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Clinical Study PGT-A vs PGT-A+ERA (PGT-A&ERA)

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ClinicalTrials.gov Identifier: NCT03530254
Recruitment Status : Recruiting
First Posted : May 21, 2018
Last Update Posted : October 31, 2018
Sponsor:
Information provided by (Responsible Party):
Igenomix

Brief 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. 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.


Condition or disease Intervention/treatment Phase
Infertility of Uterine Origin Diagnostic Test: PGT-A Diagnostic Test: ERA Test Not Applicable

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 740 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Diagnostic
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.
Actual Study Start Date : May 15, 2018
Estimated Primary Completion Date : May 2019
Estimated Study Completion Date : May 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Infertility

Arm Intervention/treatment
PGT-A without ERA
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).
Diagnostic Test: PGT-A
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.

PGT-A and test ERA
Patients with PGT-A indication and pET in HRT cycle following the ERA test indication (when the WOI is confirmed as "Receptive").
Diagnostic Test: PGT-A
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.

Diagnostic Test: ERA 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.




Primary Outcome Measures :
  1. Live birth rate [ Time Frame: 40 weeks ]
    Number of babies born per embryo transfer


Secondary Outcome Measures :
  1. Implantation rate [ Time Frame: 12 weeks ]
    Number of implanted embryos per total number of embryos transferred

  2. Clinical pregnancy [ Time Frame: 20 weeks ]
    Number of clinical pregnancies per total number of pregnancies

  3. Biochemical pregnancy [ Time Frame: 20 weeks ]
    Number of biochemical pregnancies per total number of pregnancies

  4. Clinical miscarriages [ Time Frame: 20 weeks ]
    Number of clinical miscarriages per total number of pregnancies

  5. Ectopic pregnancies [ Time Frame: 20 weeks ]
    Number of ectopic pregnancies per total number of pregnancies

  6. Obstetric complications [ Time Frame: 40 weeks ]
    Type and number of obstetric complications during pregnancy



Information from the National Library of Medicine

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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   Female
Gender Based Eligibility:   Yes
Gender Eligibility Description:   Majority of age infertile patients who already have frozen euploids blastocysts (day 5/6 development) obtained from their own oocytes, fertilized by ICSI and analysed by PGT-A, with an expected embryo transfer of one or two embryos in a Hormone Replacement Therapy cycle (HRT cycle).
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03530254


Contacts
Contact: Carlos Gomez, BSc MSc +34963905310 ext 18543 carlos.gomez@igenomix.es
Contact: Diana Valbuena, MD PhD +34963905310 ext 18544 diana.valbuena@igenomix.es

Locations
United States, Connecticut
RMA CT Recruiting
Norwalk, Connecticut, United States, 06851
Contact: Christina Portela-Dias, BSN RN    203-750-7400    Cdias@rmact.com   
Contact: Mark Leondires, MD PhD    (+1) 203-956-2265    mleondires@rmact.com   
Principal Investigator: Mark Leondires, MD PhD         
United States, Florida
IVF Florida Recruiting
Margate, Florida, United States, 33063
Contact: Susan Sciandra, BSN RN    954-247-6258    Susan.Sciandra@integramed.com   
Contact: Marcelo Barrionuevo, MD PhD    (+1) 954-247-6200    barrionue@aol.com   
Principal Investigator: Marcelo Barrionuevo, MD PhD         
United States, Massachusetts
Fertility Centers of New England Recruiting
Reading, Massachusetts, United States, 01867
Contact: Joseph Hill, MD    781-942-7000    hillj@FertilityCenter.com   
Contact: Peter Wieckowski, pHD    781-942-7000    wieckowskip@FertilityCenter.com   
Argentina
Pregna Medicina Reproductiva Not yet recruiting
Caba, Argentina, C1425
Contact: Laura Kopcow, MD    +54 1148341600    lkopcow@pregna.com.ar   
Contact: Mariana Degani, MD    +54 1148341600    mdegani@pregna.com.ar   
Brazil
Geare Clinic Not yet recruiting
Recife, Pernambuco, Brazil, 52011-040
Contact: Madalena Caldas, MD    (+81) 30341147    ppmatheus@uol.com.br   
Principal Investigator: Madalena Caldas, MD         
Canada
Olive Fertility Center Not yet recruiting
Vancouver, Canada, BC V5Z 3X7
Contact: Gary Nakhuda, MD PhD    (+1) 604-559-9950    GNakhuda@olivefertility.com   
Principal Investigator: Gary Nakhuda, MD PhD         
Chile
Shady Grove Fertility Chile Not yet recruiting
Vitacura, Chile, 6800
Contact: Michael Freudenthal, MD    (+56) 232638900    michael.freudenthal@sgfertility.com   
Principal Investigator: Michael Freudenthal, MD         
Georgia
Georgian- American Center for Reproductive Medicine ReproART Recruiting
Tbilisi, Georgia, 0179
Contact: Tamuna Barbakadze, MD PhD    (+995) 322515909    tamar.barbakadze@yahoo.com   
Principal Investigator: Tamuna Barbakadze, MD PhD         
India
Mother And Child Hospital Recruiting
Defence Colony, Delhi, India, 110024
Contact: Nalini Mahajan, MBBS, MD    (+91) 1141030715    drnalinimahajan@gmail.com   
Principal Investigator: Nalini Mahajan, MBBS, MD         
OASIS centre for reproductive medicine Recruiting
Banjara Hills, Hyderabad, India, 500034
Contact: Durga Rao, MD PhD    (+91) 9490624638    durga@oasisindia.in   
Principal Investigator: Durga Rao, MD PhD         
Mexico
NASCERE Recruiting
Mexico City, Cdmx, Mexico, 05120
Contact: Lucia Daniela Garcia Montes, BS PhD    (+52) 15554521311    lucia.daniela.garcia.montes@gmail.com   
Contact: Gerardo Barroso, MD PhD    (+52) 15554521311    barrosog@me.com   
Principal Investigator: Gerardo Barroso, MD PhD         
Spain
Milenium Centro Médico y de Bienestar de Alcobendas - Sanitas Recruiting
Alcobendas, Madrid, Spain, 28108
Contact: Ana Gaitero, MD PhD    (+34) 917165820    agaitero@sanitas.es   
Principal Investigator: Ana Gaitero, MD PhD         
Taiwan
Center of Reproductive Medicine and Sciences - Taipei Medical University Not yet recruiting
Taipei, Taiwan, 110
Contact: Chii Ruey Tzeng, MD    (+886) 227372181 ext 8540    tzengcr@tmu.edu.tw   
Principal Investigator: Chii Ruey Tzeng, MD         
Taiwan IVF Group Active, not recruiting
Zhubei, Taiwan, 302
Turkey
Bahceci Group Not yet recruiting
Istanbul, Turkey, 07720
Contact: Necati Findikli, BS MSc PhD    (+90) 2123103100    nfindikli@bahceci.com   
Contact: Mustafa Bahceci, MD PhD    (+90) 2123103166    mbahceci@bahceci.com   
Principal Investigator: Mustafa Bahceci, MD PhD         
Sponsors and Collaborators
Igenomix
Investigators
Study Chair: Carlos Simón, MD PhD Igenomix

Responsible Party: Igenomix
ClinicalTrials.gov Identifier: NCT03530254     History of Changes
Other Study ID Numbers: IGX1-P&E-DV-17-08
First Posted: May 21, 2018    Key Record Dates
Last Update Posted: October 31, 2018
Last Verified: June 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Igenomix:
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)

Additional relevant MeSH terms:
Infertility
Infertility, Female
Genital Diseases, Male
Genital Diseases, Female