Michael P Rimmer1, Katherine Fishwick2, Ian Henderson2,3, David Chinn4, Bassel H Al Wattar2,3,5, Siobhan Quenby2,3. 1. MRC Centre for Reproductive Health, Queens Medical Research Institute, Edinburgh BioQuarter, University of Edinburgh, Edinburgh, UK. 2. Warwick Medical School, University of Warwick, Coventry, UK. 3. University Hospital Coventry and Warwickshire NHS Trust, UK. 4. Research and Development Office, NHS Fife, Queen Margaret Hospital, Whitefield Road, Dunfermline, Fife, UK. 5. Women's Health Research Unit, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
Abstract
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.
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.
Authors: Michael P Rimmer; Ruth A Howie; Venkatesh Subramanian; Richard A Anderson; Ricardo Pimenta Bertolla; Yusuf Beebeejaun; Pietro Bortoletto; Sesh K Sunkara; Rod T Mitchell; Allan Pacey; Madelon van Wely; Cindy M Farquhar; James M N Duffy; Craig Niederberger Journal: Hum Reprod Open Date: 2022-03-04