Infertility of Uterine OriginPGT-A&ERANCT03530254
Clinical Study of PGT-A Versus PGT-A+ERA
A study testing PGT-A and ERA Test in people with Infertility of Uterine Origin, run by Igenomix at 15 sites in 12 countries.
Trial summary
Patients who have shown previous implantation failures, despite transferring good quality and chromosomally normal embryos (diagnosed by PGT-A), could have a displaced Window of Implantation (WOI) and consequently, alterations in their endometrial receptivity. Read more about this study
- Who is it for?
- Any age, women only
- Conditions the study is for
- Infertility of Uterine Origin
- What is being tested?
- PGT-A and ERA Test
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 368 participants
- Where
- 15 sitesin 12 countries
- Study dates
- 28 May 2018to 22 Feb 2022
- 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 Any age
- Women only
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Majority of age patients whose written informed consent approved by the Ethics Committee (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 who already have frozen euploid blastocysts (day 5/6 development) analysed by PGT-A.
- Patients with embryos obtained from their own oocytes fertilized by Intracytoplasmic Sperm Injection (ICSI) or In vitro fertilization (IVF).
- Patients with an expected embryo transfer of one or two embryos (Single ET or Double ET) in a HRT cycle.
- Body Mass Index: 18,5-30 Kg/m2.
Who cannot join
- Presence of pathologies or malformations that affect the uterine cavity such as polyps, intramural myomas ≥ 4cm or submucosal, septum or hydrosalpinx during the patient's participation in the study. Patients suffering these pathologies before or after their inclusion in the study are allowed to participate if the pathology is corrected before performing any study procedure.
- Any illness or medical condition that is unstable or which, according to medical criteria, may put at risk the patient's safety and her compliance in the study.
Trial locations and contacts
15 sites in 12 countries.
15 sites in 12 countries
United States2 sites
Ovation Fertility Newport Beach
Newport Beach, California, 92663
Fertility Centers of New England
Reading, Massachusetts, 01867
India2 sites
OASIS centre for reproductive medicine
Banjara Hills, Hyderabad, 500034
Mother And Child Hospital
Defence Colony, National Capital Territory of Delhi, 110024
Spain2 sites
Milenium Centro Médico y de Bienestar de Alcobendas - Sanitas
Alcobendas, Madrid, 28108
Instituto Extremeño de Reproducción Asistida S.L. (IERA)
Badajoz, 06006
Georgia1 site
Georgian- American Center for Reproductive Medicine ReproART
Tbilisi, 0179
About this study
Official title: International Multi-center, Randomized and Controlled Clinical Study, to Evaluate the Clinical Benefit of the ERA Test in Infertile Patients Undergoing Assisted Reproduction Treatment and Medical Indication of PGT-A.
Patients who have shown previous implantation failures, despite transferring good quality and chromosomally normal embryos (diagnosed by PGT-A), could have a displaced Window of Implantation (WOI) and consequently, alterations in their endometrial receptivity. The correction of this displacement can improve the results of the Assisted Reproduction Treatments (ART).
The ERA test (Endometrial Receptivity Analysis) evaluates the transcriptomic endometrial profile to determine if the patient's uterus is receptive when the embryo is transferred during an In Vitro Fertilization (IVF) process, and identifies the personalized WOI of the patient. This process is called Personalized Embryo Transfer (pET).
Read more
The Preimplantation Genetic Test of Aneuploidies or PGT-A (Preimplantation Genetic Testing for Aneuploidy), is currently carried out using Next Generation Sequencing (NGS) and serves to identify chromosomally normal embryos prior to their transfer in an IVF treatment. Aneuploidies are rarely compatible with life or can cause congenital diseases. So, the identification of chromosomally normal embryos, improves the success of reproduction in cases in which infertility is caused by such aneuploidies.
Therefore, the aim of this study is to determine, in a randomized and prospective way, the clinical benefit of adding the ERA test to the embryonic aneuploidies test for patients with a PGT-A indication.
Read the detailed description
The lack of receptivity of the uterus and chromosomal abnormalities in the embryo are the two main causes of implantation failure. Patients with implantation failure, should consider the PGT-A test to identify and select euploid embryos. In addition, it should be evaluated the endometrium receptivity state at the time of Embryo Transfer (ET).
The PGT-A is an important genetic test that was developed to select embryos during IVF treatment and avoid embryonic chromosomal abnormalities that lead to miscarriage or life born with chromosomal diseases. Embryonic aneuploidy is linked to maternal age. The most common consequences are implantation failure, miscarriage or life born with multiple congenital anomalies. The transfer of euploid embryos (chromosomally normal) diagnosed by PGT-A has shown an increase in implantation rates.
