Impact of lymphocyte immunotherapy (LIT) on fertility rates in recurrent pregnancy loss (RPL) women with antinuclear antibodies: A randomized clinical trial

Abstract

To further evaluate the effects of lymphocyte immunotherapy (LIT) for the treatment of RPL patients this study aimed to utilize this type of treatment in RPL patients with positive antinuclear antibodies (ANA) in comparison to ANA-negative RPL women. To this aim, 84 ANA-positive, 114 ANA negative, and 50 healthy pregnant women were recruited. To examine the frequency of cells before and after LIT, flowcytometry technique was employed. The levels of cytokines gene expression were also measured using real-time PCR. The ELISA technique was employed to assess the level of secreted cytokines in serum. Initial evaluation before LIT showed significantly lower NK cells and Th1/Th2 ratio in healthy pregnant women compared to both ANA-negative, and positive patients. Moreover, healthy pregnant women had significantly lower pro-inflammatory cytokine (IFN-γ) and higher anti-inflammatory cytokines (TGF-β and IL-4) compared to RPL patients. After LIT, NK cells frequency significantly decreased in both ANA-negative and -positive groups, however, reduced Th1/Th2 ratio was only significant in ANA-negative group. Significantly increased and decreased IL-4 and IFN-γ were only observed in ANA-negative patients. Furthermore, patients receiving routine treatment did not experience any remarkable changes in terms of cell frequency and cytokine levels. This study showed a significant improvement in pregnancy outcomes including increased pregnancy rate and live birth, and decreased miscarriages in both ANA-negative and positive RPL patients, which were notably higher in ANA-negative group.

Keywords: ANA; Antinuclear antibodies; LIT; Lymphocyte immunotherapy; Recurrent pregnancy loss.