Amphiregulin Versus Non-Amphiregulin Supplementation to Maturation Culturing Medium in IVM.

NCT03915054 | Completed DMC

• 1 other identifier: CS/BVMD/19/03
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Clinical use of IVM was pioneered in the nineties, but has not yet become a realistic option for wide-scale practice, for several reasons. Fundamentally, despite recent progress in improving the implantation and the pregnancy rates using in-vitro matured oocytes, results of IVM remain lower than treatment cycles utilizing conventional ART. To improve the outcome of IVM cycles, this study focuses on improving in-vitro culture conditions. In-vitro maturation (IVM) of human oocytes obtained from minimally stimulated or unstimulated ovaries offers a more "patient friendly" treatment option than the conventional Assisted Reproductive Technology (ART) treatment with controlled ovarian hyperstimulation (COH). Typically, IVM will be offered to women with polycystic ovaries (PCO/PCOS), or to patients with an excellent ovarian reserve, i.e. a high antral follicle count. IVM treatment is characterized by minimal administration of FSH or hMG and NO hCG trigger. The IVM approach is less disruptive to patients' daily life through the reduced need for hormonal and ultrasound monitoring, avoids a range of minor and major complications, such as ovarian hyperstimulation syndrome, and aims to reduce the total cost of infertility treatment for the patient and for the health care budget. Human oocytes retrieved from small antral follicles are able to resume meiosis by undergoing germinal vesicle breakdown and extrusion of the first polar body, if oocytes have reached meiotic competence. These oocytes can be fertilized although only a proportion (less than 50%) of them can develop further into viable embryos. It has been hypothesized that failure of embryonic development may, at least in part, be due to an immature oocyte cytoplasm. A novel human in vitro maturation (IVM) culture system (named CAPACITATION-IVM is being investigated, hereafter named "CAPA") using 1°) natural compounds known to influence cAMP levels within the cumulus-oocyte-complex and 2°) compounds that are crucial for the oocyte-cumulus cross-talk. Keeping cyclic AMP high after retrieval in the GV oocyte prevents the occurrence of nuclear maturation, enabling increased communication between the oocyte and the cumulus cells. This allows for the improvement in the synchronization of nuclear and cytoplasmic maturation processes in the oocyte, to the benefit of embryo quality.

Conditions

PCOS; IVM

Outcome Measures

Primary Outcomes (2)

• Meiotic maturation efficiency

  Percentage of PB, GVBD, GV by the two types of trigger. The PB (or MII) oocyte displays the first PB in the PVS. GVBD oocytes have neither a visible GV nor PBI. GV oocyte presents an intracytoplasmic nucleus called the 'germinal vesicle'.

  Two days after oocytes pick-up

• Number of transferable day 3 embryos

  Number of transferable day 3 embryos obtained by the two meiotic trigger types

  Five days after oocytes pick-up

Secondary Outcomes (5)

• Ongoing pregnancy rate

  At a minimum of 12 weeks from the beginning of the last menstrual cycle (each cycle is 4 weeks) up to the time of delivery

• Live birth rate

  At least 24 weeks of gestation up to the time of delivery

• Genetic and epigenetic analysis of cord blood of newborns (Will be done in a separate study)

  1 day (Prior to the initiation of IVF/IVM) and 1 day (at the time of delivery)

• Genetic and epigenetic analysis of cells from buccal smears of newborns (Will be done in a separate study)

  1 day (Prior to the initiation of IVF/IVM) and 1 day (at the time of delivery)

• Genetic and epigenetic analysis of placenta of newborns (Will be done in a separate study)

  1 day (Prior to the initiation of IVF/IVM) and 1 day (at the time of delivery)

Study Arms (2)

AREG-TRIGGER

ACTIVE COMPARATOR

Per case (6mL) 5940 µL "Basal Medium" * 60 µL "IVM MIX" Do not need to filtrate media.

Drug: AREG-TRIGGER

CONTROL-TRIGGER

ACTIVE COMPARATOR

Per case (5 mL) 4.3 ml IVM Medicult Medium (Vial 2) 0.5 ml HSA (from stock 10% solution) 50µl FSH (from stock 7.5 IU/ml) 5µl hCG (from stock 100 IU/ml) 75 µl GH (from stock 0.66mg/ml)

Drug: CONTROL-TRIGGER

Interventions

AREG-TRIGGER DRUG

Oocytes in AREG-TRIGGER medium will be mature in AREG + FSH + HSA + Insulin + Estradiol medium. Per case (6mL) 5940 µL "Basal Medium" * 60 µL "IVM MIX" Do not need to filtrate media.

Also known as: Capacitation IVM medium

AREG-TRIGGER

CONTROL-TRIGGER DRUG

Oocytes in CONTROL-TRIGGER medium will be mature in FSH + hCG + GH + HSA medium. Per case (5 mL) 4.3 ml IVM Medicult Medium (Vial 2) 0.5 ml HSA (from stock 10% solution) 50µl FSH (from stock 7.5 IU/ml) 5µl hCG (from stock 100 IU/ml) 75 µl GH (from stock 0.66mg/ml)

Also known as: CAPA Control Medium

CONTROL-TRIGGER

Eligibility Criteria

• Age: 18 Years - 37 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Having polycystic ovarian morphology: at least 24 follicles in both ovaries and/or increased ovarian volume (\>10ml) (it is sufficient that 1 ovary fits these criteria)
• Undergoing ≤ 2 previous IVM or IVF attempts
• Agreeing to have ≤ 2 embryos transferred

You may not qualify if:

• High grade endometriosis
• Oocyte donation and pre-implantation genetic diagnosis cycles
• Cases with extremely poor sperm quality.

Sponsors & Collaborators

• Mỹ Đức Hospital: lead

Study Sites (1)

My Duc Hospital

Ho Chi Minh City, Vietnam

Location

Related Publications (1)

• Akin N, Le AH, Ha UDT, Romero S, Sanchez F, Pham TD, Nguyen MHN, Anckaert E, Ho TM, Smitz J, Vuong LN. Positive effects of amphiregulin on human oocyte maturation and its molecular drivers in patients with polycystic ovary syndrome. Hum Reprod. 2021 Dec 27;37(1):30-43. doi: 10.1093/humrep/deab237.

  PMID: 34741172 DERIVED

Study Officials

• Tuong M Ho, MD,MCE

  Hope Research Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 3, 2019
• First Posted: April 16, 2019
• Study Start: April 17, 2019
• Primary Completion: December 12, 2019
• Study Completion: January 31, 2020
• Last Updated: June 16, 2021

Record last verified: 2021-06

Data Sharing

• IPD Sharing: Will not share

Locations

VN (1)