Clinical trial NCT02567552: Clinical Trial Comparing Endometrial Transformation With Subcutaneous Progesterone Versus Intramuscular Progesterone
Official title: Randomized Clinical Trial Comparing Endometrial Transformation With Subcutaneous Progesterone (Prolutex) 25 mg/Day Versus Intramuscular Progesterone (Prontogest) 50 mg/Day
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Reproductive Techniques, Assisted
Keywords: endometrial receptivity
endometrial predecidualization
endometrial genomics
endometrial receptivity array
Lead sponsor: IVI Barcelona
Sponsor class: OTHER
First posted: 2015-10-05
Enrollment: 24
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 34
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Parallel Assignment
Primary purpose: TREATMENT

Brief summary: 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: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Predecidual Transformation
timeFrame: 5 days
measure: Decidualization of Stromal Cell
timeFrame: 5 days
measure: Endometrial Maturation Using Noyes' Criteria
timeFrame: 5 days
measure: Endometrial Gene Expression
timeFrame: 5 days
measure: Endometrial Gene Expression Difference
timeFrame: 5 days
Secondary outcomes:
measure: Endometrial Thickness
timeFrame: 5 days
measure: Blood Estradiol Level
timeFrame: day 0
measure: Blood Progesterone Level
timeFrame: day 0
measure: Blood LH Level
timeFrame: day 0
measure: Blood Estradiol Level
timeFrame: 5 days
measure: Blood Progesterone Level
timeFrame: 5 days
measure: Blood LH Level
timeFrame: 5 days
measure: Number of Participants With Side Effects During the Study
timeFrame: 5 days
Other outcomes:
Locations:
city: Barcelona
country: Spain
facility: IVI Barcelona
Study officials:
affiliation: IVI Barcelona
name: Agustín B Boluda
role: PRINCIPAL_INVESTIGATOR
References: