ERA Test in Patients With Recurrent Implantation Failure (ERA)

The Endometrial Receptivity Array (ERA) as Diagnosis and Personalized Embryo Transfer (pET) as Treatment in Patients With Receptive Implantation Failure (RIF).

The purpose of this study is to demonstrate the clinical efficiency of the Endometrial Receptivity Array (ERA) diagnostic tool in patients with repetitive implantation failure (RIF), leading to the new concept of the personalized window of implantation (pWOI) as diagnostic and treatment of patients with RIF of endometrial origin.

Study Overview

• Status: Unknown
• Conditions: Repetitive Implantation Failure
• Intervention / Treatment: Other: ERA (Endometrial Receptivity Array); Other: Personalized Embryo Transfer; Other: Second ERA

Detailed Description

Intervention(s): Endometrial sampling, either at LH+7 in a natural cycle or after 5 days of progesterone in a hormonal replacement cycle (HRT) and personalized embryo transfer (pET) on the designated day guided by the ERA prediction.

Repeated implantation failure (RIF) is an unsolved not well characterized major cause of infertility in otherwise healthy women. Although various definitions of RIF exist, the clinical community agrees that after failure of three IVF cycles, in which one to two morphologically high-grade embryos have been transferred, special protocols must be enforced, although no hard data from RCTs demonstrates that any of the current approaches in RIF have a significant clinical value .

Based on the large amount of information generated about the regulation and deregulation of the genes implicated in the endometrial window of receptivity (WOR), our group has developed a molecular diagnostic tool based on the specific transcriptomic signature that identifies the receptive endometrium at LH+7 in a natural cycle or on day 5 of progesterone impregnation (P+5) after proper estradiol priming in a hormonal replacement therapy (HRT) cycle. The endometrial receptivity array (ERA) consists of a customized array containing 238 genes differentially expressed that is coupled to a computational predictor able to diagnose the personalized endometrial WOI of a given patient, regardless of its histological appearance. The accuracy of the diagnostic tool ERA has been demonstrated to be superior to endometrial histology and results are completely reproducible 29 to 40 months later.

Compelling evidence indicates the existence of an endometrial receptivity alteration in patients with RIF.

The aim of this study is to demonstrate the diagnostic efficiency of the ERA test in RIF patients by identifying putative alterations related to the displacement of their personalized window of receptivity, and the therapeutic implications through personalization of the day of embryo transfer (pET), following the diagnosis obtained by this molecular diagnostic tool. An endometrial biopsy on day LH+7 in a natural cycle or on day P+5 in an HRT cycle and ERA diagnosis of receptive or non-receptive is informed. In receptive cases, embryo transfer (ET) will be performed in subsequent cycles on the indicated day. In non-receptive ERA, the test is to be repeated on the dayindicated by the predictor, and personalized ET guided in subsequent cycles according to ERA diagnosis.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Carlos Simon, MD PhD; Phone Number: +34963050900; Email: carlos.simon@ivi.es
• Study Contact Backup: Name: Carlos Gómez, Ma; Phone Number: +34670506469; Email: carlos.gomez@igenomix.com

Study Locations

• Spain
  • VAencia
    • Valencia, VAencia, Spain
      • Recruiting
      • IVI
      • Contact: Carlos Simon

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 38 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Women ≤38 years old
• Normal ovarian reserve
• FSH <8mIU/mL
• Cycle with ≥6 MII oocytes/oocyte retrieval
• ≥3 implantation failures in previous IVF/ICSI cycles with transfer of atleast two good quality embryos in each cycle Inclusion Criteria for ovum donation recipients
• ≥3 implantation failures with transfer of atleast two good quality embryos in each cycle
• Endometrial thickness ≥ 6 mm
• Trilaminar pattern after proper progesterone priming

Exclusion Criteria:

• Existance of hydrosalpinx
• Atrophic endometrium < 6 mm
• Previous ectopic or uterine miscarriages
• Presence of myomas or polyps
• Previous embryo transfer with high difficulty and/or bleeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: RIF ERA Receptive 1; With the "receptive" results from the first Endometrial Receptivity Array (ERA), the patients will undergo embryo transfer on Day 5 of Progesterone administration in the cycle following the ERA diagnosis.	Other: ERA (Endometrial Receptivity Array); The diagnostic tool ERA will be performed on all of the patients in order to allocate them in the group "Receptive" or "Non Receptive" and to predict the number of days of Progesterone administration necesary to obtain the "Receptive" prediction.; Other: Personalized Embryo Transfer; When the ERA indicates receptivity, the patient will undergo the embryo transfer on the day indicated by the diagnostic tool.
Experimental: RIF ERA Non Receptive; The "Non Receptive" results of the ERA diagnotic tool will indicate how many more days of Progesterone are necesary in order to obtain the "Receptive" daignosis. A second ERA will take place to confirm receptivity and in the following cycle, the personalized embryo transfer will take place on the day predicted by this diagnostic tool.	Other: ERA (Endometrial Receptivity Array); The diagnostic tool ERA will be performed on all of the patients in order to allocate them in the group "Receptive" or "Non Receptive" and to predict the number of days of Progesterone administration necesary to obtain the "Receptive" prediction.; Other: Personalized Embryo Transfer; When the ERA indicates receptivity, the patient will undergo the embryo transfer on the day indicated by the diagnostic tool.; Other: Second ERA; A second ERA will be performed to confirm receptivity after further administration of Progesterone.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Detection of the Receptive or Non Receptive endometrial status according to the ERA test.	1 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Pregnancy	6 weeks
Implantation	4 months

Collaborators and Investigators

• Sponsor: Igenomix
• Investigators: Principal Investigator: Carlos Simón, MD PhD, ºIGENOMIX / IVI Valencia

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Anticipated): April 1, 2016
• Study Completion (Anticipated): December 1, 2016

Study Registration Dates

• First Submitted: August 13, 2012
• First Submitted That Met QC Criteria: August 16, 2012
• First Posted (Estimate): August 20, 2012

Study Record Updates

• Last Update Posted (Estimate): October 19, 2015
• Last Update Submitted That Met QC Criteria: October 16, 2015
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: ERA; Endometrial receptivity; recurrent implantation failure; predictor tool; customized microarray; personalized embryo transfer
• Other Study ID Numbers: 0600-E-905-JH