International Non-selection Study for ERA® Test in Patients With Previous Implantation Failures

NCT06097559 | Active Not Recruiting

• 1 other identifier: IGX1-ENS-MR-22-05
• Study Type: observational
• Target: 738
• Locations: 4 countries
• Sites: 8

Brief Summary

Women´s period comprises different hormonal stages, being one of them the stage for maximum receptivity and proper embryo implantation. This stage is named window of implantation (WOI), and is characterized by a specific molecular pattern than can be assessed by the Endometrial Receptivity Analysis (ERA® test), developed by Igenomix. Determining the WOI allows to schedule a personalized embryo transfer (pET) when the endometrium is most receptive for the implantation. The main objective of the present study is to improve our knowledge on the endometrial factor in an infertile population with previous implantation failures. To do so, a diagnosis of the endometrial receptivity to determine the WOI (ERA®) and the microbiome (EMMA®) of each participant will be performed, assessing its impact on deferred embryo transfers in terms of reproductive outcomes. Participants will follow their previously programmed IVF/ICSI treatment and, only when one embryo with no major anomalies is reported by PGT-A (Preimplantation Genetic Testing for Aneuploidies), they will be asked to attend to the specific study visit for endometrial fluid and biopsy samples collection. These samples will be used to determine the patient's WOI (ERA®) and endometrial microbiome (EMMA®). The results of neither of the tests will be disclosed to the patient or the doctor, being only used for the study purpose. After this visit, the patient will follow the pre-established schedule for an embryo transfer and pregnancy assessment.

Conditions

Infertility of Uterine Origin; Implantation Failure

Keywords

Infertility; Implantation failure; Uterine microbiome; Preimplantational Genetic Testing for Aneuploidies; Endometrial factor; Window of implantation; Endometrial receptivity; Personalized embryo transfer; Frozen embryo transfer; Endometrial Receptivity Analysis (ERA)

Outcome Measures

Primary Outcomes (1)

• Refinement of the ERA® computational analysis

  Comparison of the OPR (≥ 12 gestational weeks; fetal heartbeat diagnosis) in patients with receptive endometrium vs displaced WOI in the 1st FET.

  At least 12 gestational weeks

Secondary Outcomes (18)

• Pregnancy rate (PR) in the FET

  2 weeks after the embryo transfer

• Implantation rate (IR) in the FET

  Up to 4 weeks after the embryo transfer

• Biochemical pregnancy rate (BPR) in the FET

  4 weeks after the embryo transfer

• Ectopic pregnancy rate (EPR) in the FET

  4-5 weeks after the embryo transfer

• Clinical miscarriage rate (CMR) in the FET

  Up to 22 gestational weeks

Study Arms (2)

Clinical Outcomes in a Receptive Endometrium

Enrolled patients that according to the ERA® report are receptive. The only additional intervention that patients will undergo, apart from those already scheduled for their ART, is the collection of an endometrial biopsy and endometrial fluid. No drugs will be administered as per the study.

Diagnostic Test: Endometrial fluid and biopsy collection

Clinical Outcomes in a Non-receptive Endometrium

Enrolled patients that according to the ERA® report have a displaced WOI and are non-receptive. The only additional intervention that patients will undergo, apart from those already scheduled for their ART, is the collection of an endometrial biopsy and endometrial fluid. No drugs will be administered as per the study.

Diagnostic Test: Endometrial fluid and biopsy collection

Interventions

Endometrial fluid and biopsy collection DIAGNOSTIC_TEST

The ERA and EMMA test require an endometrial biopsy to be taken at P+5 (after 120±6 hours of exogenous progesterone administration) in a HRT cycle, according to the common clinical practice. On the same day, a sample of endometrial fluid will be aspirated immediately prior to the biopsy. Regardless of the endometrial receptivity profile, a subsequent regular FET will be performed within the standard WOI (after 120±6 hours of progesterone exposure) in an HRT cycle following the clinical standard practice. Those patients willing to participate in the rescue phase will follow the recommendation of the ERA test for the subsequent pET.

