FET Protocols for Infertility

(PREFER Trial)

Recruiting at 1 trial location

Overseen By Caroline Zuckerman, BS, RN

Age: 18 - 65

Sex: Female

Trial Phase: Academic

Sponsor: Reproductive Medicine Associates of New Jersey

Must not be taking: Anticoagulants, Antihistamines

Disqualifiers: Hypertension, Uterine defects, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 1 Jurisdiction This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: 6-8 weeks

9 Participants Needed

Trial Summary

What is the purpose of this 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.

Do I have to stop taking my current medications for the trial?

The trial protocol does not specify if you must stop taking all current medications. However, you must discontinue any adjunctive therapies for endometrial proliferation or receptivity, such as anticoagulation and antihistamines, upon enrollment.

What data supports the idea that FET Protocols for Infertility is an effective treatment?

The available research shows that FET Protocols for Infertility, particularly the modified natural cycle (mNC), may be more effective than other methods. Studies suggest that mNC protocols have higher success rates compared to natural cycle (NC) and artificial cycle (AC) protocols. For example, one study found that mNC protocols resulted in better outcomes for preparing the body for frozen embryo transfers. Another study indicated that mNC protocols might lead to more successful pregnancies and live births compared to artificial cycles. Overall, these findings suggest that FET Protocols, especially the modified natural cycle, are effective treatments for infertility. ^{1 2 3 4 5}

What safety data is available for FET Protocols for Infertility?

The provided research does not directly address safety data for FET Protocols for Infertility, such as Frozen Embryo Transfer or its variations. The studies focus on adverse event monitoring frameworks, national incidence of adverse events, and reporting practices for other medical treatments. Specific safety data for FET Protocols would require targeted studies or reviews in reproductive medicine literature. ^{6 7 8 9 10}

Is the FET Protocol a promising treatment for infertility?

The FET Protocol, which includes methods like Frozen Embryo Transfer and Natural Cycle FET, is considered a promising treatment for infertility. It offers a way to use embryos that have been frozen for later use, which can increase the chances of pregnancy. This approach allows for better timing and preparation of the body for embryo transfer, potentially leading to higher success rates in achieving pregnancy. ^{11 12 13 14 15}

Research Team

Emre U Seli, MD

Principal Investigator

Reproductive Medicine Associates of New Jersey

Eligibility Criteria

This trial is for women aged 18-53 with a BMI of 16-45 kg/m2 who have had one unsuccessful frozen embryo transfer (FET) using a programmed cycle. They must have at least one euploid blastocyst left, regular menstrual cycles or detectable LH surge, and an endometrial thickness ≥7 mm from the last cycle.

Inclusion Criteria

My embryo was tested for genetic normality after January 1, 2017.

My recent tests show a normal uterus.

My first frozen embryo transfer did not result in a successful pregnancy.

Exclusion Criteria

You had a previous failed fertility treatment that resulted in a lost pregnancy or pregnancy occurring outside the uterus.

Patients with an endometrial thickness < 7 mm prior to progesterone start in prior cycle

My embryo was tested before January 1, 2017.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a second FET transfer attempt with either a programmed or modified natural protocol, including routine FET monitoring and shear wave elastography.

6-8 weeks

Follow-up

Participants are monitored for pregnancy outcomes, including biochemical and clinical pregnancy rates, and obstetrical and neonatal outcomes.

40 weeks

Long-term Follow-up

Participants are monitored for sustained implantation rate and live birth rate.

16-32 weeks post discharge at 8 weeks gestational age

Treatment Details

Interventions

• FET Protocol

Trial Overview The study compares two FET protocols in patients needing a second attempt after an initial failure. Participants will be randomly assigned to either repeat the programmed protocol or switch to a modified natural protocol, assessing pregnancy outcomes and uterine flexibility.

Participant Groups

Group I: Programmed FET Protocol Experimental Treatment 1 Intervention

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.

Group II: Modified Natural FET Protocol Experimental Treatment 1 Intervention

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.

Who Is Running the Clinical Trial?

Reproductive Medicine Associates of New Jersey

Lead Sponsor

Trials

56

Recruited

38,200+

Findings from Research

In a study of 129 patients undergoing frozen embryo transfer, the modified natural cycle (mNC) protocol showed a higher clinical pregnancy rate (65.2%) compared to the artificial endometrial preparation (AC) and natural cycle (NC) protocols, although this difference was not statistically significant.

The implantation rate was significantly higher in the mNC group (50%) compared to the AC (34%) and NC (12%) groups, suggesting that mNC may be more effective for endometrial preparation in FET cycles.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified natural protocol seems superior to natural and artificial protocols for preparing the endometrium in frozen embryo transfer cycles. Isikoglu, M., Aydinuraz, B., Avci, A., et al.[2021]

The modified natural cycle (mNC) protocol for frozen embryo transfer (FET) resulted in significantly higher clinical pregnancy rates (CPR) and live birth rates (LBR) compared to both natural cycle (NC) and programmed/artificial cycle (AC) protocols, with LBRs of 36.3% for mNC versus 32.3% for NC and 26.6% for AC.

