Clinical trial NCT05332769: Cumulus Cell Mitochondrial Activity as a Non-invasive Marker of Embryo Quality (FLIM)
Official title: Cumulus Cell Mitochondrial Activity as a Non-invasive Marker of Embryo Quality
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: IVF/ICSI
Frozen Embryo Transfer
Cumulus Cell
Fluorescence Lifetime Imaging Microscopy
Keywords: Cumulus cell
Day 5/6 frozen embryo
Fluorescence lifetime imaging microscopy
FLIM
IVF/ICSI
Lead sponsor: Mỹ Đức Hospital
Sponsor class: OTHER
Collaborators: name: The Needleman Lab, Northwest Lab Building 359,52 Oxford Street Cambridge MA 02138.
name: Harvard University Faculty of Medicine
name: Hospital Foch, Suresnes, France.
First posted: 2022-04-18
Enrollment: 200
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: All Vietnamese infertile women who have IVF/ICSI cycle with at least 8 follicles ≥ 10 mm on ultrasonography at induced ovulation date agreed to freeze-all day 5-6 embryos at IVFMD and IVFMD PN will be enrolled in the study.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Live birth rate after one frozen embryo transfer cycle
timeFrame: After 24 week's gestation
Secondary outcomes:
measure: Positive pregnancy test
timeFrame: At 2 weeks after embryo placement
measure: Clinical pregnancy
timeFrame: 7 week's gestation
measure: Implantation rate
timeFrame: 3 weeks after the first transfer
measure: Ongoing pregnancy
timeFrame: At 10 weeks after embryo placement
Other outcomes:
Locations:
city: Ho Chi Minh
country: Vietnam
facility: My Duc Hospital
state: Ho Chi Minh City
Study officials:
affiliation: Mỹ Đức Hospital
name: Tuong M Ho, MD, MCE
role: PRINCIPAL_INVESTIGATOR
References:
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citation: Chakraborty S, Nian FS, Tsai JW, Karmenyan A, Chiou A. Quantification of the Metabolic State in Cell-Model of Parkinson's Disease by Fluorescence Lifetime Imaging Microscopy. Sci Rep. 2016 Jan 13;6:19145. doi: 10.1038/srep19145.
citation: Becker W. Fluorescence lifetime imaging--techniques and applications. J Microsc. 2012 Aug;247(2):119-36. doi: 10.1111/j.1365-2818.2012.03618.x. Epub 2012 May 24.
citation: Sanchez T, Wang T, Pedro MV, Zhang M, Esencan E, Sakkas D, Needleman D, Seli E. Metabolic imaging with the use of fluorescence lifetime imaging microscopy (FLIM) accurately detects mitochondrial dysfunction in mouse oocytes. Fertil Steril. 2018 Dec;110(7):1387-1397. doi: 10.1016/j.fertnstert.2018.07.022. Epub 2018 Nov 14.
citation: Sanchez T, Zhang M, Needleman D, Seli E. Metabolic imaging via fluorescence lifetime imaging microscopy for egg and embryo assessment. Fertil Steril. 2019 Feb;111(2):212-218. doi: 10.1016/j.fertnstert.2018.12.014.