Quantifying CD138+ cells in the endometrium to assess chronic endometritis in women at risk of recurrent pregnancy loss: A prospective cohort study and rapid review.

OBJECTIVE: To determine the value of uterine CD138+ cells, as a marker of chronic endometritis, in predicting subsequent reproductive outcome in women with history of recurrent pregnancy loss. DESIGN: A prospective longitudinal study. SETTING: Tertiary specialized clinic. PATIENTS: Women with history of recurrent pregnancy loss or implantation failure over a 12-months follow-up period. INTERVENTION: We quantified the CD138+ cells/high powered field (hpf) using immunohistochemistry and image analysis of endometrial biopsies obtained during the secretory stage post ovulation. MAIN OUTCOME MEASURES: Live birth and subsequent pregnancy loss. We calculated the receiver operator curve for predicting subsequent pregnancy loss and reported using relative risk (RR) and 95% confidence intervals (CI). RESULTS: We enrolled 344 women of whom 88 became pregnant (88/344, 25.5%). Half of them had a subsequent live birth (47/88, 53%) and the rest lost their pregnancy (41/88, 46%). The median CD138+ score was significantly lower in the live birth group (P < 0.005) and women with a CD138+ score ≥ 16/hpf had a higher risk of subsequent miscarriage (RR 10.0, 95% CI 2.78-36.02). CD138+ cells count showed a good prediction for subsequent pregnancy loss in high-risk women with an area under the curve of 0.75 (95% CI 0.59-0.82, P = 0.01). A cut-off value of 4-6 cells/hpf offered the best predictive accuracy with higher scores predicting worse reproductive outcome. Our findings are limited by the small event rate and the sample size of our cohort. CONCLUSION: Quantifying CD138+ cells by immunohistochemistry in women with a history of recurrent pregnancy loss is helpful to diagnose chronic endometritis and predict subsequent reproductive outcome.