Progesterone Supplementation for Frozen Embryo Transfer

(P4R Trial)

Overseen By Marion Vivien, PhD

Age: 18 - 65

Sex: Female

Trial Phase: Phase 2

Sponsor: Clinique Ovo

Must be taking: Progesterone

Must not be taking: Methotrexate, NSAIDs

Disqualifiers: Cancer, Thromboembolism, Renal disease, others

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

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 10 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial aims to determine if adjusting the dose of Endometrin, a progesterone supplement used in IVF, can improve pregnancy outcomes. The researchers will compare two groups: women with lower progesterone levels will receive a higher dose, while those with adequate levels will continue with the standard dose. Women who have undergone a frozen embryo transfer cycle and meet certain conditions, such as a normal uterine cavity and adequate endometrial thickness, may be suitable candidates. The goal is to find the optimal dose to reduce miscarriage risk and improve pregnancy chances. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants, offering them a chance to contribute to significant findings.

Will I have to stop taking my current medications?

The trial information does not specify if you need to stop taking your current medications. However, if you are using methotrexate at doses of 15mg/week or more, you may not be eligible to participate.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that Endometrin, a progesterone supplement, has been safely used by many women. Studies found that 808 women took Endometrin without major problems. This supplement is usually administered as a vaginal tablet. Most women tolerate it well, but like any treatment, it can have side effects.

Common side effects include vaginal discharge and headaches, while more serious side effects are rare. The treatment has been used in different doses, typically 100 mg two to three times a day. This trial is testing a higher dose for some women to see if it improves pregnancy outcomes.

Endometrin has FDA approval for use in fertility treatments, which supports its general safety. However, the higher dose being tested in this trial remains under study. Participants should feel reassured by the existing safety data but should also discuss any concerns with their doctor. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about the Progesterone Effervescent Vaginal Tablet because it offers a unique delivery method for progesterone supplementation during frozen embryo transfer cycles. Unlike traditional progesterone treatments that might involve injections or suppositories, this effervescent tablet is designed for vaginal use, potentially improving comfort and ease of administration. This innovative approach may enhance absorption and effectiveness, offering a promising alternative for women undergoing fertility treatments.

What evidence suggests that this treatment might be an effective treatment for improving pregnancy outcomes in IVF?

Research has shown that adding progesterone can improve outcomes in frozen embryo transfer cycles. Studies have found that progesterone shots, or their combination with vaginal progesterone, may lead to better birth outcomes and fewer miscarriages. Using only vaginal progesterone can reduce the chance of a live birth by about 40% compared to using both methods. However, effervescent progesterone vaginal tablets appear promising. In this trial, participants will receive varying doses of Endometrin based on their progesterone levels. For instance, some groups achieved ongoing pregnancy rates of 28.1%. Overall, different approaches, including higher doses for women with low progesterone, are being tested to enhance pregnancy success. ^{3 6 7 8 9}

Who Is on the Research Team?

Wael Jamal, MD

Principal Investigator

Clinique Ovo

Are You a Good Fit for This Trial?

This trial is for women aged 18-42 undergoing their first or second frozen embryo transfer (FET) with a normal uterine cavity and adequate endometrial thickness. It's not for those with uterine abnormalities, cancer, certain drug use, gastrointestinal issues, thromboembolism history, severe organ disease, allergies to NSAIDs or progesterone components.

Inclusion Criteria

I am prescribed a cycle with FET substitution.

My uterus lining is thick enough for treatment after preparation.

I am in my first or second cycle of FET (frozen embryo transfer).

Exclusion Criteria

Previous allergic reactions to progesterone or any of the ingredients of Endometrin

I have been diagnosed with porphyria.

I have or had serious blood clot issues.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive Endometrin based on progesterone levels: 100 mg TID for levels ≥ 8.8 ng/ml or 200 mg TID for levels < 8.8 ng/ml until the 10th week of pregnancy

Up to 10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including viability ultrasound and blood tests for PIBF and progesterone levels

6 to 8 weeks

Viability ultrasound and blood tests at specified intervals

What Are the Treatments Tested in This Trial?

