RCT to Assess the Clinical Benefit of the ERA Test in Infertile Women at Their First IVF/ICSI Cycle

Not Applicable

• Conditions: IVF/ICSI; Infertility, Female
• Interventions: Diagnostic Test: ERA

• Registration Number: NCT04687670
• Lead Sponsor: Peking University Third Hospital

Brief Summary

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).

Detailed Description

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.

All the statistical analysis performed on the data, as well as the procedures, will be registered in a detailed Statistical Analysis Plan (SAP) that will be developed during the study and before starting data analysis.

An interim analysis of this data is planned once 50% of the recruitment has been achieved. Besides and at that same moment, the study will be overseen by an independent Data Monitoring Committee.

All the statistical procedures will be done systematically by both, intention to treat analysis (ITT) and per protocol analysis (PP). The ITT analysis will include all randomized patients recruited and assigned to one of two groups after endometrial biopsy collection. The PP analysis will be applied to those patients who adequately follow the protocol assigned according to their group and arm and in whom the transfer of the good quality blastocyst is performed.

Study Timeline

• Study First Submitted: 2020-12-18
• Study First Submitted QC: 2020-12-23
• Study First Posted: 2020-12-29
• Status Verified: 2021-04
• Last Update Submitted: 2021-07-05
• Last Update Posted: 2021-07-08
• Study Start: 2021-08
• Primary Completion: 2023-03
• Study Completion: 2023-04

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 714

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Control group(FET)	ERA	Frozen embryo transfer of a single vitrified blastocyst in a HRT cycle according to the clinical standard practice.
Intervention group(pET)	ERA	Personalized embryo transfer of a single vitrified blastocyst in a HRT cycle according to the ERA test results.

Primary Outcome Measures

Name	Time	Method
Live birth rate	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.

Secondary Outcome Measures

Name	Time	Method
Incidence of WOI displacement in the study population	From date of randomization until 1-2 months	Number of patients with the WOI displaced during their participation
Biochemical pregnancy rate	From date of embryo transfer until 5-6 weeks	Number of pregnancies diagnosed only by βhCG detection without a gestational sac visualized by vaginal ultrasound at the 5th week of pregnancy, per number of pregnancies.
Obstetric complications	From date of embryo transfer until 40 weeks	Type and number of obstetric complications during pregnancy
Implantation rate	From date of embryo transfer until 5-6 weeks	The number of gestational sacs observed by vaginal ultrasound at the 5th gestational week divided by the number of embryos transferred.
Clinical miscarriage rate	From date of embryo transfer until 20 weeks	Number of spontaneous pregnancy losses in which a gestational sac/s was previously observed, per number of pregnancies.
Ectopic pregnancy rate	From date of embryo transfer until 8 weeks	Number of pregnancies outside the uterine cavity, diagnosed by ultrasound, surgical visualization or histopathology, per number of pregnancies.
Delivery complications	From date of embryo transfer until 40 weeks	Type and number of delivery complications
pregnancy rate	From date of embryo transfer until 2 weeks	Pregnancy rate is the number of patients with positive serum level of beta-HCG per embryo transfer.
Cost-effectiveness between pET and FET groups	2 years	To estimate the average cost per patient in each treatment to achieve a live newborn.

Trial Locations

Locations (3)

Northwest Women's and Children's Hospital; 🇨🇳 Xi'an, Shaanxi, China

Renji Hospital; 🇨🇳 Shanghai, China

Peking University Third Hospital; 🇨🇳 Beijing, China