.5 years after study start | The expression profile of cumulus of oocytes leading to pregnancy and the expression profiles of oocytes not leading to pregnancy are established using RNA seq. |
| Normalized messenger ribonucleic acid (mRNA) expression | 2.5 years after study start | Quantitative Polymerase Chain Reaction (QPCR) data of samples informative for blastocyst formation and pregnancy prediction have been collected |
| Clinical pregnancy with positive fetal heartbeat | 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Live birth | 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) |
| 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 |
| Cumulative pregnancy | 2.5 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. Live birth 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 live birth | 2.5 years after study start | The number of deliveries with at least one live birth resulting from one initiated or aspirated 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. |
| Miscarriage rate | week 22 after embryo transfer | the spontaneous loss of an intra-uterine pregnancy prior to 22 completed weeks of gestational age |
Countries
Spain
Contacts
Primary ContactTom Adriaenssens, PhD
Outcome results
None listed