PRogrammed Versus Modified Natural Cycle After Euploid Failed Embryo Transfer (PREFER)

February 4, 2025 updated by: Reproductive Medicine Associates of New Jersey

PREFER: PRogrammed Versus Modified Natural Cycle After Euploid Failed Embryo Transfer: a Randomized Control Trial

The goal of this randomized clinical trial is to compare frozen embryo transfer protocols in patients undergoing a second frozen embryo transfer (FET) after a unsuccessful first programmed FET cycle as a possible treatment for people undergoing infertility treatment.

The purpose of this research study is to:

  • Determine if there is a difference between FET protocols in patients who require a second FET cycle.
  • Investigate if switching the FET protocol after a failed programmed cycle is beneficial for patients undergoing a second FET cycle.
  • Examine pregnancy outcomes including obstetrical and neonatal outcomes (if applicable)
  • Obtain uterine flexibility/stiffness measurements via transvaginal ultrasound prior to the embryo transfer procedure. This is called shear wave elastography.

Participants will be randomized in their second FET transfer attempt to either another programmed protocol or a modified natural protocol.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This research study is studying if there is a difference in frozen embryo transfer protocols used (modified natural versus programmed) after a failed first programmed FET cycle, defined as either a negative pregnancy test or a biochemical loss, as a possible treatment for people undergoing infertility treatment and in vitro fertilization (IVF). Participants will be randomized, in a 1:1 ratio, in their second FET transfer attempt to either another programmed protocol or a modified natural protocol. Once randomized, participants will undergo routine FET monitoring based on their randomization allocation, transfer procedure and pregnancy monitoring as applicable. Additional ultrasound images will be obtained prior to the transfer procedure to assess the stiffness or flexibility of the uterus, called shear wave elastography. A participant blood sample and infant buccal swab will be collected for future research studies.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
9

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • New Jersey
      • Basking Ridge, New Jersey, United States, 07920
        • Reproductive Medicine Associates of new Jersey
      • Marlton, New Jersey, United States, 08053
        • Reproductive Medicine Associates of new Jersey

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

No

Description

Major Inclusion Criteria: The following are major inclusion criteria:

  1. Patients planning to undergo frozen embryo transfer cycle with a single euploid blastocyst.
  2. Patients who have previously undergone their first unsuccessful frozen embryo transfer cycle, defined as either failure of implantation with negative pregnancy test or biochemical pregnancy, using a programmed cycle protocol.
  3. Preimplantation genetic testing for aneuploidy (PGT-A) of the embryo used in failed programmed embryo transfer cycle must have occurred after January 1, 2017.
  4. Patients ages 18 to 53 years old as per practice guidelines.
  5. Patients with BMI between 16-45 kg/m2.
  6. Patients with at least one embryo remaining in storage, from either the same or a separate cohort.
  7. Patients with proven ovulatory function, as defined by the presence of regular menstrual cycles or detection of luteinizing hormone surge on serum or urinary test kits.
  8. Patients with ≥ 7 mm endometrial thickness prior to progesterone start in prior transfer cycle.
  9. Normal uterine cavity as evidenced by recent (within 1 year) saline sonogram or hysteroscopy.

Major Exclusion Criteria: The following are exclusion criteria:

