The ERA Test as a Diagnostic Guide for Personalized Embryo Transfer (ERA RCT)

Clinical Study, International, Multicentre, Prospective, Randomised, Interventional and Controlled, Comparing Fresh Embryo Transfer (ET) Versus Frozen Embryo Transfer (FET) and Personalised Embryo Transfer (pET) Guided by the ERA (Endometrial Receptivity Analysis) Test as a Diagnostic Tool in Patients Treated by IVF/ICSI (in Vitro Fertilisation; Intra-cytoplasmic Sperm Injection)

This project seeks to demonstrate the clinical value of the personalised diagnosis of the endometrial factor in infertility.

Study Overview

• Status: Completed
• Conditions: Endometrial Receptivity
• Intervention / Treatment: Other: personalized Embryo Transfer (pET); Other: Frozen Embryo Transfer (FET); Other: Fresh Embryo Transfer (ET)

Detailed Description

This project seeks to investigate differences in implantation (IR), pregnancy (PR), ongoing pregnancy (OP) rates, miscarriages, deliveries (LB) and obstetrical, delivery and neonatal outcomes among women undergoing IVF treatment with own oocytes, at first site appointment (up to 3 previous implantation failures in other sites) and blastocyst stage (day 5 or 6). Patients are allocated through computer-generated randomization into one of the three groups: Fresh embryo transfer (ET), Frozen embryo transfer (FET) or personalized embryo transfer (pET) after identification of the personalized window of implantation using the endometrial receptivity analysis (ERA) test, all of them following the usual clinical practice in a same-cycle embryo transfer.

A total of 546 infertile women under 38 years old undergoing her first IVF/ICSI cycle with elective blastocyst transfer are randomized in this prospective, multicenter, open label and controlled trial.

• Study Type: Interventional
• Enrollment (Actual): 569
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium, 1090
    • Centre of Reproductive Medicine UZ Brussles
• Brazil
  • Sao Paulo, Brazil
    • Centro de Reprodução Governador Mario Covas
  • Rio De Janeiro
    • Campos dos Goytacazes, Rio De Janeiro, Brazil, 28035-210
      • Centro de Infertilidade e Medicina Fetal do Norte Fluminence
  • Rio Grande Del Sur
    • Porto Alegre, Rio Grande Del Sur, Brazil
      • Centro de Reproduçao Humana Nilo Frantz
• Bulgaria
  • Sofia, Bulgaria, 1000
    • Sofia Hospital of Reproductive Medicine - SBALAGRM
• Japan
  • Osaka, Japan, 557-0045
    • Oak Clinic Sumiyoshi
• Panama
  • Panama, Panama, 0819
    • IVI Panama
• Spain
  • Alicante, Spain, 03015
    • IVI Alicante
  • Barcelona, Spain, 08017
    • IVI Barcelona
  • Madrid, Spain, 28036
    • ProcreaTec
  • Sevilla, Spain, 41011
    • IVI Sevilla
  • Valencia, Spain, 46015
    • IVI Valencia
  • Bizkaia
    • Leioa, Bizkaia, Spain, 48940
      • IVI Bilbao
  • Madrid
    • Aravaca, Madrid, Spain, 24527
      • IVI Madrid
  • Pontevedra
    • Vigo, Pontevedra, Spain, 36203
      • IVI Vigo
• Turkey
  • Istanbul, Turkey, 34500
    • Bahceci Health Group

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years to 33 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

1. Patients indicated to undergo a cycle of IVF/ICSI with their own oocytes.
2. Age ≤ 37 years
3. BMI: 18.5 to 30
4. Normal ovarian reserve (AFC ≥ 8; FSH < 8)
5. The most appropriated stimulation protocol will be decided by their doctor.
6. Blastocyst transfer (on day 5 or 6)
7. Blastocyst vitrification with open protocols (Cryotop, Cryoleaf, or Cryolock) or closed protocols (Cryotip or CBSStraw.)
8. Any pathology affecting the endometrial cavity such as polyps/sub-mucosal myomas, intramural myomas > 4 cm, or hydrosalpinx affecting the endometrial cavity must be previously operated.

Exclusion Criteria:

1. Patients with recurrent miscarriages (> 2 previous biochemical pregnancies or > 2 spontaneous miscarriages)
2. Patients with a severe male factor (spermatozoa < 2 million/ml)
3. Patients with implantation failure (>3 failed cycles with good quality embryos)

Post-Randomization Exclusion Criteria:

1. Endogenous progesterone level ≥ 1,5 ng/ml at the day of hCG administration in all groups.
2. Absence of blastocysts (day 5 or 6) for embryo transfer.
3. Risk of ovarian hyperstimulation syndrome in any of the three groups and therefore a clinical indication to cancel the transfer cycle where the stimulated patient is from group A (ET).

