Abstract

Granulocyte macrophage colony stimulating factor (GM-CSF) is a cytokine/growth factor produced by epithelial cells that exerts embryotrophic effects during the early stages of embryo development. We performed a systematic review, and six studies that were performed in humans undergoing assisted reproduction technologies (ART) were located. We wanted to evaluate if embryo culture media supplementation with GM-CSF could improve success rates. As the type of studies and the outcome parameters investigated were heterogeneous, we decided not to perform a meta-analysis. Most of them had a trend favoring the supplementation with GM-CSF, when outcomes were measured in terms of increased percentage of good-quality embryos reaching the blastocyst stage, improved hatching initiation and number of cells in the blastocyst, and reduction of cell death. However, no statistically significant differences were found in implantation and pregnancy rates in all apart from one large multicenter trial, which reported favorable outcomes, in terms of implantation and live birth rates. We propose properly conducted and adequately powered randomized controlled trials (RCTs) to further validate and extrapolate the current findings with the live birth rate to be the primary outcome measure.

Highlights

  • Assisted reproduction technologies (ARTs) are those methods that treat subfertility by providing the medical means to overcome the pathological obstacles in the fertilization process in a controlled laboratory environment, mimicking to a large extent the biological reproductive processes

  • Six studies were identified [3,4,5,6,7,8]; of these, four were randomized controlled trials (RCTs) and two were prospective observational studies; of these, two RCTs and one observational were published only as abstracts, whereas one RCT was presented in the 27th Annual Meeting of ESHRE in 2011 and is not published yet

  • Sjoblom et al [3] examined the effect of the addition of Granulocyte macrophage colony stimulating factor (GM-CSF) on in vitro embryo development donated by couples undergoing in vitro fertilization (IVF); they found increased percentage of embryos that reached the blastocyst stage (75.5 versus 30%, P < 0.001), improved hatching initiation (78 versus 47%, P < 0.001), and rise in the number of cells in the blastocyst by approximately 35%—the effect appearing

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Summary

Introduction

Assisted reproduction technologies (ARTs) are those methods that treat subfertility by providing the medical means to overcome the pathological obstacles in the fertilization process in a controlled laboratory environment, mimicking to a large extent the biological reproductive processes. Various factors have an impact on these processes, with the unfortunate upshot that successful fertilization does not invariably lead to the birth of a healthy offspring, as the growth and development of even confirmed embryo(s) in the laboratory does not always result in successful implantation, clinical pregnancy, and birth. For this reason, different culture media of the preimplantation embryo have been developed, which first appeared on the market in the early 80s [1]. Its survival-promoting effects on the inner cell mass of embryos grown in vitro and in vivo characterize its embryotrophic properties [3, 12], which are essential for embryo development at early stages, shortly before and after its implantation

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