Background: Recurrent implantation failure remains a challenge in assisted reproduction. Intralipid has been proposed as an immunomodulatory intervention to improve outcomes, although evidence remains inconsistent.
Objective: This study aimed to evaluate the effect of intralipid on pregnancy outcomes in women with a history of at least 2 failed embryo transfer cycles.
Materials and Methods: In this retrospective cohort study, data of 270 women with ≥ 2 failed embryo transfer cycles, who underwent a subsequent frozen embryo transfer (FET) at Avicenna Fertility Center, Tehran, Iran, from March 2021–2022 were extracted from medical records. Participants were allocated to the intralipid group (n = 132), receiving 100 mL intravenous intralipid 20% 1 wk before FET, if beta-human chorionic gonadotropin was positive, the same dose was given every 4 wk until the end of the first trimester, or to the control group (n = 138), undergoing routine FET treatments. Outcomes included biochemical, clinical, and ongoing pregnancy, abortion, and live birth.
Results: Biochemical pregnancy rate was significantly higher in the intralipid group compared with controls (51.5% vs. 37.7%, p = 0.022). Clinical pregnancy (43.2% vs. 36.2%), ongoing pregnancy (28.8% vs. 18.8%), and live birth (25.8% vs. 17.4%) also favored the intralipid group, although these differences did not reach statistical significance (p > 0.05). Abortion rates were comparable between groups (25.8% vs. 21.0%, p = 0.357).
Conclusion: Intralipid may improve biochemical pregnancy rates and shows a non-significant positive trend in other pregnancy outcomes in recurrent implantation failure cases, warranting confirmation in larger randomized controlled trials.
Keywords: Fat emulsions, Intravenous, Embryo implantation failure, Fertilization in vitro, Pregnancy outcome, Immunomodulation
[1] Vander Borght M, Wyns C. Fertility and infertility: Definition and epidemiology. Clin Biochem 2018; 62: 2–10.
[2] Coughlan C, Ledger W, Wang Q, Liu F, Demirol A, Gurgan T, et al. Recurrent implantation failure: Definition and management. Reprod Biomed Online 2014; 28: 14–38.
[3] Bashiri A, Halper KI, Orvieto R. Recurrent implantation failure-update overview on etiology, diagnosis, treatment and future directions. Reprod Biol Endocrinol 2018; 16: 121.
[4] Lédée N, Vasseur C, Petitbarat M, Chevrier L, Vezmar K, Dray G, et al. Intralipid® may represent a new hope for patients with reproductive failures and simultaneously an over-immune endometrial activation. J Reprod Immunol 2018; 130: 18–22.
[5] Kumar P, Marron K, Harrity C. Intralipid therapy and adverse reproductive outcome: Is there any evidence? Reprod Fertil 2021; 2: 173–186.
[6] Coulam CB. Intralipid treatment for women with reproductive failures. Am J Reprod Immunol 2021; 85: e13290.
[7] Rimmer MP, Black N, Keay S, Quenby S, Al Wattar BH. Intralipid infusion at time of embryo transfer in women with history of recurrent implantation failure: A systematic review and meta-analysis. J Obstet Gynaecol Res 2021; 47: 2149–2156.
[8] Kandi SK, Shareef OO, Obeid A, Abushama M, Ahmed B, Konje JC. Evaluating the impact of intralipid infusion on pregnancy outcomes in infertility treatments: A retrospective study. Reprod Med 2025; 6: 34.
[9] Al-AlZebeidi J, Lary S, Al-Jaroudi D. The effect of fat emulsion intralipid 20% in reproductive outcome for patients with multiple implantation failure. Int J Women’s Health Reprod Sci 2018; 6: 144–149.
[10] Hirshfeld-Cytron JE, Kukora S, Lazzarone M, Cohen D, Kim YS, Talwar P, et al. Does intralipid infusion improve outcomes in RPL/RIF patients undergoing IVF? Fertil Steril 2016; 106: e342.
[11] Foyle KL, Sharkey DJ, Moldenhauer LM, Green ES, Wilson JJ, Roccisano CJ, et al. Effect of intralipid infusion on peripheral blood T cells and plasma cytokines in women undergoing assisted reproduction treatment. Clin Transl Immunology 2021; 10: e1328.
[12] Habibi S, Ramezanali F, Mostafaei P, Amirchaghmaghi E. [Recurrent implantation failure from an immunological point of view]. Journal of Shahid Sadoughi University of Medical Sciences Received 2023; 31: 7295–7320. (In Persian).
[13] Anya OC, Ajayi ER, Solanke HR, Ohanaka AI, Ubana KD. The use of intralipid infusions in the prevention of embryo implantation failure. Cureus 2024; 16: e53368.
[14] Plaçais L, Kolanska K, Kraiem YB, Cohen J, Suner L, Bornes M, et al. Intralipid therapy for unexplained recurrent miscarriage and implantation failure: Case-series and literature review. Eur J Obstet Gynecol Reprod Biol 2020; 252: 100–104.
[15] Peivandi S, Mortazavi L, Gordani N, Zamaniyan M, Asgarian-Omran H, Ajami A et al. [Effect of intralipid infusion on pregnancy outcome in infertile women with history of implantation failure: A single blind randomized clinical trial]. J Mazandaran Univ Med Sci 2022; 32: 16–26. (in Persian)
[16] Li Y, Lan P, Tang J, Wang W, Chen H. The efficacy of immunotherapies for pregnancy outcomes of patients with recurrent implantation failure as defined by ESHRE guidelines: A systematic review and network meta-analysis. J Reprod Immunol 2026; 173: 104825.
[17] Marchand GJ, Masoud AT, Ulibarri H, Arroyo A, Coriell C, Goetz S, et al. Effect of a 20% intravenous fat emulsion therapy on pregnancy outcomes in women with RPL or RIF undergoing IVF/ICSI: A systematic review and meta-analysis. J Clin Transl Res 2023; 9: 236–245.
[18] Han EJ, Lee HN, Kim MK, Lyu SW, Lee WS. Efficacy of intralipid administration to improve in vitro fertilization outcomes: A systematic review and meta-analysis. Clin Exp Reprod Med 2021; 48: 203–210.
[19] ESHRE Working Group on Recurrent Implantation Failure, Cimadomo D, de Los Santos MJ, Griesinger G, Lainas G, Le Clef N, et al. ESHRE good practice recommendations on recurrent implantation failure. Hum Reprod Open 2023; 2023: hoad023.
[20] Ehrlich R, Hull ML, Walkley J, Sacks G. Intralipid immunotherapy for repeated IVF failure. Fertil Reprod 2019; 1: 154–160.
[21] Ma J, Gao W, Li D. Recurrent implantation failure: A comprehensive summary from etiology to treatment. Front Endocrinol (Lausanne) 2023; 13: 1061766.
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