Cumulus Cell Mitochondrial Activity as a Non-invasive Marker of Embryo Quality (FLIM)

Frozen Embryo Transfer Clinical Trial

Official title:

Cumulus Cell Mitochondrial Activity as a Non-invasive Marker of Embryo Quality

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05332769
• Other study ID #: 11/21/DD/BVMD
• Status: Recruiting
• Start date: April 25, 2022
• Est. completion date: March 30, 2025

Study information

• Verified date: March 2024
• Source: M? Ð?c Hospital
• Contact: Tuong M HO, MD, MCE
• Phone: +84903633377
• Email: homanhtuong[@]yahoo.com
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 200
• Est. completion date: March 30, 2025
• Est. primary completion date: June 30, 2024
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Frozen Embryo Transfer
• IVF/ICSI

Intervention

Genetic:
• FLIM 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.

Locations

Country	Name	City	State
Vietnam	My Duc Hospital	Ho Chi Minh	Ho Chi Minh City

Sponsors (4)

Lead Sponsor	Collaborator
M? Ð?c Hospital	Harvard University Faculty of Medicine, Hospital Foch, Suresnes, France., The Needleman Lab, Northwest Lab Building 359,52 Oxford Street Cambridge MA 02138.

Country where clinical trial is conducted

Vietnam, 

References & Publications (9)

Babayev E, Seli E. Oocyte mitochondrial function and reproduction. Curr Opin Obstet Gynecol. 2015 Jun;27(3):175-81. doi: 10.1097/GCO.0000000000000164. — View 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. — View 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. — View Citation

Dumollard R, Duchen M, Carroll J. The role of mitochondrial function in the oocyte and embryo. Curr Top Dev Biol. 2007;77:21-49. doi: 10.1016/S0070-2153(06)77002-8. — View Citation

Fauser BC. Towards the global coverage of a unified registry of IVF outcomes. Reprod Biomed Online. 2019 Feb;38(2):133-137. doi: 10.1016/j.rbmo.2018.12.001. Epub 2018 Dec 14. No abstract available. — View Citation

May-Panloup P, Boucret L, Chao de la Barca JM, Desquiret-Dumas V, Ferre-L'Hotellier V, Moriniere C, Descamps P, Procaccio V, Reynier P. Ovarian ageing: the role of mitochondria in oocytes and follicles. Hum Reprod Update. 2016 Nov;22(6):725-743. doi: 10.1 — View 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) — View 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. — View Citation

Scott R 3rd, Zhang M, Seli E. Metabolism of the oocyte and the preimplantation embryo: implications for assisted reproduction. Curr Opin Obstet Gynecol. 2018 Jun;30(3):163-170. doi: 10.1097/GCO.0000000000000455. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Live birth rate after one frozen embryo transfer cycle	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	After 24 week's gestation
Secondary	Positive pregnancy test	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	At 2 weeks after embryo placement
Secondary	Clinical pregnancy	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	7 week's gestation
Secondary	Implantation rate	Implantation rate is defined as the number of gestational sacs per number of embryos transferred 3 weeks after the first transfer	3 weeks after the first transfer
Secondary	Ongoing pregnancy	Having at least 1 gestational sac on ultrasound at 12 weeks' gestation with heart beat activity	At 10 weeks after embryo placement

External Links

•   T. H. F. and E. A. (HFEA), "Fertility treatment 2019: trends and figures," 2021.