The uterine immunological changes may be responsible for repeated implantation failure

Abstract

A significant part of couples in IVF-ICSI cycles experience Repeated Implantation Failure (RIF). Screening of the embryos with new methods like Next Generation Sequencing and arrays showed that even euploid embryos fail to implant. Immunology is a potent window maybe resolve the RIF problem. In this investigation we employed innate and adaptive immune system PCR array to compare the transcriptome profiles of endometrium in unexplained RIF and healthy fertile women. A total of 21 women were enrolled in the present study, 11women with unexplained RIF and 10 healthy fertile women. After RNA extraction and cDNA synthesis PCR array was performed using RT2 profiler PCR array human innate and adaptive immune responses kit (Qiagen, Cat.No: PAHS-052A). PCR Array data analysis identified significantly greater expression of IL6, IFNG, IL17A, IL23A, IFNA1, IFNB1, CD40 L, CCR4, CCR5, CCR6, CXR3, CCL2, IL2, TLR4, IRF3, STAT3, RAG1, IFNAR1 in unexplained RIF women than in controls (P < 0.05). However, expression of IL1B, IL8, NFKB, HLA-A, HLA-E, CD80, CD40 was significantly lower in unexplained RIF group than in controls (P < 0.05). Our results showed that modulation of immune system in RIF patient is shifted to inflammatory responses as pNK cells, Th17 signaling pathway and TLR signaling pathway are activated. So, by stimulation of immune system and initiation of humoral immune responses the panel of immunity and immunotolerance is completely changed in RIF patients comparing normal. It seems that attention to these alterations individually help physician to manage RIF patients better.

Keywords: Endometrium; Implantation window; QPCR array; RIF.