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Frozen Blastocyst Transfer Using Conventional Timing Versus Timing by Endometrial Receptivity Analysis (Synchrony)

Primary Purpose

Implantation Failure, Infertility, Female

Status
Unknown status
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
FET according to ERA
FET according to standard protocol
Sponsored by
Shady Grove Fertility Reproductive Science Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Implantation Failure focused on measuring Endometrial receptivity analysis, Window of implantation, Euploid, Infertility, Female, Implantation failure, Frozen embryo transfer FET, ERA, WOI, FET, Synchrony

Eligibility Criteria

30 Years - 40 Years (Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  1. Signed informed consent
  2. Female age between 30 and 40 years and deemed likely by her physician, based on ovarian reserve testing, to produce at least one euploid blastocyst via one IVF/intracytoplasmatic sperm injection (ICSI) cycle
  3. Having ≥ 1 euploid embryo available for embryo transfer
  4. Standard eligibility criteria to undergo IVF and FET at Shady Grove Fertility Center.

Exclusion Criteria:

  1. Known uterine factor impacting the endometrium
  2. Use of surgically aspirated sperm for fertilization
  3. Presence of any clinically relevant systemic disease that contraindicates assisted reproductive technology.
  4. Since the subject last had a live birth (if any), there have been more than two embryo transfers that have not resulted in ongoing pregnancy
  5. Body mass index >40 kg/m2 at screening
  6. Recurrent pregnancy loss, defined as two or more clinical pregnancy losses without live birth
  7. Planned testing of embryos for single gene disorder(s) or structural chromosome rearrangements
  8. Currently breast feeding, pregnant, or contraindication to pregnancy

Sites / Locations

  • Shady Grove Fertility Reproductive Science Center

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

FET according to ERA

FET according to standard protocol

Arm Description

In preparation for frozen embryo transfer (FET), estradiol will be administered for approximately 10 to 14 days or until endometrial criteria are met. These endometrial criteria will be assessed with transvaginal ultrasound and serum estradiol levels. Women will then begin intramuscular progesterone injection and if assigned to the study arm, a single euploid embryo will be transferred at the time indicated by the ERA test results. Merely the timing of embryo transfer will distinguish the study from the control group.

In preparation for frozen embryo transfer (FET), estradiol will be administered for approximately 10 to 14 days or until endometrial criteria are met. These endometrial criteria will be assessed with transvaginal ultrasound and serum estradiol levels. Women will then begin intramuscular progesterone injection and if assigned to the control arm, a single euploid embryo will be transferred according to our standard FET protocol.

Outcomes

Primary Outcome Measures

The primary outcome measure of this clinical trial is to assess live birth after euploid embryo transfer according to an individual's ERA result as opposed to routine protocol for frozen embryo transfer (FET) cycles.

Secondary Outcome Measures

A secondary outcome measure of this clinical trial is to assess ongoing implantation rate after embryo transfer according to an individual's ERA result as opposed to routine protocol for frozen embryo transfer (FET) cycles.
The ongoing implantation rate is defined as maximum number of fetal heartbeats divided by total number of embryos transferred
A secondary outcome measure of this clinical trial is to assess implantation rate after embryo transfer according to an individual's ERA result as opposed to routine protocol for frozen embryo transfer (FET) cycles.
The implantation rate is defined as the maximum number of gestational sacs per patient
A secondary outcome measure of this clinical trial is to assess biochemical pregnancy after embryo transfer according to an individual's ERA result as opposed to routine protocol for frozen embryo transfer (FET) cycles.
Biochemical pregnancy is defined as detection of beta hCG above 5 IU/L
A secondary outcome measure of this clinical trial is to assess clinical pregnancy after embryo transfer according to an individual's ERA result as opposed to routine protocol for frozen embryo transfer (FET) cycles.
The clinical pregnancy rate is defined as the presence of gestational sacs

Full Information

First Posted
April 25, 2018
Last Updated
December 1, 2020
Sponsor
Shady Grove Fertility Reproductive Science Center
Collaborators
Igenomix
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1. Study Identification

Unique Protocol Identification Number
NCT03558399
Brief Title
Frozen Blastocyst Transfer Using Conventional Timing Versus Timing by Endometrial Receptivity Analysis
Acronym
Synchrony
Official Title
A Randomized Controlled Trial Comparing Live Birth From Single, Euploid Frozen Blastocyst Transfer Using Conventional Timing Versus Timing by Endometrial Receptivity Analysis
Study Type
Interventional

