Does in Vivo Culture of Pre-cleavage Stage Embryo Reduce the Incidence of Aneuploidy?

Does in Vivo Culture of Pre-cleavage Stage Embryo Reduce the Incidence of Aneuploidy? A Sibling Oocyte, Prospective, Multi-centric, Randomized, Open Study, Clinical Study in Subjects With Subfertility Undergoing Assisted Reproductive Medical Treatment

This Clinical Study has been designed to assess and compare the impact of in vitro or in vivo culture conditions on the euploidy of sibling blastocysts.

Study Overview

• Status: Terminated
• Conditions: Infertility; Reproductive Sterility
• Intervention / Treatment: Device: AneVivo (Medical device for in vivo culture of embryos); Other: comparator for embryo culture in vitro

Detailed Description

As soon as the very first minute of the fertilization process, very important biological events, critical for the future developmental competency of the embryo are taking place.

These biological events, after the sperm cell entry in the oocyte cytoplasm and prior to the first cleavage, include: the completion of the meiosis, the exclusion of the second polar body, the pronuclei formation, the replication of the male and female DNA and the chromosome segregation on the newly formed mitotic spindle.

If any of these events is aberrant, one or both of the two daughter cells and their descendants may carry chromosomal anomalies. In other words an uneven first cleavage in size or in content is associated with chromosomal abnormality and aneuploidy.

In vivo all these events occur in a natural environment where the presence of specific molecules and of a dynamic and physiological environment might be an advantage over in vitro culture conditions to ensure optimal cellular functions.

Preliminary data from the pilot study have shown a higher proportion of euploid embryos for sibling oocytes cultured in vivo vs. in vitro. Moreover, in animal models, in vivo cultured embryos have been described with significant reduction of aneuploidies and with differences in the gene expression levels patterns when compared to in vitro cultured embryos. There is also growing evidence that the culture conditions of human pre-implantation embryos can affect the gene expression regulation with measurable effects on embryos and on newborn children.

The investigators hypothesis is that in vivo produced embryos might have a higher percentage of euploidy when compared to their siblings cultured in vitro.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Spain
  • Bilbao, Spain
    • IVI Bilbao

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 38 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Signed Informed Consent by the subject and her partner
• Women, aged between 18 and 38 years (up to 38th birthday)
• ≤ 2 previous stimulation cycles
• Routinely measured hormonal levels within normal range (i.e. FSH, LH, E2, PRL)
• No uterine or ovarian anatomical abnormalities and/or alterations that would compromise device delivery or function in the uterus as demonstrated by ultrasound and trial insertion
• 19 ≤ BMI ≤ 29 kg/m2

Exclusion Criteria:

• History of previous moderate or severe ovarian hyperstimulation syndrome (OHSS)
• Severe endometriosis
• Any active infection that would contraindicate ART, at the discretion of the investigator
• Severe male factor in the partner (cryptozoospermia or non-obstructive azoospermia)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: sibling oocytes in vivo; randomized oocytes assigned to in vivo culture	Device: AneVivo (Medical device for in vivo culture of embryos); Other Names: Anecova
Active Comparator: sibling oocyte in vitro; randomized oocytes assigned to in vitro culture	Other: comparator for embryo culture in vitro

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Euploidy status after a biopsy on all viable day 5 embryos	full genome analysis on 24 chromosomes	1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implantation rate	number of gestational sac per transferred embryos	9 weeks
Pregnancy rate	beating heart	9 weeks

Collaborators and Investigators

• Sponsor: Anecova SA
• Investigators: Principal Investigator: Marcos Ferrando, MD, IVI Bilbao

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2016
• Primary Completion (Actual): April 1, 2016
• Study Completion (Actual): June 1, 2016

Study Registration Dates

• First Submitted: January 7, 2016
• First Submitted That Met QC Criteria: January 8, 2016
• First Posted (Estimate): January 11, 2016

Study Record Updates

• Last Update Posted (Actual): April 4, 2019
• Last Update Submitted That Met QC Criteria: April 3, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: in vivo culture
• Additional Relevant MeSH Terms: Pathologic Processes; Chromosome Aberrations; Infertility; Aneuploidy
• Other Study ID Numbers: NCVd20H

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED