PURPOSE

Is plasma cell (PC)-diagnosed chronic endometritis a common phenomenon in patients with recurrent implantation failure, and what can be learned from it?

METHODS

In this retrospective case-control study at Wiesbaden Fertility Centre, 147 patients with recurrent implantation failure (RIF) underwent endometrial biopsy (EB) between January 2017 and December 2021 to rule out chronic endometritis (CE). For diagnosis, samples were labelled immunohistochemically with anti-CD138 and anti-MUM1 antibodies for the detection of PCs. The cut-off for the diagnosis of CE was at least five PCs per 10 evaluated high-power fields (HPFs). Patients with four PCs or fewer in the endometrial stroma (ES) formed Group A. Patients with at least five PCs in the ES were subsequently treated with doxycycline for 14 days and formed Group B. Those patients in Group B with persistent findings in a control biopsy received a combination of ciprofloxacin and metronidazole for 7 days. The EB time was documented, and the outcomes of assisted reproductive technology (ART), pregnancy and birth within 9 months of diagnosis were evaluated, as well as patient characteristics for both groups.

RESULTS

Following the calculation of a threshold value using receiver operating characteristic curve analysis to determine the optimal time for EB (between cycle days 8 and 9 in this study), 65 patients were excluded from further evaluation due to an inadequate EB time point. Of the remaining 82 patients, 49 (59.8%) were assigned to Group A and 33 (40.2%) were assigned to Group B. In four patients in Group B, the control biopsy revelated that they still had at least five PCs per 10 HPFs, and these patients were treated following the previously described protocol. A comparison of the two groups revealed no significant differences in terms of medical history, characteristics, ART used, and pregnancy and live birth rates. However, the timing of EB is crucial for a correct diagnosis of CE.

CONCLUSION

In this retrospective case-control study, patients with RIF frequently (40%) exhibited histological signs (at least five PCs per 10 HPFs in ES) of CE. These findings indicate that EB for the detection of CE should be performed in the late follicular phase or after day 8 of an ovulatory cycle if a cut-off value of at least five PCs is used. Antibiotic treatment with doxycycline led to a reduction in PCs in over 80% of cases. Persistent findings can be treated successfully with ciprofloxacin and metronidazole. After treatment of CE, the outcomes of patients were found to be comparable with those without CE. Therefore, an investigation to exclude CE using PCs in patients with RIF seems advisable before performing further ART.