ERA Test in Patients With Recurrent Implantation Failure

NCT ID: NCT01668693

Last Updated: 2015-10-19

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-01-31
• Study Completion Date: 2016-12-31

Brief Summary

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.

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.

Conditions

Repetitive Implantation Failure

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: DIAGNOSTIC
• Blinding Strategy: NONE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

ERA (Endometrial Receptivity Array)

Intervention Type: OTHER

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.

Personalized Embryo Transfer

Intervention Type: OTHER

When the ERA indicates receptivity, the patient will undergo the embryo transfer on the day indicated by the diagnostic tool.

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.

Group Type: EXPERIMENTAL

ERA (Endometrial Receptivity Array)

Intervention Type: OTHER

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.

Personalized Embryo Transfer

Intervention Type: OTHER

When the ERA indicates receptivity, the patient will undergo the embryo transfer on the day indicated by the diagnostic tool.

Second ERA

Intervention Type: OTHER

A second ERA will be performed to confirm receptivity after further administration of Progesterone.

Interventions

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.

Intervention Type: OTHER

Personalized Embryo Transfer

When the ERA indicates receptivity, the patient will undergo the embryo transfer on the day indicated by the diagnostic tool.

Intervention Type: OTHER

Second ERA

A second ERA will be performed to confirm receptivity after further administration of Progesterone.

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Women ≤38 years old
• Normal ovarian reserve
• FSH <8mIU/mL
• Cycle with ≥6 MII oocytes/oocyte retrieval
• ≥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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 38 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: Yes

Sponsors

Igenomix

INDUSTRY

Sponsor Role: lead

Responsible Party

Carlos Simon

MD PhD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Carlos Simón, MD PhD

Role: PRINCIPAL_INVESTIGATOR

ºIGENOMIX / IVI Valencia

Locations

IVI

Valencia, VAencia, Spain

Site Status: RECRUITING

Countries

Spain

Central Contacts

Carlos Simón, MD PhD

Role: CONTACT

carlos.simon@ivi.es

+34963050900

Carlos Gómez, MA

Role: CONTACT

carlos.gomez@igenomix.com

+34670506469

Facility Contacts

Carlos Simon

Role: primary

Other Identifiers

0600-E-905-JH

Identifier Type: -

Identifier Source: org_study_id