  1. More than 1 prior unsuccessful frozen embryo transfer cycle.
  2. The prior FET failure having had resulted in a clinical loss or ectopic pregnancy
  3. Previously cancelled frozen embryo transfer cycle for inadequate endometrial response.
  4. Patients who required a different route of estrogen administration in the prior programmed cycle (vaginal, transdermal, intramuscular).
  5. PGT-A analysis of the available embryo for transfer performed prior to January 1, 2017.
  6. Anovulatory or oligo-ovulatory patients unable to undergo modified natural endometrial preparation.
  7. Patients with an endometrial thickness < 7 mm prior to progesterone start in prior cycle.
  8. History of hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and eclampsia.
  9. Mullerian anomalies, excluding arcuate uterus and repaired septum.
  10. No euploid embryos available for transfer.
  11. Concurrent submucosal fibroids, unrepaired uterine defects or present indication for uterine surgery.
  12. Communicating hydrosalpinx without plans for surgical correction prior to study enrollment.
  13. Failure of patient to agree to enrollment in study with written consent.
  14. Concurrent pregnancy.
  15. Concomitant use of adjunctive therapies for endometrial proliferation or receptivity, including anticoagulation and antihistamines. These must be discontinued upon enrollment.
  16. Embryo planned to be used for transfer generated from surgically obtained sperm.
  17. Recurrent/persistent endometrial fluid in prior cycles visualized on the majority of transvaginal ultrasound monitoring.
  18. Third party reproduction patients (donor sperm sources can be included).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: Programmed FET Protocol
Patients in this arm of the study will proceed with another programmed FET protocol which involves taking exogenous estrogen by mouth to stimulate the uterine lining to grow and develop. Once the lining has reached ≥ 7 mm and an endometrial pattern of type 1 or type 2, intramuscular progesterone in oil (50mg/ml daily) will be started at 8am on the morning that progesterone is initiated and continued per routine.
Other: FET Protocol
Participants are randomized to either another programmed FET Protocol vs. a modified natural FET protocol
Other: Modified Natural FET Protocol
Following development of at least one dominant follicle and endometrial proliferation ≥ 7 mm during cycle monitoring, patient will undergo administration of human chorionic gonadotropin (hCG) trigger shot followed by initiation of vaginal progesterone administration in accordance with institutional protocols.
Other: FET Protocol
Participants are randomized to either another programmed FET Protocol vs. a modified natural FET protocol

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Sustained implantation rate
Time Frame: approximately 6 weeks after embryo transfer
presence of an intrauterine clinical pregnancy with fetal heart tones at 8 weeks gestational age
approximately 6 weeks after embryo transfer

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Biochemical Pregnancy Rate
Time Frame: approximately 9 days after transfer
Biochemical (positive serum beta human chorionic gonadotropin (bHCG) post transfer procedure)
approximately 9 days after transfer
Biochemical pregnancy loss rate
Time Frame: typically 1 month post initial bHCG test
serum bHCG level ≥ 5 milli-International unit (mIU/mL) after FET without any ultrasound evidence of pregnancy until serum bHCG is < 5 mIU/mL
typically 1 month post initial bHCG test
Clinical Pregnancy Rate
Time Frame: approximately 10 days after initial pregnancy test
presence of an intrauterine gestational sac
approximately 10 days after initial pregnancy test
Clinical Pregnancy Loss Rate
Time Frame: approximately 2 months after FET procedure
a pregnancy after FET that had at minimum ultrasound evidence of a gestational sac, but did not progress to a live birth and was not terminated nor was an ectopic pregnancy.
approximately 2 months after FET procedure
Live Birth Rate
Time Frame: approximately 16-32 weeks post discharge at 8 weeks gestational age
delivery of a live born infant greater than 24 weeks gestational age.
approximately 16-32 weeks post discharge at 8 weeks gestational age
Rate of pregnancies of undetermined location and ectopic pregnancies
Time Frame: approximately 1-2 months post initial bHCG
Pregnancies that are not intrauterine
approximately 1-2 months post initial bHCG
Rate of maternal obstetrical outcomes and complications
Time Frame: approximately 40 weeks gestation
mode of delivery, placental issues, preterm delivery
approximately 40 weeks gestation
Rate of neonatal outcomes and complications
Time Frame: approximately 40 weeks gestational age or after delivery of infant
gestational age at delivery, birth weight, any complications
approximately 40 weeks gestational age or after delivery of infant
Elastography Data
Time Frame: prior to the embryo transfer procedure
shear wave elastography measurements of the uterus
prior to the embryo transfer procedure

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Reproductive Medicine Associates of New Jersey

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Emre U Seli, MD, Reproductive Medicine Associates of new Jersey

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 25, 2023

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
May 10, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 21, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 20, 2023

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
October 5, 2023

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
October 10, 2023

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
February 4, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
February 1, 2025

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 2302-BRG-024-ES

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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