The PrISICE Clinical Trial (Pre-Implantation Screening and Investigation on the Cryopreservation of Embryos)

Study Overview
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Brief Summary
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The trial objective is to determine whether the deferred transfer of embryos following cryopreservation at the blastocyst stage following pre-implantation genetic screening (PGS-FET) improves live birthrates compared to both the deferred transfer of cryopreserved embryos without PGS (FET) and immediate transfer at the conclusion of a fresh in vitro fertilization (IVF) cycle (Fresh). Additionally, whether freeze-only (FET) improves live birth rates compared to fresh will be determined.

Detailed Description
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This will be a multi-center, prospective randomized clinical trial comparing three standards of care: Group 1: PGS-FET group: deferred transfer of day 5/6/7 (blastocyst stage) embryos cryopreserved following trophectoderm biopsy Group 2: freeze-only (FET) group: deferred transfer of frozen/thawed embryos without biopsy Group 3: fresh ET group: immediate transfer of fresh embryos in the stimulation cycle. 1539 eligible couples will be recruited to participate. Couples will be randomized at retrieval to undergo cryopreservation with deferred embryo transfer, with or without PGS, or fresh embryo transfer during the cycle of egg retrieval. Number of embryos to transfer will be based on clinical estimation of embryo quality and will not exceed ASRM guidelines for embryo transfer number including newly revised guidelines. We are aware that the number of embryos transferred, to maintain enrollment, may not be equivalent, with likely more embryos transferred in patients not having PGS. The primary outcome of live birth/retrieval, with a secondary outcome of healthy singleton birth, may reflect the true benefit of PGS.

Official Title
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A Prospective, Randomized, Controlled Clinical Trial Evaluating the Superiority of Preimplantation Genetic Screening (PGS) and Deferred Transfer of Cryopreserved Embryos Over Freeze-Only Deferred Transfer Without PGS or Immediate Embryo Transfer During a Fresh In Vitro Fertilization Cycle

Conditions
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Infertility

Intervention / Treatment
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* Procedure: Trophectoderm biopsy
* Procedure: Cryopreservation
* Procedure: Embryo Transfer


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Scheduled to undergo in vitro fertilization for treatment of infertility (1st or 2nd fresh attempt); subject can have had no more than one prior failed fresh IVF cycle Couple able to participate in a research project Able to understand study requirements Willing to sign informed consent Able to return for required follow-up Access to telephone Ability to read and write Normal uterine cavity evaluation within one year of enrollment Exclusion Criteria: Medical conditions which may complicate treatment No plans to undergo embryo transfer Medical contraindication to the transfer of more than a single embryo (i.e. congenital uterine anomaly). Concurrent participation in any other interventional trial Recurrent pregnancy loss Known chromosomal abnormality (e.g. translocation) Pre-implantation genetic diagnosis requiring blastocyst biopsy

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: PGS-FET<br>The PGS-FET arm involves deferred transfer of embryos following cryopreservation at the blastocyst stage following pre-implantation genetic screening. This arm will culture embryos to day 5/6/7 (blastocyst stage). The embryos will be cryopreserved following trophectoderm biopsy. A subsequent frozen embryo transfer cycle will be performed during which 1 euploid (chromosomally normal) embryo will be thawed and transferred. | Procedure: Trophectoderm biopsy<br>* Biopsy at blastocyst stage of trophectoderm cells for comprehensive evaluation of the eupolid status of the embryo.<br>Procedure: Cryopreservation<br>* Rapid freezing using vitrification<br>Procedure: Embryo Transfer<br>* Transfer of embryo that has been cultured in vitro into the uterus<br>|
| Active Comparator: FET<br>The Freeze only arm involves the deferred transfer of embryos following cryopreservation. In this arm embryos will be cryopreserved. A subsequent frozen embryo transfer cycle will be performed during which one or more embryos will be thawed and transfered based on local clinical site, age-specific embryo number transfer guidelines. | Procedure: Cryopreservation<br>* Rapid freezing using vitrification<br>Procedure: Embryo Transfer<br>* Transfer of embryo that has been cultured in vitro into the uterus<br>|
| Active Comparator: Fresh<br>The Fresh arm will have an immediate embryo(s) transfer based on local clinical site, age-specific embryo number transfer guidelines within the stimulation cycle. | Procedure: Embryo Transfer<br>* Transfer of embryo that has been cultured in vitro into the uterus<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Live Birth | The number of subjects who deliver a live born infant which will be calculated into a live born delivery rate. | up to 9 months or time of birth |