Comparison of Standard ART Practice vs. Trophectoderm Biopsy and Whole Chromosome Analysis

NCT ID: NCT01946945

Last Updated: 2014-09-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

Get a concise snapshot of the trial, including recruitment status, study phase, enrollment targets, and key timeline milestones.

Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

240 participants

Study Classification

INTERVENTIONAL

Study Start Date

2013-09-30

Brief Summary

Review the sponsor-provided synopsis that highlights what the study is about and why it is being conducted.

We propose to perform a clinical randomized trial to evaluate the effect of blastocyst biopsy and whole chromosome analysis by Next Generation Sequencing (NGS) in comparison to standard Assisted Reproductive Technologies (ART) methods on on implantation rates, miscarriage rates, and pregnancy rates.

This will be three studies into one: a) a comparison of treatment (NGS) and no treatment, b) a non-selection study based on the control group for which we will replace without knowing the ploidy of the embryos, but we will know it later, c) a retrospective study about the use of Mitochondrial DNA as a selection tool.

Detailed Description

Dive into the extended narrative that explains the scientific background, objectives, and procedures in greater depth.

Patients following the inclusion criteria will be randomized into two groups:

1. Control group: All blastocyst embryos will be biopsied on day 5/6, but the biopsies will be frozen and will not be analyzed before replacement. Blastocyst embryos will be vitrified for future frozen embryo transfer (FET) cycle. Patients will have a single hatching blastocyst (\*) thawed and transferred into the uterus in a FET cycle based on standard embryo quality assessment without NGS. After transfer, all biopsied samples will be analyzed (the replaced embryo also, in order to do a non-selection study). If patients in the control group do not have a pregnancy to term from that FET cycle, euploid frozen blastocysts will be thawed and transferred on the next FET transfer.
2. Test group: All blastocyst embryos will be biopsied on day 5/6, and the biopsies will be analyzed using NGS. (\*) and Biopsied blastocyst embryos will be vitrified for a future frozen embryo transfer (FET) cycle. Patients will have a single hatching euploid blastocyst (\*) thawed and transferred into the uterus in a FET cycle

(\*) Hatching blastocysts as described by Gardner and Schoolcraft (1999)

The Primary efficacy endpoint of comparing the study group with the control will be ongoing implantation rate (# fetus reaching 2nd trimester / # embryos replaced).

All biopsied embryos from the test and control group will have their mitochondrial DNA analyzed, but that information will not be used for purposes of choosing embryos for replacement. Retrospectively but blindly (see blinding of results section), the information will be used at the end of the study to determine which embryos have a higher chance of implanting. If at that point the participating patients have remaining embryos frozen, they will be able to use that information for purposes of embryo selection.

Conditions

See the medical conditions and disease areas that this research is targeting or investigating.

Infertility Recurrent Pregnancy Loss

Study Design

Understand how the trial is structured, including allocation methods, masking strategies, primary purpose, and other design elements.

Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

SCREENING

Blinding Strategy

DOUBLE

Participants Outcome Assessors

Study Groups

Review each arm or cohort in the study, along with the interventions and objectives associated with them.

Control - Standard ART treatment

Group Type NO_INTERVENTION

No interventions assigned to this group

Test - PGS

All embryos will be hatched on day 3. Patients will have hatching blastocysts (\*) biopsied on day 5,/6. Embryos will be vitrified. Patients will have a single hatching euploid blastocyst (\*) replaced on a thawed cycle.

Group Type EXPERIMENTAL

Next Generation Sequencing after Blastocyst biopsy

Intervention Type GENETIC

PGD using blastocyst biopsy and testing of the biopsy by NGS

Interventions

Learn about the drugs, procedures, or behavioral strategies being tested and how they are applied within this trial.

Next Generation Sequencing after Blastocyst biopsy

PGD using blastocyst biopsy and testing of the biopsy by NGS

Intervention Type GENETIC

Other Intervention Names

Discover alternative or legacy names that may be used to describe the listed interventions across different sources.

PGD: Preimplantation Genetic Diagnosis

Eligibility Criteria

Check the participation requirements, including inclusion and exclusion rules, age limits, and whether healthy volunteers are accepted.

