Preimplantation Genetic Diagnosis Using Blastocyst Biopsy and Array CGH

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Infertility, Recurrent Pregnancy Loss

Intervention / Treatment
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* Genetic: PGD
* Procedure: PGD


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 32 Years
Maximum Age: 42 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Screening
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Control - regular ART treatment<br>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. | |
| Experimental: Test - PGD<br>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. | Genetic: PGD<br>* array CGH after blastocyst biopsy<br>* Other names: PGD: Preimplantation Genetic Diagnosis;Procedure: PGD<br>* PGD using blastocyst biopsy and testing of the biopsy by array CGH<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Implantation rate | fetal sacs / embryos replaced | First month after replacement | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spontaneous miscarriage rate | pregnancies lost / pregnancies of cycles randomized | during first and second trimester of pregnancy | 
| ongoing pregnancy rate | pregnancies past second trimester / cycles started | third trimester of pregnancy | 
| Multiple pregnancy rate | Twin or multiple order pregnancies / total pregnancies | first month after transfer | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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infertility, recurrent pregnancy loss, miscarriage