Assessing the Endometrial Environment in Recurrent Pregnancy Loss and Unexplained Infertility

Recurrent Pregnancy Loss Clinical Trial

Official title:

Assessing the Endometrial Environment in Recurrent Pregnancy Loss and Unexplained Infertility

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03401918
• Other study ID #: 40761
• Status: Completed
• Phase: Phase 2
• Start date: August 1, 2017
• Est. completion date: July 1, 2021

Study information

• Verified date: May 2022
• Source: Stanford University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

Recurrent pregnancy loss and unexplained infertility are emotional and difficult diagnoses. Despite a thorough medical investigation, many cases of recurrent pregnancy loss and infertility remain unexplained. Understanding endometrial factors that may contribute to these diseases may lead to improved treatment options in the future. 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. A standard evaluation for infertility includes a uterine cavity evaluation, evaluation for ovarian reserve testing, and for patients with recurrent pregnancy loss parental testing for uterine infection, chromosome analysis, autoimmune and thyroid screening. This standard workup, however, does not include a molecular or microbial assessment of the endometrium. Endometrial factors may contribute to unexplained infertility or recurrent pregnancy loss however the extent of this is unknown. We are recruiting patients who have recurrent pregnancy loss, unexplained infertility, and healthy control patients who have had a term delivery in order to compare differences between these groups. Subjects will undergo an endometrial biopsy that will specifically test the receptivity of your endometrium as well as identify the bacterial composition of the uterine environment (microbiome). The endometrial receptivity array and microbiome testing will be performed at no cost. The endometrial receptivity array provides information on the receptivity of a patient's endometrium to the implantation of an embryo. This may yield additional information regarding the etiology of a patient's infertility and/or recurrent pregnancy loss. If this testing is abnormal we may repeat the biopsy after vaginal progesterone supplementation to see if this normalizes the results. If the microbiome is abnormal we may repeat the biopsy after oral antibiotics and vaginal probiotics to see if this normalizes your microbiome results.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 41
• Est. completion date: July 1, 2021
• Est. primary completion date: July 1, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 18 Years to 45 Years

Eligibility

Inclusion/Exclusion Criteria:

1. Recurrent Pregnancy Loss

Inclusion:

• Age 18-45
• 3 or more SABs including biochemical pregnancies OR 2 or more SABs if one is documented to be euploid

Exclusion:

• irregular menstrual cycles
• Submucosal fibroid >3cm
• Stage 3-4 endometriosis
• BMI >40
• IUD within the last 3 months

2. Unexplained infertility Patients

Inclusion:

• 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

Exclusion:

• Irregular menstrual cycles
• Submucosal fibroid >3cm
• Stage 3-4 endometriosis
• BMI >40
• IUD within the last 3 months
• Less then 2 SABs including biochemical pregnancies

3. Healthy control patients

Inclusion:

• Patients who present for fertility preservation, sex selection, same sex couples needing fertility care, preconception counseling
• 1 or more live births

Exclusion:

• Irregular menstrual cycles
• Submucosal fibroid >3cm
• Stage 3-4 endometriosis
• BMI >40
• IUD within the last 3 months
• Less then 2 SABs including biochemical pregnancies
• No history of RPL or infertility

Related Conditions & MeSH terms

• Abortion, Habitual
• Abortion, Spontaneous
• Fetal Death
• Infertility
• Recurrent Pregnancy Loss
• Unexplained Infertility

Intervention

Diagnostic Test:
• Uterine ERA and microbiome testing
Uterine fluid and endometrial biopsy collection to test uterine endometrial receptivity array and microbiome.

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

Locations

Country	Name	City	State
United States	Reproductive Endocrinology and Infertility Center at Stanford University	Sunnyvale	California

Sponsors (2)

Lead Sponsor	Collaborator
Stanford University	Instituto Valenciano de Infertilidad, IVI VALENCIA

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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