Assessing the Endometrial Environment in Recurrent Pregnancy Loss and Unexplained Infertility
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|ClinicalTrials.gov Identifier: NCT03401918|
Recruitment Status : Recruiting
First Posted : January 17, 2018
Last Update Posted : January 17, 2018
|Condition or disease||Intervention/treatment||Phase|
|Recurrent Pregnancy Loss Unexplained Infertility||Diagnostic Test: Uterine ERA and microbiome testing Drug: Oral antibiotics and vaginal probiotics||Phase 2|
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.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||300 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||Single (Outcomes Assessor)|
|Official Title:||Assessing the Endometrial Environment in Recurrent Pregnancy Loss and Unexplained Infertility|
|Actual Study Start Date :||September 6, 2017|
|Estimated Primary Completion Date :||July 1, 2018|
|Estimated Study Completion Date :||May 1, 2019|
Experimental: Comparing the microbiome and ERA in RPL and infertility
In this arm we will assess the uterine environment at the time of implantation in recurrent pregnancy loss patients and unexplained infertility patients and compare the environment in these patient populations to healthy parous controls.
We will test the uterine endometrial gene expression using the ERA test and the uterine micro biome.
Diagnostic Test: Uterine ERA and microbiome testing
Uterine fluid and endometrial biopsy collection to test uterine endometrial receptivity array and microbiome.
Experimental: The impact of progesterone and antibiotics/probiotics
In this arm, recurrent pregnancy loss and unexplained infertility patients 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.
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.
- abnormal microbiome bacterial sequencing [ Time Frame: 1 month ]The primary outcome will abnormal microbiome results. An abnormal microbiome will be defined as less then 90% lactobacilli on DNA sequencing
- abnormal endometrial receptivity array [ Time Frame: 1 months ]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.
- normalized microbiome bacterial sequencing [ Time Frame: 3-6 months ]The primary outcome will be normal microbiome results defined as >90% lactobacilli after oral antibiotics and vaginal probiotics after initially abnormal microbiome results
- normalized endometrial receptivity array [ Time Frame: 3-6 months ]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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03401918
|United States, California|
|Reproductive Endocrinology and Infertility Center at Stanford University||Recruiting|
|Sunnyvale, California, United States, 94087|
|Contact: Sara J Churchill, MD 617-513-4997 firstname.lastname@example.org|