Comparison of Frozen-thawed Embryo Transfers and Fresh Embryo Transfers With Whole Chromosome Analysis Using Next Generation Sequencing

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 a frozen-thawed embryo transfer and a fresh embryo transfer on pregnancy and implantation rates; with the added benefit of a blastocyst biopsy and whole chromosome analysis by Next Generation Sequencing (NGS).

Detailed Description
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Fresh group: All embryos will be hatched on day 3. Patients will have hatching blastocysts (*) biopsied on day 5, analyzed by NGS, and will have one or two euploid embryo transferred on day 6, in the am. If more than two euploid blastocysts are available the one(s) to be transferred will be selected based on morphology (*). Any morulas developing to hatching blastocyst on day-6 will be also analyzed but vitrified for use in a future cycle. Frozen group: All embryos will be hatched on day 3. Patients will have hatching blastocysts (*) biopsied on day 5 or day 6, embryos will then be vitrified, analyzed by NGS, and will have one or two euploid embryo(s) thawed and transferred on a FET cycle, before noon. If more than two euploid blastocysts are available the one(s) to be transferred will be selected based on morphology (*). (*) Hatching blastocysts as described by Gardner and Schoolcraft (1999):

Conditions
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Infertility

Intervention / Treatment
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* Other: PGD


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria (pre-stimulation): Age up to 42 years Exclusion Criteria (pre-stimulation): MESA and TESE patients At least one partner carrier of a chromosomal abnormality Egg donor cycle (sperm donor is acceptable) Gender selection cycles Thaw cycles Any patient who cannot have a fresh embryo transfer FSH above 12 or AMH less than 1

Ages Eligible for Study
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Minimum Age: 18 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Frozen Embryo Transfer with PGD<br>All embryos will be hatched on day 3. Patients will have hatching blastocysts (*) biopsied on day 5 or day 6, embryos will then be vitrified, analyzed by NGS, and will have one or two euploid embryo(s) thawed and transferred on a FET cycle, before noon. If more than two euploid blastocysts are available the one(s) to be transferred will be selected based on morphology (*). | Other: PGD<br>* PGD using Next generation sequencing<br>* Other names: NGS (Next Generation Sequencing);|
| Experimental: Fresh Embryo Transfer with PGD<br>All embryos will be hatched on day 3. Patients will have hatching blastocysts (*) biopsied on day 5, analyzed by NGS, and will have one or two euploid embryo transferred on day 6, in the am. If more than two euploid blastocysts are available the one(s) to be transferred will be selected based on morphology (*). Any morulas developing to hatching blastocyst on day-6 will be also analyzed but vitrified for use in a future cycle. | Other: PGD<br>* PGD using Next generation sequencing<br>* Other names: NGS (Next Generation Sequencing);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Implantation rate | determining whether a frozen or a fresh embryo transfer will improve implantation rate. | 8 weeks after replacement | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Correlation of Mitochondrial DNA and implantation | The second aim of this study is to determine retrospectively if mt DNA content is linked to implantation potential and if that is measurable by NGS. NGS provides the additional advantage that it can measure mitochondrial DNA, which it's content, seems to be inversely correlated with implantation (Fragouli et al 2013, ASRM). | When a fetal heartbeat is detected (8 weeks after implantation) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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infertility, next generation sequencing