RCT to Assess the Clinical Benefit of the ERA Test in Infertile Women at Their First IVF/ICSI Cycle

NCT ID: NCT04687670

Last Updated: 2021-07-08

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

714 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-08-31

Study Completion Date

2023-04-30

Brief Summary

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Endometrial receptivity takes place in a self-limited period of time during the endometrial mid-secretory stage. This period, named as window of implantation (WOI), is modulated by molecular changes allowing embryo implantation to take place.

It has been already demonstrated the existence of transcriptomic profiles that are characteristics of each endometrial phase: pre-receptive, receptive and post-receptive. 'Igenomix' group developed a molecular tool able to classify the endometrium based on its transcriptomic profile, the Endometrial Receptivity Analysis (ERA). This molecular tool analyses, by next generation sequencing (NGS), the expression of 248 genes related to implantation coupled to a computational predictor to identify the specific transcriptomic profile for each endometrial stage. This test has been applied at clinical level from 2010, helping to synchronize a viable embryo with a receptive endometrium through the personalized embryo transfer (pET). It aims to improve clinical implantation by personalizing, diagnosing, and synchronizing the endometrial factor.

Our goal in this project is to investigate at what extent, if any, the analysis of the endometrial factor, at receptivity level, in patients at their first in vitro fertilization (IVF) cycle improves their clinical outcome through a personalized embryo transfer by the ERA test in comparison to embryo transfer(FET).

Detailed Description

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When the transcriptomic signature of human endometrial receptivity was reported, Igenomix developed the ERA, a molecular tool able to diagnose the endometrial receptivity by NGS and a computational predictor. The accuracy of this diagnostic tool has been shown to be superior to endometrial histology, and its results are reproducible 29 to 40 months later.

The ERA test allows to transfer in a personalized manner by synchronizing the embryo with the WOI of the patient. Nowadays, it has been published that around 30% of patients present 1 or 2 days of displacements and about 50% show 12 hours of displacement.

The ERA has been broadly applied around the world in order to increase the probabilities of recurrent implantation failure patients becoming pregnant. Recently, a multicenter international open-label randomized controlled trial comparing personalized embryo transfer guided by the ERA test versus frozen and fresh embryo transfer was carried out at first appointment of infertile patients undergoing IVF. The current project aims to assess in a randomized way the potential improvement on the clinical outcome of Chinese infertile patients at their first IVF cycle by diagnosing, personalizing and synchronizing the endometrial factor with the ERA. To do that, only the outcomes of the first single embryo transfers performed after the inclusion of each patient will be considered.

Considering a 30% of possible drop-outs, a total of 714 patients will be recruited (357 randomized in each group). They will be allocated on a balanced way (assigned by chance like the flip of a coin) in one of the two arms described below. Reproductive outcomes (defined following The International Glossary on Infertility and Fertility Care, 2017) will be compared between the two groups.

Data exported from the source documents will be duly codified and treated in order to protect the clinical and personal information of participants in accordance with the current local legislation.

All the statistical analysis performed on the data, as well as the procedures, will be registered in a detailed Statistical Analysis Plan (SAP) that will be developed during the study and before starting data analysis.

An interim analysis of this data is planned once 50% of the recruitment has been achieved. Besides and at that same moment, the study will be overseen by an independent Data Monitoring Committee.

All the statistical procedures will be done systematically by both, intention to treat analysis (ITT) and per protocol analysis (PP). The ITT analysis will include all randomized patients recruited and assigned to one of two groups after endometrial biopsy collection. The PP analysis will be applied to those patients who adequately follow the protocol assigned according to their group and arm and in whom the transfer of the good quality blastocyst is performed.

Conditions

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Infertility, Female IVF/ICSI

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

DIAGNOSTIC

Blinding Strategy

NONE

Study Groups

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Intervention group(pET)

Personalized embryo transfer of a single vitrified blastocyst in a HRT cycle according to the ERA test results.

Group Type EXPERIMENTAL

ERA

Intervention Type DIAGNOSTIC_TEST

Before the randomization, Endometrial Fluid (EF) and Endometrial Biopsy (EB) samples will be collected from all participants. EF will be obtained by aspiration immediately prior to the EB after around 120 hours of progesterone (P) impregnation following the standard HRT cycle. The results of the ERA test will be provided to participants and their gynecologists for the personalized embryo transfer.

Control group(FET)

Frozen embryo transfer of a single vitrified blastocyst in a HRT cycle according to the clinical standard practice.

