Clinical trial NCT01546350: Preimplantation Genetic Diagnosis Using Blastocyst Biopsy and Array CGH
Official title: Comparison of Standard ART Practice vs. Trophectoderm Biopsy, Array CGH Analysis, and Day-6 Replacement of a Single Euploid Embryo
Study type: INTERVENTIONAL
Overall status: SUSPENDED
Phase: PHASE2
Conditions: Infertility
Recurrent Pregnancy Loss
Keywords: infertility, recurrent pregnancy loss, miscarriage
Lead sponsor: Reprogenetics
Sponsor class: INDUSTRY
Collaborators: name: Reprogenetics, Livingston, NJ
name: Long Island IVF, Melville, NY
name: Reproductive Associates of Illinois, Highland Park, IL
name: Yale University
name: McGill University
name: BlueGnome, Cambridge, UK
name: Southern California Reproductive Center, CA
First posted: 2012-03-07
Enrollment: 200
Sex: FEMALE
Minimum age (years): 32
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SCREENING

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Implantation rate
timeFrame: First month after replacement
Secondary outcomes:
measure: Spontaneous miscarriage rate
timeFrame: during first and second trimester of pregnancy
measure: ongoing pregnancy rate
timeFrame: third trimester of pregnancy
measure: Multiple pregnancy rate
timeFrame: first month after transfer
Other outcomes:
Locations:
city: Beverly Hills
country: United States
facility: Southern California Reproductive Center
state: California
city: Highland Park
country: United States
facility: Reproductive Associates of Illinois
state: Illinois
city: Livingston
country: United States
facility: Reprogenetics
state: New Jersey
city: Melville
country: United States
facility: Long Island IVF
state: New York
Study officials:
affiliation: Reprogenetics
name: Santiago Munne, PhD
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.
citation: 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.
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.
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.