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

Primary Purpose

Infertility, Female

Status
Not yet recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
FET Protocol
Sponsored by
Reproductive Medicine Associates of New Jersey
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Infertility, Female

Eligibility Criteria

18 Years - 53 Years (Adult)FemaleDoes not accept healthy volunteers

Major Inclusion Criteria: The following are major inclusion criteria: Patients planning to undergo frozen embryo transfer cycle with a single euploid blastocyst. 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. Preimplantation genetic testing for aneuploidy (PGT-A) of the embryo used in failed programmed embryo transfer cycle must have occurred after January 1, 2017. Patients ages 18 to 53 years old as per practice guidelines. Patients with BMI between 16-45 kg/m2. Patients with at least one embryo remaining in storage, from either the same or a separate cohort. 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. Patients with ≥ 7 mm endometrial thickness prior to progesterone start in prior transfer cycle. Normal uterine cavity as evidenced by recent (within 1 year) saline sonogram or hysteroscopy. Major Exclusion Criteria: The following are exclusion criteria: More than 1 prior unsuccessful frozen embryo transfer cycle. The prior FET failure having had resulted in a clinical loss or ectopic pregnancy Previously cancelled frozen embryo transfer cycle for inadequate endometrial response. Patients who required a different route of estrogen administration in the prior programmed cycle (vaginal, transdermal, intramuscular). PGT-A analysis of the available embryo for transfer performed prior to January 1, 2017. Anovulatory or oligo-ovulatory patients unable to undergo modified natural endometrial preparation. Patients with an endometrial thickness < 7 mm prior to progesterone start in prior cycle. History of hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and eclampsia. Mullerian anomalies, excluding arcuate uterus and repaired septum. No euploid embryos available for transfer. Concurrent submucosal fibroids, unrepaired uterine defects or present indication for uterine surgery. Communicating hydrosalpinx without plans for surgical correction prior to study enrollment. Failure of patient to agree to enrollment in study with written consent. Concurrent pregnancy. Concomitant use of adjunctive therapies for endometrial proliferation or receptivity, including anticoagulation and antihistamines. These must be discontinued upon enrollment. Embryo planned to be used for transfer generated from surgically obtained sperm. Recurrent/persistent endometrial fluid in prior cycles visualized on the majority of transvaginal ultrasound monitoring. Third party reproduction patients (donor sperm sources can be included).

Sites / Locations

  • Reproductive Medicine Associates of New Jersey
  • Reproductive Medicine Associates of New Jersey

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Programmed FET Protocol

Modified Natural FET Protocol

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

Sustained implantation rate
presence of an intrauterine clinical pregnancy with fetal heart tones at 8 weeks gestational age

Secondary Outcome Measures

Biochemical Pregnancy Rate
Biochemical (positive serum beta human chorionic gonadotropin (bHCG) post transfer procedure)
Biochemical pregnancy loss rate
serum bHCG level ≥ 5 milli-International unit (mIU/mL) after FET without any ultrasound evidence of pregnancy until serum bHCG is < 5 mIU/mL
Clinical Pregnancy Rate
presence of an intrauterine gestational sac
Clinical Pregnancy Loss Rate
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.
Live Birth Rate
delivery of a live born infant greater than 24 weeks gestational age.
Rate of pregnancies of undetermined location and ectopic pregnancies
Pregnancies that are not intrauterine
Rate of maternal obstetrical outcomes and complications
mode of delivery, placental issues, preterm delivery
Rate of neonatal outcomes and complications
gestational age at delivery, birth weight, any complications
Elastography Data
shear wave elastography measurements of the uterus

Full Information

First Posted
September 20, 2023
Last Updated
October 5, 2023
Sponsor
Reproductive Medicine Associates of New Jersey
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1. Study Identification

Unique Protocol Identification Number
NCT06074055
Brief Title
PRogrammed Versus Modified Natural Cycle After Euploid Failed Embryo Transfer
Acronym
PREFER
Official Title
PREFER: PRogrammed Versus Modified Natural Cycle After Euploid Failed Embryo Transfer: A Randomized Control Trial
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Not yet recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
December 2025 (Anticipated)
Study Completion Date
August 2026 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Reproductive Medicine Associates of New Jersey

