Assessing the Endometrial Environment in Recurrent Pregnancy Loss and Unexplained Infertility

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:

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