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

150 Participants Needed

Trial Summary

What is the purpose of this trial?

Endometrin is a progesterone supplement prescribed during in vitro fertilization (IVF) for preparation for embryo transfer. 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. The purpose of this research project is to evaluate the dose response of the Endometrin when determined based on the blood level of progesterone on the day of the FET. According to the literature, a predefined level of progesterone in the blood should be reached in order to have favorable conditions for pregnancy. The hypothesis being that a woman with low progesterone levels would benefit from a dose of Endometrin of 600 mg (200 mg 3x/day) to decrease the risk of miscarriage and improve the chances of pregnancy. Women with adequate progesterone levels according to the literature, would continue with the standard dose of progesterone prescribed at clinique ovo which is 300 mg (100 mg 3x/day). PIBF (Progesterone Induced Blocking Factor) levels, a protein found in the blood that could also predict pregnancy outcomes in women using IVF will also be looked at.

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.

What data supports the effectiveness of the drug Progesterone Effervescent Vaginal Tablet for frozen embryo transfer?

Research shows that using vaginal progesterone tablets after transferring frozen embryos can improve the chances of a successful pregnancy and live birth. This suggests that progesterone supplementation is beneficial in these situations. ^{1 2 3 4 5}

Is progesterone supplementation safe for humans?

Research on progesterone supplementation, including vaginal tablets, has been conducted to support fertility treatments like embryo transfer. These studies generally focus on its effectiveness, but they also monitor safety, suggesting it is considered safe for use in humans during these treatments. ^{1 3 6 7 8}

How is the drug Progesterone Effervescent Vaginal Tablet unique for frozen embryo transfer?

The Progesterone Effervescent Vaginal Tablet is unique because it is administered vaginally, which can provide direct support to the uterus, potentially improving pregnancy outcomes in frozen embryo transfer cycles. This method of delivery is different from other forms like injections or oral tablets, and it may offer a more convenient and less invasive option for patients. ^{1 2 3 9 10}

Research Team

Wael Jamal, MD

Principal Investigator

Clinique Ovo

Eligibility Criteria

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 a woman aged between 18 and 42.

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

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

Treatment Details

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.

Participant Groups

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

References

1. England pubmed.ncbi.nlm.nih.gov

Progesterone supplementation in natural cycles improves live birth rates after embryo transfer of frozen-thawed embryos-a randomized controlled trial. [2022]

2. Japan pubmed.ncbi.nlm.nih.gov

Effectiveness of high-dose transvaginal progesterone supplementation for women who are undergoing a frozen-thawed embryo transfer. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Vaginal progesterone as luteal phase support in natural cycle frozen-thawed embryo transfer (ProFET): protocol for a multicentre, open-label, randomised controlled trial. [2022]

4. England pubmed.ncbi.nlm.nih.gov

Effects of early luteal-phase vaginal progesterone supplementation on the outcome of in vitro fertilization and embryo transfer. [2013]

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

Progesterone support for frozen embryo transfer: intramuscular versus vaginal suppository demonstrates no difference in a cohort. [2015]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Subcutaneous versus vaginal progesterone for vitrified-warmed blastocyst transfer in artificial cycles. [2021]

7. Japan pubmed.ncbi.nlm.nih.gov

A multi-center, randomized, open-label, parallel group study of a natural micronized progesterone vaginal tablet as a luteal support agent in Japanese women undergoing assisted reproductive technology. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Oral micronized progesterone versus vaginal progesterone for luteal phase support in fresh embryo transfer cycles: a multicenter, randomized, non-inferiority trial. [2023]

9. Netherlands pubmed.ncbi.nlm.nih.gov

The importance of serum progesterone concentration at embryo transfer day and effect of rescue additional progesterone during programmed artificial frozen embryo transfer cycles. [2022]

10. Australia pubmed.ncbi.nlm.nih.gov

Progesterone concentrations and dosage with frozen embryo transfers - What's best? [2019]