Identification of nucleolar channel systems (NCSs) in endometrial secretions at the time of frozen embryo transfer in artificial cycles with successful implantation

NCSs are histological markers of the window of implantation in natural and controlled ovarian hyperstimulation cycles. Thus far, NCSs have not been detected in frozen embryo transfer artificial (FET-A) cycles. This study aims to detect NCSs in endometrial aspirations obtained immediately prior to embryo transfer during blastocyst FET-A cycles without affecting implantation. Prospective study at a single university-affiliated site Patients undergoing FET-A using estradiol and progesterone for endometrial preparation are consented for a lower uterine segment aspiration using an open tip embryo transfer catheter during a mock embryo transfer performed immediately prior to the actual embryo transfer. The aspirated endometrial secretions containing endometrial cells are then analyzed for the presence of NCSs using indirect immunofluorescence. Based on a prior study, positive NCS status was defined as the presence of NCSs in at least 3 endometrial epithelial cells (EECs). Pregnancy outcomes are monitored to ensure that there is no effect of the aspiration on implantation rates. Uterine secretions were obtained from 5 patients immediately prior to embryo transfer. The average age of women was 37.2 ± 4.2 years. NCSs were detected in exfoliated EECs of uterine secretions in 4 of 5 (80%) samples and could not be unequivocally identified in 1 of 5 (20%), which was designated as indeterminate. Implantation as evidenced by a positive BHCG was seen in 5 of 5 (100%) of the patients who underwent aspiration with a clinical pregnancy rate of 40% and an ongoing pregnancy rate of 20%. This is the first report of NCS detection in FET-A cycles in the absence of follicular development and ovulation. NCS status can be determined in exfoliated EECs of uterine secretions obtained at the time of embryo transfer while maintaining implantation. Our study provides proof of principle to determine endometrial receptivity through individualized point of care testing of NCS status during frozen embryo transfer in artificial cycles.