Clinical Outcomes in a Receptive Endometrium

Eligibility Criteria

• Age: 18 Years - 41 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)
• Sampling Method: Non-Probability Sample

Study Population

Infertile women scheduled for an in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle with one or more previous failed euploid/low-range mosaic embryo transfer(s) or with two or more previous failed transfers with non-tested good quality embryos, who will receive a transfer of a frozen euploid/low-range mosaic blastocyst (day 5/6) in an HRT cycle.

You may qualify if:

• Study ICF signature.
• Female age between 18 and 41 years (both included).
• IVF/ICSI (own or donated gametes) patients with ≥1 previous failed euploid/low-range mosaic embryo transfer(s) or ≥2 previous failed transfers with non-tested good quality embryos. (ROPA method is allowed).
• ≥1 PGT-A tested euploid/low-range mosaic blastocyst (day 5/6) available to be transferred (SET or DET according to medical recommendation).
• BMI 18.0 - 30.0 Kg/m2.
• Negative serological tests for HIV, HBV, HCV, RPR.

You may not qualify if:

• No HRT in the biopsy and/or the embryo transfer cycle.
• Intrauterine device (IUD) carriers within 3 months before sample collection.
• Surrogate pregnancy (in those countries where it is allowed).
• Adenomyosis or any pathological finding affecting the endometrial cavity such as polyps/sub-mucosal myomas, intramural myomas \> 4 cm, or hydrosalpinx. (Note: Patients are allowed to participate if the pathology is previously operated at least 3 months before the endometrial samples are obtained).
• Recurrent Pregnancy Loss (RPL ≥2 previous intrauterine miscarriages).
• Endometriosis stage \> I (stages II, III and IV) according to ASRM classification.
• Atrophic endometrium (\< 6 mm) in the ERA® and/or embryo transfer cycle.
• Endometrial receptivity test and/or microbiome test done before ICF signature.
• Preimplantation Genetic Testing for Chromosomal Structural Rearrangements (PGT-SR) or Preimplantation Genetic Testing for Monogenic Disorders (PGT-M) concomitant indications.
• DuoStim IVF protocol (double ovarian stimulation and two egg retrievals in the same ovarian cycle).
• 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.

Sponsors & Collaborators

• Igenomix: lead

Study Sites (8)

In Vitro Buenos Aires

Buenos Aires, Buenos Aires, C1058 AAL, Argentina

Location

The Fertile Group

Panama City, Panama

Location

Inmater

San Borja, Lima region, 15036, Peru

Location

Ovoclinic Madrid

Madrid, Madrid, 28035, Spain

Location

Ovoclinic Marbella

Marbella, Málaga, 29603, Spain

Location

URE Centro Gutenberg

Málaga, Málaga, 29016, Spain

Location

Vida Recoletas Sevilla

Seville, Sevilla, 41092, Spain

Location

Vida Recoletas Valladolid

Valladolid, 47004, Spain

Location

Biospecimen

Retention: SAMPLES WITH DNA

DNA from endometrial fluid and biopsy to analyze the WOI and the endometrial microbiome. Provided that the patient (or representative) has granted the corresponding authorization, the endometrial biopsy remnants may be used to continue improving knowledge about diseases that affect infertility in related future studies. These samples will be stored at the Igenomix facilities as part of an Official Biological Sample Collection registered in the name of Dr. Carmen Rubio, Vice President of Genetic Services R\&D in Igenomix Research \& Development, (reference code of the collection in the National Biobank Registry of the Instituto de Salud Carlos III: C.0007917).

MeSH Terms

Conditions

Infertility

Condition Hierarchy (Ancestors)

Genital Diseases; Urogenital Diseases

Study Officials

• Maria Ruiz, MSc

  Igenomix

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 18, 2023
• First Posted: October 24, 2023
• Study Start: January 16, 2024
• Primary Completion: April 1, 2026
• Study Completion (Estimated): December 1, 2026
• Last Updated: August 5, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

PA (1); AR (1); PE (1); ES (5)