Clinical value of histologic dating of the endometrium for personalized frozen-thawed embryo transfer (pFET) in patients with repeated implantation failure (RIF) in natural cycles

Background: Displacement of the window of implantation (WOI) has been proposed as an important factor contributing to RIF. However, histologic dating of the endometrium as a diagnostic tool of endometrial receptivity has been questioned. Methods: This is a prospective intervention trial that entailed 205 infertile patients from July 2017 to December 2017. Endometrial biopsies from 50 good-prognosis patients were conducted on day 3 (n=6), 5 (n=6), 7 (n=26), 9 (n=6) or 11 (n=6) post-ovulation (PO+3/5/7/9/11) of the previous natural cycle before their conventional frozen-thawed embryo transfer (FET) cycle. We conducted endometrial biopsies of 155 RIF patients on day PO +7. Results: The verification of the Noyes criteria for endometrial dating was conducted at different times (PO +3/+5/+7/+9/+11) on 41 good-prognosis patients who achieved an ongoing pregnancy in their first conventional FET cycle after endometrial biopsy. The agreement between two pathologists for endometrial biopsy dating in infertile patients was determined to be acceptable (weighted kappa = 0.672, P < 0.001). The rate of out-of-phase dating on day PO+7 was significantly higher in RIF patients than good- prognosis patients (31.6% vs . 3.8%, P=0.003). pFET was performed in 47 RIF patients diagnosed to be out of phase, and the cumulative live-birth rate was 61.7%. Conclusions: Histologic endometrial dating of RIF patients in natural cycles may be a biomarker for a receptive endometrium in diagnosing the displacement of WOI.