Clinical trial NCT06616077: Endometrial Transcript Profile with Progesterone After Post-ovulatory Mifepristone
Official title: Determinaton of Changes in the Endometrial Gene Expression Profile Induced by Exogenous Progesterone After Post-ovulatory Administration of Mifepristone
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: EARLY_PHASE1
Conditions: Endometrial Endocrine Regulation
Progesterone Supplementation in Women After Mifepristone
Keywords: Endometrial gene expression
Progesterone
Mifepristone
RU486
Secretory endometrium
Lead sponsor: Reproductive Health Research Insritute, Chile
Sponsor class: OTHER
First posted: 2024-09-27
Enrollment: 9
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 43
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: The goal of this exploratory trial is to determine the endometrial gene expression profile induced by exogenous progesterone after postovulatory administration of mifepristone. It will also learn about the plasticity ofr the endometrial response to progesterone. The main questions it aims to answer are:

Is exogenous progesterone able to modulate the gene expression of endometrial transcripts that have been altered by mifepristone?

Researchers will compare the endometrial gene expression profiles with exogeonous progesterone to a placebo (a look-alike substance that contains no drug) after postovulatory administration of mifepristone.

Participants will:

Do ovulation follow-up tests at home assesing LH in urine Visit the hospital 2 days after a positive LH for mifepristone administration and ultrasonography check of ovaries and uterus.

Starting from the next day, take progesterone or placebo for 3 days. Visit the hospital 2 days after that for ultrasonography check of ovaries and uterus and for an endometrial and blood sample collection.

The endometrial samples will be processed to isolate the RNA and for histological assessment. Gene expression profiles will be determined by RNA-seq.

Detailed description: Objective: To determine the effect of progesterone supplementation on the mid-secretory endometrial transcript profile after postovulatory administration of mifepristone.

Design: A randomized, double-blind, placebo-controlled study. Setting: Tertiary academic medical center Subjects: A total of 9 Hispanic women of proven fertility who had been surgically sterilized.

Interventions: Participating women received a single dose of mifepristone 200mg 48 hours after the LH peak (LH+2, LH+0=LH peak). Endometrial samples were obtained on LH+7 after vaginal administration of micronized progesterone (600mg/day) for 3 days (LH+3 to LH+5). Each woman contributed with one cycle treated with placebo and another with progesterone (group A). Additionally, endometrial samples were obtained on LH+7 from subset of 4 women who did not receive mifepristone; with each one contributing with one cycle treated with vaginal progesterone supplementation or placebo as a reference (group B). Endometrial thickness, circulating progesterone levels, and endometrial histology were also documented in all cycles. RNA-seq was used to identify genes whose transcript levels significantly changed by the administration of progesterone versus placebo, with postovulatory administration of mifepristone. The transcript profiles of these genes were further evaluated in the endometrial samples from group B.

Eligibility criteria: Inclusion Criteria:

* proven fertility
* regular menstrual cycles
* surgically sterilized at least one year before participating in the protocol

Exclusion Criteria:

* chronic medical problems
* abnormal results of screening blood tests
* ovarian masses
* symptomatic endometriosis
* uterine leiomyomata
* being under chronic medication or taking hormones or drugs able to modify the metabolism of steroid hormones in the 3 preceding months to study enrollment

Primary outcomes:
measure: Endometrial Gene Expression Profile
timeFrame: From enrollment to the end of treatments after aproximately 12 weeks
Secondary outcomes:
measure: Endometrial dating
timeFrame: From enrollment to the end of treatments after aproximately 8 months
Other outcomes:
measure: Uterine ultrasonographic features
timeFrame: From enrrollment to the end of treatments after 12 weeks
measure: Circulating progesterone levels
timeFrame: From enrollment to after the treatments after 12 weeks
Locations:
city: Santiago
country: Chile
facility: Hospital San Borja Arriarán
state: Región Metropolitana
Study officials:
affiliation: University of Chile
name: Alejandro A Tapia-Pizarro, Biologist, PhD
role: STUDY_DIRECTOR
References: