Cumulus Cell, Fluorescence Lifetime Imaging Microscopy, Frozen Embryo Transfer, IVF/ICSI
Conditions
Keywords
Cumulus cell, Day 5/6 frozen embryo, Fluorescence lifetime imaging microscopy, FLIM, IVF/ICSI
Brief summary
This study aims to test the extent of association of FLIM parameters of cumulus cells with clinical outcomes (clinical pregnancy, ongoing pregnancy at 12 weeks, and live birth) of the embryos that result from the enclosed oocytes.
Detailed description
This study aims to test the extent of association of FLIM parameters of cumulus cells with clinical outcomes (clinical pregnancy, ongoing pregnancy at 12 weeks, and live birth) of the embryos that result from the enclosed oocytes. Participants will be consented to and pre-signed following standard regimens of IVFMD, My Duc Hospital and IVFMD PN, My Duc Phu Nhuan Hospital. The standard is for patients with at least 8 follicles ≥ 10 mm on ultrasonography at the induced ovulation date. Cumulus samples (CCs) will be collected following the protocol on the day of oocyte pick up (OPU), being assigned with the same number as the oocyte from which it was collected, and vitrified with a Cryotech kit until FLIM measurements are performed. Insemination will be performed by using ICSI, 3 - 4 hours after oocyte retrieval. A sample of CCs will be sliced off the cumulus mass of each oocyte judged to be mature based on the cumulus mass disposition (absence of tight corona layers). The remaining cumulus cells will be stripped from the OCCs using hyaluronidase. Only mature oocytes will be inseminated. The fertilization check will be performed under an inverted microscope for a period of 16-18 hours after insemination. On day 3, embryo evaluation will be performed at a fixed time point 66±2 hours after fertilization and, for day 5/6 transfers at 116±2 hours or 140±2 hours, respectively, using the Istanbul consensus. Freeze-all strategy for day 5 embryo will be applied and the first frozen embryo transfer cycle is single embryo transfer. On the other hand, the investigators will stratify embryos into two groups based on the measured FLIM parameters from their associated cumulus cells, corresponding to the "high" 35% and "low" 65% of metabolic scores. The investigators aim for embryos in the "high" metabolic scoring group to have a 10% higher live birth rate than controls. Assuming a current live birth rate of 32%, this corresponds to a hoped-for 42% live birth rate in the "high" group (and a 25% live birth rate in the "low" group). A total of 450 patients are required to detect an effect of this size (power 0.90, two-sided alpha 5%). The primary endpoint of the study will be the live birth rate after the first embryo transfer of the started treatment cycle.
Interventions
GENETICFLIM parameters
Cumulus samples (CCs) will be collected following the protocol on the day of oocyte pick up (OPU). CCs are frozen by the cryo-tech method, then stored in liquid nitrogen at -196oC. Information of CC samples and processed date/time is recorded. After all, samples are collected, they will be transferred to The Needleman Lab, Northwest Lab Building 359,52 Oxford Street Cambridge MA 02138 to measure mitochondria metabolism using FLIM.
Sponsors
Mỹ Đức Hospital
The Needleman Lab, Northwest Lab Building 359,52 Oxford Street Cambridge MA 02138.
Harvard University Faculty of Medicine
Hospital Foch, Suresnes, France.
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Having any number of IVF/ICSI attempts * Ovarian stimulation with any stimulation protocol * Patients with at least 8 follicles ≥ 10 mm on ultrasonography at induced ovulation date * Agreed to freeze-all day 5-6 embryos * Agreed to have a single day 5-6 embryo transfer. * Agreed to participate in the research (signed the consent form)
Exclusion criteria
* In vitro maturation (IVM) cycles * Cycles using testicular biopsy or epididymal sperm * Cycles not having an oocyte freeze-all cycle * Cycles using standard insemination * Participating in another research
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Live birth rate after one frozen embryo transfer cycle | After 24 week's gestation | The birth of at least one newborn, after 24 week's gestation that exhibits any sign of life, such as respiration, heartbeat, umbilical pulsation, or movement of voluntary muscles |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Positive pregnancy test | At 2 weeks after embryo placement | Positive pregnancy test is defined as a serum human chorionic gonadotropin level greater than 25 mIU/mL after2 weeks after embryo placement of the first transfer |
| Clinical pregnancy | 7 week's gestation | The presence of at least one gestational sac on ultrasound at 7 week's gestation with the detection of heartbeat activity, after the completion of the first transfer |
| Implantation rate | 3 weeks after the first transfer | Implantation rate is defined as the number of gestational sacs per number of embryos transferred 3 weeks after the first transfer |
| Ongoing pregnancy | At 10 weeks after embryo placement | Having at least 1 gestational sac on ultrasound at 12 weeks' gestation with heart beat activity |
Countries
Vietnam
Contacts
PRINCIPAL_INVESTIGATORTuong M Ho, MD, MCE
Mỹ Đức Hospital
Outcome results
None listed