Assessing the Endometrial Environment in Recurrent Pregnancy Loss and Unexplained Infertility

Stanford University

Status and phase: Completed; Phase 2

Conditions: Recurrent Pregnancy Loss; Unexplained Infertility

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

Study type: Interventional

Funder types: Other

Identifiers

NCT03401918

40761

Details and patient eligibility

About

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.

Full 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.

Enrollment: 41 patients

Sex: Female

Ages: 18 to 45 years old

Volunteers: Accepts Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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41 participants in 2 patient groups

Patients with recurrent pregnancy loss or unexplained infertility

Experimental group

Description:

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.

Treatment:

Diagnostic Test: Uterine ERA and microbiome testing

Drug: Oral antibiotics and vaginal probiotics

Healthy Control Patients

Experimental group

Description:

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.

Treatment:

Diagnostic Test: Uterine ERA and microbiome testing