Note: PGT-A is not an inclusion criteria neither an exclusion criteria, therefore those cycles in which PGT-A was performed will be included

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Personalized embryo transfer (pET); Patients will undergo a cycle of endometrial preparation following hormone replacement therapy (HRT) and an endometrial biopsy in a substituted cycle after 5 days (around 120 hours) of progesterone administration. The ERA test will determine the window of implantation (WOI) for each patient and will recommend the best time for embryo transfer thereby increasing the chances of a successful outcome. In some specific cases (≤ 10%) a second biopsy will be required to help the bioinformatic predictor to ensure the most appropriated moment for the embryo transfer. In a different cycle, patients will undergo a cycle of controlled ovarian stimulation (COS) to obtain oocytes which will be fertilized by IVF/ICSI and vitrified. In a subsequent cycle, following the ERA result, a personalized embryo transfer (pET) will be carried out following the same conditions in which the ERA test was obtained, using 1 or 2 viable blastocysts previously obtained (day 5 or 6 stage)	Other: personalized Embryo Transfer (pET)
Active Comparator: Frozen embryo transfer (FET); Patients will undergo a cycle of controlled ovarian stimulation (COS) to obtain oocytes which will be fertilized by IVF/ICSI. In a subsequent cycle, following hormone replacement therapy (HRT), a frozen embryo transfer (FET) will be performed using 1 or 2 viable blastocysts previously obtained (day 5 or 6 stage).	Other: Frozen Embryo Transfer (FET)
Active Comparator: Fresh embryo transfer (ET); Patients will undergo a controlled ovarian stimulation cycle (COS) to obtain oocytes which will be fertilized by IVF/ICSI. In the same cycle, a fresh embryo transfer will be performed using 1 or 2 viable blastocysts previously obtained (day 5 or 6 stage).	Other: Fresh Embryo Transfer (ET)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Live birth delivery rate	Percentage of deliveries that resulted in at least one live birth per embryo transfer.	40 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Implantation rate	The percentage of gestational sacs observed divided by the number of embryos transferred	12 weeks
Pregnancy rate	The percentage of positive pregnancy test divided by the number of embryo transfers	20 weeks
Biochemical pregnancies	A pregnancy diagnosed only by the detection of beta hCG in serum	20 weeks
Ectopic pregnancies	A pregnancy outside the uterine cavity, diagnosed by ultrasound, surgical visualization or histopathology	20 weeks
Clinical miscarriages	Spontaneous loss of a clinical pregnancy before 20 completed weeks of gestational age	20 weeks
Cumulative pregnancy rate	Cumulative pregnancy rate in the 12 months after the first study embryo transfer	12 months
Cumulative implantation rate	Cumulative implantation rate in the 12 months after the first study embryo transfer	12 months
Cumulative live birth delivery rate	Cumulative live birth delivery rate per embryo transfer in the 12 months after the first study embryo transfer	12 months

Collaborators and Investigators

• Sponsor: Igenomix
• Investigators: Principal Investigator: Carlos Simon, MDPhD, IVI Valencia / Igenomix

Publications and helpful links

General Publications

• Katzorke N, Vilella F, Ruiz M, Krussel JS, Simon C. Diagnosis of Endometrial-Factor Infertility: Current Approaches and New Avenues for Research. Geburtshilfe Frauenheilkd. 2016 Jun;76(6):699-703. doi: 10.1055/s-0042-103752.

Study record dates

Study Major Dates

• Study Start (Actual): November 25, 2013
• Primary Completion (Actual): August 31, 2018
• Study Completion (Actual): August 31, 2018

Study Registration Dates

• First Submitted: September 26, 2013
• First Submitted That Met QC Criteria: October 4, 2013
• First Posted (Estimate): October 7, 2013

Study Record Updates

• Last Update Posted (Actual): February 27, 2019
• Last Update Submitted That Met QC Criteria: February 26, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Frozen embryo transfer; Window of implantation; Personalized embryo transfer; Fresh embryo transfer; Delayed embryo transfer; Elective deferred embryo transfer; Endometrial receptivity array; Endometrial receptivity analysis; Endometrial receptivity test
• Other Study ID Numbers: 1304-C-107-CS

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No