A Phase 2 interventional study of Uterine ERA and microbiome testing and Oral antibiotics and vaginal probiotics in Recurrent Pregnancy Loss and Unexplained Infertility, sponsored by Stanford University. Completed at 1 site in United States. Open to female participants aged 18 Years to 45 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2025-04-01.
Sponsored by Stanford University · Phase 2, Interventional, and Treatment
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.
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.
Inclusion/Exclusion Criteria:
Recurrent Pregnancy Loss
Inclusion:
Exclusion:
Unexplained infertility Patients
Inclusion:
Exclusion:
Inclusion:
Exclusion:
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
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
Uterine fluid and endometrial biopsy collection to test uterine endometrial receptivity array and microbiome.
For subjects with abnormal microbiome results, oral antibiotics and vaginal probiotic treatment will be offered followed by a repeat uterine microbiome biopsy.
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
Time frame: 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.
Time frame: 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
Time frame: 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
Time frame: 3-6 months
| Milestone | Patients With Recurrent Pregnancy Loss or Unexplained Infertility | Healthy Control Patients |
|---|---|---|
| Started | 25 | 16 |
| Completed | 25 | 16 |
| Not completed | 0 | 0 |
The primary outcome will abnormal microbiome results. An abnormal microbiome will be defined as less then 90% lactobacilli on DNA sequencing
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
The primary outcome will be normal microbiome results defined as \>90% lactobacilli after oral antibiotics and vaginal probiotics after initially abnormal microbiome results
No measurements were reported for this outcome.
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
No measurements were reported for this outcome.
Collected over Up to 6 months. Non-serious events are listed at a 5% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Patients With Recurrent Pregnancy Loss or Unexplained Infertility | 0/25 (0%) | 0/25 (0%) | 0/25 (0%) |
| Healthy Control Patients | 0/16 (0%) | 0/16 (0%) | 0/16 (0%) |
| Age, Categorical(Participants) | Patients With Recurrent Pregnancy Loss or Unexplained Infertility | Healthy Control Patients | Total |
|---|---|---|---|
| <=18 years | 0 | 0 | 0 |
| Between 18 and 65 years | 25 | 16 | 41 |
| >=65 years | 0 | 0 | 0 |
| Sex: Female, Male(Participants) | Patients With Recurrent Pregnancy Loss or Unexplained Infertility | Healthy Control Patients | Total |
|---|---|---|---|
| Female | 25 | 16 | 41 |
| Male | 0 | 0 | 0 |
| Race/Ethnicity, Customized(Participants) | Patients With Recurrent Pregnancy Loss or Unexplained Infertility | Healthy Control Patients | Total |
|---|---|---|---|
| Asian | 13 | 2 | 15 |
| Caucasian | 12 | 12 | 24 |
| Black | 0 | 1 | 1 |
| Hispanic | 0 | 1 | 1 |
| Region of Enrollment(Participants) | Patients With Recurrent Pregnancy Loss or Unexplained Infertility | Healthy Control Patients | Total |
|---|---|---|---|
| United States | 25 | 16 | 41 |
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Stanford University