Evaluation of implantation markers and immune cell infiltration in endometrial biopsy of female genital tuberculosis.

BACKGROUND

Female genital tuberculosis (FGTB) causes infertility in a significant number of females. The immunological impact of tuberculosis on endometrium in infertile females has not been studied before. The present study was designed to evaluate markers related to infiltrating immune cells and implantation in endometrial aspiration from infertile females and correlate with conventional tests and polymerase chain reaction (PCR) for tuberculosis (TB).

METHODS

It was a prospective cohort study with 385 patients out of which IHC was done in 306 over a period of 3 years from 2013 to 2016 in a tertiary care hospital. Women with infertility, 20-35 years of age, without history of pulmonary TB or intake of antitubercular therapy were included. Endometrial samples were subjected to PCR for TB along with microbiological and histological examination for TB. Immunohistochemistry for CD45, CD3, CD20, CD4, CD8, CD68, CD138, Interferon gamma, Interleukin 10 (IL-10) and implantation markers MUC1 and Notch 1 were done on the endometrial samples along with 25 control subjects.

RESULTS

Conventional tests for tuberculosis like staining for acid fast bacilli (AFB), granuloma on histology or culture positivity were seen in 2.61% (6/306; 1.96% had granulomas, 1/306; 0.32% was AFB positive, 2/306; 0.6% were liquid culture positive). PCR was positive in 190/306 (62.09%). CD3, CD20, CD45, CD68, CD4, CD8 and CD 138 expressing infiltrating cells were not significantly related to PCR positive cases. Interferon gamma expressing lymphocytes were significantly higher (38.94%) in PCR positive endometria compared to 26.72% in the PCR negative (p = 0.04). Notch -1 expression correlated significantly with the occurrence of pregnancy. A trend towards high intensity expression of Notch1 was seen in PCR negative cases. MUC-1 expression did not correlate with pregnancy although interferon gamma expression was significantly related to low intensity MUC1 expression.

CONCLUSIONS

Immunohistochemical markers are not reliable tests in diagnosis of FGTB. Notch 1 expression though showing correlation with pregnancy has to be further evaluated with a panel of other implantation markers.

STUDY FUNDING: Indian Council of Medical Research, New Delhi, India.