Treatment following hysteroscopy and endometrial diagnostic biopsy increases the chance for live birth in women with chronic endometritis

Abstract

Problem: Repeated implantation failure and recurrent pregnancy loss are associated with chronic endometritis, a persistent endometrial inflammation. Its diagnosis and treatment may increase pregnancy and live birth rates. The aim of this study was to assess the effectiveness of endometrial diagnostic biopsy and subsequent antibiotic treatment in cases of chronic endometritis on reproductive outcomes over a long observation period.

Method of study: We conducted a historical cohort study (2014-2018) at our University-based infertility center that included women (n = 108) with repeated implantation failure or recurrent pregnancy loss without known pathologies associated with either condition. Forty-one women underwent a hysteroscopy only (reference group); the remaining 67 women underwent, in addition to the hysteroscopy, an endometrial diagnostic biopsy with immunohistochemically staining for CD138 to detect plasma cells (biopsy group). If one or more plasma cells were detected, the women were treated with doxycycline 100 mg twice a day orally for 2 weeks. We performed stratified survival analysis (Kaplan-Meier) and Cox regression.

Results: The biopsy group had higher chances of pregnancy (hazard ratio 2.28; 95% confidence interval 1.23-4.24; p = .009) and of live birth (hazard ratio 2.76; 95% confidence interval 1.30-5.87; p = .008) compared with the reference group. In the sensitivity analysis, repeated implantation failure or recurrent pregnancy loss did not affect the outcome.

Conclusion: Endometrial diagnostic biopsy followed by antibiotic treatment in case of chronic endometritis in women with repeated implantation failure or recurrent pregnancy loss may increase the chances for live birth.

Keywords: chronic endometritis; endometrial diagnostic biopsy; plasma cells; recurrent pregnancy loss; repeated implantation failure; time to live birth; time to pregnancy.

FIGURE 1

Study population. CE, chronic endometritis; CEneg, women diagnosed negative for chronic endometritis; CEpos, women diagnosed positive for chronic endometritis; HSC, hysteroscopy; RIF, repeated implantation failure; RPL, recurrent pregnancy loss; TESE, testicular sperm extraction

FIGURE 2

Images of patients with and without CE in hysteroscopy, hemalaun‐eosin staining and immunohistochemically CD138 staining. Comparison of patients with bland endometrium (A,C,E) vs. chronic endometritis (B,D,F) in hysteroscopy (A,B), conventional histology (C,D) and immunohistochemistry for CD138 (E,F). Note, the reddish inflamed mucosal surface in chronic endometritis (B) and the intermingled plasma cells in endometrial stroma in immunohistochemistry (F, central region). These differences in plasma cell densities cannot be distinguished in conventional histology (C,D) of the same patients. Of note, regular endometrial glands serve as a positive internal control as CD138 also known as syndecan‐1 is positive in epithelial cells. Pictures were taken at 200× magnification. CE, chronic endometritis; HE, hemalaun‐eosin staining; HSC, hysteroscopy

FIGURE 3

Time to pregnancy and time to live birth. Kaplan‐Meier failure estimates. Observation time: from hysteroscopy or biopsy date to clinical pregnancy or live birth; with applied inverse probability weighting to account for the proportion of women with repeated implantation failure and recurrent pregnancy loss, respectively, as well as the maternal age structure within each of the groups compared (according to Cole SR & Hernan MA). p‐values for the two groups compared: (a) p = .009 B) p = .008 C) Reference group compared with biopsy CEpos group: p = .010; biopsy CEpos group compared with biopsy CEneg group: p = .800. (b) D) Reference group compared with biopsy CEpos group: p = .004; biopsy CEpos group compared with biopsy CEneg group: p = .327