Infertility, FemaleNCT04687670
RCT to Assess the Clinical Benefit of the ERA Test in Infertile Women at Their First IVF/ICSI Cycle
A study testing ERA in people with Infertility, Female and IVF/ICSI, run by Peking University Third Hospital at 3 sites in China.
Trial summary
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. Read more about this study
- Who is it for?
- Ages Up to 37 years, women only
- Conditions the study is for
- Infertility, Female, IVF/ICSI
- What is being tested?
- ERA
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 714 participants
- Where
- 3 sitesChina
- Study dates
- Aug 2021to Apr 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Up to 37 years
- Women only
- No healthy volunteers
- Child, Adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
3 sites in 1 country.
China3 sites, 3 recruiting
- Recruiting
Peking University Third Hospital
Beijing, 100191
Yang LIU, Ms, 18710224022, liuy66@dra100.com
Xiyang LI, Ms, 15821668537, 51209391@qq.com
- Recruiting
Renji Hospital
Shanghai
Wen LIN, Ms, 13524701804, 616512988@qq.com
Yaqiong HE, Ms, 18817821443, heya.qiong@163.com
- Not yet recruiting
Northwest Women's and Children's Hospital
Xi'an, Shaanxi, 710000
Xiaofang LI, Ms, 15686469882, xiaofangtr@163.com
Zan SHI, Ms, 15094057993, elainsz@126.com
About this study
Official title: Randomized Controlled Trial Comparing Personalized Embryo Transfer (pET) by the ERA Test Versus Conventional Frozen Embryo Transfer (FET) of Blastocysts in Infertile Women at Their First IVF/ICSI Cycle
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).
Read the detailed description
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
- Infertility, Female, IVF/ICSI
- Being tested
- ERA
- Keywords
- Personalized Embryo Transfer, Endometrial Receptivity Analysis, Conventional Frozen Embryo Transfer, Randomized Controlled Trial
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
ERADiagnostic 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.
ERADiagnostic 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.
| Study group | Role | What they receive |
|---|---|---|
| Intervention group(pET) | Experimental | Personalized embryo transfer of a single vitrified blastocyst in a HRT cycle according to the ERA test results. Receives: Diagnostic Test: ERA |
| Control group(FET) | Active comparator | Frozen embryo transfer of a single vitrified blastocyst in a HRT cycle according to the clinical standard practice. Receives: Diagnostic Test: ERA |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live birth rate
The number of deliveries that resulted in at least one live birth per ET (transferred patient). Live birth is defined as the complete expulsion or extraction from a woman of a product of conception after 22 weeks of gestation, which, after such separation, breathes or shows any other evidence of life, such as heartbeat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached.
Measured: From date of embryo transfer until 40 weeks
Secondary outcomes (9)
Implantation rate
The number of gestational sacs observed by vaginal ultrasound at the 5th gestational week divided by the number of embryos transferred.
Measured: From date of embryo transfer until 5-6 weeks
Clinical miscarriage rate
Number of spontaneous pregnancy losses in which a gestational sac/s was previously observed, per number of pregnancies.
Measured: From date of embryo transfer until 20 weeks
Biochemical pregnancy rate
Number of pregnancies diagnosed only by βhCG detection without a gestational sac visualized by vaginal ultrasound at the 5th week of pregnancy, per number of pregnancies.
Measured: From date of embryo transfer until 5-6 weeks
Ectopic pregnancy rate
Number of pregnancies outside the uterine cavity, diagnosed by ultrasound, surgical visualization or histopathology, per number of pregnancies.
Measured: From date of embryo transfer until 8 weeks
Incidence of WOI displacement in the study population
Number of patients with the WOI displaced during their participation
Measured: From date of randomization until 1-2 months
pregnancy rate
Pregnancy rate is the number of patients with positive serum level of beta-HCG per embryo transfer.
