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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Infertility, Reproductive Sterility

Intervention / Treatment
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* Device: AneVivo (Medical device for in vivo culture of embryos)
* Other: comparator for embryo culture in vitro


Participation Criteria
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Eligibility Criteria
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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)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 38 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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in vivo culture