Preimplantation Genetic Diagnosis Using Blastocyst Biopsy and Array CGH

Infertility Clinical Trial

Official title:

Comparison of Standard ART Practice vs. Trophectoderm Biopsy, Array CGH Analysis, and Day-6 Replacement of a Single Euploid Embryo

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT01546350
• Other study ID #: Reprogenetics study 389
• Secondary ID: Reprogenetics st
• Status: Suspended
• Phase: Phase 2
• First received: March 2, 2012
• Last updated: August 20, 2013
• Start date: March 2012
• Est. completion date: June 2014

Study information

• Verified date: May 2013
• Source: Reprogenetics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The investigators propose to perform a clinical randomized trial to evaluate the effect of single embryo (blastocyst) transfer (SET) with array CGH for the evaluation of the complete chromosome complement of the blastocyst in comparison to standard ART methods in which one or more embryo are replaced. Patients will be randomized into two groups:

• Control group: patients will have up to two embryos replaced on day 5 based on morphological and developmental characteristics, and the other embryos reaching blastocyst stage will be vitrified. If patients in the control group do not have a pregnancy to term from that fresh cycle, they will be offered free PGD either for the frozen embryos of that cycle or for the next cycle (up to the center and patient). Data from that PGD is not part of the study.

• Test group: patients will have grade A,B or C blastocysts hatched on day 5, biopsied on day 5, analyzed by array CGH, and a single euploid embryo transferred on day 6. Any morulas developing to grade A,B or C blastocyst on day-6 will be also analyzed but vitrified for use in a future cycle.

Description:

Patients will be randomized after fertilization, and will be dropped from the study if they produce 3 or less blastocysts on day 5. The Primary efficacy endpoint of comparing the study group with the control will be (I) implantation rates and (II) multiple pregnancies (twin or higher order) comparing the first transfer.

The study may be extended to evaluate secondary efficacy endpoints which will be miscarriage rate and take home baby rates comparing the two groups.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 200
• Est. completion date: June 2014
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 32 Years to 42 Years

Eligibility

Inclusion Criteria:

• Maternal age 33 to 42 years old (included)

Exclusion Criteria:

• MESA and TESE patients

• At least one partner carrier of a chromosomal or genetic disease

• Abnormal ovarian reserve, defined as FSH of >10 IU/L on day 2-4 of the cycle and AMH < 1ng /ml (If only one of the two parameters altered then patients is acceptable).

• Egg donor cycle (sperm donor is acceptable)

Exclusion criteria during stimulation:

• Less than eight antral follicles on day 2-4 of cycle

Exclusion criteria on day 5 post retrieval:

• Patients will be excluded if they produce less than 3 grade A,B or C blastocysts by day 5.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Screening

Related Conditions & MeSH terms

• Infertility
• Recurrent Pregnancy Loss

Intervention

Genetic:
• PGD
array CGH after blastocyst biopsy

Procedure:
• PGD
PGD using blastocyst biopsy and testing of the biopsy by array CGH

Locations

Country	Name	City	State
United States	Southern California Reproductive Center	Beverly Hills	California
United States	Reproductive Associates of Illinois	Highland Park	Illinois
United States	Reprogenetics	Livingston	New Jersey
United States	Long Island IVF	Melville	New York

Sponsors (8)

Lead Sponsor	Collaborator
Reprogenetics	BlueGnome, Cambridge, UK, Long Island IVF, Melville, NY, McGill University, Reproductive Associates of Illinois, Highland Park, IL, Reprogenetics, Livingston, NJ, Southern California Reproductive Center, CA, Yale University

Country where clinical trial is conducted

United States, 

References & Publications (5)

Cohen J, Wells D, Munné 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. Epub 2006 Dec 4. — View Citation

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. — View Citation

Gutiérrez-Mateo C, Colls P, Sánchez-García J, Escudero T, Prates R, Ketterson K, Wells D, Munné 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. — View Citation

Munné 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. Review. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Implantation rate	fetal sacs / embryos replaced	First month after replacement	No
Secondary	Spontaneous miscarriage rate	pregnancies lost / pregnancies of cycles randomized	during first and second trimester of pregnancy	Yes
Secondary	ongoing pregnancy rate	pregnancies past second trimester / cycles started	third trimester of pregnancy	No
Secondary	Multiple pregnancy rate	Twin or multiple order pregnancies / total pregnancies	first month after transfer	Yes