Morphology is the most traditional and routine method of embryo selection being used. However, it is difficult to distinguish normal and abnormal embryos by observing their morphology under a microscope. Therefore, morphological analysis should not be the only technique used to decide which embryo should be transferred. Application of NGS in PGT-A cycles demonstrates that this methodology is reliable, allowing identification and transfer of euploid embryos resulting in ongoing pregnancies. However, despite the transfer of morphologically normal euploid embryos, it is not always possible to acquire optimal results in Assisted Reproductive Techniques (ART).
On the other hand, the endometrial gene expression profile allows the diagnosis of the endometrium receptivity status. This is carried out by a molecular tool developed and patented by Igenomix (PCT/ES2009/00386). The ERA test is a customized expression microarray that identifies the transcriptomic expression profile signature of the personalized Window of Implantation (pWOI). A bioinformatic predictor determines the moment of maximum receptivity, indicating the best time to perform a pET.
If the result of the ERA test is "Receptive", the WOI and the moment of taking the biopsy overlap. Nevertheless, if the result is "Pre-Receptive", the optimal implantation window is expected to be after the moment in which the biopsy is taken, and if the diagnosis is "Post-Receptive", the optimal window of implantation is prior to the biopsy. In a subsequent cycle, a pET will be performed according to the ERA test results.
Recently, it has been conducted a pilot study in patients with previous implantation failures with PGT-A and euploid embryo transfer (ET). The results of the ERA test have shown that a high percentage of these patients have been diagnosed as Non-receptive (90%). This percentage is higher than the expected in the normal population (12-20%) or in the Repeated Implantation Failure (RIF) patients without PGT-A (25-30%). Once the pET was performed according to the results of the ERA test, the gestation rate was 55.55%.
So, the objective of the present study is to validate these preliminary results in a prospective, multi-center, randomized and controlled study to demonstrate the value of the endometrial factor and the improvement of the results obtained in patients with PGT-A indication. If confirmed, it would be recommended the ERA test for all ART patients, not only for those with PGT-A, demonstrating the significance in searching for the pWOI to improve reproductive outcomes.
Considering a maximum drop-out rate of 30%, a total of 750 participants are expected to be included. According to the approved protocol, an interim analysis is planned at 50% of the total enrolment.
- Conditions
- Infertility of Uterine Origin
- Being tested
- PGT-A, ERA Test
- Keywords
- Endometrial receptivity, Preimplantation Genetic Diagnosis (PGD), Preimplantation Genetic Testing for Aneuploidy (PGT-A), Embryo Transfer (ET), Endometrial Receptivity Analysis (ERA), Endometrial Diagnosis, Live Newborn Rate (LBR)
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
PGT-ADiagnostic test
PGT-A will be carried out following the usual clinical practice. Trophectoderm biopsy samples from blastocysts are analyzed by NGS to screen for numerical chromosomal abnormalities.
ERA TestDiagnostic test
The ERA test requires an endometrial biopsy and will determine if the endometrium is receptive or not by analysing the expression levels of 236 genes involved in endometrial receptivity, to assess the optimal time to place an embryo into the uterus and promote a successful implantation and pregnancy.
| Study group | Role | What they receive |
|---|---|---|
| PGT-A without ERA | Other | Patients with PGT-A indication and ET in a Hormone Replacement Therapy (HRT cycle) according to the usual clinical practice (day 5 of progesterone supplementation: P+5/120h). Receives: Diagnostic Test: PGT-A |
| PGT-A and test ERA | Other | Patients with PGT-A indication and pET in HRT cycle following the ERA test indication (when the WOI is confirmed as "Receptive"). Receives: Diagnostic Test: PGT-A; Diagnostic Test: ERA Test |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live birth rate
Number of babies born per embryo transfer
Measured: 40 weeks
Secondary outcomes (6)
Implantation rate
Number of implanted embryos per total number of embryos transferred
Measured: 12 weeks
Clinical pregnancy
Number of clinical pregnancies per total number of pregnancies
Measured: 20 weeks
Biochemical pregnancy
Number of biochemical pregnancies per total number of pregnancies
Measured: 20 weeks
Clinical miscarriages
Number of clinical miscarriages per total number of pregnancies
Measured: 20 weeks
Ectopic pregnancies
Number of ectopic pregnancies per total number of pregnancies
Measured: 20 weeks
Obstetric complications
Type and number of obstetric complications during pregnancy
Measured: 40 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2018
- Study start28 May 2018
- Primary completion22 Feb 2022
- Study completion22 Feb 2022
Why it stopped: Low recruitment speed, higher percentage drop-out and SARS-CoV-2 pandemic situation
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Infertility of Uterine OriginStudies of the same condition, open and under way.
