Clinical Trial Comparing Endometrial Transformation With Subcutaneous Progesterone Versus Intramuscular Progesterone

Study Overview
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Brief Summary
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Study the endometrial predecidualization by using subcutaneous progesterone 25 mg/day versus intramuscular progesterone 50 mg/day, to determine whether there are differences in the endometrial transformation and endometrial receptivity.

Detailed Description
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The aim of this study is to compare predecidualization and endometrial receptivity as gene expression by using subcutaneous progesterone 25 mg/day versus intramuscular progesterone 50 mg/day in healthy women of childbearing age. Both, the two drugs and the doses administered in this clinical trial, are routine clinical practice. A controlled ovarian stimulation will be previously performed and following routine clinical practice for 10-12 days at standard doses of subcutaneous FSH 150-225 IU/day, according to BMI and number of antral follicles. A GnRH antagonist shall be administered, being initiated according to donor's follicular growth from greater or equal14 mm diameter follicles. Final maturation shall be performed with a bolus of GnRH agonist when there exist at least 3 follicles greater or equal17 mm diameter, and therefore performing follicular puncture 36 hours after the bolus of agonist has been administered. If the donor meets the inclusion criteria, she will be informed of the study and, if she agrees, she will sign the informed consent. Randomization shall be performed in 2 arms; arm 1 will be administered subcutaneous progesterone 25 mg/day (Prolutex; Angelini, Spain), and arm 2, intramuscular progesterone 50 mg/day (Prontogest IBSA, Italy). In each arm 12 donors (ITT population) will be included. The randomization to a treatment group shall be performed the day the follicular puncture has been programmed. To that purpose, a randomized consecutive sampling will be used by means of assignment tables. The medication will be administered by a person not involved in the assessments and responsible for group assignment, data centralization and drug assignment. At day 5 (5 days after follicular puncture):endometrial thickness measurement by means of transvaginal ultrasound and perform endometrial biopsy and take two samples: 1 sample to Anatomical Pathology and 1 sample to Endometrial Receptivity Array (ERA).

Official Title
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Randomized Clinical Trial Comparing Endometrial Transformation With Subcutaneous Progesterone (Prolutex) 25 mg/Day Versus Intramuscular Progesterone (Prontogest) 50 mg/Day

Conditions
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Reproductive Techniques, Assisted

Intervention / Treatment
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* Drug: Subcutaneous progesterone
* Drug: Intramuscular progesterone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female aged between 18 and 34 years BMI between 18 and 28 kg/m2 Endometrial thickness > 7 mm the day of progesterone treatment initiation (day of follicular puncture) Follicular maturation with a single bolus of GnRH agonist Egg donors who undergo a cycle of ovarian stimulation in the IVI Barcelona Centre Egg donors selected in accordance with the requirements of Law 14/2006 of 26 May 2006 on Assisted Human Reproduction Techniques Informed consent has been signed and dated Exclusion Criteria: Known allergy to progesterone formulations or their excipients Known allergy to estrogens Known thrombophilias Alcohol, drug or psychotropic medication dependence Concurrent participation in another study Concomitant medication that may interfere with the study medication and ovarian stimulation Failure to comply with the requirements for egg donors in accordance with Law 14/2006 of 26 May 2006 on Assisted Human Reproduction Techniques

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 34 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Prolutex<br>Subcutaneous progesterone | Drug: Subcutaneous progesterone<br>* subcutaneous progesterone 25 mg/day<br>* Other names: Prolutex;|
| Active Comparator: Prontogest<br>Intramuscular progesterone | Drug: Intramuscular progesterone<br>* intramuscular progesterone 50 mg/day<br>* Other names: Prontogest;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Predecidual Transformation | Histologic dating of the endometrium at day 5: early secretory phase, media secretory phase or late secretory phase | 5 days | 
| Decidualization of Stromal Cell | Rate of transformation of endometrial stromal fibroblasts into specialized secretory decidual cells (three categories: less than 25%, between 26% and 50%, and over 50%) | 5 days | 
| Endometrial Maturation Using Noyes' Criteria | Endometrial dating of luteal phase days according to the Noyes criteria | 5 days | 
| Endometrial Gene Expression | Gene expression profile of endometrial | 5 days | 
| Endometrial Gene Expression Difference | Genes with a significantly high gene expression difference (adj-p-value < 0.05, Fold Change>3) | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endometrial Thickness | Endometrial thickness measurement by means of transvaginal ultrasound. | 5 days | 
| Blood Estradiol Level | Blood estradiol level on the day of follicular puncture | day 0 | 
| Blood Progesterone Level | Blood progesterone level on the day of follicular puncture | day 0 | 
| Blood LH Level | Blood Luteinizing hormone level on the day of follicular puncture | day 0 | 
| Blood Estradiol Level | Blood estradiol level 5 days after progesterone treatment | 5 days | 
| Blood Progesterone Level | Blood progesterone level 5 days after progesterone treatment | 5 days | 
| Blood LH Level | Blood Luteinizing hormone level 5 days after progesterone treatment | 5 days | 
| Number of Participants With Side Effects During the Study | Number of Participants with side effects during the study | 5 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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endometrial receptivity, endometrial predecidualization, endometrial genomics, endometrial receptivity array