Clinical Trial Comparing Endometrial Transformation With Subcutaneous Progesterone Versus Intramuscular Progesterone

Phase 4

Completed

Conditions: Reproductive Techniques, Assisted

Interventions: Drug: Subcutaneous progesterone
Drug: Intramuscular progesterone

Registration Number: NCT02567552

Lead Sponsor: IVI Barcelona

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).

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 24

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Prolutex	Subcutaneous progesterone	Subcutaneous progesterone
Prontogest	Intramuscular progesterone	Intramuscular progesterone

Primary Outcome Measures

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

Secondary Outcome Measures

Name	Time	Method
Endometrial Thickness	5 days	Endometrial thickness measurement by means of transvaginal ultrasound.
Blood Progesterone Level	5 days	Blood progesterone level 5 days after progesterone treatment
Number of Participants With Side Effects During the Study	5 days	Number of Participants with side effects during the study"
Blood Estradiol Level	5 days	Blood estradiol level 5 days after progesterone treatment
Blood LH Level	5 days	Blood Luteinizing hormone level 5 days after progesterone treatment