- 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
- 368 participants (actual)
Sponsor and investigators
- Lead sponsor
- Igenomix
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Carlos Simón, MD PhD, Study chair, Igenomix
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03530254
- Sponsor's protocol ID
- IGX1-P&E-DV-17-08
- Acronym
- PGT-A&ERA
- Status last verified
- Apr 2022
- First submitted
- 8 May 2018
- Last updated
- 4 May 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- International Multi-center, Randomized and Controlled Clinical Study, to Evaluate the Clinical Benefit of the ERA Test in Infertile Patients Undergoing Assisted Reproduction Treatment and Medical Indication of PGT-A.
- ClinicalTrials.gov ID
- NCT03530254
- Acronym / sponsor ID
- PGT-A&ERA / IGX1-P&E-DV-17-08
- Conditions
- Infertility of Uterine Origin
- Keywords
- Endometrial receptivity, Preimplantation Genetic Diagnosis (PGD), Preimplantation Genetic Testing for Aneuploidy (PGT-A), Embryo Transfer (ET), Endometrial Receptivity Analysis (ERA), Endometrial Diagnosis, Live Newborn Rate (LBR)
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low recruitment speed, higher percentage drop-out and SARS-CoV-2 pandemic situation
- Enrolment
- 368 participants (actual)
- Lead sponsor
- IgenomixIndustry (pharma, biotech, devices)
- Study start
- 28 May 2018 (actual)
- Primary completion
- 22 Feb 2022 (actual)
- Study completion
- 22 Feb 2022 (actual)
- First posted
- 21 May 2018 (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.
Patients who have shown previous implantation failures, despite transferring good quality and chromosomally normal embryos (diagnosed by PGT-A), could have a displaced Window of Implantation (WOI) and consequently, alterations in their endometrial receptivity. The correction of this displacement can improve the results of the Assisted Reproduction Treatments (ART).
The ERA test (Endometrial Receptivity Analysis) evaluates the transcriptomic endometrial profile to determine if the patient's uterus is receptive when the embryo is transferred during an In Vitro Fertilization (IVF) process, and identifies the personalized WOI of the patient. This process is called Personalized Embryo Transfer (pET).
The Preimplantation Genetic Test of Aneuploidies or PGT-A (Preimplantation Genetic Testing for Aneuploidy), is currently carried out using Next Generation Sequencing (NGS) and serves to identify chromosomally normal embryos prior to their transfer in an IVF treatment. Aneuploidies are rarely compatible with life or can cause congenital diseases. So, the identification of chromosomally normal embryos, improves the success of reproduction in cases in which infertility is caused by such aneuploidies.
Therefore, the aim of this study is to determine, in a randomized and prospective way, the clinical benefit of adding the ERA test to the embryonic aneuploidies test for patients with a PGT-A indication.
Detailed description
The lack of receptivity of the uterus and chromosomal abnormalities in the embryo are the two main causes of implantation failure. Patients with implantation failure, should consider the PGT-A test to identify and select euploid embryos. In addition, it should be evaluated the endometrium receptivity state at the time of Embryo Transfer (ET).
The PGT-A is an important genetic test that was developed to select embryos during IVF treatment and avoid embryonic chromosomal abnormalities that lead to miscarriage or life born with chromosomal diseases. Embryonic aneuploidy is linked to maternal age. The most common consequences are implantation failure, miscarriage or life born with multiple congenital anomalies. The transfer of euploid embryos (chromosomally normal) diagnosed by PGT-A has shown an increase in implantation rates.
Morphology is the most traditional and routine method of embryo selection being used. However, it is difficult to distinguish normal and abnormal embryos by observing their morphology under a microscope. Therefore, morphological analysis should not be the only technique used to decide which embryo should be transferred. Application of NGS in PGT-A cycles demonstrates that this methodology is reliable, allowing identification and transfer of euploid embryos resulting in ongoing pregnancies. However, despite the transfer of morphologically normal euploid embryos, it is not always possible to acquire optimal results in Assisted Reproductive Techniques (ART).
On the other hand, the endometrial gene expression profile allows the diagnosis of the endometrium receptivity status. This is carried out by a molecular tool developed and patented by Igenomix (PCT/ES2009/00386). The ERA test is a customized expression microarray that identifies the transcriptomic expression profile signature of the personalized Window of Implantation (pWOI). A bioinformatic predictor determines the moment of maximum receptivity, indicating the best time to perform a pET.
If the result of the ERA test is "Receptive", the WOI and the moment of taking the biopsy overlap. Nevertheless, if the result is "Pre-Receptive", the optimal implantation window is expected to be after the moment in which the biopsy is taken, and if the diagnosis is "Post-Receptive", the optimal window of implantation is prior to the biopsy. In a subsequent cycle, a pET will be performed according to the ERA test results.
Recently, it has been conducted a pilot study in patients with previous implantation failures with PGT-A and euploid embryo transfer (ET). The results of the ERA test have shown that a high percentage of these patients have been diagnosed as Non-receptive (90%). This percentage is higher than the expected in the normal population (12-20%) or in the Repeated Implantation Failure (RIF) patients without PGT-A (25-30%). Once the pET was performed according to the results of the ERA test, the gestation rate was 55.55%.
