Magnetic-Activated Cell Sorting (MACS): A Useful Sperm-Selection Technique in Cases of High Levels of Sperm DNA Fragmentation

Abstract

Magnetic-activated cell sorting (MACS) can be used to separate apoptotic sperm with high proportions of fragmented DNA from the rest, thus improving the overall quality of the seminal sample. Therefore, the aim of this retrospective study was to investigate the efficiency of the MACS technique to increase reproductive outcomes in patients with high levels of sperm DNA fragmentation (SDF) undergoing intracytoplasmic sperm-injection (ICSI) cycles. In this study, we analyzed a total of 724 assisted-reproduction-technique (ART) cycles that were divided into two groups: the study group (n = 366) in which the MACS selection technique was performed after density-gradient centrifugation (DGC), and the control group (n = 358) in which only DGC was used for sperm selection. Reproductive outcomes were analyzed in both groups according to three different ART procedures: preimplantation genetic testing for aneuploidy (PGT-A), and autologous and oocyte-donation cycles. The MACS group showed significantly lower miscarriage rates in autologous ICSI cycles, higher pregnancy rates in oocyte-donation cycles, and a significant increase in live-birth rates in both autologous and oocyte-donation cycles. Overall, these results suggested that the MACS technique can be effectively used to eliminate sperm with high SDF levels, and therefore may help to improve reproductive outcomes in couples undergoing ART.

Sperm Selection by Magnetic-Activated Cell Sorting before Microinjection of Autologous Oocytes Increases Cumulative Live Birth Rates with Limited Clinical Impact: A Retrospective Study in Unselected Males

“…The general scope that this study aimed to provide will progressively develop into separate analysis focused on different male and female etiologies and indications of the patients for undergoing ART, providing more information on the specific patient groups in which MACS could be more useful. As an example of a retrospective study focused on a distinct male population (>20% fDNA index) that could benefit from the use of MACS, Pacheco and colleagues recently reported a decrease in miscarriage rate and an increase in live birth rate when semen samples were processed via MACS versus the control group in cycles using autologous oocytes [36].…”

“…There is discrepant evidence on the effect of MACS sperm selection on clinical outcomes. One RCT showed increased pregnancy rates per cycle from 24.2% in the reference (DGC) group to 54.5% in the MACS-DGC, even though there was no significant improvement of fertilization or implantation rates, in couples with men factor infertility and at least two of the semen parameters below WHO 2010 normalcy criteria [18,36]. A similar RCT reported an increase of around 21% in LBR when using MACS compared to standard ICSI in normozoospermic men [38].…”

Biocompatible Nanomaterials as an Emerging Technology in Reproductive Health; a Focus on the Male

“…Damaged and apoptotic sperm remain attached to the magnetic beads whilst the flow through carries the better quality sperm from the column. Nanoparticles such as magnetic IONPs coated with lectins or a combination of lectins and Annexin V that bind to, and facilitate removal of, damaged spermatozoa have been applied to porcine ( Feugang et al, 2015a ; Durfey et al, 2019 ; Feugang et al, 2019 ) and camel ( Rateb, 2020 ) semen samples prior to downstream application in AI, and to human spermatozoa for subsequent use in ICSI ( Pacheco et al, 2020 ). Additionally, in a study aimed at improving the quality of spermatozoa in cattle semen samples, Farini et al (2016) used Cell-SELEX to discover ssDNA aptamers that bind to damaged spermatozoa and applied these to the surface of magnetic IONPs.…”

“…Additionally, in a study aimed at improving the quality of spermatozoa in cattle semen samples, Farini et al (2016) used Cell-SELEX to discover ssDNA aptamers that bind to damaged spermatozoa and applied these to the surface of magnetic IONPs. MACS has also been shown to be an effective method for the isolation of viable human sperm ( Pacheco et al, 2020 ) with normal morphology and intact mitochondrial membrane potential ( Marzano et al, 2020 ). Sperm samples processed using MACS followed by density gradient centrifugation (DGC) exhibited a significantly higher percentage of sperm with progressive motility and less sperm with fragmented DNA ( Berteli et al, 2017 ).…”

Effect of Sperm Selection by Magnetic-Activated Cell Sorting in D-IUI: A Randomized Control Trial

“…To address this problem, different sperm selection techniques have been developed based on different functional aspects and activation processes that occur during sperm cell capacitation. One of these procedures is magnetic-activated cell sorting (MACS), which is used to positively identify and eliminate apoptotic cells from the ejaculate by identifying externalized phosphatidylserine residues in apoptotic sperm [ 3 ]. This technique also reduces the proportion of sperm with fragmented DNA in the ejaculate before using it for ART procedures.…”