Rescue Progesterone Supplementation During Frozen Embryo Transfer

Study Overview
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Brief Summary
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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.

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

Conditions
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Fertility Issues, Embryo Implantation, Frozen Embryo Transfer

Intervention / Treatment
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* Drug: Progesterone Effervescent Vaginal Tablet


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 42 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single centre, prospective, open label study
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Endometrin 100 mg three times per day (TID)<br>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<br>* 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<br>* Other names: Endometrin;|
| Active Comparator: Endometrin 200 mg three times per day (TID)<br>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<br>* 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<br>* Other names: Endometrin;|

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Embryo, Frozen embryo transfer, Progesterone, Embryo implantation