Measured: From date of embryo transfer until 2 weeks
Obstetric complications
Type and number of obstetric complications during pregnancy
Measured: From date of embryo transfer until 40 weeks
Delivery complications
Type and number of delivery complications
Measured: From date of embryo transfer until 40 weeks
Cost-effectiveness between pET and FET groups
To estimate the average cost per patient in each treatment to achieve a live newborn.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2020
- Study startAug 2021 (estimated)
- Primary completionMar 2023 (estimated)
- Study completionApr 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infertility, FemaleStudies of the same condition, open and under way.
- More trials run by Peking University Third HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 714 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Peking University Third Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- RenJi Hospital, Northwest Women's and Children's Hospital, Xi'an, Shaanxi
- Responsible party
- Sponsor
- Investigators
- Jie Qiao, Principal investigator, Peking University Third Hospital, Beijing
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04687670
- Sponsor's protocol ID
- PUTH ERA 1.0
- Status last verified
- Apr 2021
- First submitted
- 18 Dec 2020
- Last updated
- 8 Jul 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Jul 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Controlled Trial Comparing Personalized Embryo Transfer (pET) by the ERA Test Versus Conventional Frozen Embryo Transfer (FET) of Blastocysts in Infertile Women at Their First IVF/ICSI Cycle
- ClinicalTrials.gov ID
- NCT04687670
- Acronym / sponsor ID
- PUTH ERA 1.0
- Conditions
- Infertility, Female, IVF/ICSI
- Keywords
- Personalized Embryo Transfer, Endometrial Receptivity Analysis, Conventional Frozen Embryo Transfer, Randomized Controlled Trial
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 714 participants (estimated)
- Lead sponsor
- Peking University Third HospitalUniversity, hospital or other
- Collaborators
- RenJi Hospital, Northwest Women's and Children's Hospital, Xi'an, Shaanxi
- Study start
- Aug 2021 (estimated)
- Primary completion
- Mar 2023 (estimated)
- Study completion
- Apr 2023 (estimated)
- First posted
- 29 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention group(pET) | Experimental | Diagnostic Test: ERAPersonalized embryo transfer of a single vitrified blastocyst in a HRT cycle according to the ERA test results. |
| Control group(FET) | Active comparator | Diagnostic Test: ERAFrozen embryo transfer of a single vitrified blastocyst in a HRT cycle according to the clinical standard practice. |
Who may qualify
- Ages
- Up to 37 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (8 listed)
- 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).
Key exclusion criteria (6 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| ERABefore 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. | Diagnostic test | Intervention group(pET) |
| ERABefore 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. | Diagnostic test | Control group(FET) |
Primary outcome
Live birth rate
Time frame: From date of embryo transfer until 40 weeks
The number of deliveries that resulted in at least one live birth per ET (transferred patient). Live birth is defined as the complete expulsion or extraction from a woman of a product of conception after 22 weeks of gestation, which, after such separation, breathes or shows any other evidence of life, such as heartbeat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached.
9 secondary outcomes
Implantation rate
Time frame: From date of embryo transfer until 5-6 weeks
Clinical miscarriage rate
Time frame: From date of embryo transfer until 20 weeks
Biochemical pregnancy rate
Time frame: From date of embryo transfer until 5-6 weeks
Ectopic pregnancy rate
Time frame: From date of embryo transfer until 8 weeks
Incidence of WOI displacement in the study population
Time frame: From date of randomization until 1-2 months
pregnancy rate
Time frame: From date of embryo transfer until 2 weeks
Obstetric complications
Time frame: From date of embryo transfer until 40 weeks
Delivery complications
Time frame: From date of embryo transfer until 40 weeks
Cost-effectiveness between pET and FET groups
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jie Qiao principal investigator
Peking University Third Hospital, Beijing
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing ERA in people with Infertility, Female and IVF/ICSI, run by Peking University Third Hospital at 3 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Jul 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Jie Qiao (+86 010-82266699, Jie.quiao@263.net), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Live birth rate (time frame: From date of embryo transfer until 40 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2021.