Recurrent Pregnancy LossPhase 2NCT03401918
Assessing the Endometrial Environment in Recurrent Pregnancy Loss and Unexplained Infertility
A Phase 2 study testing Uterine ERA and microbiome testing and Oral antibiotics and vaginal probiotics in people with Recurrent Pregnancy Loss and Unexplained Infertility, run by Stanford University at 1 site in United States.
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. Read more about this study
- Who is it for?
- Ages 18 to 45 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Recurrent Pregnancy Loss, Unexplained Infertility
- What is being tested?
- Uterine ERA and microbiome testing and Oral antibiotics and vaginal probiotics
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 41 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Aug 2017to 1 Jul 2021
- Phase
- Phase 2
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Recurrent Pregnancy Loss
- Age 18-45
- 3 or more SABs including biochemical pregnancies OR 2 or more SABs if one is documented to be euploid
- 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
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- Cycle length 25-35 days
- Patients who present for fertility preservation, sex selection, same sex couples needing fertility care, preconception counseling
- 1 or more live births
Who cannot join
- irregular menstrual cycles
- Submucosal fibroid >3cm
- Stage 3-4 endometriosis
- BMI >40
- IUD within the last 3 months
- Unexplained infertility Patients
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- 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
- Healthy control patients
- 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 locations and contacts
1 site in 1 country.
United States1 site
Reproductive Endocrinology and Infertility Center at Stanford University
Sunnyvale, California, 94087
About this study
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.
Read the 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.
- Conditions
- Recurrent Pregnancy Loss, Unexplained Infertility
- Being tested
- Uterine ERA and microbiome testing, Oral antibiotics and vaginal probiotics
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Uterine ERA and microbiome testingDiagnostic test
Uterine fluid and endometrial biopsy collection to test uterine endometrial receptivity array and microbiome.
Oral antibiotics and vaginal probioticsDrug
For subjects with abnormal microbiome results, oral antibiotics and vaginal probiotic treatment will be offered followed by a repeat uterine microbiome biopsy.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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. Receives: Diagnostic Test: Uterine ERA and microbiome testing |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: 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
Measured: 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
Measured: 3-6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Jan 2018
- Study start1 Aug 2017
- Primary completion1 Jul 2021
- Study completion1 Jul 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Recurrent Pregnancy LossStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 41 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- Instituto Valenciano de Infertilidad, IVI VALENCIA
- Responsible party
- Principal investigator, Ruth Bunker Lathi, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03401918
- Sponsor's protocol ID
- 40761
- Status last verified
- Mar 2025
- First submitted
- 1 Jan 2018
- Last updated
- 1 Apr 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No