Clinical trial NCT03401918: Assessing the Endometrial Environment in Recurrent Pregnancy Loss and Unexplained Infertility
Official title: Assessing the Endometrial Environment in Recurrent Pregnancy Loss and Unexplained Infertility
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Recurrent Pregnancy Loss
Unexplained Infertility
Lead sponsor: Stanford University
Sponsor class: OTHER
Collaborators: name: Instituto Valenciano de Infertilidad, IVI VALENCIA
First posted: 2018-01-17
Enrollment: 41
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Abnormal Microbiome Bacterial Sequencing
timeFrame: 1 month
measure: Abnormal Endometrial Receptivity Array
timeFrame: 1 month
measure: Normalized Microbiome Bacterial Sequencing
timeFrame: 3-6 months
measure: Normalized Endometrial Receptivity Array
timeFrame: 3-6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Sunnyvale
country: United States
facility: Reproductive Endocrinology and Infertility Center at Stanford University
state: California
Study officials:
References: