Histological diagnostic criterion for chronic endometritis based on the clinical outcome

Abstract

Background: The diagnostic criteria of chronic endometritis remain controversial in the treatment for infertile patients.

Methods: A prospective observational study was conducted in a single university from June 2014 to September 2017. Patients who underwent single frozen-thawed blastocyst transfer with a hormone replacement cycle after histological examination for the presence of chronic endometritis were enrolled. Four criteria were used to define chronic endometritis according to the number of plasma cells in the same group of patients: 1 or more (≥ 1) plasma cells, 2 or more (≥ 2), 3 or more (≥ 3), or 5 or more (≥ 5) in 10 high-power fields. Pregnancy rates, live birth rates, and miscarriage rates of the non-chronic endometritis and the chronic endometritis groups defined with each criterion were calculated. A logistic regression analysis was performed for live births using eight explanatory variables (seven infertility factors and chronic endometritis). A receiver operating characteristic curve was drawn and the optimal cut-off value was calculated.

Results: A total of 69 patients were registered and 53 patients were finally analyzed after exclusion. When the diagnostic criterion was designated as the presence of ≥ 1 plasma cell in the endometrial stroma per 10 high-power fields, the pregnancy rate, live birth rate, and miscarriage rate were 63.0% vs. 30.8%, 51.9% vs. 7.7%, and 17.7% vs. 75% in the non-chronic and chronic endometritis groups, respectively. This criterion resulted in the highest pregnancy and live birth rates among the non-chronic endometritis and the smallest P values for the pregnancy rates, live birth rates, and miscarriage rates between the non-chronic and chronic endometritis groups. In the logistic regression analysis, chronic endometritis was an explanatory variable negatively affecting the objective variable of live birth only when chronic endometritis was diagnosed with ≥ 1 or ≥ 2 plasma cells per 10 high-power fields. The optimal cut-off value was obtained when one or more plasma cells were found in 10 high-power fields (sensitivity 87.5%, specificity 64.9%).

Conclusions: Chronic endometritis should be diagnosed as the presence of ≥ 1 plasma cells in 10 high-power fields. According to this diagnostic criterion, chronic endometritis adversely affected the pregnancy rate and the live birth rate.

Keywords: Chronic endometritis; Diagnostic criterion; Infertility; Plasma cell.

Fig. 1

Protocol for the present study. Blastocysts were frozen following oocyte retrieval. Hysteroscopy and endometrial sampling were performed, and the number of plasma cells in 10 high-power fields (HPFs) of stromal area was evaluated with CD138 antibody staining of the endometrium. Single frozen-thawed blastocyst transfer was performed within 90 days after the endometrial evaluation with a hormone replacement cycle

Fig. 2

a Flow of patient registration and exclusion. The subjects were patients under 41 years of age who agreed and underwent the in vitro fertilization-embryo transfer (IVF-ET) protocol of our department, which includes routine hysteroscopy and local endometrial curettage (injury) before first frozen thawed embryo transfer. Patients who had a history of RIF, recurrent pregnancy loss (RPL) or diseases suspected to cause implantation failure such as submucosal myoma, adenomyosis, uterine malformation, or endometrial thinning (< 8 mm at implantation phase) were not enrolled. Genetic disorders, endocrine diseases and autoimmune diseases were not enrolled either. The presence of endometrial macropolyps and uterine malformations were evaluated by hysteroscopy, and patients with these diseases were excluded from this study at that moment. Before blastocyst transfer, patients were discussed with doctors again with respect to the treatment options, based on the result of existence of plasma cell in the stroma of the endometrium, and when the patient wanted to add the treatment which might modify the endometrial receptivity such as administration of antibiotics, or stimulated endometrium embryo transfer, the patients were excluded from the study. The patients who want to treat two-embryo transfer were also excluded to limit the study of treatment outcomes for single blastocyst transfer. b The numbers of patients registered and excluded. Sixty-nine patients were recruited, and 16 patients were excluded. Fifty-seven patients were finally analyzed

Fig. 3

Protocol of single frozen-thawed blastocyst transfer with a hormone replacement cycle. Multiple estradiol patches are started on days 2–3 of menstruation and increased gradually. When the endometrial thickness reaches 8 or more mm, oral administration of dydrogesterone (DYD) is started. Single blastocyst transfer is done 6 days after DYD is started

Fig. 4

A receiver operating characteristic curve of the non-CE group for live birth. The sensitivity and specificity of the non-CE group for live birth were calculated for each of these diagnostic criteria, and a receiver operating characteristic (ROC) curve was drawn. The area under the curve of the ROC curve was 0.785. The optimal cut-off value was obtained when ≥ 1 plasma cell was found in 10 HPFs (sensitivity of 87.5% and specificity of 64.9%)