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

NCT04499131 | Completed Phase 4

• 1 other identifier: 1901-VLC-014-EL
• Study Type: interventional
• Target: 109
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Infertility, Female; ENDOMETRIAL RECEPTIVITY

Keywords

Luteal phase; Artificial endometrial preparation cycle; Progesterone; Endometrial gene expression; Endometrial receptivity

Outcome Measures

Primary Outcomes (1)

• Endometrial gene expression profile

  Determination of gene expression

  12 months

Secondary Outcomes (5)

• Histological dating of endometrial biopsies

  12 months

• Progesterone concentration in the endometrium

  12 months

• Serum Progesterone concentrations

  12 months

• Correlation between progesterone levels in blood and uterus.

  12 months

• Correlation between serum and uterine levels with endometrial transcriptome and histological dating

  12 months

Study Arms (6)

I: Artificial endometrial preparation cycle

EXPERIMENTAL

Artificial endometrial preparation cycle with estrogens and vaginal natural micronized progesterone 400mg/12h

Drug: Progesterone

II: Artificial endometrial preparation cycle

EXPERIMENTAL

Artificial endometrial preparation cycle with estrogens and subcutaneous natural progesterone 25mg/24h

Drug: Progesterone

III: Artificial endometrial preparation cycle

EXPERIMENTAL

Artificial endometrial preparation cycle with estrogens and subcutaneous natural progesterone 25mg/12h

Drug: Progesterone

IV: Artificial endometrial preparation cycle

EXPERIMENTAL

Artificial endometrial preparation cycle with estrogens and a combination of subcutaneous natural progesterone 25mg/24h + vaginal natural micronized progesterone 400mg/24h

Drug: Progesterone

V: Artificial endometrial preparation cycle

EXPERIMENTAL

Artificial endometrial preparation cycle with estrogens and intramuscular natural progesterone 50mg/24h

Drug: Progesterone

Natural menstrual cycle

ACTIVE COMPARATOR

Natural menstrual cycle (without any exogenous steroid hormone Treatment)

Other: Artificial Cycle (no intervention)

Interventions

Progesterone DRUG

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.

I: Artificial endometrial preparation cycle; II: Artificial endometrial preparation cycle; III: Artificial endometrial preparation cycle; IV: Artificial endometrial preparation cycle; V: Artificial endometrial preparation cycle

Artificial Cycle (no intervention) OTHER

Control group of 19 subjects in the context of a natural cycle with only endogenous progesterone present

Natural menstrual cycle

Eligibility Criteria

• Age: 18 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• All women with no history of infertility who agree to participate in the study:
• Age: 18-35 years old, both inclusive
• Regular menstrual cycles
• In good health and not suffering from any mental or medical condition(s) that would preclude participation in the study.

You may not qualify if:

• Subjects who meet one or more of the following will not be considered eligible to participate in the pilot study:
• Simultaneous participation in other clinical studies that, at the researcher's criteria, could interfere with the results of this study.
• Taking oral contraceptives in the three months prior to signing informed consent.
• Presence of uterine pathology (submucosal or intramural myomas \>4 cm deforming cavity, endometrial polyps or müllerian anomalies) or adnexal pathology (communicating hydrosalpinx).
• Background of thrombosis, breast cancer, systemic diseases.
• Those unable to comprehend the investigational nature of the proposed study.

Sponsors & Collaborators

• Instituto Valenciano de Infertilidad, IVI VALENCIA: lead

Study Sites (1)

Instituto Valenciano de Infertilidad Spain

Valencia, Valencia, 46015, Spain

Location

MeSH Terms

Conditions

Infertility, Female

Interventions

Progesterone

Condition Hierarchy (Ancestors)

Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Infertility

Intervention Hierarchy (Ancestors)

Pregnenediones; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Corpus Luteum Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progesterone Congeners; Gonadal Steroid Hormones

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Masking Details: Patients will be evaluated by blinded gynecologist in order to prevent the application of personal criteria and protect the consistence of the study.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Exploratory, unicentric, with blind evaluators, randomized to six parallel arms in ratio 1:1:1:1:1:1 clinical trial conducted in healthy volunteers under an artificial endometrial preparation cycle and luteal phase support with exogenous progesterone administered by different doses and routes or natural menstrual cycles.

Study Record Dates

• First Submitted: July 30, 2020
• First Posted: August 5, 2020
• Study Start: December 9, 2021
• Primary Completion: April 30, 2025
• Study Completion: December 31, 2025
• Last Updated: February 3, 2026

Record last verified: 2026-01

Locations

ES (1)