Xu B, et al. - Researchers investigated if allograft inflammatory factor-1 (AIF-1), a cytokine associated with inflammation and allograft rejection, is aberrantly elevated in in-vitro fertilization (IVF) cycles with gonadotropin-releasing hormone (GnRH) antagonist protocol with potential effects on endometrial receptivity. In IVF cycles with GnRH antagonist protocol, increase in AIF-1 was noted. During implantation phase, AIF-1 was observed to mediate greater TNF-&alpha expression, which could be unfavorable for embryo implantation.

Methods

• In 238 patients undergoing their first cycle of IVF/ICSI between 2012 and 2014, researchers studied implantation and pregnancy rates.
• Of these, 40 patients opted to have no fresh embryo replacement; these patients were divided into two equal groups:
• (i) GnRH antagonist protocol and
• (ii) GnRH agonist long protocol.
• Group 3 included 20 infertile women with a tubal factor in untreated cycles.
• From 18 infertile women with a tubal factor, they obtained endometrial tissues in the early proliferative phase, late proliferative phase, and mid-secretory phase of the menstrual cycle (n = 6/group) during the same interval.
• The expression levels of AIF-1 and the related cytokines (TNF-α, IL1β, IL1RA, IL6, IL12, IL15 and IL18) were determined using microarray analysis, RT-qPCR, Western blot analysis, immunohistochemistry .
• in vitro adhesion experiments (coculture of JAR cells and Ishikawa cells) were used to model the effect of AIF-1 on uterine receptivity.

Results

• Early proliferative phase showed the highest expression of AIF-1, thereafter it decreased in the late proliferative phase, and almost disappeared in the mid-secretory phase, indicating the significance of low AIF-1 expression for embryo implantation during implantation phase.
• As per microarray results, the antagonist group showed upregulated AIF-1 in comparison to the control group (fold change [FC] = 3.75) and the agonist (FC = 2.20) group.
• Under the accession number of GSE107914, the raw microarray data and complete gene expression table were uploaded to GEO.
• The antagonist group demonstrated higher mRNA and protein expression levels of AIF-1 and TNF-α compared to those observed in the other two groups (P < 0.05) which did not differ significantly (P > 0.05).
• At 96 h, significantly increased protein levels of TNF-α in both Ishikawa cells and primary endometrial cells (P < 0.05) after transfection with the AIF-1 expression vector was observed, indicating that TNF-α was mediated by AIF-1 in endometrial cells.
• Adhesion of JAR cells to Ishikawa cells was inhibited due to overexpression of AIF-1 in them.
• Thus, during implantation, increased AIF-1 might inhibit adhesion via raised TNF-α.