Improved development of mouse and human embryos using a tilting embryo culture system

Abstract

Mammalian embryos experience not only hormonal but also mechanical stimuli, such as shear stress, compression, and friction force, in the fallopian tube before nidation. In order to apply mechanical stimuli to embryos in a conventional IVF culture system, we developed the Tilting Embryo Culture System (TECS). The observed embryo images from the TECS suggest that the velocities and shear stresses of TECS embryos are similar to those experienced in the oviduct. Use of TECS enhanced the development rate to the blastocyst stage and significantly increased the cell number of mouse blastocysts (P<0.05). Although not significant, human thawed embryos showed slight improvement in development to the blastocyst stage following culture in TECS compared to static controls. Rates of blastocyst formation following culture in TECS were significantly improved in low quality embryos and those embryos cultured under suboptimal conditions (P<0.05). Here, we propose that the TECS could be a promising approach to improve embryo development and blastocyst formation by exposing embryos to mechanical stimuli similar to in the fallopian tube.

Effect of micro-vibration culture system on embryo development

“…During mouse embryonic development, the number of mouse embryos in a 50 μL MTF droplet was limited to 5 to minimize the influence of group culture [36,37] and to maximize the effect of the experimental conditions between the static culture and the micro-vibration culture [20]. The mouse embryonic development rate when the O 2 pressure is low (5 %) is commonly faster than when the O 2 pressure is high (20 %) [38,39].…”

“…Furthermore, a micro-vibration embryonic culture method that mimics in vivo mechanical forces would be a valuable approach to improving the quality of in vitro fertilization (IVF) treatment. Other dynamic culture systems have been recently reported, including a microfluidic dynamic embryonic culture system [44,45] and a tilting embryonic culture system [20]. Each system has pros and cons and presents challenges for practical use [46].…”

“…These in vivo mechanical forces are believed to induce cell-to-cell communication, exert beneficial effects by refreshing the fluid surrounding the embryo and eliminate metabolites emitted from embryos [16][17][18][19]. Studies to achieve higher quality embryos by external stimuli using machines (i.e., tilting machines and micro-vibrators) to replicate in vivo mechanical forces have been recently reported [20,21]. Embryonic culture using a micro-vibrator as an external stimulus has been actively investigated [22].…”

Use of Silicone Elastomer-Based Microfluidic Devices and Systems in Reproductive Technologies

“…Positive effects using tilting culture systems were also found in a microdroplet environment. We developed a tilting embryo culture system (TECS) to move mouse, porcine, and human embryos by fluid motion of the microdroplet, and we have shown that blastocyst development rates of these embryos using TECS improved over those of static controls [85][86][87]. Gentle vibration of porcine and human embryos also appeared to yield improved blastocyst formation rates [88][89][90].…”

Improvement of Fertilization Rates of In Vitro Cultured Human Embryos by Exposure to Sound Vibrations

“…Several groups have tried to apply a variety of methods, such as mechanical microvibrations to embryo culture plates [6][7][8], the use of dynamic fluids in embryo culture [9][10][11][12][13][14][15][16] or the use of a tilting embryo culture system [17]. An improvement in the quality of in vitro human blastocysts was noted when the tilting embryo culture system was used [18,19] and also when dynamic microfunnel culture conditions were applied [12]; in the latter study a higher rate of embryo implantation and subsequent pregnancy was also noted. Pregnancy rates were as well increased with the application of pulsatile mechanical microvibrations to the culture system (20 Hz over 5 seconds, once per hour) [6].…”