PRogrammed Versus Modified Natural Cycle After Euploid Failed Embryo Transfer

Infertility, Female Clinical Trial

— PREFER  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06074055
• Other study ID #: 2302-BRG-024-ES
• Status: Recruiting
• Phase: N/A
• Start date: October 25, 2023
• Est. completion date: August 2026

Study information

• Verified date: October 2023
• Source: Reproductive Medicine Associates of New Jersey
• Contact: Caroline Zuckerman, BS, RN
• Phone: 19736562841
• Email: clinicalresearchteam[@]ivirma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 780
• Est. completion date: August 2026
• Est. primary completion date: December 2025
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years to 53 Years

Eligibility

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).

Related Conditions & MeSH terms

• Infertility
• Infertility, Female

Intervention

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

Locations

Country	Name	City	State
United States	Reproductive Medicine Associates of New Jersey	Basking Ridge	New Jersey
United States	Reproductive Medicine Associates of New Jersey	Marlton	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Reproductive Medicine Associates of New Jersey

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Biochemical Pregnancy Rate	Biochemical (positive serum beta human chorionic gonadotropin (bHCG) post transfer procedure)	approximately 9 days after transfer
Secondary	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	typically 1 month post initial bHCG test
Secondary	Clinical Pregnancy Rate	presence of an intrauterine gestational sac	approximately 10 days after initial pregnancy test
Secondary	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.	approximately 2 months after FET procedure
Secondary	Live Birth Rate	delivery of a live born infant greater than 24 weeks gestational age.	approximately 16-32 weeks post discharge at 8 weeks gestational age
Secondary	Rate of pregnancies of undetermined location and ectopic pregnancies	Pregnancies that are not intrauterine	approximately 1-2 months post initial bHCG
Secondary	Rate of maternal obstetrical outcomes and complications	mode of delivery, placental issues, preterm delivery	approximately 40 weeks gestation
Secondary	Rate of neonatal outcomes and complications	gestational age at delivery, birth weight, any complications	approximately 40 weeks gestational age or after delivery of infant
Secondary	Elastography Data	shear wave elastography measurements of the uterus	prior to the embryo transfer procedure