Rescue Progesterone Supplementation During Frozen Embryo Transfer (P4R)

Rescue Progesterone Supplementation in Patients With Low Progesterone on the Day of Embryo Transfer for Artificial Endometrial Preparation Cycles: a Non-inferiority Study

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.

Study Overview

• Status: Suspended
• Conditions: Fertility Issues; Frozen Embryo Transfer; Embryo Implantation
• Intervention / Treatment: Drug: Progesterone Effervescent Vaginal Tablet

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Quebec
    • Montreal, Quebec, Canada, H4P 2S4
      • Clinique ovo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 42 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Women 18-42 years of age
• Normal uterine cavity (according to treating physician)
• FET substituted cycle prescribed
• First or second cycle of FET
• Adequate endometrial pattern (triple layer) and thickness (>7 mm) after adequate standard endometrial preparation in artificial cycle

Exclusion Criteria:

• Any uterine abnormalities confirmed by treating physician making participant unable to proceed with FET
• Patients with personalized FET according to the endometrial receptivity assay tests
• Previous allergic reactions to progesterone or any of the ingredients of Endometrin
• Severe hepatic dysfunction or disease
• Known or suspected breast cancer or genital tract cancer
• Known active arterial or venous thromboembolism or severe thrombophlebitis or cerebro-vascular disease, or a history of these events
• Diagnosed porphyria
• Undiagnosed abnormal vaginal bleeding
• Known missed abortion or ectopic pregnancy
• Recurrent pregnancy loss excluding biochemical pregnancies
• Hypersensitivity to Acetylsalicylic acid (ASA), salicylates, non-steroidal anti-inflammatory drugs (NSAIDs), analgesics, antipyretics or other ingredients in the product or component of the container
• Acute gastrointestinal ulcer, history of gastrointestinal ulcers and hemorrhagic diathesis
• Active or severe renal disease, or congestive heart failure
• History of asthma induced by salicylates or other NSAIDs
• Use of methotrexate at doses of 15mg/week or more
• Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Endometrin 100 mg three times per day (TID); Women with progesterone levels ≥ 8.8 ng/ml during frozen embryo transfer cycle will take Endometrin 100 mg TID until 10th week of pregnancy	Drug: Progesterone Effervescent Vaginal Tablet; On the day of Frozen Embryo Transfer (FET), women will have a blood test to determine progesterone levels. Depending on the result of progesterone level, the participant will be assigned to either the Endometrin 100 mg TID dose or the Endometrin 200 mg TID dose; Other Names: Endometrin
Active Comparator: Endometrin 200 mg three times per day (TID); Women with progesterone levels < 8.8 ng/ml during frozen embryo transfer cycle will take Endometrin 200 mg TID until 10th week of pregnancy	Drug: Progesterone Effervescent Vaginal Tablet; On the day of Frozen Embryo Transfer (FET), women will have a blood test to determine progesterone levels. Depending on the result of progesterone level, the participant will be assigned to either the Endometrin 100 mg TID dose or the Endometrin 200 mg TID dose; Other Names: Endometrin

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the ongoing pregnancy rate	Viability ultrasound	6 to 8 weeks after Frozen Embryo Transfer

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluate the miscarriage rate	Viability ultrasound	6 to 8 weeks after Frozen Embryo Transfer
Evaluate progesterone levels	Progesterone levels will be tested at two different times	Before embryo transfer and 10 days after embryo transfer
Evaluate the rate of biochemical pregnancy	Serum pregnancy test to measure Beta Human Chorionic Gonadotropin (BhCG) levels	10 days after frozen embryo transfer

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood test to evaluate the prevalence of PIBF	Progesterone Inducing Blocking Factor (PIBF) has been found to to have an important part in creating a welcoming environment for the embryo	Before embryo transfer and 10 days after embryo transfer

Collaborators and Investigators

• Sponsor: Clinique Ovo
• Collaborators: Ferring Pharmaceuticals
• Investigators: Principal Investigator: Wael Jamal, MD, Clinique ovo

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2022
• Primary Completion (Estimated): April 30, 2028
• Study Completion (Estimated): June 30, 2028

Study Registration Dates

• First Submitted: September 16, 2022
• First Submitted That Met QC Criteria: September 22, 2022
• First Posted (Actual): September 26, 2022

Study Record Updates

• Last Update Posted (Estimated): December 9, 2025
• Last Update Submitted That Met QC Criteria: December 3, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Frozen embryo transfer; Progesterone; Embryo; Embryo implantation
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Polycyclic Compounds; Pregnanes; Steroids; Fused-Ring Compounds; Gonadal Steroid Hormones; Gonadal Hormones; Pregnenediones; Pregnenes; Corpus Luteum Hormones; Progesterone Congeners; Progesterone
• Other Study ID Numbers: IIS-1032

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No