Clinical Study PGT-A vs PGT-A+ERA
| Status: | Recruiting |
|---|---|
| Conditions: | Women's Studies |
| Therapuetic Areas: | Reproductive |
| Healthy: | No |
| Age Range: | Any |
| Updated: | 3/15/2019 |
| Start Date: | May 15, 2018 |
| End Date: | May 2020 |
| Contact: | Carlos Gomez, BSc MSc |
| Email: | carlos.gomez@igenomix.es |
| Phone: | +34963905310 |
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).
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.
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.
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.
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.
Inclusion Criteria:
- 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).
- 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.
Exclusion Criteria:
- 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.
We found this trial at
4
sites
Margate, Florida 33063
Principal Investigator: Marcelo Barrionuevo, MD PhD
Phone: 954-247-6258
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Norwalk, Connecticut 06851
Principal Investigator: Mark Leondires, MD PhD
Phone: 203-750-7400
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