Discovered in 1960 by electron microscopy (EM), nucleolar channel systems (NCSs) are arguably the most unique organelles of human cells, formed by membrane tubules in the normally membrane-free nucleus. They are specific to human endometrial epithelial cells (EECs) and absent from any other tissue or species. In fact, they are not even present in baboon endometrium. They form transiently each month only during a few days, which appear to mark the period when the endometrium is receptive to embryo implantation, the so-called window of implantation (WOI). Although the term WOI is firmly established among reproductive specialists, its definition is far from clear. Accurate dating of the WOI is important for assisted reproductive technologies (ART), especially for timing of embryo transfer (ET) to enhance success rates of in vitro fertilization (IVF) cycles. Ideally, timing of frozen- thawed ET (FET) would rely on ascertaining maximal endometrial receptivity right before transfer without interfering with embryo implantation. However, all current methods assessing endometrial receptivity rely on endometrial biopsy, which has been documented to both prevent and promote implantation. Consequently, most infertility specialists would be more than hesitant to perform such an invasive procedure on the day of ET. In contrast, we developed a noninvasive method to delimit the NCS window in exfoliated cells of uterine secretions. We now propose to exploit our novel approach to determine the NCS window in individual cycles by repeated sampling and to validate it as a diagnostic tool for maximal endometrial receptivity. Our proposal will lay the groundwork for timing FET live to boost success rates of IVF cycles.

Public Health Relevance

The study will provide a means to enhance success rates of in vitro fertilization cycles providing help to patients with fertility problems by determining in real time the maximal receptivity of human endometrium.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Exploratory/Developmental Grants (R21)
Project #
6R21HD094293-02
Application #
9854126
Study Section
Cellular, Molecular and Integrative Reproduction Study Section (CMIR)
Program Officer
Eisenberg, Esther
Project Start
2018-08-30
Project End
2020-07-31
Budget Start
2019-01-01
Budget End
2019-07-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Albert Einstein College of Medicine
Department
Type
DUNS #
081266487
City
Bronx
State
NY
Country
United States
Zip Code
10461