Interventions

• Progesterone Effervescent Vaginal Tablet

Trial Overview The study tests if adjusting the dose of Endometrin based on blood progesterone levels improves pregnancy chances in IVF. Women with low progesterone may receive a higher dose (600 mg), while others continue the standard (300 mg). The research also examines PIBF levels as potential predictors of IVF success.

How Is the Trial Designed?

Group I: Endometrin 100 mg three times per day (TID) Active Control 1 Intervention

Women with progesterone levels ≥ 8.8 ng/ml during frozen embryo transfer cycle will take Endometrin 100 mg TID until 10th week of pregnancy

Group II: Endometrin 200 mg three times per day (TID) Active Control 1 Intervention

Women with progesterone levels \< 8.8 ng/ml during frozen embryo transfer cycle will take Endometrin 200 mg TID until 10th week of pregnancy

Who Is Running the Clinical Trial?

Clinique Ovo

Lead Sponsor

Trials

33

Recruited

41,600+

Ferring Pharmaceuticals

Industry Sponsor

Trials

323

Recruited

1,242,000+

Pierre-Yves Berclaz

Ferring Pharmaceuticals

Chief Medical Officer since 2023

MD from the University of Lausanne, PhD in Molecular Biology from the Cincinnati College of Medicine

Jean-Frédéric Paulsen

Ferring Pharmaceuticals

Chief Executive Officer since 2023

Master’s degree in Finance from the London School of Economics and Political Science

Citations

1. sciencedirect.com sciencedirect.com/science/article/pii/S2666334124000588

Progesterone in frozen embryo transfer cycles However, recent data have suggested that IM P daily or a combination of IM and vaginal P may improve birth outcomes and reduce miscarriage rates compared with ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9733530/

The effect of frozen embryo transfer regimen on the ... Overall, the live birth rate was 39.2% (156/398), the clinical pregnancy rate was 43.7% (174/398), the implantation rate was 39.9% (174/436), the biochemical ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT05555121

Rescue Progesterone Supplementation During Frozen ... The usual dose of Endometrin is 100 mg two to three times per day in the form of an effervescent tablet to be inserted vaginally.

4. fertstert.org fertstert.org/article/S0015-0282(21)00298-3/fulltext

Intramuscular progesterone optimizes live birth from ... The primary outcome of live birth was reduced by approximately 40% among subjects taking vaginal progesterone alone compared with those taking ...

5. worldscientific.com worldscientific.com/doi/full/10.1142/S2661318222500074?srsltid=AfmBOorxJe2PcHLz487Ehfmdrwzy3kBJXSQSmP3TDUvAlhWt0S9C7oQo

Effervescent Progesterone Vaginal Tablet Mono ... Ongoing pregnancy rate were 10.2% in cleavage stage ET group and 28.1% in blastocyst ET group. As for the secondary outcomes in the blastocyst ET group, embryo ...

6. accessdata.fda.gov accessdata.fda.gov/drugsatfda_docs/label/2008/022057s001lbl.pdf

Endometrin® (progesterone) Vaginal Insert - accessdata.fda.gov The safety data reflect exposure to Endometrin in 808 infertile women (74.9% White, 10.3% Hispanic, 5.4% Black, 5% Asian, and 4.6% Other) in a single ...

7. ferring.ca ferring.ca/media/1312/181690-eng-endometrin-product-monograph-may-11-2015-eng.pdf

Progesterone Effervescent Vaginal Tablets 100 mg The safety data reflect exposure to Endometrin in 808 infertile women (74.9% White, 10.3%. Hispanic, 5.4% Black, 5 % Asian, and 4.6% Other) ...

8. ferring.ca ferring.ca/media/1060/endometrin-pm-english.pdf

Endometrin Effervescent Vaginal Tablets 100 mg The safety data reflect exposure to Endometrin in 808 infertile women (74.9% White, 10.3%. Hispanic, 5.4% Black, 5 % Asian, and 4.6% Other) ...

9. sciencedirect.com sciencedirect.com/science/article/pii/S0015028217320472

Vitrified blastocyst transfer cycles with the use of only ... Vaginal-only P replacement for vitrified-warmed blastocyst transfer results in decreased ongoing pregnancy, due to increased miscarriage, and should be avoided.