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

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

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.

Study Overview

• Status: Terminated
• Conditions: Infertility
• Intervention / Treatment: Procedure: Trophectoderm biopsy; Procedure: Cryopreservation; Procedure: Embryo Transfer

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94115
      • University of California San Francisco
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • University of Oklahoma
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 42 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: PGS-FET; 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; Biopsy at blastocyst stage of trophectoderm cells for comprehensive evaluation of the eupolid status of the embryo.; Procedure: Cryopreservation; Rapid freezing using vitrification; Procedure: Embryo Transfer; Transfer of embryo that has been cultured in vitro into the uterus
Active Comparator: FET; 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; Rapid freezing using vitrification; Procedure: Embryo Transfer; Transfer of embryo that has been cultured in vitro into the uterus
Active Comparator: Fresh; 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; Transfer of embryo that has been cultured in vitro into the uterus

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Yale University
• Collaborators: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); University of Pennsylvania; University of Oklahoma; University of California, San Francisco; Penn State University; Augusta University; University of North Carolina
• Investigators: Study Chair: Nanette Santoro, MD, University of Colorado, Denver; Principal Investigator: Christos Coutifaris, MD PhD, University of Pennsylvania; Principal Investigator: Marcelle I Cedars, MD, University of California, San Francisco; Study Director: Esther Eisenberg, MD, Eunice Kennedy Shriver National Institue of Child Health and Human Development

Publications and helpful links

General Publications

• Cornelisse S, Zagers M, Kostova E, Fleischer K, van Wely M, Mastenbroek S. Preimplantation genetic testing for aneuploidies (abnormal number of chromosomes) in in vitro fertilisation. Cochrane Database Syst Rev. 2020 Sep 8;9(9):CD005291. doi: 10.1002/14651858.CD005291.pub3.

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): August 21, 2018
• Primary Completion (Actual): October 31, 2019
• Study Completion (Actual): December 31, 2019

Study Registration Dates

• First Submitted: December 8, 2017
• First Submitted That Met QC Criteria: December 8, 2017
• First Posted (Actual): December 13, 2017

Study Record Updates

• Last Update Posted (Actual): October 3, 2022
• Last Update Submitted That Met QC Criteria: September 29, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infertility
• Other Study ID Numbers: PrISICE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD data will be deposited in DASH following publication of the results of the primary paper and when the deidentified data have been put into a format that is acceptable for DASH submission.
• IPD Sharing Time Frame: After publication of the results of the primary paper and when the de-identified data have been put into a format that is acceptable for DASH submission.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No