PRogrammed Versus Modified Natural Cycle After Euploid Failed Embryo Transfer

NCT06074055 | Terminated

• 1 other identifier: 2302-BRG-024-ES
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 2

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.

Conditions

Infertility, Female

Outcome Measures

Primary Outcomes (1)

• Sustained implantation rate

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

  approximately 6 weeks after embryo transfer

Secondary Outcomes (9)

• Biochemical Pregnancy Rate

  approximately 9 days after transfer

• Biochemical pregnancy loss rate

  typically 1 month post initial bHCG test

• Clinical Pregnancy Rate

  approximately 10 days after initial pregnancy test

• Clinical Pregnancy Loss Rate

  approximately 2 months after FET procedure

• Live Birth Rate

  approximately 16-32 weeks post discharge at 8 weeks gestational age

Study Arms (2)

Programmed FET Protocol

OTHER

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

Modified Natural FET Protocol

OTHER

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

Interventions

FET Protocol OTHER

Participants are randomized to either another programmed FET Protocol vs. a modified natural FET protocol

Modified Natural FET Protocol; Programmed FET Protocol

Eligibility Criteria

• Age: 18 Years - 53 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Reproductive Medicine Associates of New Jersey: lead

Study Sites (2)

Reproductive Medicine Associates of New Jersey

Basking Ridge, New Jersey, 07920, United States

Location

Reproductive Medicine Associates of New Jersey

Marlton, New Jersey, 08053, United States

Location

MeSH Terms

Conditions

Infertility, Female

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Study Officials

• Emre U Seli, MD

  Reproductive Medicine Associates of New Jersey

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 20, 2023
• First Posted: October 10, 2023
• Study Start: October 25, 2023
• Primary Completion: May 10, 2024
• Study Completion: October 21, 2024
• Last Updated: February 7, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (2)