BCL6 AND SIRT1 expression in unexplained infertility versus unexplained recurrent pregnancy loss

The purpose of the study is to compare BCL6 and SIRT1 expression in women with unexplained infertility and unexplained recurrent pregnancy loss to determine if these proteins can explain why one group gets pregnant and the other does not. Retrospective case control Human endometrial samples were collected from patients with unexplained infertility, unexplained recurrent pregnancy loss, and fertile controls with laparoscopically proven normal pelvic anatomy. Immunohistochemical staining was performed on these samples to determine the level of nuclear expression of BCL6 and SIRT1. The degree of nuclear expression was assessed using the H-score semiquantitative assessment. In women with proven endometriosis, SIRT1 and BCL6 were found to co-localize in the secretory phase. In women with unexplained infertility, a positive correlation was noted between BCL6 and SIRT1 expression. In contrast, no correlation was observed between BCL6 and SIRT1 in patients with uRPL. Higher levels of SIRT1 expression were demonstrated in endometrial samples from patients with UI which were not seen in the fertile control population or in many women with uRPL. BCL6 and SIRT1 nuclear expression appear to be biomarkers of progesterone resistance. We found BCL6 and SIRT1 expression has a positive correlation in patients with UI, but not in women with uRPL. While BCL6 is a marker of inflammation and is expressed in patients with endometriosis, it is up-regulated in uRPL and low in fertile controls without endometriosis. SIRT1 was elevated in UI but not consistently elevated in uRPL and may be a determining factor for progesterone resistance and explain why patients with UI do not implant. These results suggest a role for the BCL6/SIRT1 complex as a potential diagnostic and/or therapeutic target in women with uRPL and may account for the difference in UI versus uRPL.