Clinical trial NCT03558399: Frozen Blastocyst Transfer Using Conventional Timing Versus Timing by Endometrial Receptivity Analysis
Official title: A Randomized Controlled Trial Comparing Live Birth From Single, Euploid Frozen Blastocyst Transfer Using Conventional Timing Versus Timing by Endometrial Receptivity Analysis
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Implantation Failure
Infertility, Female
Keywords: Endometrial receptivity analysis
Window of implantation
Euploid
Infertility, Female
Implantation failure
Frozen embryo transfer FET
ERA
WOI
FET
Synchrony
Lead sponsor: Shady Grove Fertility Reproductive Science Center
Sponsor class: OTHER
Collaborators: name: Igenomix
First posted: 2018-06-15
Enrollment: 800
Sex: FEMALE
Minimum age (years): 30
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: DIAGNOSTIC

Brief summary: 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: 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.

Eligibility criteria: Inclusion Criteria:

1. Signed informed consent
2. 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
3. Having ≥ 1 euploid embryo available for embryo transfer
4. Standard eligibility criteria to undergo IVF and FET at Shady Grove Fertility Center.

Exclusion Criteria:

1. Known uterine factor impacting the endometrium
2. Use of surgically aspirated sperm for fertilization
3. Presence of any clinically relevant systemic disease that contraindicates assisted reproductive technology.
4. 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
5. Body mass index \>40 kg/m2 at screening
6. Recurrent pregnancy loss, defined as two or more clinical pregnancy losses without live birth
7. Planned testing of embryos for single gene disorder(s) or structural chromosome rearrangements
8. Currently breast feeding, pregnant, or contraindication to pregnancy

Primary outcomes:
measure: 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.
timeFrame: From date of randomization until live born infant at an estimated gestational age of at least 23 weeks or greater
Secondary outcomes:
measure: 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.
timeFrame: From date of randomization until 7-8 weeks estimated gestational age
measure: 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.
timeFrame: From date of randomization until 5-6 weeks estimated gestational age
measure: 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.
timeFrame: From date of randomization until ~10 days following embryo transfer
measure: 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.
timeFrame: From date of randomization until 5-7 weeks estimated gestational age
Other outcomes:
Locations:
city: Rockville
country: United States
facility: Shady Grove Fertility Reproductive Science Center
state: Maryland
Study officials:
affiliation: Shady Grove Fertility
name: Kathleen Devine, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Ruiz-Alonso M, Blesa D, Diaz-Gimeno P, Gomez E, Fernandez-Sanchez M, Carranza F, Carrera J, Vilella F, Pellicer A, Simon C. The endometrial receptivity array for diagnosis and personalized embryo transfer as a treatment for patients with repeated implantation failure. Fertil Steril. 2013 Sep;100(3):818-24. doi: 10.1016/j.fertnstert.2013.05.004. Epub 2013 Jun 4.
citation: 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.
citation: Horcajadas JA, Pellicer A, Simon C. Wide genomic analysis of human endometrial receptivity: new times, new opportunities. Hum Reprod Update. 2007 Jan-Feb;13(1):77-86. doi: 10.1093/humupd/dml046. Epub 2006 Sep 7.
citation: Ponnampalam AP, Weston GC, Trajstman AC, Susil B, Rogers PA. Molecular classification of human endometrial cycle stages by transcriptional profiling. Mol Hum Reprod. 2004 Dec;10(12):879-93. doi: 10.1093/molehr/gah121. Epub 2004 Oct 22.
citation: Galliano D, Pellicer A. MicroRNA and implantation. Fertil Steril. 2014 Jun;101(6):1531-44. doi: 10.1016/j.fertnstert.2014.04.023.
citation: Ruiz-Alonso M, Blesa D, Simon C. The genomics of the human endometrium. Biochim Biophys Acta. 2012 Dec;1822(12):1931-42. doi: 10.1016/j.bbadis.2012.05.004. Epub 2012 May 24.