The ERA Test as a Diagnostic Guide for Personalized Embryo Transfer

Not Applicable

Completed

• Conditions: Endometrial Receptivity
• Interventions: Other: Frozen Embryo Transfer (FET); Other: personalized Embryo Transfer (pET); Other: Fresh Embryo Transfer (ET)

• Registration Number: NCT01954758
• Lead Sponsor: Igenomix

Brief Summary

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

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 Timeline

• Study First Submitted: 2013-09-26
• Study First Submitted QC: 2013-10-04
• Study First Posted: 2013-10-07
• Study Start: 2013-11-25
• Primary Completion: 2018-08-31
• Study Completion: 2018-08-31
• Status Verified: 2019-02
• Last Update Submitted: 2019-02-26
• Last Update Posted: 2019-02-27

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 569

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Frozen embryo transfer (FET)	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).
Personalized embryo transfer (pET)	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)
Fresh embryo transfer (ET)	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).

Primary Outcome Measures

Name	Time	Method
Live birth delivery rate	40 weeks	Percentage of deliveries that resulted in at least one live birth per embryo transfer.

Secondary Outcome Measures

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

Trial Locations

Locations (16)

IVI Panama; 🇵🇦 Panama, Panama

IVI Madrid; 🇪🇸 Aravaca, Madrid, Spain

IVI Barcelona; 🇪🇸 Barcelona, Spain

IVI Alicante; 🇪🇸 Alicante, Spain

ProcreaTec; 🇪🇸 Madrid, Spain

IVI Sevilla; 🇪🇸 Sevilla, Spain

IVI Valencia; 🇪🇸 Valencia, Spain

Centre of Reproductive Medicine UZ Brussles; 🇧🇪 Brussels, Belgium

Centro de Reproduçao Humana Nilo Frantz; 🇧🇷 Porto Alegre, Rio Grande Del Sur, Brazil

Centro de Reprodução Governador Mario Covas; 🇧🇷 Sao Paulo, Brazil

IVI Vigo; 🇪🇸 Vigo, Pontevedra, Spain

Sofia Hospital of Reproductive Medicine - SBALAGRM; 🇧🇬 Sofia, Bulgaria

Oak Clinic Sumiyoshi; 🇯🇵 Osaka, Japan

Bahceci Health Group; 🇹🇷 Istanbul, Turkey

IVI Bilbao; 🇪🇸 Leioa, Bizkaia, Spain

Centro de Infertilidade e Medicina Fetal do Norte Fluminence; 🇧🇷 Campos dos Goytacazes, Rio De Janeiro, Brazil