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

A Randomized Controlled Trial Comparing Live Birth From Single, Euploid Frozen Blastocyst Transfer Using Conventional Timing Versus Timing by Endometrial Receptivity Analysis

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.

Study Overview

• Status: Unknown
• Conditions: Infertility, Female; Implantation Failure
• Intervention / Treatment: Other: FET according to ERA; Other: FET according to standard protocol

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.

• Study Type: Interventional
• Enrollment (Anticipated): 800
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Shady Grove Fertility Reproductive Science Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 28 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: FET according to ERA; 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.	Other: FET according to ERA; Single euploid FET will be performed at the time indicated by the ERA test results.
Active Comparator: FET according to standard protocol; 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.	Other: FET according to standard protocol; Single euploid FET will be performed according to our standard FET protocol.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
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.	From date of randomization until live born infant at an estimated gestational age of at least 23 weeks or greater

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	From date of randomization until 7-8 weeks estimated gestational age
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	From date of randomization until 5-6 weeks estimated gestational age
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	From date of randomization until ~10 days following embryo transfer
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	From date of randomization until 5-7 weeks estimated gestational age

Collaborators and Investigators

• Sponsor: Shady Grove Fertility Reproductive Science Center
• Collaborators: Igenomix
• Investigators: Principal Investigator: Kathleen Devine, MD, Shady Grove Fertility

Publications and helpful links

General Publications

• 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.
• 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.
• 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.
• 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.
• Galliano D, Pellicer A. MicroRNA and implantation. Fertil Steril. 2014 Jun;101(6):1531-44. doi: 10.1016/j.fertnstert.2014.04.023.
• 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.

Study record dates

Study Major Dates

• Study Start (Actual): April 25, 2018
• Primary Completion (Anticipated): September 23, 2021
• Study Completion (Anticipated): September 23, 2021

Study Registration Dates

• First Submitted: April 25, 2018
• First Submitted That Met QC Criteria: June 4, 2018
• First Posted (Actual): June 15, 2018

Study Record Updates

• Last Update Posted (Actual): December 3, 2020
• Last Update Submitted That Met QC Criteria: December 1, 2020
• Last Verified: December 1, 2020

More Information

Terms related to this study

• Keywords: Infertility, Female; Implantation failure; FET; ERA; Window of implantation; Endometrial receptivity analysis; Euploid; Frozen embryo transfer FET; WOI; Synchrony
• Additional Relevant MeSH Terms: Infertility; Infertility, Female
• Other Study ID Numbers: 1183343

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

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