So, the objective of the present study is to validate these preliminary results in a prospective, multi-center, randomized and controlled study to demonstrate the value of the endometrial factor and the improvement of the results obtained in patients with PGT-A indication. If confirmed, it would be recommended the ERA test for all ART patients, not only for those with PGT-A, demonstrating the significance in searching for the pWOI to improve reproductive outcomes.
Considering a maximum drop-out rate of 30%, a total of 750 participants are expected to be included. According to the approved protocol, an interim analysis is planned at 50% of the total enrolment.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| PGT-A without ERA | Other | Diagnostic Test: PGT-APatients with PGT-A indication and ET in a Hormone Replacement Therapy (HRT cycle) according to the usual clinical practice (day 5 of progesterone supplementation: P+5/120h). |
| PGT-A and test ERA | Other | Diagnostic Test: PGT-A, Diagnostic Test: ERA TestPatients with PGT-A indication and pET in HRT cycle following the ERA test indication (when the WOI is confirmed as "Receptive"). |
Who may qualify
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (5 listed)
- Majority of age patients whose written informed consent approved by the Ethics Committee (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 who already have frozen euploid blastocysts (day 5/6 development) analysed by PGT-A.
- Patients with embryos obtained from their own oocytes fertilized by Intracytoplasmic Sperm Injection (ICSI) or In vitro fertilization (IVF).
- Patients with an expected embryo transfer of one or two embryos (Single ET or Double ET) in a HRT cycle.
- Body Mass Index: 18,5-30 Kg/m2.
Key exclusion criteria (2 listed)
- Presence of pathologies or malformations that affect the uterine cavity such as polyps, intramural myomas ≥ 4cm or submucosal, septum or hydrosalpinx during the patient's participation in the study. Patients suffering these pathologies before or after their inclusion in the study are allowed to participate if the pathology is corrected before performing any study procedure.
- Any illness or medical condition that is unstable or which, according to medical criteria, may put at risk the patient's safety and her compliance in the study.
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 |
|---|---|---|
| PGT-APGT-A will be carried out following the usual clinical practice. Trophectoderm biopsy samples from blastocysts are analyzed by NGS to screen for numerical chromosomal abnormalities. | Diagnostic test | PGT-A and test ERA, PGT-A without ERA |
| ERA TestThe ERA test requires an endometrial biopsy and will determine if the endometrium is receptive or not by analysing the expression levels of 236 genes involved in endometrial receptivity, to assess the optimal time to place an embryo into the uterus and promote a successful implantation and pregnancy. | Diagnostic test | PGT-A and test ERA |
Primary outcome
Live birth rate
Time frame: 40 weeks
Number of babies born per embryo transfer
6 secondary outcomes
Implantation rate
Time frame: 12 weeks
Clinical pregnancy
Time frame: 20 weeks
Biochemical pregnancy
Time frame: 20 weeks
Clinical miscarriages
Time frame: 20 weeks
Ectopic pregnancies
Time frame: 20 weeks
Obstetric complications
Time frame: 40 weeks
Results and safety
The study was stopped early (reason given: Low recruitment speed, higher percentage drop-out and SARS-CoV-2 pandemic situation). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2022.
- Individual participant dataSharing planned: No
Related trials for Infertility of Uterine Origin
Recruiting
Deceased Uterine Transplant in Absolute Uterine Infertility (AUIF)
Infertility of Uterine Origin
Active, not recruiting
The University of Pennsylvania Uterus Transplant for Uterine Factor Infertility Trial
Mayer Rokitansky Kuster Hauser Syndrome, Uterine Agenesis
Recruiting
Platelet Rich Plasma for Insufficient Endometrium
Infertility of Uterine Origin
Recruiting
Uterine Transplant for Women With Absolute Uterine Factor Infertility (AUFI)
Mayer Rokitansky Kuster Hauser Syndrome, Absence of Uterus
Active, not recruitingObservational study
International Non-selection Study for ERA® Test in Patients With Previous Implantation Failures
Infertility of Uterine Origin, Implantation Failure
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.
Carlos Simón, MD PhD study chair
Igenomix
15 sites in 12 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing PGT-A and ERA Test in people with Infertility of Uterine Origin, run by Igenomix at 15 sites in 12 countries.
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 5 inclusion and 2 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: stopped early, as of the sponsor's last update on 4 May 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 15 sites in United States, India, Spain, Argentina, Brazil and 7 more countries. 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?
The study was stopped early (reason given: Low recruitment speed, higher percentage drop-out and SARS-CoV-2 pandemic situation). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Live birth rate (time frame: 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 4 May 2022.