Does the Timing of Endometrial Biopsy Impact the Detection of Endometrial Plasma Cells?

Abstract

OBJECTIVE: Chronic endometritis (CE) has been associated with recurrent pregnancy loss (RPL) and recurrent implantation failure. Incidence rates vary due to significant heterogeneity in biopsy timing and diagnostic criteria. Our group previously demonstrated that plasma cells are found in 59% of endometrial biopsies (EMBs) in the follicular phase compared to 18% in the luteal phase, which led us to question whether menstruation or hormonal changes in the follicular phase impact the diagnosis of CE. The purpose of this study was to assess the incidence and density of endometrial plasma cells in the early versus late follicular phase.DESIGN: This is a retrospective cohort study of patients undergoing EMB in the follicular phase at a single academic center.MATERIALS AND METHODS: EMBs performed between 2018 and 2020 were included. The early follicular phase was defined as the end of menses through day 8 of the menstrual cycle. The late follicular phase was defined as 9-14 days after menses. Patients with a prior CE diagnosis or abnormal uterine pathology were excluded. EMBs were assessed by gynecologic pathologists via H&E stain and CD138 immunohistochemistry. Plasma cell density was reported as rare (1-2 per slide), scattered (R 3 per slide), or clusters. Continuous variables were compared using t-tests, and categorical variables were compared with chi-square tests.RESULTS: Plasma cells were found in 74% of EMBs performed in the early follicular phase compared to 45% in the late follicular phase. Although the study was not powered to detect differences in plasma cell density, plasma cells were most commonly noted to be scattered (39%) in the early follicular and rare (18%) in the late follicular phase. See Table 1 for complete results.CONCLUSIONS: Our data demonstrate that plasma cells are more likely to be detected at higher densities in EMBs performed during the early compared to the late follicular phase. These findings may represent the influence of estrogen levels or menstruation on the endometrium. Further studies with larger cohorts are needed to establish the optimal timing of EMB and determine the clinical significance of low-density endometrial plasma cells.

Association between Endometrial Polyps and Chronic Endometritis: Is It Time for a Paradigm Shift in the Pathophysiology of Endometrial Polyps in Pre-Menopausal Women? Results of a Systematic Review and Meta-Analysis

“…Of the manuscripts identified, 61 studies were excluded after the evaluation of the abstracts, and 14 studies were further evaluated. Six studies were excluded after the evaluation of full text (see Table A1 and Table A2 ) [ 4 , 9 , 30 , 32 , 33 , 34 ].…”

“…Tolani et al 2020 [34] Intracavitary pathology is associated with a significantly higher frequency and density of endometrial plasma cells (71% vs. 41%).…”

“… Kosei et al 2017 [ 30 ] Progesterone deficiency and local immune imbalance with severe hypofunctional NK cells against viral and fungal infestations result in excessive endometrial cell proliferation and development of an isolated polyp. Tolani et al 2020 [ 34 ] Intracavitary pathology is associated with a significantly higher frequency and density of endometrial plasma cells (71% vs. 41%). CE: chronic endometritis; EPs: endometrial polyps; IFN: interferon; NK: natural killer.…”