There were no significant differences in outcomes between the NC and AC protocols, indicating that both methods are equally effective, but mNC is the preferred option for better success rates in women undergoing FET.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Endometrial preparation methods prior to frozen embryo transfer: A retrospective cohort study comparing true natural cycle, modified natural cycle and artificial cycle. Mensing, L., Dahlberg, ES., Bay, B., et al.[2022]

In a study of 490 frozen embryo transfer cycles, the modified natural cycle (mNC) and artificial cycle (AC) protocols showed comparable rates of live births and clinical pregnancies, indicating that both methods are effective for embryo transfer.

However, for patients undergoing double embryo transfers, the mNC protocol resulted in significantly higher live birth (48% vs. 31.4%) and clinical pregnancy rates (53.9% vs. 38.8%) compared to the AC protocol, suggesting mNC may be a better option in these cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Live birth after frozen-thawed embryo transfer: which endometrial preparation protocol is better? Sahin, G., Acet, F., Calimlioglu, N., et al.[2021]

In a study of 428 patients undergoing 493 frozen-thawed blastocyst transfers, the modified natural cycle frozen embryo transfer (NC-FET) protocol showed comparable clinical pregnancy rates (54.3%) and delivery rates (47.2%) to the down-regulated hormonally controlled frozen embryo transfer (HC-FET) protocol (52.5% and 43.6%, respectively).

Factors such as patient age, number of blastocysts transferred, and the year of transfer significantly influenced clinical pregnancy outcomes, indicating that while both protocols are effective, individual patient characteristics play a crucial role in success.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modified natural cycle for embryo transfer using frozen-thawed blastocysts: A satisfactory option. Le, QV., Abhari, S., Abuzeid, OM., et al.[2022]

Most U.S. Assisted Reproductive Technology (ART) clinics offer natural cycle frozen embryo transfer (NC-FET), but only a small percentage of cycles utilize this method, with 76% of clinics reporting that less than 25% of their FET cycles use NC-FET for endometrial preparation.

Common barriers to offering NC-FET include concerns about timing predictability and increased workload for staff, with 65% of clinics expressing a positive attitude towards NC-FET despite these challenges.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Natural cycle frozen embryo transfer: a survey of current assisted reproductive technology practices in the U.S. Lee, JC., Calzada-Jorge, NS., Hipp, HS., et al.[2023]

From 2013 to 2016, the incidence of adverse events (AEs) in Swedish hospitals decreased from 13.1% to an average of 11.4%, indicating improvements in patient safety during this period.

Preventable AEs were significantly more common (84% more) in patients cared for in inappropriate units ('off-site'), highlighting the importance of proper patient placement and the substantial economic burden of these events, which accounted for 13%-14% of total hospital care costs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Incidence of adverse events in Sweden during 2013-2016: a cohort study describing the implementation of a national trigger tool. Nilsson, L., Borgstedt-Risberg, M., Soop, M., et al.[2019]

In a study of 796 women undergoing reproductive surgery, the overall rate of adverse events (AEs) was 6%, with 12 of these events deemed preventable, highlighting the importance of monitoring for safety in surgical settings.

The duration of surgery was identified as a significant risk factor for AEs, with longer surgeries increasing the likelihood of complications, suggesting that surgical time management could improve patient outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical outcome monitoring in a reproductive surgery unit: a prospective cohort study in 796 patients. Bentz, EK., Imhof, M., Pateisky, N., et al.[2009]

A study analyzing 4703 insulin and 6487 somatropin adverse event reports revealed inconsistent reporting practices and a lack of manufacturer identifiability, which could complicate the attribution of adverse events to specific biologics or their biosimilars.

The findings highlight the urgent need for clear biosimilar naming conventions to enhance drug safety monitoring and ensure accurate reporting of adverse events as more biosimilars enter the market.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluating AE Reporting of Two Off-Patent Biologics to Inform Future Biosimilar Naming and Reporting Practices. Stergiopoulos, S., Getz, K.[2018]

A comparison of adverse event reports (AERs) for mifepristone abortions from 2009 to 2010 revealed significant discrepancies, with Cleland et al. documenting 1530 cases while the FDA's FAERS reported only 664 total AERs.

The findings suggest that the FAERS system may be inadequate for accurately assessing the safety of mifepristone abortions, as it reported only a fraction of ongoing pregnancies (95) compared to Cleland's documentation (1158).

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mifepristone Adverse Events Identified by Planned Parenthood in 2009 and 2010 Compared to Those in the FDA Adverse Event Reporting System and Those Obtained Through the Freedom of Information Act. Cirucci, CA., Aultman, KA., Harrison, DJ.[2022]

A new framework for monitoring adverse events (AEs) in pregnancy trials has been developed, which includes specific definitions and severity grading for both maternal and fetal AEs, enhancing safety assessments for drugs and interventions.

