The ERA Test as a Diagnostic Guide for Personalized Embryo Transfer

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

Detailed Description
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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.

Official Title
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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)

Conditions
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Endometrial Receptivity

Intervention / Treatment
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* Other: personalized Embryo Transfer (pET)
* Other: Frozen Embryo Transfer (FET)
* Other: Fresh Embryo Transfer (ET)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients indicated to undergo a cycle of IVF/ICSI with their own oocytes. Age ≤ 37 years BMI: 18.5 to 30 Normal ovarian reserve (AFC ≥ 8; FSH < 8) The most appropriated stimulation protocol will be decided by their doctor. Blastocyst transfer (on day 5 or 6) Blastocyst vitrification with open protocols (Cryotop, Cryoleaf, or Cryolock) or closed protocols (Cryotip or CBSStraw.) 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: Patients with recurrent miscarriages (> 2 previous biochemical pregnancies or > 2 spontaneous miscarriages) Patients with a severe male factor (spermatozoa < 2 million/ml) Patients with implantation failure (>3 failed cycles with good quality embryos) Post-Randomization Exclusion Criteria: Endogenous progesterone level ≥ 1,5 ng/ml at the day of hCG administration in all groups. Absence of blastocysts (day 5 or 6) for embryo transfer. 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 37 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Personalized embryo transfer (pET)<br>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)<br> <br> |
| Active Comparator: Frozen embryo transfer (FET)<br>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)<br> <br> |
| Active Comparator: Fresh embryo transfer (ET)<br>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)<br> <br> |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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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, Frozen embryo transfer