Inclusion Criteria

* All patients medically cleared to do a fresh or frozen embryo transfer.
* Age up to 42 years

Exclusion Criteria

* microsurgical epididymal sperm aspiration (MESA) and Testicular sperm extraction (TESE) patients
* At least one partner carrier of a chromosomal or genetic disease
* Abnormal ovarian reserve, defined as follicle stimulating hormone (FSH) of \>10 IU/L on day 2-4 of the cycle and anti-mullerian hormone (AMH) \< 1ng /ml (If only one of the two parameters altered then patients is acceptable). This is based on Mandy Katz abstract at American Society for Reproductive Medicine (ASRM) 2011 where they showed that these patients have 35% chance of having no euploid embryos - They are excluded only to make the study size smaller, otherwise, if an euploid embryo is found in these patients, they implant as well as patients with normal ovarian reserve. Not all centers do AMH testing - we recommend first to run FSH and only test AMH if FSH is abnormal.
* Egg donor cycle (sperm donor is acceptable)
* Gender selection cycles
* Thaw cycles
Minimum Eligible Age

18 Years

Maximum Eligible Age

42 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

Meet the organizations funding or collaborating on the study and learn about their roles.

Main Line Fertility Center

OTHER

Sponsor Role collaborator

Reprogenetics

INDUSTRY

Sponsor Role lead

Responsible Party

Identify the individual or organization who holds primary responsibility for the study information submitted to regulators.

Responsibility Role SPONSOR

Principal Investigators

Learn about the lead researchers overseeing the trial and their institutional affiliations.

Santiago Munne, PhD

Role: STUDY_DIRECTOR

Reprogenetics

Locations

Explore where the study is taking place and check the recruitment status at each participating site.

Reprogenetics

Livingston, New Jersey, United States

Site Status RECRUITING

Countries

Review the countries where the study has at least one active or historical site.

United States

Facility Contacts

Find local site contact details for specific facilities participating in the trial.

Allen Kung, BSc

Role: primary

973-758-7970

References

Explore related publications, articles, or registry entries linked to this study.

Cohen J, Wells D, Munne S. Removal of 2 cells from cleavage stage embryos is likely to reduce the efficacy of chromosomal tests that are used to enhance implantation rates. Fertil Steril. 2007 Mar;87(3):496-503. doi: 10.1016/j.fertnstert.2006.07.1516. Epub 2006 Dec 4.

Reference Type BACKGROUND
PMID: 17141767 (View on PubMed)

De Vos A, Staessen C, De Rycke M, Verpoest W, Haentjens P, Devroey P, Liebaers I, Van de Velde H. Impact of cleavage-stage embryo biopsy in view of PGD on human blastocyst implantation: a prospective cohort of single embryo transfers. Hum Reprod. 2009 Dec;24(12):2988-96. doi: 10.1093/humrep/dep251. Epub 2009 Sep 21.

Reference Type BACKGROUND
PMID: 19773223 (View on PubMed)

Gutierrez-Mateo C, Colls P, Sanchez-Garcia J, Escudero T, Prates R, Ketterson K, Wells D, Munne S. Validation of microarray comparative genomic hybridization for comprehensive chromosome analysis of embryos. Fertil Steril. 2011 Mar 1;95(3):953-8. doi: 10.1016/j.fertnstert.2010.09.010. Epub 2010 Oct 25.

Reference Type BACKGROUND
PMID: 20971462 (View on PubMed)

Munne S, Wells D, Cohen J. Technology requirements for preimplantation genetic diagnosis to improve assisted reproduction outcomes. Fertil Steril. 2010 Jul;94(2):408-30. doi: 10.1016/j.fertnstert.2009.02.091. Epub 2009 May 5.

Reference Type BACKGROUND
PMID: 19409550 (View on PubMed)

Schoolcraft WB, Fragouli E, Stevens J, Munne S, Katz-Jaffe MG, Wells D. Clinical application of comprehensive chromosomal screening at the blastocyst stage. Fertil Steril. 2010 Oct;94(5):1700-6. doi: 10.1016/j.fertnstert.2009.10.015. Epub 2009 Nov 25.

Reference Type BACKGROUND
PMID: 19939370 (View on PubMed)

Ata B, Kaplan B, Danzer H, Glassner M, Opsahl M, Tan SL, Munne S. Array CGH analysis shows that aneuploidy is not related to the number of embryos generated. Reprod Biomed Online. 2012 Jun;24(6):614-20. doi: 10.1016/j.rbmo.2012.02.009. Epub 2012 Feb 25.

Reference Type BACKGROUND
PMID: 22503277 (View on PubMed)

Cohen J, DeVane GW, Elsner CW, Kort HI, Massey JB, Norbury SE. Cryopreserved zygotes and embryos and endocrinologic factors in the replacement cycle. Fertil Steril. 1988 Jul;50(1):61-7. doi: 10.1016/s0015-0282(16)60009-2.

