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HLA\u2010G, an Immuno\u2010modulatory molecule is a non\u2010classical MHC\u20101 protein, expressed abundantly on extravillous trophoblastic cells, responsible for spiral artery remodeling, maintaining maternal immune tolerance and fetal growth by adjusting pro and anti\u2010inflammatory milieu during different gestational phases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method of study<\/jats:title><jats:p>In the present case\u2010control study CD4+HLA\u2010G+ tTreg cells were enumerated by flow cytometry and estimation of the circulating levels of sHLA\u2010G in the blood samples of 300 mid\u2010gestation pregnant women with (iRPL) and without history of RPL (nRPL) by Enzyme\u2010linked Immunosorbent assay was done. The cases included 92 primary and 58 secondary RPL cases<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A significant reduction in number of tTregs and elevated levels of circulating sHLA\u2010G in iRPL (.03, 200.9) versus nRPL (.09, 90.32) was observed. Further, the primary cases showed higher circulating sHLA\u2010G and no difference in relation to CD4+HLA\u2010G+ tTregs compared to the secondary cases. Receiver operating curve (ROC) characteristics of sHLA\u2010G (AUC\u00a0=\u00a0.8) was superior to CD4+HLA\u2010G+ (AUC\u00a0=\u00a0.7) for iRPL patients over nRPL group. Conclusions: Our results are suggestive of the over\u2010expression of sHLA\u2010G which may be caused due to its shedding from surface of trophoblast as a compensatory mechanism to save the on\u2010going pregnancy. 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