Comparison of Frozen-thawed Embryo Transfers and Fresh Embryo Transfers With Whole Chromosome Analysis Using Next Generation Sequencing

NCT02000349 | Unknown Phase 2 DMC

• 1 other identifier: Reprogenetics-3.117
• Study Type: interventional
• Target: 186
• Locations: 1 country
• Sites: 1

Brief Summary

The investigators propose to perform a clinical randomized trial to evaluate the effect of a frozen-thawed embryo transfer and a fresh embryo transfer on pregnancy and implantation rates; with the added benefit of a blastocyst biopsy and whole chromosome analysis by Next Generation Sequencing (NGS).

Conditions

Infertility

Keywords

infertility; next generation sequencing

Outcome Measures

Primary Outcomes (1)

• Implantation rate

  determining whether a frozen or a fresh embryo transfer will improve implantation rate.

  8 weeks after replacement

Secondary Outcomes (1)

• Correlation of Mitochondrial DNA and implantation

  When a fetal heartbeat is detected (8 weeks after implantation)

Study Arms (2)

Frozen Embryo Transfer with PGD

EXPERIMENTAL

All embryos will be hatched on day 3. Patients will have hatching blastocysts (\*) biopsied on day 5 or day 6, embryos will then be vitrified, analyzed by NGS, and will have one or two euploid embryo(s) thawed and transferred on a FET cycle, before noon. If more than two euploid blastocysts are available the one(s) to be transferred will be selected based on morphology (\*).

Other: PGD

Fresh Embryo Transfer with PGD

EXPERIMENTAL

All embryos will be hatched on day 3. Patients will have hatching blastocysts (\*) biopsied on day 5, analyzed by NGS, and will have one or two euploid embryo transferred on day 6, in the am. If more than two euploid blastocysts are available the one(s) to be transferred will be selected based on morphology (\*). Any morulas developing to hatching blastocyst on day-6 will be also analyzed but vitrified for use in a future cycle.

Other: PGD

Interventions

PGD OTHER

PGD using Next generation sequencing

Also known as: PGD (Preimplantation Genetic Diagnosis), NGS (Next Generation Sequencing)

Fresh Embryo Transfer with PGD; Frozen Embryo Transfer with PGD

Eligibility Criteria

• Age: 18 Years - 42 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Age up to 42 years

You may not qualify if:

• MESA and TESE patients
• At least one partner carrier of a chromosomal abnormality
• Egg donor cycle (sperm donor is acceptable)
• Gender selection cycles
• Thaw cycles
• Any patient who cannot have a fresh embryo transfer
• FSH above 12 or AMH less than 1

Sponsors & Collaborators

• Reprogenetics: lead
• Reproductive Medicine Lab, LLC: collaborator

Study Sites (1)

Reproductive Medicine Lab, LLC

Portland, Oregon, 97210, United States

Location

Related Publications (13)

• 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.

  PMID: 22503277 BACKGROUND

• 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.

  PMID: 3384119 BACKGROUND

• 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.

  PMID: 17141767 BACKGROUND

• 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.

  PMID: 19773223 BACKGROUND

• Sagoskin AW, Levy MJ, Tucker MJ, Richter KS, Widra EA. Laser assisted hatching in good prognosis patients undergoing in vitro fertilization-embryo transfer: a randomized controlled trial. Fertil Steril. 2007 Feb;87(2):283-7. doi: 10.1016/j.fertnstert.2006.07.1498. Epub 2006 Nov 13.

  PMID: 17094975 BACKGROUND

• 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)

  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

  BACKGROUND

• 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.

  PMID: 20971462 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.

  PMID: 22683012 BACKGROUND

• 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.

  PMID: 19409550 BACKGROUND

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

  BACKGROUND

• Zaat T, Zagers M, Mol F, Goddijn M, van Wely M, Mastenbroek S. Fresh versus frozen embryo transfers in assisted reproduction. Cochrane Database Syst Rev. 2021 Feb 4;2(2):CD011184. doi: 10.1002/14651858.CD011184.pub3.

  PMID: 33539543 DERIVED

• Coates A, Kung A, Mounts E, Hesla J, Bankowski B, Barbieri E, Ata B, Cohen J, Munne S. Optimal euploid embryo transfer strategy, fresh versus frozen, after preimplantation genetic screening with next generation sequencing: a randomized controlled trial. Fertil Steril. 2017 Mar;107(3):723-730.e3. doi: 10.1016/j.fertnstert.2016.12.022. Epub 2017 Jan 27.

  PMID: 28139240 DERIVED

MeSH Terms

Conditions

Infertility

Interventions

Prostaglandins D; High-Throughput Nucleotide Sequencing

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Intervention Hierarchy (Ancestors)

Prostaglandins; Eicosanoids; Fatty Acids, Unsaturated; Fatty Acids; Lipids; Autacoids; Inflammation Mediators; Biological Factors; Sequence Analysis; Genetic Techniques; Investigative Techniques

Study Officials

• Santiago Munne, PhD

  Reprogenetics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: SCREENING
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2013
• First Posted: December 4, 2013
• Study Start: September 1, 2013
• Primary Completion: December 1, 2015
• Study Completion: December 1, 2016
• Last Updated: November 17, 2015

Record last verified: 2015-11

Locations

US (1)