Embryo Developmental Potential in a Novel 2-step IVM System

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

23 participants

Study Classification

INTERVENTIONAL

Study Start Date

2020-07-16

Study Completion Date

2023-12-31

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

In vitro maturation is a valid option for PCO(S) patients in the daily ART clinic, however maturation and embryologic development are not yet matching the efficiency levels obtained by standard COS treatment. To further enhance embryo quality after IVM, it was hypothesized to keep the connection and communication between oocyte and cumulus cells intact for a prolonged pre-maturation culture before IVM was initiated. This has been investigated and established using a meiotic blocker C-type Natriuretic peptide (CNP).

The CNP peptide is present in high concentrations in the growing follicle, is produced by the mural granulosa cell compartment and binds to the Natriuretic peptide receptor 2 (NRP2) present in the cumulus cells. Binding of CNP on NRP2 leads to intracellular cGMP increase in cumulus cells, which travels through the transzonal projections to the oocyte. In the oocyte, cGMP will block the resumption of meiosis.

Using CNP as natural inhibitor of meiosis, a new medium was designed to allow oocyte and surrounding cumulus cells to communicate and hence gain in competence for an additional culture period: the pre-maturation phase or Capacitation phase (CAPA). This system was devel-oped in mouse, tested in human in UZ Brussel on research material (toelating federaal EC: CFE-FCE ADV\_073\_ZUBrussel, toelating lokaal EC: 2016/411 BUN 143201630723) and used in a clinical setting in Vietnam.

Related Clinical Trials

Explore similar clinical trials based on study characteristics and research focus.

CAPA-IVM Culture With Low Oxygen Tension

NCT06367985

In Vitro Fertilization

COMPLETED NA

CAPA In-vitro Oocyte Maturation

NCT06984081

Infertility, Female

RECRUITING NA

CAPA In-vitro Oocyte Maturation (CUHK Medical Centre Limited)

NCT07083427

Infertility, Female

NOT_YET_RECRUITING NA

Effect of Super-GDF9 on CAPA-IVM of COCs From Small Antral Follicles

NCT06766604

In Vitro Fertilization

RECRUITING NA

In Vitro Maturation of Human Eggs

NCT02516462

Infertility Reproductive Techniques, Assisted

UNKNOWN NA

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

The current IVM system in use in the clinic has a single step approach and seems to be less efficient compared to research and literature findings using a biphasic CAPA-IVM system in terms of maturation.

To ascertain the efficiency of the biphasic CAPA-IVM system, both standard IVM and CAPA-IVM will be performed on sibling oocytes: maturation in standard IVM in the investigator's center is on average 47.5%, where CAPA-IVM reaches 62% maturation in literature.

The investigators aim to prove superiority of the CAPA-IVM system in terms of maturation. Also fertilization and embryo development will be compared.

The participants admitted to the study will be receiving both the standard IVM treatment for part of the participant's oocytes and the biphasic CAPA IVM system for the second part of the participant's oocytes.

In one ovary a regular oocyte pick up (OPU) will take place with oocytes assigned to the standard IVM treatment, in the other ovary the CAPA IVM system will be applied. This means oocytes that are liberated from the follicular environment need to be exposed immediately to the inhibiting CNP peptide and herefore the tubes to collect the follicle fluid from the punctured follicles are prefilled with CNP supplemented medium. The OPU procedure is identical for both ovaries and according to our standard OPU IVM procedure with the sole difference of empty or prefilled tubes to collect follicle fluid.

Oocytes from the 2 ovaries are separately processed in the lab according to attributed protocol.

After IVM of oocytes, mature oocytes are subjected to ICSI with partner's sperm or donor sperm. Partner's sperm sample will be frozen at the latest the day of egg retrieval and will be thawed the day of intracytoplasmic sperm injection (ICSI): due to the use of 2 different IVM protocols with 2 different time lines (30 hours maturation versus 24 hours+30 hours maturation), ICSI will take place on two consecutive days with a freshly thawed straw of sperm cells for each day.

Embryo development is followed until day 3 (cleavage stage) after ICSI. All embryos of sufficient quality will be vitrified for a deferred embryo transfer in a hormone replacement therapy (HRT) cycle. One embryo will be selected for embryo transfer based on the morphological quality assessment parameters, with the better quality as first choice for transfer, regardless the preceding IVM method. Frozen single embryo transfer cycles are repeated until pregnancy.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

In Vitro Maturation of Oocytes

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

prospective randomized control trial

Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

CAPA IVM

CAPA IVM is a 2-step In vitro Maturation system in which an additional culture step, in which the oocytes are kept in meiotic arrest by the presence of the C-type Natriuretic peptide (CNP) for 22-24 hours, is preceding the in vitro maturation step in which maturation medium is supplemented with amphiregulin (AREG). The 'IVM System' of Medicult-Origio is used as a base medium.

Group Type EXPERIMENTAL

CAPA-IVM

Intervention Type DEVICE

CAPA medium keeps oocytes in meiotic arrest for 22-24 hours. IVM medium allows oocytes to resume meiosis.

CAPA medium: 10% human serum albumin (HSA) + 10nM estradiol (E2) + 25nM CNP + 5ng/ml Insulin + 1mIU/ml follicle stimulating hormone (FSH) IVM medium: 10% HSA + 10nM E2 + 5ng/ml Insulin + 101mIU/ml FSH + 100ng/ml AREG CNP: peptide naturally occurring in follicles to maintain meiotic arrest, E2: estrogen, enhances effects of CNP, Insulin: basic growth factor used in cell cultures and component of commercially available LAG medium of the standard IVM system, AREG: downstream effector of the LHCG receptor which helps meiotic resumption. HSA, FSH and hCG are CE labeled. CAPA IVM medium is currently not yet available as CE marked commercially available medium and needs to be prepared in house.

Standard IVM

The IVM is performed as a single step protocol in which oocytes are immediately exposed to in vitro maturation medium for 30 hours. This is the current standard procedure in the clinical practice using the commercially available 'IVM System' of Medicult-Origio. Standard IVM medium: 10% HSA + 75mIU/ml FSH + 100mIU/ml hCG

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

CAPA-IVM

CAPA medium keeps oocytes in meiotic arrest for 22-24 hours. IVM medium allows oocytes to resume meiosis.

CAPA medium: 10% human serum albumin (HSA) + 10nM estradiol (E2) + 25nM CNP + 5ng/ml Insulin + 1mIU/ml follicle stimulating hormone (FSH) IVM medium: 10% HSA + 10nM E2 + 5ng/ml Insulin + 101mIU/ml FSH + 100ng/ml AREG CNP: peptide naturally occurring in follicles to maintain meiotic arrest, E2: estrogen, enhances effects of CNP, Insulin: basic growth factor used in cell cultures and component of commercially available LAG medium of the standard IVM system, AREG: downstream effector of the LHCG receptor which helps meiotic resumption. HSA, FSH and hCG are CE labeled. CAPA IVM medium is currently not yet available as CE marked commercially available medium and needs to be prepared in house.

Intervention Type DEVICE

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* PCO(S) patients
* Anti-Mullerian Hormone ≥ 3.6 ng/mL
* Basal Antral Follicle Count ≥ 20
* All ranks of trial

Exclusion Criteria

* Surgically obtained semen sample
* Grade 3 or 4 endometriosis, minor or major uterine abnormalities
* Preimplantation Genetic Testing
* Priming with Letrozole

Minimum Eligible Age

18 Years

Maximum Eligible Age

36 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No