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Trial record 3 of 4 for:    niPGT-A

Non-invasive Preimplantation Genetic Testing for Aneuploidies Using Cell-free DNA in Spent Culture Media (niPGT-A)

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ClinicalTrials.gov Identifier: NCT04711239
Recruitment Status : Not yet recruiting
First Posted : January 15, 2021
Last Update Posted : July 22, 2021
Sponsor:
Information provided by (Responsible Party):
Souraya Jaroudi, ART Fertility Clinics LLC

Brief Summary:

Analysis of embryonic cell-free DNA (cfDNA) present in the spent culture media (SCM) is a non-invasive alternative for preimplantation genetic testing for aneuploidies (PGT-A) that avoids the technical challenges and limitations of biopsy. Initial studies investigating this non-invasive PGT-A (niPGT-A) method reported variable concordance between cfDNA in SCM and the trophectoderm sample (~ 30%-86%) and indicated a contribution from both the inner cell mass and trophectoderm to the cfDNA in SCM.

This study aims to evaluate the use of the embryo culture medium as a source of genetic material for PGT-A and validate a niPGT-A protocol using cfDNA in SCM.


Condition or disease Intervention/treatment
Secondary Infertility Diagnostic Test: PGT-A / niPGT-A

Detailed Description:

Multiple studies have demonstrated the ability to detect and amplify cfDNA from SCM, at different stages of embryonic development, with varying rates of amplification success. Differences in analytes, timing of SCM collection and the duration of embryo culture within the collected medium, performance of assisted hatching (AH), whole genome amplification methods, comprehensive chromosome screening methods and next generation sequencing (NGS) platforms, bioinformatic analyses and strategies for identifying maternal contamination all contribute to the ultimate performance of niPGT-A.

This study aims to validate a noninvasive PGT-A (niPGT-A) method utilizing cfDNA released from the human blastocyst into the SCM.

Patients undergoing a fertility treatment with PGT-A due to secondary infertility will be recruited. On day 6 post fertilization, SCM will be collected prior to blastocyst biopsy. The SCM is normally discarded at this stage. Trophectoderm biopsy and sample collection will follow the IVF laboratory's standard practices for clinical PGT-A.

Three aneuploidy screening kits, relying on different whole genome amplification methods followed by NGS on the Ion GeneStudio™ S5 Prime System (ThermoFisher Scientific), will be compared. The concordance between cfDNA and trophectoderm biopsies will be evaluated for approximately 150 blastocysts with the best performing niPGT-A protocol.

Selection of the embryo(s) for transfer will be based solely on the PGT-A result from the biopsied cells. The patient's IVF+PGT-A treatment plan and timeline will not be altered.

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Study Type : Observational
Estimated Enrollment : 40 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Non-invasive Preimplantation Genetic Testing for Aneuploidies (niPGT-A) - Evaluation of the Analysis of Cell-free DNA in Spent Culture Medium
Estimated Study Start Date : August 15, 2021
Estimated Primary Completion Date : November 30, 2021
Estimated Study Completion Date : January 31, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Genetic Testing

Group/Cohort Intervention/treatment
Two types of samples (TE and SCM) will be collected for all blastocysts included in the study Diagnostic Test: PGT-A / niPGT-A
PGT-A and niPGT-A will be performed using next generation sequencing (NGS) analysis for chromosome copy number variation (CNV). Embryo transfers will rely solely on the results of PGT-A for trophectoderm biopsies.




Primary Outcome Measures :
  1. General concordance between results for cfDNA in SCM and trophectoderm biopsies [ Time Frame: 4 months ]
    General ploidy concordance rate: number of matched (euploid-euploid or aneuploid-aneuploid) result/total number cfDNA samples with a result

  2. Discordance per chromosome between results for cfDNA in SCM and trophectoderm biopsies [ Time Frame: 4 months ]
    Discordance per chromosome: number of misidentified chromosomal errors/24*total number of embryos with cfDNA result

  3. Concordance per chromosome between results for cfDNA in SCM and trophectoderm [ Time Frame: 4 months ]
    Chromosome error concordance: number of correctly identified chromosomal errors/total number of chromosomal errors detected

