Table 3.

Suggested immunotherapies for addressing uNK related RIF and RM.

Immunotherapies	Mechanisms of Action	Outcomes	Adverse Effects
Glucocorticoids	Regulate uNK cells’ proliferation and functionality via uNK cells’ glucocorticoid receptors	Decreased uNK cell numbers in endometrium	No pregnancy complications have been reported
	Reduce abnormal high uNK cell numbers	Positive effect on endometrial immunological profile	In utero exposure to glucocorticoids may be associated with a higher incidence of preterm births and low birth weight
	Reduce abnormal high uNK cytotoxicity	No established beneficial effect on pregnancy outcomes	Mood alterations, headache, nausea
Intralipid therapy	Intralipid molecules act as ligands for the G-protein-coupled receptor that results in activating the cAMP signaling pathway that is associated with the NFkB pathway	Modulates abnormal uNK activity	No side effects have been reported in cases of young women with reproductive failure
	NFkB pathway ultimately modulates transcription of DNA and controls essential immune responses	Trigger uNK cells’ cytokine secretion	Reduced risk of teratogenesis and congenital abnormalities has been reported
	Reduce abnormal high uNK cytotoxicity	No established beneficial effect on pregnancy outcomes	Risk for thrombophlebitis, dyspnea, nausea, hyperlipemia, and allergic reactions
Intravenous immunoglobulin (IVIg)	IVIgs mitigate the function of NK cells and promote alterations in the cytokine production	IVIgs decrease elevated NK levels in peripheral blood	Data advocating safe use of IVIg prior to or during pregnancy are still missing
	IVIgs inhibit cytotoxic activity of NK cells both in vitro and in vivo	No evidence concerning implementation of IVIg therapy in mitigating the effects of uNK cells has been reported	Anaphylactic reactions and renal insufficiency have been reported in high-dose IVIg treatments
	IVIgs induce spontaneous degranulation of NK cells and promote IFNγ production that results in the exhaustion of the NK cell cytotoxic machinery	No significant effect of IVIgs in patients with RM in terms of live birth rate has been reported	Fever, myalgia, headache, fatigue constitute some of the mild side effects. In extremely severe cases, myocardial infarction, alopecia, thrombosis, hemolytic anemia, and aseptic meningitis have been reported