Randomized Controlled Trial Comparing Personalized Embryo Transfer (pET) by the ERA Test Versus Conventional Frozen Embryo Transfer (FET) of Blastocysts in Infertile Women at Their First IVF/ICSI Cycle
试验速览
- 阶段
- 不适用
- 入组人数
- 714
- 试验地点
- 3
- 主要终点
- Live birth rate
研究概览
简要总结
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 to take place.
It has been already demonstrated the existence of transcriptomic profiles that are characteristics of each endometrial phase: pre-receptive, receptive and post-receptive. 'Igenomix' group developed a molecular tool able to classify the endometrium based on its transcriptomic profile, the Endometrial Receptivity Analysis (ERA). This molecular tool analyses, 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 stage. This test has been applied at clinical level from 2010, helping to synchronize a viable embryo with a receptive endometrium through the personalized embryo transfer (pET). It aims to improve clinical implantation by personalizing, diagnosing, and synchronizing the endometrial factor.
Our goal in this project is to investigate at what extent, if any, the analysis of the endometrial factor, at receptivity level, in patients at their first in vitro fertilization (IVF) cycle improves their clinical outcome through a personalized embryo transfer by the ERA test in comparison to embryo transfer(FET).
详细描述
When the transcriptomic signature of human endometrial receptivity was reported, Igenomix developed the ERA, a molecular tool able to diagnose the endometrial receptivity by NGS and a computational predictor. The accuracy of this diagnostic tool has been shown to be superior to endometrial histology, and its results are reproducible 29 to 40 months later.
The ERA test allows to transfer in a personalized manner by synchronizing the embryo with the WOI of the patient. Nowadays, it has been published that around 30% of patients present 1 or 2 days of displacements and about 50% show 12 hours of displacement.
The ERA has been broadly applied around the world in order to increase the probabilities of recurrent implantation failure patients becoming pregnant. Recently, a multicenter international open-label randomized controlled trial comparing personalized embryo transfer guided by the ERA test versus frozen and fresh embryo transfer was carried out at first appointment of infertile patients undergoing IVF. The current project aims to assess in a randomized way the potential improvement on the clinical outcome of Chinese infertile patients at their first IVF cycle by diagnosing, personalizing and synchronizing the endometrial factor with the ERA. To do that, only the outcomes of the first single embryo transfers performed after the inclusion of each patient will be considered.
Considering a 30% of possible drop-outs, a total of 714 patients will be recruited (357 randomized in each group). They will be allocated on a balanced way (assigned by chance like the flip of a coin) in one of the two arms described below. Reproductive outcomes (defined following The International Glossary on Infertility and Fertility Care, 2017) will be compared between the two groups.
Data exported from the source documents will be duly codified and treated in order to protect the clinical and personal information of participants in accordance with the current local legislation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- — 至 37 Years（Child, Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Patients whose written ICF approved by the EC has been obtained, after having been duly informed of the nature of the study and voluntarily accepted to participate after being fully aware of the potential risks, benefits and any discomfort involved.
- •Patients undergoing their first IVF/ICSI cycle (first oocyte pick up, freezing all) with their own oocytes that will receive single embryo transfer of frozen blastocyst stage embryos (day 5/6) on an HRT cycle.
- •At least 2 morphologically good quality embryos already vitrified in blastocyst stage (day 5/6).
- •Maternal Age: ≤37 years to rule out embryo factor in aging patients.
- •BMI: 18.5 - 30.0 kg / m2 (both inclusive).
- •Normal ovarian reserve (defined as: AFC ≥ 8; AMH level ≥1.0 ng/ml and/or FSH < 8 mU/ml) before the controlled ovarian stimulation (COS) initiation.
- •Serum P levels ≤ 1.5 ng/ml, measured within 24 hours before the hCG administration in the COS cycle.
- •Negative serological tests for HIV, HBV, HCV, RPR.
排除标准
- •Patients with repeated miscarriages (> 2 previous biochemical pregnancies or > 2 spontaneous miscarriages).
- •Male partner with severe male factor (spermatozoa < 2 million/ml). Semen donor is allowed.
- •Patients who are intrauterine device (IUD) carriers in the last 3 months before sample collection.
- •Adenomyosis or any pathological finding affecting the endometrial cavity such as polyps/sub-mucosal myomas, intramural myomas > 4 cm, or hydrosalpinx must be previously operated at least 3 months before the endometrial samples are obtained. (Note: Patients are allowed to participate if the pathology is corrected before performing any study procedure).
- •Embryos analysed using preimplantation genetic testing for aneuploidies (PGT-A).
- •Any illness or medical condition that is unstable or affect the safety of the patient and compliance of the study.
研究组 & 干预措施
Intervention group(pET)
Personalized embryo transfer of a single vitrified blastocyst in a HRT cycle according to the ERA test results.
干预措施: ERA (Diagnostic Test)
Control group(FET)
Frozen embryo transfer of a single vitrified blastocyst in a HRT cycle according to the clinical standard practice.
干预措施: ERA (Diagnostic Test)
结局指标
主要结局
Live birth rate
时间窗: From date of embryo transfer until 40 weeks
The number of deliveries that resulted in at least one live birth per ET (transferred patient). Live birth is defined as the complete expulsion or extraction from a woman of a product of conception after 22 weeks of gestation, which, after such separation, breathes or shows any other evidence of life, such as heartbeat, umbilical cord pulsation or definite movement of voluntary muscles, irrespective of whether the umbilical cord has been cut or the placenta is attached.
次要结局
- Incidence of WOI displacement in the study population(From date of randomization until 1-2 months)
- Biochemical pregnancy rate(From date of embryo transfer until 5-6 weeks)
- Obstetric complications(From date of embryo transfer until 40 weeks)
- Implantation rate(From date of embryo transfer until 5-6 weeks)
- Clinical miscarriage rate(From date of embryo transfer until 20 weeks)
- Ectopic pregnancy rate(From date of embryo transfer until 8 weeks)
- Delivery complications(From date of embryo transfer until 40 weeks)
- pregnancy rate(From date of embryo transfer until 2 weeks)
- Cost-effectiveness between pET and FET groups(2 years)