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

Reprogenetics

Status and phase: Unknown; Phase 2

Conditions: Recurrent Pregnancy Loss; Infertility

Treatments: Genetic: Next Generation Sequencing after Blastocyst biopsy

Study type: Interventional

Funder types: Other; Industry

Identifiers

NCT01946945

Reprogenetics-3.109

Details and patient eligibility

About

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.

Full description

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.

Enrollment: 240 estimated patients

Sex: Female

Ages: 18 to 42 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Screening

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Double Blind

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240 participants in 2 patient groups

Control - Standard ART treatment

No Intervention group

Test - PGS

Experimental group

Description:

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.

Treatment:

Genetic: Next Generation Sequencing after Blastocyst biopsy