Group Type ACTIVE_COMPARATOR

ERA

Intervention Type DIAGNOSTIC_TEST

Before the randomization, Endometrial Fluid (EF) and Endometrial Biopsy (EB) samples will be collected from all participants. EF will be obtained by aspiration immediately prior to the EB after around 120 hours of progesterone (P) impregnation following the standard HRT cycle. The results of the diagnosis will not be disclosed with the patients randomized into this arm nor with their gynecologists.

Interventions

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ERA

Before the randomization, Endometrial Fluid (EF) and Endometrial Biopsy (EB) samples will be collected from all participants. EF will be obtained by aspiration immediately prior to the EB after around 120 hours of progesterone (P) impregnation following the standard HRT cycle. The results of the ERA test will be provided to participants and their gynecologists for the personalized embryo transfer.

Intervention Type DIAGNOSTIC_TEST

ERA

Before the randomization, Endometrial Fluid (EF) and Endometrial Biopsy (EB) samples will be collected from all participants. EF will be obtained by aspiration immediately prior to the EB after around 120 hours of progesterone (P) impregnation following the standard HRT cycle. The results of the diagnosis will not be disclosed with the patients randomized into this arm nor with their gynecologists.

Intervention Type DIAGNOSTIC_TEST

Eligibility Criteria

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Inclusion Criteria

* Patients whose written ICF approved by the EC has been obtained, after having been duly informed of the nature of the study and voluntarily accepted to participate after being fully aware of the potential risks, benefits and any discomfort involved.
* Patients undergoing their first IVF/ICSI cycle (first oocyte pick up, freezing all) with their own oocytes that will receive single embryo transfer of frozen blastocyst stage embryos (day 5/6) on an HRT cycle.
* At least 2 morphologically good quality embryos already vitrified in blastocyst stage (day 5/6).
* Maternal Age: ≤37 years to rule out embryo factor in aging patients.
* BMI: 18.5 - 30.0 kg / m2 (both inclusive).
* Normal ovarian reserve (defined as: AFC ≥ 8; AMH level ≥1.0 ng/ml and/or FSH \< 8 mU/ml) before the controlled ovarian stimulation (COS) initiation.
* Serum P levels ≤ 1.5 ng/ml, measured within 24 hours before the hCG administration in the COS cycle.
* Negative serological tests for HIV, HBV, HCV, RPR.

Exclusion Criteria

* Patients with repeated miscarriages (\> 2 previous biochemical pregnancies or \> 2 spontaneous miscarriages).
* Male partner with severe male factor (spermatozoa \< 2 million/ml). Semen donor is allowed.
* Patients who are intrauterine device (IUD) carriers in the last 3 months before sample collection.
* Adenomyosis or any pathological finding affecting the endometrial cavity such as polyps/sub-mucosal myomas, intramural myomas \> 4 cm, or hydrosalpinx must be previously operated at least 3 months before the endometrial samples are obtained. (Note: Patients are allowed to participate if the pathology is corrected before performing any study procedure).
* Embryos analysed using preimplantation genetic testing for aneuploidies (PGT-A).
* Any illness or medical condition that is unstable or affect the safety of the patient and compliance of the study.
Maximum Eligible Age

37 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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RenJi Hospital

OTHER

Sponsor Role collaborator

Northwest Women's and Children's Hospital, Xi'an, Shaanxi

OTHER

Sponsor Role collaborator

Peking University Third Hospital

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jie Qiao

Role: PRINCIPAL_INVESTIGATOR

Peking University Third Hospital, Beijing

Locations

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Northwest Women's and Children's Hospital

Xi'an, Shaanxi, China

Site Status NOT_YET_RECRUITING

Peking University Third Hospital

Beijing, , China

Site Status RECRUITING

Renji Hospital

Shanghai, , China

Site Status RECRUITING

Countries

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China

Central Contacts

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Jie Qiao

Role: CONTACT

+86 010-82266699

Facility Contacts

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Xiaofang LI, Ms

Role: primary

15686469882

Zan SHI, Ms

Role: backup

15094057993

Yang LIU, Ms

Role: primary

18710224022

Xiyang LI, Ms

Role: backup

15821668537

Wen LIN, Ms

Role: primary

13524701804

Yaqiong HE, Ms

Role: backup

18817821443

Other Identifiers

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PUTH ERA 1.0

Identifier Type: -

Identifier Source: org_study_id

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