Assessing the Endometrial Environment in Recurrent Pregnancy Loss and Unexplained Infertility
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 41
- 试验地点
- 1
- 主要终点
- Normalized Microbiome Bacterial Sequencing
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 45 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- •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
- •irregular menstrual cycles
- •Submucosal fibroid >3cm
- •Stage 3-4 endometriosis
- •IUD within the last 3 months
- •Unexplained infertility Patients
- •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
- •Irregular menstrual cycles
- •Submucosal fibroid >3cm
- •Stage 3-4 endometriosis
- •IUD within the last 3 months
- •Less then 2 SABs including biochemical pregnancies
- •Healthy control patients
- •Patients who present for fertility preservation, sex selection, same sex couples needing fertility care, preconception counseling
- •1 or more live births
- •Irregular menstrual cycles
- •Submucosal fibroid >3cm
- •Stage 3-4 endometriosis
- •IUD within the last 3 months
- •Less then 2 SABs including biochemical pregnancies
- •No history of RPL or infertility
研究组 & 干预措施
Patients with recurrent pregnancy loss or unexplained infertility
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.
干预措施: Uterine ERA and microbiome testing (Diagnostic Test)
Patients with recurrent pregnancy loss or unexplained infertility
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.
干预措施: Oral antibiotics and vaginal probiotics (Drug)
Healthy Control Patients
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.
干预措施: Uterine ERA and microbiome testing (Diagnostic Test)
结局指标
主要结局
Normalized Microbiome Bacterial Sequencing
时间窗: 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
Abnormal Endometrial Receptivity Array
时间窗: 1 month
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.
Abnormal Microbiome Bacterial Sequencing
时间窗: 1 month
The primary outcome will abnormal microbiome results. An abnormal microbiome will be defined as less then 90% lactobacilli on DNA sequencing
Normalized Endometrial Receptivity Array
时间窗: 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
次要结局
未报告次要终点
研究者
Ruth Bunker Lathi
Professor
Stanford University