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Infertility, Female

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
780 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Programmed FET Protocol
Arm Type
Other
Arm Description
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.
Arm Title
Modified Natural FET Protocol
Arm Type
Other
Arm Description
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.
Intervention Type
Other
Intervention Name(s)
FET Protocol
Intervention Description
Participants are randomized to either another programmed FET Protocol vs. a modified natural FET protocol
Primary Outcome Measure Information:
Title
Sustained implantation rate
Description
presence of an intrauterine clinical pregnancy with fetal heart tones at 8 weeks gestational age
Time Frame
approximately 6 weeks after embryo transfer
Secondary Outcome Measure Information:
Title
Biochemical Pregnancy Rate
Description
Biochemical (positive serum beta human chorionic gonadotropin (bHCG) post transfer procedure)
Time Frame
approximately 9 days after transfer
Title
Biochemical pregnancy loss rate
Description
serum bHCG level ≥ 5 milli-International unit (mIU/mL) after FET without any ultrasound evidence of pregnancy until serum bHCG is < 5 mIU/mL
Time Frame
typically 1 month post initial bHCG test
Title
Clinical Pregnancy Rate
Description
presence of an intrauterine gestational sac
Time Frame
approximately 10 days after initial pregnancy test
Title
Clinical Pregnancy Loss Rate
Description
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.
Time Frame
approximately 2 months after FET procedure
Title
Live Birth Rate
Description
delivery of a live born infant greater than 24 weeks gestational age.
Time Frame
approximately 16-32 weeks post discharge at 8 weeks gestational age
Title
Rate of pregnancies of undetermined location and ectopic pregnancies
Description
Pregnancies that are not intrauterine
Time Frame
approximately 1-2 months post initial bHCG
Title
Rate of maternal obstetrical outcomes and complications
Description
mode of delivery, placental issues, preterm delivery
Time Frame
approximately 40 weeks gestation
Title
Rate of neonatal outcomes and complications
Description
gestational age at delivery, birth weight, any complications
Time Frame
approximately 40 weeks gestational age or after delivery of infant
Title
Elastography Data
Description
shear wave elastography measurements of the uterus
Time Frame
prior to the embryo transfer procedure

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
53 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Major Inclusion Criteria: The following are major inclusion criteria: Patients planning to undergo frozen embryo transfer cycle with a single euploid blastocyst. 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. Preimplantation genetic testing for aneuploidy (PGT-A) of the embryo used in failed programmed embryo transfer cycle must have occurred after January 1, 2017. Patients ages 18 to 53 years old as per practice guidelines. Patients with BMI between 16-45 kg/m2. Patients with at least one embryo remaining in storage, from either the same or a separate cohort. 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. Patients with ≥ 7 mm endometrial thickness prior to progesterone start in prior transfer cycle. Normal uterine cavity as evidenced by recent (within 1 year) saline sonogram or hysteroscopy. Major Exclusion Criteria: The following are exclusion criteria: More than 1 prior unsuccessful frozen embryo transfer cycle. The prior FET failure having had resulted in a clinical loss or ectopic pregnancy Previously cancelled frozen embryo transfer cycle for inadequate endometrial response. Patients who required a different route of estrogen administration in the prior programmed cycle (vaginal, transdermal, intramuscular). PGT-A analysis of the available embryo for transfer performed prior to January 1, 2017. Anovulatory or oligo-ovulatory patients unable to undergo modified natural endometrial preparation. Patients with an endometrial thickness < 7 mm prior to progesterone start in prior cycle. History of hypertensive disorders of pregnancy, including gestational hypertension, preeclampsia, and eclampsia. Mullerian anomalies, excluding arcuate uterus and repaired septum. No euploid embryos available for transfer. Concurrent submucosal fibroids, unrepaired uterine defects or present indication for uterine surgery. Communicating hydrosalpinx without plans for surgical correction prior to study enrollment. Failure of patient to agree to enrollment in study with written consent. Concurrent pregnancy. Concomitant use of adjunctive therapies for endometrial proliferation or receptivity, including anticoagulation and antihistamines. These must be discontinued upon enrollment. Embryo planned to be used for transfer generated from surgically obtained sperm. Recurrent/persistent endometrial fluid in prior cycles visualized on the majority of transvaginal ultrasound monitoring. Third party reproduction patients (donor sperm sources can be included).
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Caroline Zuckerman, BS, RN
Phone
19736562841
Email
clinicalresearchteam@ivirma.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Emre U Seli, MD
Organizational Affiliation
Reproductive Medicine Associates of New Jersey
Official's Role
Principal Investigator
Facility Information:
Facility Name
Reproductive Medicine Associates of New Jersey
City
Basking Ridge
State/Province
New Jersey
ZIP/Postal Code
07920
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caroline Zuckerman, BS, RN
Phone
973-656-2841
Email
clinicalresearchteam@ivirma.com
First Name & Middle Initial & Last Name & Degree
Emre U Seli, MD
Facility Name
Reproductive Medicine Associates of New Jersey
City
Marlton
State/Province
New Jersey
ZIP/Postal Code
08053
Country
United States
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Caroline Zuckerman, BS, RN
Phone
973-656-2841
Email
clinicalresearchteam@ivirma.com
First Name & Middle Initial & Last Name & Degree
Emre U Seli, MD

12. IPD Sharing Statement

Plan to Share IPD
No

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PRogrammed Versus Modified Natural Cycle After Euploid Failed Embryo Transfer

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