Clinical trial NCT03371745: The PrISICE Clinical Trial (Pre-Implantation Screening and Investigation on the Cryopreservation of Embryos)
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Infertility
Lead sponsor: Yale University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: University of California, San Francisco
name: University of Pennsylvania
name: Augusta University
name: Penn State University
name: University of North Carolina
name: University of Oklahoma
First posted: 2017-12-13
Enrollment: 32
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 42
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Live Birth
timeFrame: up to 9 months or time of birth
Secondary outcomes:
Other outcomes:
Locations:
city: San Francisco
country: United States
facility: University of California San Francisco
state: California
city: Oklahoma City
country: United States
facility: University of Oklahoma
state: Oklahoma
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
Study officials:
affiliation: Eunice Kennedy Shriver National Institue of Child Health and Human Development
name: Esther Eisenberg, MD
role: STUDY_DIRECTOR
affiliation: University of Colorado, Denver
name: Nanette Santoro, MD
role: STUDY_CHAIR
affiliation: University of California, San Francisco
name: Marcelle I Cedars, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: University of Pennsylvania
name: Christos Coutifaris, MD PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Yale University
name: Heping Zhang, PhD
role: STUDY_DIRECTOR
References:
citation: 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.