Reference Type BACKGROUND
PMID: 3384119 (View on PubMed)

Forman EJ, Hong KH, Ferry KM, Tao X, Taylor D, Levy B, Treff NR, Scott RT Jr. In vitro fertilization with single euploid blastocyst transfer: a randomized controlled trial. Fertil Steril. 2013 Jul;100(1):100-7.e1. doi: 10.1016/j.fertnstert.2013.02.056. Epub 2013 Mar 30.

Reference Type BACKGROUND
PMID: 23548942 (View on PubMed)

Fragouli E, Spath K, Alfarawati S, Wells D (2013) Quantification of mitochondrial DNA predicts the implantation potential of chromosomally normal embryos. Fertil Steril, in press (ASRM abstract)

Reference Type BACKGROUND

Gardner DK and Schoolcraft WB. In vitro culture of human blastocysts. In: Jansen R, Mortimer D. eds. Towards Reproductive Certainty: Fertility and Genetics Beyond 1999. Carnforth, Parthenon Publishin, 1999, 378-88

Reference Type BACKGROUND

Hodes-Wertz B, Grifo J, Ghadir S, Kaplan B, Laskin CA, Glassner M, Munne S. Idiopathic recurrent miscarriage is caused mostly by aneuploid embryos. Fertil Steril. 2012 Sep;98(3):675-80. doi: 10.1016/j.fertnstert.2012.05.025. Epub 2012 Jun 7.

Reference Type BACKGROUND
PMID: 22683012 (View on PubMed)

SART (2011): https://www.sartcorsonline.com/rptCSR_PublicMultYear.aspx?ClinicPKID=0

Reference Type BACKGROUND

Scott RT Jr, Ferry K, Su J, Tao X, Scott K, Treff NR. Comprehensive chromosome screening is highly predictive of the reproductive potential of human embryos: a prospective, blinded, nonselection study. Fertil Steril. 2012 Apr;97(4):870-5. doi: 10.1016/j.fertnstert.2012.01.104. Epub 2012 Feb 2.

Reference Type BACKGROUND
PMID: 22305103 (View on PubMed)

Treff NR, Su J, Tao X, Levy B, Scott RT Jr. Accurate single cell 24 chromosome aneuploidy screening using whole genome amplification and single nucleotide polymorphism microarrays. Fertil Steril. 2010 Nov;94(6):2017-21. doi: 10.1016/j.fertnstert.2010.01.052. Epub 2010 Feb 26.

Reference Type BACKGROUND
PMID: 20188357 (View on PubMed)

Treff NR, Ferry KM, Zhao T, Su J, Forman EJ, Scott RT (2011) Cleavage stage embryo biopsy significantly impairs embryonic reproductive potential while blasto- cyst biopsy does not: a novel paired analysis of cotransferred biopsied and non-biopsied sibling embryos. Fertil Steril, 96: Supplement, S2

Reference Type BACKGROUND

Wells W, Kaur K, Fragouli E, Munné S (2013) Next generation sequencing. Reprod Biomed Online 26: Suppl 1, 55.

Reference Type BACKGROUND

Yang Z, Liu J, Collins GS, Salem SA, Liu X, Lyle SS, Peck AC, Sills ES, Salem RD. Selection of single blastocysts for fresh transfer via standard morphology assessment alone and with array CGH for good prognosis IVF patients: results from a randomized pilot study. Mol Cytogenet. 2012 May 2;5(1):24. doi: 10.1186/1755-8166-5-24.

Reference Type BACKGROUND
PMID: 22551456 (View on PubMed)

Cornelisse S, Zagers M, Kostova E, Fleischer K, van Wely M, Mastenbroek S. Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro fertilisation. Cochrane Database Syst Rev. 2020 Sep 8;9(9):CD005291. doi: 10.1002/14651858.CD005291.pub3.

Reference Type DERIVED
PMID: 32898291 (View on PubMed)

Other Identifiers

Review additional registry numbers or institutional identifiers associated with this trial.

Reprogenetics-3.109

Identifier Type: -

Identifier Source: org_study_id

More Related Trials

Additional clinical trials that may be relevant based on similarity analysis.

Discarded Materials Study
NCT01219335 RECRUITING
Cell Free Preimplantation Genetic Testing
NCT04628507 NOT_YET_RECRUITING
Study of Abnormally Fertilized Embryos
NCT06940973 NOT_YET_RECRUITING