2. Study Status

Record Verification Date
December 2020
Overall Recruitment Status
Unknown status
Study Start Date
April 25, 2018 (Actual)
Primary Completion Date
September 23, 2021 (Anticipated)
Study Completion Date
September 23, 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Shady Grove Fertility Reproductive Science Center
Collaborators
Igenomix

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
To assess live birth after embryo transfer according to an individual's ERA results as opposed to routine protocol for frozen embryo transfer (FET) cycles.
Detailed Description
It has been proposed, that the receptivity status of the endometrium shifts among individual women and that repeated implantation failure is ascribable to an endometrial factor in up to 25%. The endometrial receptivity analysis (ERA) is a diagnostic method that was developed based on the unique genomic signature of the endometrium during the window of implantation and classifies the endometrium as receptive, pre-receptive or post-receptive to guide embryo transfer. The purpose of this assessor-blind, randomized clinical study is to determine whether live birth from vitrified/thawed euploid embryo transfer is improved when transfer is timed according to endometrial receptivity analysis (ERA) results. Approximately 800 women (n=400 in each arm) will be enrolled according to the inclusion/exclusion criteria among patients of Shady Grove Fertility. Participants will undergo a standard in vitro fertilization (IVF) cycle, followed by preimplantation genetic screening (PGS) provided a high quality blastocyst is available. Participants with at least one PGS normal (euploid) embryo will be randomized (assigned by chance, like the flip of a coin) to one of two study groups. Women in both study arms will then undergo ERA testing and neither the patients nor their treating physicians will know to which group the women have been assigned to, or the ERA testing results. Up until this point there is no difference between the study and control group. The investigational aspect of this trial is described as follows: If the participant is assigned to the study arm, the single, euploid, frozen embryo transfer (FET) during the subsequent cycle will be performed at the time indicated by the ERA test results. If she is in the control arm, the embryo will be transferred according to our standard FET protocol. Patients enrolling in the study will receive PGS and ERA free of charge.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Implantation Failure, Infertility, Female
Keywords
Endometrial receptivity analysis, Window of implantation, Euploid, Infertility, Female, Implantation failure, Frozen embryo transfer FET, ERA, WOI, FET, Synchrony

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderOutcomes Assessor
Masking Description
Results of the ERA analysis will not be disclosed to the patient or the physician or the outcome assessor, nor will the study arm to which the patient was assigned, though the patient/physician may be able to intuit assignment to the ERA arm based on the frozen embryo transfer time that she is assigned. The date and time of embryo transfer will be provided by the investigator/research team.
Allocation
Randomized
Enrollment
800 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
FET according to ERA
Arm Type
Experimental
Arm Description
In preparation for frozen embryo transfer (FET), estradiol will be administered for approximately 10 to 14 days or until endometrial criteria are met. These endometrial criteria will be assessed with transvaginal ultrasound and serum estradiol levels. Women will then begin intramuscular progesterone injection and if assigned to the study arm, a single euploid embryo will be transferred at the time indicated by the ERA test results. Merely the timing of embryo transfer will distinguish the study from the control group.
Arm Title
FET according to standard protocol
Arm Type
Active Comparator
Arm Description
In preparation for frozen embryo transfer (FET), estradiol will be administered for approximately 10 to 14 days or until endometrial criteria are met. These endometrial criteria will be assessed with transvaginal ultrasound and serum estradiol levels. Women will then begin intramuscular progesterone injection and if assigned to the control arm, a single euploid embryo will be transferred according to our standard FET protocol.
Intervention Type
Other
Intervention Name(s)
FET according to ERA
Intervention Description
Single euploid FET will be performed at the time indicated by the ERA test results.
Intervention Type
Other
Intervention Name(s)
FET according to standard protocol
Intervention Description
Single euploid FET will be performed according to our standard FET protocol.
Primary Outcome Measure Information:
Title
The primary outcome measure of this clinical trial is to assess live birth after euploid embryo transfer according to an individual's ERA result as opposed to routine protocol for frozen embryo transfer (FET) cycles.
Time Frame
From date of randomization until live born infant at an estimated gestational age of at least 23 weeks or greater
Secondary Outcome Measure Information:
Title
A secondary outcome measure of this clinical trial is to assess ongoing implantation rate after embryo transfer according to an individual's ERA result as opposed to routine protocol for frozen embryo transfer (FET) cycles.
Description
The ongoing implantation rate is defined as maximum number of fetal heartbeats divided by total number of embryos transferred
Time Frame
From date of randomization until 7-8 weeks estimated gestational age
Title
A secondary outcome measure of this clinical trial is to assess implantation rate after embryo transfer according to an individual's ERA result as opposed to routine protocol for frozen embryo transfer (FET) cycles.
Description
The implantation rate is defined as the maximum number of gestational sacs per patient
Time Frame
From date of randomization until 5-6 weeks estimated gestational age
Title
A secondary outcome measure of this clinical trial is to assess biochemical pregnancy after embryo transfer according to an individual's ERA result as opposed to routine protocol for frozen embryo transfer (FET) cycles.
Description
Biochemical pregnancy is defined as detection of beta hCG above 5 IU/L
Time Frame
From date of randomization until ~10 days following embryo transfer
Title
A secondary outcome measure of this clinical trial is to assess clinical pregnancy after embryo transfer according to an individual's ERA result as opposed to routine protocol for frozen embryo transfer (FET) cycles.
Description
The clinical pregnancy rate is defined as the presence of gestational sacs
Time Frame
From date of randomization until 5-7 weeks estimated gestational age

