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

Not Applicable
Terminated
Conditions
Infertility
Reproductive Sterility
Interventions
Other: comparator for embryo culture in vitro
Device: AneVivo (Medical device for in vivo culture of embryos)
Registration Number
NCT02652143
Lead Sponsor
Anecova SA
Brief Summary

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.

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.

Recruitment & Eligibility

Status
TERMINATED
Sex
Female
Target Recruitment
35
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 & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
sibling oocyte in vitrocomparator for embryo culture in vitrorandomized oocytes assigned to in vitro culture
sibling oocytes in vivoAneVivo (Medical device for in vivo culture of embryos)randomized oocytes assigned to in vivo culture
Primary Outcome Measures
NameTimeMethod
Euploidy status after a biopsy on all viable day 5 embryos1 week

full genome analysis on 24 chromosomes

Secondary Outcome Measures
NameTimeMethod
Implantation rate9 weeks

number of gestational sac per transferred embryos

Pregnancy rate9 weeks

beating heart

Trial Locations

Locations (1)

Ivi Bilbao

🇪🇸

Bilbao, Spain

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