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

Last updated: February 16, 2024
Sponsor: Igenomix
Overall Status: Active - Recruiting

Phase

N/A

Condition

Infertility

Treatment

Endometrial fluid and biopsy collection

Clinical Study ID

NCT06097559
IGX1-ENS-MR-22-05
  • Ages 18-37
  • Female
  • Accepts Healthy Volunteers

Study 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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • Study ICF signature.
  • Female age between 18 and 37 years (both included).
  • IVF/ICSI patients with ≥1 previous failed euploid embryo transfer(s) or ≥2 previousfailed transfers with non-tested good quality embryos.
  • Blastocyst tested by PGT-A.
  • BMI 18.0 - 30.0 Kg/m2.
  • Normal ovarian reserve (Antral Follicle Count, AFC ≥ 8, Anti-Müllerian Hormone, AMH ≥ 1.0 ng/ml and/or Follicle-Stimulating Hormone, FSH ≤ 8 mU/mL) before starting theControlled Ovarian Stimulation (COS) cycle.
  • Negative serological tests for HIV, HBV, HCV, RPR.

Exclusion

Exclusion Criteria:

  • No euploid/low-range mosaic blastocysts (day 5/6), from own or donated gametes, for aFET. Notes:
  • Only one COS and PGT-A will be allowed per patient.
  • Low-range mosaic embryos (< 50% of mosaic cells) could be considered for transferfollowing the international recommendations (ASRM and ESHRE) and the clinicalstandard routine at the participant center.
  • Reception of Oocytes from Partner -ROPA- method is allowed.
  • Double embryo transfer is allowed by medical indication as long as bothblastocysts are transferred at once.
  • 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 aspolyps/sub-mucosal myomas, intramural myomas > 4 cm, or hydrosalpinx. (Note: Patientsare allowed to participate if the pathology is previously operated at least 3 monthsbefore the endometrial samples are obtained).
  • Recurrent Pregnancy Loss (RPL ≥2 previous intrauterine miscarriages).
  • Endometritis and salpingitis.
  • 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) orPreimplantation Genetic Testing for Monogenic Disorders (PGT-M) concomitantindications.
  • DuoStim IVF protocol (double ovarian stimulation and two egg retrievals in the sameovarian cycle).
  • Any illness or medical condition that is unstable or which, according to medicalcriteria, may put at risk the patient's safety and her compliance in the study.

Study Design

Total Participants: 738
Treatment Group(s): 1
Primary Treatment: Endometrial fluid and biopsy collection
Phase:
Study Start date:
January 16, 2024
Estimated Completion Date:
December 31, 2026

Study Description

Endometrial receptivity takes place in a self-limited period of time during the endometrial mid-secretory stage. This period, named as window of implantation (WOI), is modulated by molecular changes allowing embryo implantation. The Igenomix group developed a molecular tool able to classify the endometrium based on its transcriptomic profile, the Endometrial Receptivity Analysis (ERA®). This molecular tool analyzes, by next generation sequencing (NGS), the expression of 248 genes related to implantation, coupled to a computational predictor, to identify the specific transcriptomic profile for each endometrial phase. This test has been applied clinically since 2010 to improve clinical implantation, helping to synchronize a viable embryo with a receptive endometrium through the personalized embryo transfer (pET).

Apart from receptivity, there are other approaches to study the impact of the endometrial factor in infertility. One of those is the analysis of the endometrial microbiome (set of microorganisms that live in the endometrium). A reduced presence of certain beneficial microorganisms (mostly, bacteria of the genus Lactobacillus) or even the presence of a pathogenic microbiota in the endometrium could be associated with worse reproductive outcomes, affecting embryo implantation, pregnancy and consequently reducing the number of births. Igenomix has also developed the Endometrial Microbiome Metagenomic Analysis (EMMA®) as a diagnostic method to assess the microbiome content of the endometrium. Both, ERA® and EMMA® analyses, can be performed with a single endometrial tissue sample collected when maximum receptivity is commonly expected.

The main questions this study aims to answer are:

  1. If a pET in a specific receptive endometrial transcriptomic profile is related to a higher Ongoing Pregnancy Rate (OPR) (≥ 12 gestational weeks; fetal heartbeat diagnosis) in patients with at least one previous implantation failure.

  2. To identify new potential biomarkers and other factors that, if related with the WOI, could help to predict an optimal embryo implantation.

Once the study is approved by the competent Research Ethics Committee of each center, the recruitment and selection of patients will follow. Every potential participant will be asked to sign the study informed consent. To comply with the study design and the proposed hypothesis, a total number of 738 patients has been estimated, considering a 30% dropout rate.

This is a multicenter, international, competitive, non-selection (prospective cohort) study designed with two phases:

  • Non-selection phase (double-blinded design). Participants will follow their previously programmed IVF/ICSI treatment and the resulting embryo/s will be tested for chromosomic anomalies with the Preimplantation Genetic Testing for Aneuploidies (PGT-A) at Igenomix. When at least one euploid/low-range mosaic blastocyst is reported, the patient will be scheduled for the only additional visit related to the study to collect the endometrial fluid and biopsy samples that 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. Therefore, regardless of the endometrial status, the patient will follow the pre-established schedule for a subsequent regular frozen embryo transfer (FET) within the standard WOI (after 120±6 hours of progesterone exposure) in a hormone replacement therapy (HRT) cycle. After the FET, participants will be followed up as routine by their gynecologist.

  • Rescue phase (open design). The ERA® test result may be disclosed, under request, to those patients who did not achieve an ongoing pregnancy on the non-selection phase. These results could guide a subsequent personalized euploid/low-range mosaic blastocyst transfer (pET) in a new HRT cycle, when the patient is most receptive.

Data exported from the medical records and source documents will be duly codified to protect the clinical and personal information of patients in accordance with the current legislation on data protection. This information will be exported to an electronic Case Report Form (eCRF). An interim data analysis will be carried out once the 30% of the embryo transfers corresponding to the non-selection phase is achieved. It will help us to assess the enrollment rate, protocol compliance and an early evaluation of the study objectives.

Patient´s participation will comprise an estimated total time of up to 18 months, corresponding to 1 month for the stimulation cycle and PGT-A, 1-2 months for endometrial samples collection, 1-2 months for the embryo transfer and up to 13 months to follow-up the clinical outcomes.

Connect with a study center

  • WeFIV

    Buenos Aires, C1428
    Argentina

    Site Not Available

  • Nilo Frantz - Centro de Reprodução Humana

    Boa Vista, Porto Alegre 91330-002
    Brazil

    Site Not Available

  • The Fertile Group

    Panama City,
    Panama

    Active - Recruiting

  • Inmater

    San Borja, Lima 15036
    Peru

    Site Not Available

  • Instituto de Fertilidad Viamed

    Sevilla, Andalucía 41013
    Spain

    Site Not Available

  • Hospital Quirónsalud Málaga

    Málaga, 29004
    Spain

    Site Not Available

  • Vida Recoletas Valladolid

    Valladolid, 47004
    Spain

    Active - Recruiting

  • Orchid IVF Clinic

    Dubai,
    United Arab Emirates

    Site Not Available

  • Lister Fertility Clinic at The Portland Hospital

    London,
    United Kingdom

    Site Not Available

  • Arizona Center for Fertility Studies

    Phoenix, Arizona 85260
    United States

    Active - Recruiting

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