Comparison of Standard ART Practice vs. Trophectoderm Biopsy and Whole Chromosome Analysis
| Status: | Recruiting |
|---|---|
| Conditions: | Women's Studies, Infertility |
| Therapuetic Areas: | Reproductive |
| Healthy: | No |
| Age Range: | 18 - 42 |
| Updated: | 4/2/2016 |
| Start Date: | September 2013 |
Comparison of Standard ART Practice vs. Trophectoderm Biopsy, Whole Chromosome Analysis by Next Generation Sequencing, and Replacement of a Single Euploid Embryo
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.
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.
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.
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.
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
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