A Multicenter, Prospective, Non-selection Study for Endometrial Receptivity Analysis Test in Patients With Previous Implantation Failures
试验速览
- 阶段
- 不适用
- 状态
- 进行中（未招募）
- 发起方
- Igenomix
- 入组人数
- 738
- 试验地点
- 8
- 主要终点
- Refinement of the ERA® computational analysis
研究概览
简要总结
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.
详细描述
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:
- 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. This may help to fine-tune the ERA computational analysis for some specific endometrial receptivity profiles.
- 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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 41 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •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/m
- •Negative serological tests for HIV, HBV, HCV, RPR.
排除标准
- •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).
- •Active endometritis and salpingitis at the moment of the inclusion.
- •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.
结局指标
主要结局
Refinement of the ERA® computational analysis
时间窗: At least 12 gestational weeks
Comparison of the OPR (≥ 12 gestational weeks; fetal heartbeat diagnosis) in patients with receptive endometrium vs displaced WOI in the 1st FET.
次要结局
- Biochemical pregnancy rate (BPR) in the FET(4 weeks after the embryo transfer)
- Pregnancy rate (PR) in the FET(2 weeks after the embryo transfer)
- Ongoing Pregnancy Rate (OPR) in the FET(Over 12 gestational weeks)
- Pregnancy rate (PR) in the pET(2 weeks after the embryo transfer)
- Clinical reproductive outcomes according to the microbiome profile by the EMMA® test(Up to 40 gestational weeks)
- Implantation rate (IR) in the FET(Up to 4 weeks after the embryo transfer)
- Implantation rate (IR) in the pET(Up to 4 weeks after the embryo transfer)
- Biochemical pregnancy rate (BPR) in the pET(4 weeks after the embryo transfer)
- Clinical miscarriage rate (CMR) in the pET(Up to 22 gestational weeks)
- 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)
- Live Birth Delivery Rate (LBDR) in the FET(40 gestational weeks)
- Ongoing Pregnancy Rate (OPR) in the pET(Over 12 gestational weeks)
- Identification of new potential actionable biomarkers for endometrial receptivity(1-2 months)
- Ectopic pregnancy rate (EPR) in the pET(4-5 weeks after the embryo transfer)
- Microbiome analysis concordance between endometrial fluid and biopsy(1-2 months)
- Cost-effectiveness of OP per patient(At least 12 gestational weeks)
- Determination of immune and metabolic changes related to endometrial receptivity(1-2 months)