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

NCT ID: NCT03558399

Last Updated: 2020-12-03

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

NA

Total Enrollment

800 participants

Study Classification

INTERVENTIONAL

Study Start Date

2018-04-25

Study Completion Date

2021-09-23

Brief Summary

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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

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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.

Conditions

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Implantation Failure Infertility, Female

Keywords

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Endometrial receptivity analysis Window of implantation Euploid Infertility, Female Implantation failure Frozen embryo transfer FET ERA WOI FET Synchrony

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

TRIPLE

Participants Caregivers Outcome Assessors
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.

Study Groups

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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.

Group Type EXPERIMENTAL

FET according to ERA

Intervention Type OTHER

Single euploid FET will be performed at the time indicated by the ERA test results.

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.

Group Type ACTIVE_COMPARATOR

FET according to standard protocol

Intervention Type OTHER

Single euploid FET will be performed according to our standard FET protocol.

Interventions

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FET according to ERA

Single euploid FET will be performed at the time indicated by the ERA test results.

Intervention Type OTHER

FET according to standard protocol

Single euploid FET will be performed according to our standard FET protocol.

Intervention Type OTHER

Eligibility Criteria

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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
Minimum Eligible Age

30 Years

Maximum Eligible Age

40 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Igenomix

INDUSTRY

Sponsor Role collaborator

Shady Grove Fertility Reproductive Science Center

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Kathleen Devine, MD

Role: PRINCIPAL_INVESTIGATOR

Shady Grove Fertility

Locations

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Shady Grove Fertility Reproductive Science Center

Rockville, Maryland, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 23756099 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27365540 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 16960016 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 15501903 (View on PubMed)

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

Reference Type BACKGROUND
PMID: 24882617 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22634130 (View on PubMed)

Doyle N, Jahandideh S, Hill MJ, Widra EA, Levy M, Devine K. Effect of Timing by Endometrial Receptivity Testing vs Standard Timing of Frozen Embryo Transfer on Live Birth in Patients Undergoing In Vitro Fertilization: A Randomized Clinical Trial. JAMA. 2022 Dec 6;328(21):2117-2125. doi: 10.1001/jama.2022.20438.

Reference Type DERIVED
PMID: 36472596 (View on PubMed)

Other Identifiers

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1183343

Identifier Type: -

Identifier Source: org_study_id