Intralipid Infusion The relative paucity of inﬂammatory diseases among the Greenland Inuit population, who consume a diet high in fish oils, led investigators to study the immune modulatory effects of lipid emulsions in total parenteral nutrition preparations for preoperative patients and for burn and trauma victims (406–409). The wide range of demonstrated effects, including lipid preparations that reduced natural killer cell activity, reduced monocytes proinﬂammatory cytokine production and increased susceptibility to infection, led investigators to hypothesize, as early as 1994, that lipid infusions might promote an immune environment that would favor pregnancy maintenance (410). Since that time, a small number of publications have addressed the effects of lipid infusions (Intralipid) in women with a history of pregnancy loss (411,412). These investigations have demonstrated a decrease in peripheral natural killer cell activity in women treated with one to three infusions of Intralipid. This effect lasted from 4 to 9 weeks after the last infusion (411). The authors did not address NK cell cytokine secretion patterns nor did they assay decidual NK cell function. Despite this paucity of data, Intralipid infusions are being administered to recurrent pregnancy loss patients with increasing frequency. The existing data do not support this practice. At this time, Intralipid infusions in recurrent pregnancy loss patients should only be administered under an institutional review board–approved protocol and in a study setting. They should not generate clinical income.
TNF-α Inhibition Interest in the potent proinﬂammatory cytokine, TNF-α, as a mediator of pregnancy loss came out of the description of the TH1 and TH2 paradigm (209). Over the past 10 years, there have been several publications that link maternal serum TNF-α levels and activating TNF-α gene promoter polymorphisms to recurrent pregnancy loss (413–415). The development of antagonists of TNF-α in the form of blocking antibodies (adalimumab, inﬂiximab) and inhibitory recombinant proteins (etanercept) has allowed for successful treatment of several autoimmune disorders, including rheumatoid arthritis, psoriasis, and Crohn’s disease. Their use, however, has not been associated with universally positive outcomes and may worsen some disorders, including multiple sclerosis (416). These products are associated with rare but worrisome side effects, including liver failure, aplastic anemia, interstitial lung disease, and anaphylaxis (417). Although there exists only a single, small, retrospective, observational, nonrandomly assigned case series that involved treatment of recurrent pregnancy loss patients with inhibitors of TNF-α, these positive preliminary results have led a growing number of clinics to offer this therapy to patients, often at a significant cost (418). The safety of these compounds in pregnancy has not been appropriately studied, and preliminary reports associating exposure to TNF-α inhibitors during early pregnancy to fetal VACTERL syndrome is concerning (419). As with Intralipid therapy, use of TNF-α inhibition for the treatment of recurrent pregnancy loss should only be administered under an institutional review board–approved protocol in a study setting and should not generate clinical income.