  4. Sensitivity of niPGT-A using cfDNA in SCM [ Time Frame: 4 months ]
    False negative rate: 1- (true euploid result/total number of samples with a result)

  5. Specificity of niPGT-A using cfDNA in SCM [ Time Frame: 4 months ]
    False positive rate: 1- (true aneuploid result/total number of samples with a result)


Secondary Outcome Measures :
  1. Pregnancy outcome for patients having an embryo transfer - Implantation rate [ Time Frame: 12 months ]
    Implantation rate = number of gestational sacs observed at echographic screening at 6 weeks of pregnancy / number of embryos transferred

  2. Pregnancy outcome for patients having an embryo transfer - Biochemical pregnancy rate [ Time Frame: 12 months ]
    Biochemical pregnancy rate = positive βhCG test of > 15IU but no foetal heartbeat / gestational sac on ultrasound examination

  3. Pregnancy outcome for patients having an embryo transfer - Clinical pregnancy rate [ Time Frame: 12 months ]
    Clinical pregnancy rate (%) defined by positive βhCG test and ultrasound confirmation of gestational sac or heartbeat

  4. Pregnancy outcome for patients having an embryo transfer - Miscarriage rate [ Time Frame: 12 months ]
    Miscarriage rate (%) defined by ultrasonographic visualization of one or more gestational sacs, including ectopic pregnancies, with spontaneous pregnancy loss prior to 20 weeks

  5. Pregnancy outcome for patients having an embryo transfer - Clinical pregnancy rate [ Time Frame: 12 months ]
    Ongoing pregnancy rate (beyond 20 weeks)

  6. Pregnancy outcome for patients having an embryo transfer - Implantation failure rate [ Time Frame: 12 months ]
    Implantation Failure (%)


Biospecimen Retention:   Samples With DNA

Samples to be collected:

  • Saliva sample from female patient for maternal DNA contamination assessment
  • Spent culture media (SCM) collected on the day of biopsy
  • Trophectoderm (TE) biopsy for clinical PGT-A

All samples collected for the study will be labelled with anonymised sample identifiers and cryopreserved until time of analysis. SCM samples will be stored at -80°C and TE biopsies at -20°C. Saliva samples will be stored at room temperature prior to DNA extraction. Extracted/amplified DNA will be stored at 4°C until completion of analysis, then at -20°C.

Once the study is finalised, all stored samples will be destroyed.



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Ages Eligible for Study:   18 Years to 46 Years   (Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Sampling Method:   Non-Probability Sample
Study Population
Day 6 blastocysts generated from couples undergoing fertility treatment with PGT-A and meeting the eligibility criteria
Criteria

Inclusion Criteria:

  • Patients undergoing fertility treatment with PGT-A (Recombinant FSH antagonist protocol with dual trigger)
  • Secondary infertility
  • BMI 18- 35 kg/m2
  • Sperm: fresh ejaculated sperm (abstinence: 2-3 days)
  • At least one blastocyst biopsied on day 6

Exclusion Criteria:

  • High progesterone on day of trigger (>1.5ng/ml)
  • Vitrified oocytes
  • Frozen sperm
  • Indications for PGT-SR and PGT-M

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04711239


Contacts
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Contact: Souraya Jaroudi, PhD +971563115656 souraya.jaroudi@artfertilityclinics.com
Contact: Neelke DeMunck, PhD neelke.demunck@artfertilityclinics.com

Sponsors and Collaborators
ART Fertility Clinics LLC
Investigators
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Principal Investigator: Souraya Jaroudi ART Fertility Clinics
Publications:

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Responsible Party: Souraya Jaroudi, Director, Genomics, ART Fertility Clinics LLC
ClinicalTrials.gov Identifier: NCT04711239    
Other Study ID Numbers: 2010-ABU-011-SJ
First Posted: January 15, 2021    Key Record Dates
Last Update Posted: July 22, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Souraya Jaroudi, ART Fertility Clinics LLC:
PGT-A
cell-free DNA
spent culture media
NGS
Additional relevant MeSH terms:
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Infertility
Aneuploidy
Chromosome Aberrations
Pathologic Processes