Impact of Different Doses and Routes of Exogenous Progesterone Administration on Endometrial Receptivity Parameters (PROGENDO)

Exploratory Study on the Impact of Different Doses and Route of Administration of Exogenous Progesterone in Artificial Endometrial Preparation Cycles on Endometrial Structure and Function

After so many years conducting artificial endometrial preparation cycles for embryo transfer, there is no clear indication about which is the optimal dose of exogenous progesterone in this scenario to optimize the outcome. Taking into account that the luteal phase can be controlled by measuring serum P levels (not done until now), the next step is to find out which is the best dose and route of administration of exogenous progesterone for luteal phase in artificial cycles.

Therefore, the aim of this experimental study is to compare the endometrial function and structure, as well as the serum P levels according to the use of different types of exogenous progesterone available on the market depending on their doses and route of administration (vaginal, subcutaneous or intramuscular). The endometrial receptivity status will be compared in the different artificial cycles with the one observed in a natural cycle, without exogenous progesterone (only the endogenous one) as a control group.

Endometrial receptivity will be analysed by means of endometrial function and structure, but not by pregnancy outcome as in this study an embryo cannot be replaced in the uterus because an endometrial biopsy needs to be done to do this type of research.

Study Overview

• Status: Recruiting
• Conditions: Infertility, Female; ENDOMETRIAL RECEPTIVITY
• Intervention / Treatment: Drug: Progesterone; Other: Artificial Cycle (no intervention)

• Study Type: Interventional
• Enrollment (Anticipated): 90
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: LAURA CARACENA; Phone Number: 11054 963050999; Email: Laura.Caracena@ivirma.com

Study Locations

• Spain
  • Valencia, Spain, 46015
    • Recruiting
    • Instituto Valenciano de Infertilidad Spain
    • Sub-Investigator: Ernesto Bosch, MD
    • Sub-Investigator: Pilar Alama, MD
    • Sub-Investigator: Josep Lluis Romero, MD
    • Sub-Investigator: Patricia Diaz-Gimeno, MD
    • Sub-Investigator: Patricia Sebastian, MD
    • Sub-Investigator: Cristina Rodríguez

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 35 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Female

Description

Inclusion Criteria

All women with no history of infertility who agree to participate in the study:

1. Age: 18-35 years old, both inclusive
2. Regular menstrual cycles
3. In good health and not suffering from any mental or medical condition(s) that would preclude participation in the study.

Exclusion Criteria

Subjects who meet one or more of the following will not be considered eligible to participate in the pilot study:

1. Simultaneous participation in other clinical studies that, at the researcher's criteria, could interfere with the results of this study.
2. Taking oral contraceptives in the three months prior to signing informed consent.
3. Presence of uterine pathology (submucosal or intramural myomas >4 cm deforming cavity, endometrial polyps or müllerian anomalies) or adnexal pathology (communicating hydrosalpinx).
4. Background of thrombosis, breast cancer, systemic diseases.
5. Those unable to comprehend the investigational nature of the proposed study.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: I: Artificial endometrial preparation cycle; Artificial endometrial preparation cycle with estrogens and vaginal natural micronized progesterone 400mg/12h	Drug: Progesterone; Subjects will undergo an artificial cycle with hormone replacement therapy (HRT) with the aim of comparing the endometrial gene expression profile in the different types of exogenous progesterone with different doses and routes of administration.
Experimental: II: Artificial endometrial preparation cycle; Artificial endometrial preparation cycle with estrogens and subcutaneous natural progesterone 25mg/24h	Drug: Progesterone; Subjects will undergo an artificial cycle with hormone replacement therapy (HRT) with the aim of comparing the endometrial gene expression profile in the different types of exogenous progesterone with different doses and routes of administration.
Experimental: III: Artificial endometrial preparation cycle; Artificial endometrial preparation cycle with estrogens and subcutaneous natural progesterone 25mg/12h	Drug: Progesterone; Subjects will undergo an artificial cycle with hormone replacement therapy (HRT) with the aim of comparing the endometrial gene expression profile in the different types of exogenous progesterone with different doses and routes of administration.
Experimental: IV: Artificial endometrial preparation cycle; Artificial endometrial preparation cycle with estrogens and a combination of subcutaneous natural progesterone 25mg/24h + vaginal natural micronized progesterone 400mg/24h	Drug: Progesterone; Subjects will undergo an artificial cycle with hormone replacement therapy (HRT) with the aim of comparing the endometrial gene expression profile in the different types of exogenous progesterone with different doses and routes of administration.
Experimental: V: Artificial endometrial preparation cycle; Artificial endometrial preparation cycle with estrogens and intramuscular natural progesterone 50mg/24h	Drug: Progesterone; Subjects will undergo an artificial cycle with hormone replacement therapy (HRT) with the aim of comparing the endometrial gene expression profile in the different types of exogenous progesterone with different doses and routes of administration.
Active Comparator: Natural menstrual cycle; Natural menstrual cycle (without any exogenous steroid hormone Treatment)	Other: Artificial Cycle (no intervention); Control group of 15 subjects in the context of a natural cycle with only endogenous progesterone present

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Endometrial gene expression profile	Determination of gene expression	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Histological dating of endometrial biopsies	Endometrial classification using Noyes criteria	12 months
Histological analysis of the endometrial tissue using electron microscopy	Presence or Absence of Pinopodes	12 months
Progesterone concentration in the endometrium	Endometrial progesterone values	12 months
Serum Progesterone concentrations	Blood serum progesterone values	12 months
Correlation between progesterone levels in blood and uterus.	Presence or Absence of correlation	12 months
Correlation between serum and uterine levels with endometrial transcriptome and histological dating	Presence or Absence of correlation	12 months

Collaborators and Investigators

• Sponsor: Instituto Valenciano de Infertilidad, IVI VALENCIA

Study record dates

Study Major Dates

• Study Start (Actual): December 9, 2021
• Primary Completion (Anticipated): December 1, 2023
• Study Completion (Anticipated): December 1, 2024

Study Registration Dates

• First Submitted: July 30, 2020
• First Submitted That Met QC Criteria: July 30, 2020
• First Posted (Actual): August 5, 2020

Study Record Updates

• Last Update Posted (Estimate): February 21, 2023
• Last Update Submitted That Met QC Criteria: February 20, 2023
• Last Verified: February 1, 2023

More Information

Terms related to this study

• Keywords: Progesterone; Luteal phase; Endometrial gene expression; Endometrial receptivity; Artificial endometrial preparation cycle
• Additional Relevant MeSH Terms: Infertility; Infertility, Female; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Progesterone
• Other Study ID Numbers: 1901-VLC-014-EL

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No