Evaluation of the effectiveness of third-generation lipid emulsion therapy for early pregnancy loss

Abstract

BACKGROUND: Immune mechanisms play an important role in the pathogenesis of early pregnancy loss. To regulate disorders of immune homeostasis, immunoefferent therapy is used, such as immunocytotherapy, plasmapheresis, and intravenous administration of immunoglobulins and lipid emulsions, which may help to overcome infertility and recurrent miscarriage. Third-generation lipid emulsion (TGLE) is the modern “gold standard” of parenteral lipid therapy. It contains high concentrations of omega-3-polyunsaturated fatty acids, which can directly or indirectly affect the activity of natural killer (NK) cells. The literature comprises contradictory data on the efficacy of TGLE for repeated implantation failure. This may be due to the determination of biochemical parameters for its use and the selection of criteria for assessing the effectiveness of this therapy.

AIM: The aim of this study was to evaluate the effectiveness of TGLE therapy in patients with a history of early pregnancy loss.

MATERIALS AND METHODS: This prospective randomized controlled study enrolled 140 patients with early pregnancy loss (recurrent miscarriage and repeated implantation failure) at the Research Institute of Obstetrics, Gynecology and Reproducto logy named after D.O. Ott, Saint Petersburg, Russia from 2021 to 2023. Group 1 consisted of 50 women with TGLE therapy, and group 2 included 90 women without therapy. Patients of group 1 received lipid therapy according to the following regimen: TGLE 20% IV 6 ml per kilogram of body weight once a month for two months on end. Inclusion criteria: women from 18 to 45 years of age with two cases of reproductive failure – pregnancy loss up to 12 weeks of gestation and/or unsuccessful in vitro fertilization attempts (embryo transfers without effect) with normal karyotypes of the spouses. Exclusion criteria: women with miscarriage with an abnormal karyotype of the fetus, with anatomical abnormalities in the development of the reproductive apparatus, with an abnormal karyotype of any of the spouses, with hypersensitivity to omega-3 polyunsaturated fatty acids. We assessed the omega-3 index, functional characteristics of NK cells in the peripheral blood, and the effectiveness of lipid therapy based on biochemical and immunological parameters, as well as the clinical onset of pregnancy.

RESULTS: The difference in the omega-3 index before and after treatment with TGLE was significant (p = 0.0002), this parameter being increased by 1.23 times compared to the initial level. The functional activity of NK cells in the blood was significantly different after the administration of TGLE: NK (CD3^–CD(16⁺56⁺)) (p = 0.0041), NKT (CD3⁺CD(16⁺56⁺)) (p = 0.0498), and spontaneously activated NK (CD107a) (p = 0.0498). These parameters decreased by 1.63, 1.29, and 2.07 times relative to their initial levels. In group 1 of patients receiving TGLE therapy, clinical pregnancy occurred twice as often as compared to those who did not receive this therapy (56.41%, n = 22 vs. 31.25%, n = 20; p = 0.01).

CONCLUSIONS: TGLE has shown effectiveness in pregnancy rates by increasing the omega-3 index and reducing the functional activity of NK cells in women with early pregnancy loss.

Keywords

lipid emulsion therapy / early pregnancy loss / recurrent miscarriage / repeated implantation failure / immunotherapy / omega-3 index

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