Clinical Value of Mosaicism Diagnosis on the Trophectoderm Biopsies

NCT03673592 | Completed

• 1 other identifier: IGX14-MOS-AC-18-03
• Study Type: observational
• Target: 783
• Locations: 1 country
• Sites: 3

Brief Summary

Mosaicism within an embryo is defined as the presence of two or more cell populations with different genotypes. Blastocysts classified as mosaic by Preimplamtation Genetic Testing for Aneuploidy (PGT-A) have been reported to implant less and miscarry more frequently than embryos classified as euploid. Because of the unknown impact of mosaicism on embryo development, these embryos are given low priority and are discarded for transfer. However, recent papers on the transfer of human embryos classified by PGT-A as mosaic suggest that embryos with a low fraction of abnormal cells resulting in viable, chromosomally normal ongoing pregnancies, and high-level mosaics resulting in fewer viable pregnancies, but so far none producing mosaic babies. The apparent presence of mosaicism in an embryo is used as a selection criteria for embryo transfer (ET), introducing a strong bias in terms of patient prognosis and embryo quality. Additionally, it is also possible that some embryos are incorrectly classified as "mosaic" due to technical variability derived from the processing of a uniform aneuploid embryo. The aims of this study is to provide evidences about the clinical significance of chromosomal mosaicism in PGT-A cycles by a prospective non-selection based methodology.

Conditions

Aneuploidy; Chromosome Abnormality

Keywords

Mosaicism; PGT-A; Blastocyst biopsy; Aneuploidy testing; Preimplantation genetics

Outcome Measures

Primary Outcomes (1)

• Sustained implantation rate

  Presence of a viable pregnancy after 20 weeks of gestation measured by ultrasound scan

  20 weeks after the embryo transfer

Secondary Outcomes (1)

• Miscarriage rate

  20 weeks after the embryo transfer

Study Arms (4)

Euploid embryos analyzed by PGT-A

Embryos with a normal chromosome copy number. This embryos will be transferred to the uterus.

Diagnostic Test: PGT-A

Low-grade mosaic embryos (PGT-A)

Embryos with a lower aneuploidy percentage (\<50%). This embryos will be considered for transfer to the uterus.

Diagnostic Test: PGT-A

High-grade mosaic embryos (PGT-A)

Embryos with a high aneuploidy percentage (50-70%). This embryos will be discarded for transfer.

Diagnostic Test: PGT-A

Aneuploid embryos analyzed by PGT-A

Embryos with an abnormal number of chromosomes. This embryos will be discarded for transfer.

Diagnostic Test: PGT-A

Interventions

PGT-A DIAGNOSTIC_TEST

PGT-A will be carried out following the usual clinical practice: Trophectoderm biopsy samples from blastocysts are analyzed by NGS to screen for numerical chromosomal abnormalities.

Aneuploid embryos analyzed by PGT-A; Euploid embryos analyzed by PGT-A; High-grade mosaic embryos (PGT-A); Low-grade mosaic embryos (PGT-A)

Eligibility Criteria

• Age: 18 Years - 44 Years
• Gender Eligibility Details: Embryos from IVF patients up to 44 years of age (also included) undergoing PGT-A.
• Healthy Volunteers: No
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Embryos from In Vitro Fertilization (IVF) patients up to 44 years old (also included) with medical indication of PGT-A and own oocytes.

You may qualify if:

• PGT-A cases for any medical indication and sign the written informed consent form approved by the Ethics Committee (EC) after having been duly informed of the nature of the research and voluntarily accepted to participate in the study.
• Only PGT-A cycles with own oocytes.
• Female age up to 44 years old (also included).
• ICSI treatment must be done in all oocytes.
• Have at least one euploid blastocyst or one low-grade mosaicism diagnosis for a single chromosome after PGT-A analysis (excluding aneuploidies compatible with life, e.g. chromosomes 13, 18, 21 and X/Y).
• Single or Double Embryo Transfer (SET or DET). The patient remains included in the study until the 4th ET (fresh or frozen) from the initial stimulation cycle or until patient's enrolment period ends (whichever comes first). The data collected until one of these points will be included in the study, whilst clinical outcomes from additional ET will be disregarded.

You may not qualify if:

• No embryo reaching blastocyst stage with a proper morphology for trophectoderm biopsy.
• Embryo transfer coming from the worst grade blastocyst morphology according to Gardner's criteria (Annex 1) will be excluded.
• DET resulting in singletons. (Note: DET resulting in dizygotic twins or implantation failure to the both embryos transferred will be allowed).
• Any illness or medical condition that is unstable or can put patient safety at risk and compliance in the study.

Sponsors & Collaborators

• Igenomix: lead

Study Sites (3)

Demetra

Florence, 50141, Italy

Location

Genera

Roma, 00197, Italy

Location

Humanitas Fertility Center

Roma, Italy

Location

Related Publications (1)

• Capalbo A, Poli M, Rienzi L, Girardi L, Patassini C, Fabiani M, Cimadomo D, Benini F, Farcomeni A, Cuzzi J, Rubio C, Albani E, Sacchi L, Vaiarelli A, Figliuzzi M, Findikli N, Coban O, Boynukalin FK, Vogel I, Hoffmann E, Livi C, Levi-Setti PE, Ubaldi FM, Simon C. Mosaic human preimplantation embryos and their developmental potential in a prospective, non-selection clinical trial. Am J Hum Genet. 2021 Dec 2;108(12):2238-2247. doi: 10.1016/j.ajhg.2021.11.002. Epub 2021 Nov 18.

  PMID: 34798051 DERIVED

Biospecimen

Retention: SAMPLES WITH DNA

DNA analysis of each patient's embryos

MeSH Terms

Conditions

Aneuploidy; Chromosome Aberrations

Condition Hierarchy (Ancestors)

Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Antonio Capalbo, BSc PhD

  Igenomix S.L.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 13, 2018
• First Posted: September 17, 2018
• Study Start: September 3, 2018
• Primary Completion: December 31, 2019
• Study Completion: May 20, 2020
• Last Updated: October 19, 2020

Record last verified: 2020-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (3)