Assessing the Endometrial Environment in Recurrent Pregnancy Loss and Unexplained Infertility

NCT03401918 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: 40761
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine if patients with recurrent pregnancy loss or unexplained infertility have an altered uterine gene expression or uterine microbiome (micro-organism composition) during the window of embryo implantation. Furthermore we would like to assess for women with an abnormal uterine gene expression whether vaginal progesterone medication improves or alters gene expression and for women with an abnormal microbiome whether antibiotic treatment followed by probiotic treatment normalizes the microbiome.

Conditions

Recurrent Pregnancy Loss; Unexplained Infertility

Outcome Measures

Primary Outcomes (4)

• Abnormal Microbiome Bacterial Sequencing

  The primary outcome will abnormal microbiome results. An abnormal microbiome will be defined as less then 90% lactobacilli on DNA sequencing

  1 month

• Abnormal Endometrial Receptivity Array

  The second primary outcome will be abnormal endometrial receptivity array defined as non-receptive (pre or post receptive) based on RNA sequencing of an endometrial gene array.

  1 month

• Normalized Microbiome Bacterial Sequencing

  The primary outcome will be normal microbiome results defined as \>90% lactobacilli after oral antibiotics and vaginal probiotics after initially abnormal microbiome results

  3-6 months

• Normalized Endometrial Receptivity Array

  The primary outcome will be normal endometrial receptivity array results defined as receptive after luteal phase progesterone support after initially abnormal endometrial receptivity array results

  3-6 months

Study Arms (2)

Patients with recurrent pregnancy loss or unexplained infertility

EXPERIMENTAL

Patients with recurrent pregnancy loss or unexplained infertility will have an assessment of the uterine environment at the time of implantation, followed by testing of uterine endometrial gene expression using the ERA test and the uterine micro biome. Those who have abnormal results (an abnormal microbiome or an abnormal ERA) will have the option to undergo treatment followed by retesting of the uterine environment. For an abnormal ERA suggesting a pre-receptive result, luteal phase vaginal progesterone supplementation will be offered prior to re-testing of the ERA. For an abnormal microbiome a combination of oral antibiotics and vaginal probiotics will be offered prior to re-testing the uterine microbiome.

Diagnostic Test: Uterine ERA and microbiome testing; Drug: Oral antibiotics and vaginal probiotics

Healthy Control Patients

EXPERIMENTAL

Patients who have had a normal delivery and no history of infertility or recurrent pregnancy loss will have assessment of the uterine environment at the time of implantation.

Diagnostic Test: Uterine ERA and microbiome testing

Interventions

Uterine ERA and microbiome testing DIAGNOSTIC_TEST

Uterine fluid and endometrial biopsy collection to test uterine endometrial receptivity array and microbiome.

Healthy Control Patients; Patients with recurrent pregnancy loss or unexplained infertility

Oral antibiotics and vaginal probiotics DRUG

For subjects with abnormal microbiome results, oral antibiotics and vaginal probiotic treatment will be offered followed by a repeat uterine microbiome biopsy.

Patients with recurrent pregnancy loss or unexplained infertility

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may not qualify if:

• Recurrent Pregnancy Loss
• Age 18-45
• or more SABs including biochemical pregnancies OR 2 or more SABs if one is documented to be euploid
• irregular menstrual cycles
• Submucosal fibroid \>3cm
• Stage 3-4 endometriosis
• BMI \>40
• IUD within the last 3 months
• Unexplained infertility Patients
• TTC x \>= 1 year
• At least one SA with TMS \>10 mil within last 2 years
• At least one patent fallopian tube documented by HSG or SHG
• Cycle length 25-35 days
• Irregular menstrual cycles
• Submucosal fibroid \>3cm

Sponsors & Collaborators

• Stanford University: lead
• Instituto Valenciano de Infertilidad, IVI VALENCIA: collaborator

Study Sites (1)

Reproductive Endocrinology and Infertility Center at Stanford University

Sunnyvale, California, 94087, United States

Location

MeSH Terms

Interventions

Anti-Bacterial Agents

Intervention Hierarchy (Ancestors)

Anti-Infective Agents; Therapeutic Uses; Pharmacologic Actions; Chemical Actions and Uses

Results Point of Contact

• Title: Ruth Bunker Lathi
• Organization: Stanford University

clinicaltrials-gov@stanford.edu

(650) 498-7911

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 1, 2018
• First Posted: January 17, 2018
• Study Start: August 1, 2017
• Primary Completion: July 1, 2021
• Study Completion: July 1, 2021
• Last Updated: April 1, 2025
• Results First Posted: May 13, 2022

Record last verified: 2025-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)