10. Eligibility

Sex
Female
Gender Based
Yes
Gender Eligibility Description
Only biological female subjects will be recruited for this study as an evaluation of the endometrium requires a uterus to be present and therefore this is only possible in the biological female sex.
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
40 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Signed informed consent Female age between 30 and 40 years and deemed likely by her physician, based on ovarian reserve testing, to produce at least one euploid blastocyst via one IVF/intracytoplasmatic sperm injection (ICSI) cycle Having ≥ 1 euploid embryo available for embryo transfer Standard eligibility criteria to undergo IVF and FET at Shady Grove Fertility Center. Exclusion Criteria: Known uterine factor impacting the endometrium Use of surgically aspirated sperm for fertilization Presence of any clinically relevant systemic disease that contraindicates assisted reproductive technology. Since the subject last had a live birth (if any), there have been more than two embryo transfers that have not resulted in ongoing pregnancy Body mass index >40 kg/m2 at screening Recurrent pregnancy loss, defined as two or more clinical pregnancy losses without live birth Planned testing of embryos for single gene disorder(s) or structural chromosome rearrangements Currently breast feeding, pregnant, or contraindication to pregnancy
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kathleen Devine, MD
Organizational Affiliation
Shady Grove Fertility
Official's Role
Principal Investigator
Facility Information:
Facility Name
Shady Grove Fertility Reproductive Science Center
City
Rockville
State/Province
Maryland
ZIP/Postal Code
20850
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
23756099
Citation
Ruiz-Alonso M, Blesa D, Diaz-Gimeno P, Gomez E, Fernandez-Sanchez M, Carranza F, Carrera J, Vilella F, Pellicer A, Simon C. The endometrial receptivity array for diagnosis and personalized embryo transfer as a treatment for patients with repeated implantation failure. Fertil Steril. 2013 Sep;100(3):818-24. doi: 10.1016/j.fertnstert.2013.05.004. Epub 2013 Jun 4.
Results Reference
background
PubMed Identifier
27365540
Citation
Katzorke N, Vilella F, Ruiz M, Krussel JS, Simon C. Diagnosis of Endometrial-Factor Infertility: Current Approaches and New Avenues for Research. Geburtshilfe Frauenheilkd. 2016 Jun;76(6):699-703. doi: 10.1055/s-0042-103752.
Results Reference
background
PubMed Identifier
16960016
Citation
Horcajadas JA, Pellicer A, Simon C. Wide genomic analysis of human endometrial receptivity: new times, new opportunities. Hum Reprod Update. 2007 Jan-Feb;13(1):77-86. doi: 10.1093/humupd/dml046. Epub 2006 Sep 7.
Results Reference
background
PubMed Identifier
15501903
Citation
Ponnampalam AP, Weston GC, Trajstman AC, Susil B, Rogers PA. Molecular classification of human endometrial cycle stages by transcriptional profiling. Mol Hum Reprod. 2004 Dec;10(12):879-93. doi: 10.1093/molehr/gah121. Epub 2004 Oct 22.
Results Reference
background
PubMed Identifier
24882617
Citation
Galliano D, Pellicer A. MicroRNA and implantation. Fertil Steril. 2014 Jun;101(6):1531-44. doi: 10.1016/j.fertnstert.2014.04.023.
Results Reference
background
PubMed Identifier
22634130
Citation
Ruiz-Alonso M, Blesa D, Simon C. The genomics of the human endometrium. Biochim Biophys Acta. 2012 Dec;1822(12):1931-42. doi: 10.1016/j.bbadis.2012.05.004. Epub 2012 May 24.
Results Reference
background

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Frozen Blastocyst Transfer Using Conventional Timing Versus Timing by Endometrial Receptivity Analysis

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