Clinical Trial Comparing Endometrial Transformation With Subcutaneous Progesterone Versus Intramuscular Progesterone

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

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.

Study Overview

• Status: Completed
• Conditions: Reproductive Techniques, Assisted
• Intervention / Treatment: Drug: Subcutaneous progesterone; Drug: Intramuscular progesterone

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).

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Barcelona, Spain, 08017
    • IVI Barcelona

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 34 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Prolutex; Subcutaneous progesterone	Drug: Subcutaneous progesterone; subcutaneous progesterone 25 mg/day; Other Names: Prolutex
Active Comparator: Prontogest; Intramuscular progesterone	Drug: Intramuscular progesterone; intramuscular progesterone 50 mg/day; Other Names: Prontogest

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: IVI Barcelona
• Investigators: Principal Investigator: Agustín B Boluda, IVI Barcelona

Study record dates

Study Major Dates

• Study Start: May 1, 2015
• Primary Completion (Actual): December 1, 2015
• Study Completion (Actual): January 1, 2016

Study Registration Dates

• First Submitted: October 2, 2015
• First Submitted That Met QC Criteria: October 2, 2015
• First Posted (Estimate): October 5, 2015

Study Record Updates

• Last Update Posted (Actual): December 16, 2019
• Last Update Submitted That Met QC Criteria: December 13, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: endometrial receptivity; endometrial predecidualization; endometrial genomics; endometrial receptivity array
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: 1412-BCN-087-AB; 2015-000290-12 (EudraCT Number)

Plan for Individual participant data (IPD)

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