Abstract

Controversy exists regarding the benefits of intravenous intralipid therapy in patients with a poor reproductive history. It is frequently reported that there is no evidence to support the effectiveness, utility or safety for this treatment. While individual studies may be perceived as weak, a systematic review and meta-analysis were performed to determine if there is any advantage to patients. PubMed, Embase and Scopus searches were performed with the target populations being either recurrent pregnancy loss (RPL), or recurrent implantation failure (RIF) undergoing assisted reproductive technology (ART) and receiving intralipid infusions. These cohorts were compared with either placebo, no intervention or alternative treatments. The most relevant outcome measures were considered to be clinical pregnancy rate (CPR), live birth rate (LBR), implantation rate (IR) and miscarriage rate (MR). Twelve studies encompassing 2676 participants met the criteria for selection and were included and reviewed. Treatment of the target population with intralipid led to an improvement in IR (Odds Ratio (OR): 2.97, 2.05–4.29), pregnancy rate (OR: 1.64, 1.31–2.04), and LBR (OR: 2.36, 1.75–3.17), with a reduction in MR (OR: 0.2, 0.14–0.30). Although intravenous intralipid is not recommended as a routine treatment for recurrent miscarriage or implantation failure, there is enough data to suggest consideration in selected patients where routine testing is unremarkable, standard treatments have failed and immunological risk factors are present. The presence of abnormal uterine natural killer (uNK) cells needs more study as a target marker to determine those who could benefit.Lay summaryThere is controversy regarding the benefits and efficacy of intravenous intralipid therapy in patients with a poor reproductive history. It is frequently reported that there is no credible evidence to support their use. A situation we frequently face as medical professionals is patients asking us to consider immune therapy (such as intralipid) for reproductive failure where good quality embryos have been used. Intralipid infusions have been reported to improve pregnancy rates with IVF, and reduce the miscarriage risk in selected patient groups, but study results are not universally accepted. We have performed a detailed review and analysis of the literature to determine if there is any benefit to this immune treatment in specific patient groups. Our paper identified and analyzed 12 studies, finding that treatment with intravenous intralipid leads to an improvement in implantation, pregnancy and live birth rates, with a decrease in miscarriage rate. This study shows that there is evidence to suggest consideration of intralipid in certain patients where standard treatments have failed.

Highlights

  • Repeated Implantation failure (RIF) and recurrent pregnancy loss (RPL) are among the most challenging scenarios in reproductive medicine

  • Citations identified by searches were scrutinized by title/ abstract, full manuscripts were obtained for those meeting the inclusion criteria

  • Studies were selected if the target populations were women with RPL or RIF ± IVF/ICSI treatment, using IL infusions

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Summary

Introduction

Repeated Implantation failure (RIF) and recurrent pregnancy loss (RPL) are among the most challenging scenarios in reproductive medicine. Assisted Reproduction has many of these 'Add-Ons', whose value has not been confirmed, often with additional cost implications (Macklon et al 2019). One such intervention is intralipid (IL) to improve pregnancy outcomes. Chromosomal abnormalities are the main cause of early pregnancy failure, and the probability of a euploid embryo decreases with female age. Implantation failure is a separate entity but with partially overlapping causes and treatments (Christiansen et al 2006). Immunological factors remain a controversial cause for both failed implantation and pregnancy loss

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