CENP-V As a Potential Diagnostic Marker of Damage in Human Oocytes (CENP-PILOT)

January 20, 2025 updated by: IVI Sevilla

Proper chromosome segregation is essential to avoid aneuploidy, yet in mammalian oocytes it progressively fails in an age-dependent manner. The ageing population and the increasing age of parenthood are leading to a declined fertility. Proteins contributing to correct chromosome segregation and oocyte ageing are therefore of central interest. Mouse oocytes deficient in CENP-V are strongly impaired in meiosis I. The spindle assembly checkpoint (SAC)-dependent arrest of about half of the Cenp-V -/- oocytes at metaphase I is only found in oocytes from young adults, not in oocytes >12 months. This suggests SAC weakening in ageing oocytes allowing them to proceed despite continuous presence of mis-aligned chromosomes and present CENP-V depleted oocytes as a model for age dependent weakening of the SAC. Sporadic cases of very-low oocyte survival rate have been observed after vitrification and thawing protocols in the clinical practice. However, no diagnostic tools are currently available to detect these cases. The relevance of this problem has led to a demand on the scientific community to obtain specific and early biomarkers to predict decreased oocyte survival rates after thawing. The main goal of this project is to establish the expression levels of the CENP-V protein in human oocytes as a diagnostic tool for the aging of a cohort of oocytes. With this purpose, the immature oocytes from the oocytes cohort recovered from women with advanced maternal age (AMA) and control, will be matured in vitro in order to compare the CENP-V expression levels between both populations. In addition, in patients with AMA, these expression levels will be correlated with the aneuploidy rate from the blastocyst of the same oocyte cohort. CENP-V-deleted mouse oocytes show higher rate of aneuploidy and spindle aberrations after cold treatment compared to control oocytes. We hypothesize that alterations in the expression level of CENP-V could be responsible of the decrease in oocyte survival rate after thawing. The main objective of this project is to establish the expression levels of the CENP-V protein in human oocytes as a diagnostic tool to assess the damage of a cohort of oocytes. For this purpose, oocytes retrieved from advanced maternal age (AMA) and control patients, as well as oocytes undergoing vitrification / thawing procedures and controls oocytes, will be analyzed. In this study, only the immature oocytes of the patients, which are destined to be discarded and not used in their treatment, will be analyzed.

Study Overview

Status

Recruiting

Conditions

Detailed Description

This is a prospective, unicentric, descriptive and transversal study. The main objective of this project is to establish the expression levels of the CENP-V protein in human oocytes as a diagnostic tool of damage in a cohort of human oocytes. With this purpose, CENP-V levels of discarded oocytes retrieved from Advanced Maternal Age (AMA) and control patients will be analyzed in fresh state and after vitrification-thawing procedures. As mature oocytes will be used for the patient's treatment, only immature oocytes, that would otherwise have been discarded, or mature oocyte donated to research, will be used in this project.

Study Type

Observational

Enrollment (Estimated)

160

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: ESTHER SANTAMARÍA LÓPEZ
Phone Number: +34954286274
Email: esther.santamaria@gruporecoletas.com

Study Locations

Spain
- - Sevilla, Spain, 41009
    - Recruiting
    - Vida Recoletas Sevilla S.L.
    - Contact:
      
      ESTHER SANTAMARÍA LÓPEZ
      
      Phone Number: +34954286274
      
      Email: esther.santamaria@gruporecoletas.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

Adult

Accepts Healthy Volunteers

Sampling Method

Non-Probability Sample

Study Population

The reference population will be constituted of patients and donors with immature oocytes(GV, MI), obtained after oocyte collection, and mature oocytes (MII) vitrified from patients who decide not to use them and are willing to donate them to research projects. Women willing to participate in this study will be previously informed and will have to sign the informed consent form of the study. The recruitment of patients will be performed in IVI RMA Seville clinic.

Description

Inclusion Criteria:

Group of patients with advanced maternal age (AMA): patients aged 36-45 years with AMA etiology as the main factor of infertility undergoing controlled ovarian stimulation.
Group of patients with vitrification / thawing of their oocytes: patients between 18-45 years of age who underwent oocyte vitrification to later, in the study cycle, thaw their oocytes. In this group we contemplate two subgroups:
- Patients with vitrified / thawed oocytes and AMA: between 36-45 years at the moment of oocytes vitrification.
- Patients with vitrified / thawed oocytes and non-AMA: between 18-35 years at the moment of oocytes vitrification.
Group of control patients: patients and donors with normal etiology, aged 18-35 years, undergoing controlled ovarian stimulation and collection procedures.

Exclusion Criteria:

Patients with pathologies affecting the oocyte quality (PCO, POI, endometriosis, oncology patients, etc.).
Patients/donors with oocyte cryopreserved by slow freezing technique.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Number of groups / cohorts

Cohorts and Interventions

Group / Cohort
Patients with advanced maternal age (AMA) Patients aged 36-45 years with AMA etiology as the main factor of infertility undergoing controlled ovarian stimulation
Control patients Patients and donors with normal etiology, aged 18-35 years, undergoing controlled ovarian stimulation and collection procedures.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
CENP-V levels y distribution in oocyte Time Frame: From enrollment to oocyte retrieval, two days	From enrollment to oocyte retrieval, two days

Secondary Outcome Measures

Outcome Measure	Time Frame
Survival rate of the oocyte cohort Time Frame: From enrollment to oocyte retrieval, two days	From enrollment to oocyte retrieval, two days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

IVI Sevilla

Collaborators

University of Seville, Spain

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

October 4, 2024

Primary Completion (Estimated)

June 30, 2026

Study Completion (Estimated)

December 31, 2026

Study Registration Dates

First Submitted