The framework was created through a comprehensive literature review and consensus from an international group of experts, resulting in 12 maternal and 19 fetal AE definitions that can be systematically applied in clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Development of standard definitions and grading for Maternal and Fetal Adverse Event Terminology. Spencer, RN., Hecher, K., Norman, G., et al.[2022]

Follicular unit transplantation (FUT) is a highly refined hair restoration technique that uses microscopic dissection to transplant hair in natural groupings, resulting in outcomes that closely resemble natural hair growth.

FUT is recognized for providing natural-looking hairlines with good density and low recovery time, but the success of the procedure heavily relies on the skill and planning of the technician performing it.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Follicular unit transplantation. Rousso, DE., Presti, PM.[2008]

The two new hair transplant designs are reported to be safer than standard methods, potentially reducing the risk of complications during surgery.

These innovative designs aim to provide a more natural appearance for patients, enhancing the aesthetic outcomes of hair transplant procedures.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hair transplant surgery: innovative designs. Norwood, OT., Taylor, BJ.[2019]

The method described for hair transplanting involves creating recipient sites that mimic natural hair directions and angles, which helps achieve a more natural appearance.

Using grafts with multiple follicular units can enhance the density of the transplanted hair without accelerating the loss of existing hair in the recipient area.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Recipient area hair direction and angle in hair transplanting. Unger, WP.[2022]

Follicular Unit Transplantation (FUT) effectively moves hair from donor to recipient areas while mimicking natural hair patterns and minimizing damage to hair follicles.

By following established standards for dissection and implantation, surgeons can reliably achieve specific aesthetic outcomes with FUT.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Follicular unit transplantation: dissecting and planting techniques. Harris, JA.[2006]

Both Follicular Unit Excision (FUE) and Follicular Unit Transplantation (FUT) are effective methods for harvesting high-quality hair grafts, as confirmed by a comprehensive review of existing literature.

FUE results in less noticeable punctate scars, while FUT leaves a linear scar, allowing patients to choose a method based on their scarring preferences and eligibility.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Old Friend or New Ally: A Comparison of Follicular Unit Transplantation and Follicular Unit Excision Methods in Hair Transplantation. Gupta, AK., Love, RP., Harris, JA.[2021]

References

1. Italy pubmed.ncbi.nlm.nih.gov

Modified natural protocol seems superior to natural and artificial protocols for preparing the endometrium in frozen embryo transfer cycles. [2021]

2. Germany pubmed.ncbi.nlm.nih.gov

Endometrial preparation methods prior to frozen embryo transfer: A retrospective cohort study comparing true natural cycle, modified natural cycle and artificial cycle. [2022]

3. France pubmed.ncbi.nlm.nih.gov

Live birth after frozen-thawed embryo transfer: which endometrial preparation protocol is better? [2021]

4. Ireland pubmed.ncbi.nlm.nih.gov

Modified natural cycle for embryo transfer using frozen-thawed blastocysts: A satisfactory option. [2022]

5. Netherlands pubmed.ncbi.nlm.nih.gov

Natural cycle frozen embryo transfer: a survey of current assisted reproductive technology practices in the U.S. [2023]

6. England pubmed.ncbi.nlm.nih.gov

Incidence of adverse events in Sweden during 2013-2016: a cohort study describing the implementation of a national trigger tool. [2019]

7. United States pubmed.ncbi.nlm.nih.gov

Clinical outcome monitoring in a reproductive surgery unit: a prospective cohort study in 796 patients. [2009]

8. New Zealand pubmed.ncbi.nlm.nih.gov

Evaluating AE Reporting of Two Off-Patent Biologics to Inform Future Biosimilar Naming and Reporting Practices. [2018]

9. United States pubmed.ncbi.nlm.nih.gov

Mifepristone Adverse Events Identified by Planned Parenthood in 2009 and 2010 Compared to Those in the FDA Adverse Event Reporting System and Those Obtained Through the Freedom of Information Act. [2022]

10. England pubmed.ncbi.nlm.nih.gov

Development of standard definitions and grading for Maternal and Fetal Adverse Event Terminology. [2022]

11. United States pubmed.ncbi.nlm.nih.gov

Follicular unit transplantation. [2008]

12. United States pubmed.ncbi.nlm.nih.gov

Hair transplant surgery: innovative designs. [2019]

13. United States pubmed.ncbi.nlm.nih.gov

Recipient area hair direction and angle in hair transplanting. [2022]

14. United States pubmed.ncbi.nlm.nih.gov

Follicular unit transplantation: dissecting and planting techniques. [2006]

15. United States pubmed.ncbi.nlm.nih.gov

Old Friend or New Ally: A Comparison of Follicular Unit Transplantation and Follicular Unit Excision Methods in Hair Transplantation. [2021]