Timing Endometrial Receptivity

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ABSTRACT 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.