Frozen Blastocyst Transfer Using Conventional Timing Versus Timing by Endometrial Receptivity Analysis

Study Overview
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Brief Summary
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To assess live birth after embryo transfer according to an individual's ERA results as opposed to routine protocol for frozen embryo transfer (FET) cycles.

Detailed Description
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It has been proposed, that the receptivity status of the endometrium shifts among individual women and that repeated implantation failure is ascribable to an endometrial factor in up to 25%. The endometrial receptivity analysis (ERA) is a diagnostic method that was developed based on the unique genomic signature of the endometrium during the window of implantation and classifies the endometrium as receptive, pre-receptive or post-receptive to guide embryo transfer. The purpose of this assessor-blind, randomized clinical study is to determine whether live birth from vitrified/thawed euploid embryo transfer is improved when transfer is timed according to endometrial receptivity analysis (ERA) results. Approximately 800 women (n=400 in each arm) will be enrolled according to the inclusion/exclusion criteria among patients of Shady Grove Fertility. Participants will undergo a standard in vitro fertilization (IVF) cycle, followed by preimplantation genetic screening (PGS) provided a high quality blastocyst is available. Participants with at least one PGS normal (euploid) embryo will be randomized (assigned by chance, like the flip of a coin) to one of two study groups. Women in both study arms will then undergo ERA testing and neither the patients nor their treating physicians will know to which group the women have been assigned to, or the ERA testing results. Up until this point there is no difference between the study and control group. The investigational aspect of this trial is described as follows: If the participant is assigned to the study arm, the single, euploid, frozen embryo transfer (FET) during the subsequent cycle will be performed at the time indicated by the ERA test results. If she is in the control arm, the embryo will be transferred according to our standard FET protocol. Patients enrolling in the study will receive PGS and ERA free of charge.

Official Title
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A Randomized Controlled Trial Comparing Live Birth From Single, Euploid Frozen Blastocyst Transfer Using Conventional Timing Versus Timing by Endometrial Receptivity Analysis

Conditions
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Infertility, Female, Implantation Failure

Intervention / Treatment
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* Other: FET according to ERA
* Other: FET according to standard protocol


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent Female age between 30 and 40 years and deemed likely by her physician, based on ovarian reserve testing, to produce at least one euploid blastocyst via one IVF/intracytoplasmatic sperm injection (ICSI) cycle Having ≥ 1 euploid embryo available for embryo transfer Standard eligibility criteria to undergo IVF and FET at Shady Grove Fertility Center. Exclusion Criteria: Known uterine factor impacting the endometrium Use of surgically aspirated sperm for fertilization Presence of any clinically relevant systemic disease that contraindicates assisted reproductive technology. Since the subject last had a live birth (if any), there have been more than two embryo transfers that have not resulted in ongoing pregnancy Body mass index >40 kg/m2 at screening Recurrent pregnancy loss, defined as two or more clinical pregnancy losses without live birth Planned testing of embryos for single gene disorder(s) or structural chromosome rearrangements Currently breast feeding, pregnant, or contraindication to pregnancy

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 40 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: FET according to ERA<br>In preparation for frozen embryo transfer (FET), estradiol will be administered for approximately 10 to 14 days or until endometrial criteria are met. These endometrial criteria will be assessed with transvaginal ultrasound and serum estradiol levels. Women will then begin intramuscular progesterone injection and if assigned to the study arm, a single euploid embryo will be transferred at the time indicated by the ERA test results. Merely the timing of embryo transfer will distinguish the study from the control group. | Other: FET according to ERA<br>* Single euploid FET will be performed at the time indicated by the ERA test results.<br>|
| Active Comparator: FET according to standard protocol<br>In preparation for frozen embryo transfer (FET), estradiol will be administered for approximately 10 to 14 days or until endometrial criteria are met. These endometrial criteria will be assessed with transvaginal ultrasound and serum estradiol levels. Women will then begin intramuscular progesterone injection and if assigned to the control arm, a single euploid embryo will be transferred according to our standard FET protocol. | Other: FET according to standard protocol<br>* Single euploid FET will be performed according to our standard FET protocol.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome measure of this clinical trial is to assess live birth after euploid embryo transfer according to an individual's ERA result as opposed to routine protocol for frozen embryo transfer (FET) cycles. |  | From date of randomization until live born infant at an estimated gestational age of at least 23 weeks or greater | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| A secondary outcome measure of this clinical trial is to assess ongoing implantation rate after embryo transfer according to an individual's ERA result as opposed to routine protocol for frozen embryo transfer (FET) cycles. | The ongoing implantation rate is defined as maximum number of fetal heartbeats divided by total number of embryos transferred | From date of randomization until 7-8 weeks estimated gestational age | 
| A secondary outcome measure of this clinical trial is to assess implantation rate after embryo transfer according to an individual's ERA result as opposed to routine protocol for frozen embryo transfer (FET) cycles. | The implantation rate is defined as the maximum number of gestational sacs per patient | From date of randomization until 5-6 weeks estimated gestational age | 
| A secondary outcome measure of this clinical trial is to assess biochemical pregnancy after embryo transfer according to an individual's ERA result as opposed to routine protocol for frozen embryo transfer (FET) cycles. | Biochemical pregnancy is defined as detection of beta hCG above 5 IU/L | From date of randomization until  10 days following embryo transfer | 
| A secondary outcome measure of this clinical trial is to assess clinical pregnancy after embryo transfer according to an individual's ERA result as opposed to routine protocol for frozen embryo transfer (FET) cycles. | The clinical pregnancy rate is defined as the presence of gestational sacs | From date of randomization until 5-7 weeks estimated gestational age | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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WOI, ERA, Endometrial receptivity analysis, Window of implantation, Euploid, Infertility, Female, Implantation failure, Frozen embryo transfer FET, FET, Synchrony