الفهرس 
Pregnancy and Immune SystemOnly 14 pages are availabe for public view
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Abstract
Summary
Maternal immunological modulation in pregnancy is a well-established concept, but interpretation of variations in the immune status of those attempting to conceive but appearing to have implantation failure of good quality embryos, or with recurrent pregnancy loss, is controversial. Many factors are accepted as necessary for the successful completion of an assisted reproductive technology (ART) cycle from implantation to birth. Oocyte and sperm quality along with the endometrial environment are a few examples of the hurdles which must be cleared early in the process, while maternal allograft suppression and thrombotic risk must be achieved later. The active and particularly innate immune systems are accepted components of this process and many studies link various immunological abnormalities with recurrent implantation failure (RIF) and recurrent pregnancy loss (RPL).
Auto-immune factors such as anti-phospholipid antibody syndrome and anti-thyroid peroxidase antibodies have also been shown to influence pregnancy outcome and empirical treatment in these cases is recommended. Although not standard practice, testing for immunological abnormalities in the lymphocyte populations specifically, is gaining more attention in this field. Circulating T cells, cytokine expression bias and natural killer cells are known to be fundamental to a successful pregnancy so in this regard, testing of this nature seems justified. NK cytotoxicity, for example, has been reported as being predictive of RPL. Glucocorticoid steroids have long been the agents of choice in attempts to influence the expression and activity of pro-inflammatory mediators and have been used as a key component of many proposed immunomodulatory regimens.
Similarly, IVIG and intralipid infusions have been used as adjunctive agents to both supress and confuse the maternal adaptive immune system around the window of implantation. Intralipid has been proposed to exert a modulating effect on certain immune cellular This effect may act synergistically with the concomitant administration of corticosteroids, such as dexamethasone or prednisolone, to suppress cytotoxic/ activated T-lymphocytes. A potential net effect of combined intralipid and corticosteroid therapy might be the ability to suppress pro-inflammatory cellular (Type-1) cytokines such as interferon gamma and TNF-alpha. Indeed, in-vitro testing has shown that Intravenous Intralipid administration can successfully downregulate natural killer cell activation (NKa) within 2–3 weeks in up to 78% of women experiencing suspected immunologic implantation dysfunction.
This work aimed to assess correlation between gene expression of (TNFα, IFN-ɣ, TGF-β) in peripheral lymphocytes from women suffering from repeated implantation failure before and after intravenous Intra-lipid IL therapy, also assessment of correlation between change in gene expression with (IL) infusion and success rate of IVF cycles.
Twenty-three women with history of recurrent IVF cycles failure were included, two blood samples taken from each woman after taking informed written consent from these women.
• First sample before Intralipid infusion (before start of induction of ovulation).
• Second sample at day of embryo transfer ET 14-21 days after first sample and Intralipid infusion.
Each blood sample was centrifuged to obtain peripheral blood lymphocytes PBLCs, washed and an RNA stabilization buffer was added. Then stored till all samples were collected and labelled. Finally, RNA extraction was done.
The resulting RNA reversely transcribed for obtaining complementary DNA, complementary DNAs were subjected to amplification by real-time PCR to estimate cytokines (TNF-α, IFN-ɣ and TGF-β) genes expression levels.
Expression of cytokines genes was compared between the two blood samples obtained from each patient.
Clinical success rates of IVF-ET cycles were correlated with change of cytokines expression and Intralipid infusion.
Results of this work demonstrated that intralipid infusion therapy as immunomodulator reduced the expression of TNF-α and IFN-ɣ also increased expression of TGF-β in PBMNCs of included women. These changes in studied cytokines improved outcomes of IVF-ET cycles in women with history of recurrent failure to conceive after IVF-ET cycles.
Conclusion
Consistent with previous studies, findings of the present study indicate that intralipid infusion therapy might induce immune modulation of expression of related cytokines. Interestingly, this effect was only observed mostly in the women with successful IVF outcomes. Unfortunately, this change was not significant nor sufficient to control the inflammation in some women with recurrent implantation failure.
This discrepancy may have been due to a difference in response to different immune modulators. This possibility should be investigated further. Moreover, IL therapy might reduce the risk of complications of pregnancy, some studies have suggested that women with pregnancy disorders such as recurrent pregnancy loss (RPL) had a proinflammatory tendency and a decrease in immune regulatory function which could be controlled by immunomodulators. Results of the present study indicate that IVF failure was associated with imbalanced Th1/Th2/Th17/Treg responses and cytokines production. IntraLipid might have an immunomodulatory effect with positive effects on IVF outcomes via changes in peripheral lymphocytic cytokines expression.
Recommenndations
Results of current study recommend that use of intravenous infusion therapy of Intralipid as immunomodulator improve outcome of IVF-ET cycles specially in women with history of unexplained implantation failure, findings should be considered cautiously, and that large-scale confirmatory studies are necessary to prove the efficacy if intralipid before it should be recommended for routine use.
Hoping to explore many methods and factors for better understanding of unexplained infertility and poor pregnancies outcome, moreover better management planes.