Implantation FailureSynchronyNCT03558399
Frozen Blastocyst Transfer Using Conventional Timing Versus Timing by Endometrial Receptivity Analysis
A study testing FET according to ERA and FET according to standard protocol in people with Implantation Failure and Infertility, Female, run by Shady Grove Fertility Reproductive Science Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 30 to 40 years, women only
- Conditions the study is for
- Implantation Failure, Infertility, Female
- What is being tested?
- FET according to ERA and FET according to standard protocol
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 800 participants
- Where
- 1 siteUnited States
- Study dates
- 25 Apr 2018to 23 Sep 2021
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 30 to 40 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
Shady Grove Fertility Reproductive Science Center
Rockville, Maryland, 20850
About this study
Official title: A Randomized Controlled Trial Comparing Live Birth From Single, Euploid Frozen Blastocyst Transfer Using Conventional Timing Versus Timing by Endometrial Receptivity Analysis
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.
Read the 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.
- Conditions
- Implantation Failure, Infertility, Female
- Being tested
- FET according to ERA, FET according to standard protocol
- Keywords
- Endometrial receptivity analysis, Window of implantation, Euploid, Infertility, Female, Implantation failure, Frozen embryo transfer FET, ERA, WOI, FET, Synchrony
- Medical subject headings
- Infertility, Female
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
FET according to ERAOther
Single euploid FET will be performed at the time indicated by the ERA test results.
FET according to standard protocolOther
Single euploid FET will be performed according to our standard FET protocol.
| Study group | Role | What they receive |
|---|---|---|
| FET according to ERA | Experimental | 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. Receives: Other: FET according to ERA |
| FET according to standard protocol | Active comparator | 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. Receives: Other: FET according to standard protocol |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: From date of randomization until live born infant at an estimated gestational age of at least 23 weeks or greater
Secondary outcomes (4)
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
Measured: 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
Measured: 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
Measured: 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
Measured: From date of randomization until 5-7 weeks estimated gestational age
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Jun 2018
- Study start25 Apr 2018
- Primary completion23 Sep 2021 (estimated)
- Study completion23 Sep 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Implantation FailureStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 800 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Shady Grove Fertility Reproductive Science Center
- Sponsor type
- University, hospital or other
- Collaborators
- Igenomix
- Responsible party
- Sponsor
- Investigators
- Kathleen Devine, MD, Principal investigator, Shady Grove Fertility
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03558399
- Sponsor's protocol ID
- 1183343
- Acronym
- Synchrony
- Status last verified
- Dec 2020
- First submitted
- 25 Apr 2018
- Last updated
- 3 Dec 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 23756099Katzorke 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.
PubMed 27365540Horcajadas 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.
PubMed 16960016Ponnampalam 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.
PubMed 15501903Galliano D, Pellicer A. MicroRNA and implantation. Fertil Steril. 2014 Jun;101(6):1531-44. doi: 10.1016/j.fertnstert.2014.04.023.
PubMed 24882617Ruiz-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.
PubMed 22634130Doyle N, Jahandideh S, Hill MJ, Widra EA, Levy M, Devine K. Effect of Timing by Endometrial Receptivity Testing vs Standard Timing of Frozen Embryo Transfer on Live Birth in Patients Undergoing In Vitro Fertilization: A Randomized Clinical Trial. JAMA. 2022 Dec 6;328(21):2117-2125. doi: 10.1001/jama.2022.20438.
PubMed 36472596
Study at a glance
From the registry record, last updated by the sponsor on 3 Dec 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Controlled Trial Comparing Live Birth From Single, Euploid Frozen Blastocyst Transfer Using Conventional Timing Versus Timing by Endometrial Receptivity Analysis
- ClinicalTrials.gov ID
- NCT03558399
- Acronym / sponsor ID
- Synchrony / 1183343
- Conditions
- Implantation Failure, Infertility, Female
- Keywords
- Endometrial receptivity analysis, Window of implantation, Euploid, Infertility, Female, Implantation failure, Frozen embryo transfer FET, ERA, WOI
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 800 participants (estimated)
- Lead sponsor
- Shady Grove Fertility Reproductive Science CenterUniversity, hospital or other
- Collaborators
- Igenomix
- Study start
- 25 Apr 2018 (actual)
- Primary completion
- 23 Sep 2021 (estimated)
- Study completion
- 23 Sep 2021 (estimated)
- First posted
- 15 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Diagnosis
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| FET according to ERA | Experimental | Other: FET according to ERAIn 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. |
| FET according to standard protocol | Active comparator | Other: FET according to standard protocolIn 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. |
Who may qualify
- Ages
- 30 to 40 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (4 listed)
- 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.
Key exclusion criteria (8 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| FET according to ERASingle euploid FET will be performed at the time indicated by the ERA test results. | Other | FET according to ERA |
| FET according to standard protocolSingle euploid FET will be performed according to our standard FET protocol. | Other | FET according to standard protocol |
Primary outcome
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.
Time frame: From date of randomization until live born infant at an estimated gestational age of at least 23 weeks or greater
4 secondary outcomes
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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: From date of randomization until 5-7 weeks estimated gestational age
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 3 Dec 2020.
- Background: PubMed 23756099Ruiz-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.
- Background: PubMed 27365540Katzorke 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.
- Background: PubMed 16960016Horcajadas 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.
- Background: PubMed 15501903Ponnampalam 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.
- Background: PubMed 24882617Galliano D, Pellicer A. MicroRNA and implantation. Fertil Steril. 2014 Jun;101(6):1531-44. doi: 10.1016/j.fertnstert.2014.04.023.
- Background: PubMed 22634130Ruiz-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.
- Derived from this study: PubMed 36472596Doyle N, Jahandideh S, Hill MJ, Widra EA, Levy M, Devine K. Effect of Timing by Endometrial Receptivity Testing vs Standard Timing of Frozen Embryo Transfer on Live Birth in Patients Undergoing In Vitro Fertilization: A Randomized Clinical Trial. JAMA. 2022 Dec 6;328(21):2117-2125. doi: 10.1001/jama.2022.20438.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathleen Devine, MD principal investigator
Shady Grove Fertility
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing FET according to ERA and FET according to standard protocol in people with Implantation Failure and Infertility, Female, run by Shady Grove Fertility Reproductive Science Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 3 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome 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. (time frame: From date of randomization until live born infant at an estimated gestational age of at least 23 weeks or greater). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03558399, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 3 Dec 2020.