Automated Vitrification of Embryos: A Robotics Approach

Abstract

T his article reports on the first robotic system for vitrification of mammalian embryos. Vitrification is a technique used for preserving oocytes and embryos in clinical in vitro fertilization (IVF). The procedure involves multiple steps of stringently timed pick-andplace operation for processing an oocyte/embryo in vitrification media. In IVF clinics, the vitrification is conducted manually by highly skilled embryologists. Processing one oocyte/embryo takes the embryologist 15-20 min, depending on the protocols chosen to implement. Due to poor reproducibility and inconsistency across operators, the success and survival rates also vary significantly. Through collaboration with IVF clinics, we are in the process of realizing robotic vitrification (RoboVitri) and ultimately aim to standardize clinical vitrification from manual operation to fully automated robotic operation. Our robotic system is embedded with two contact detection methods to determine the relative z positions of the vitrification micropipette, embryo, and vitrification straw. A three-dimensional (3-D) tracking algorithm is developed for visually served embryo transfer and real-time monitoring of embryo volume changes during vitrification. The excess medium is automatically removed from around the vitrified embryo on the vitrification straw to achieve a high cooling rate.Tests on mouse embryos demonstrate that the system is capable of performing vitrification with a throughput at least three times that of manual operation and a high survival (88.9%) and development rate (93.8%).

Vitrification within a nanoliter volume: oocyte and embryo cryopreservation within a 3D photopolymerized device

“…The embryologist is thus required to constantly adjust the focus of the microscope to trace the rapidly moving oocyte or embryo within the solution [ 17 , 21 ]. Finally, a single oocyte or embryo is transferred within a microliter-volume (typically 1 —3 µl) onto a carrier device and directly placed into LN 2 [ 15 , 16 , 22 , 23 ]. The volume in which the oocyte or embryo is cryopreserved must be kept to a minimum to enable rapid cooling and avoid ice crystal formation [ 24 , 25 ].…”

Exploiting Microfluidics for Extracellular Vesicle Isolation and Characterization: Potential Use for Standardized Embryo Quality Assessment

“…In recent years, significant effort has been made to implement the use of these microfluidic technologies to improve assisted reproductive technologies (ARTs). Microfluidics have already been applied to: sperm capacitation and selection [as reviewed by (124)]; oocyte maturation and selection (125,126); in vitro fertilization and embryo development [reviewed by (127)(128)(129)]; ovary-, oviductand testis-on-a-chip development (130)(131)(132)(133); full menstrual cycle-on-a-chip development (134); and gametes and embryo cryopreservation (135,136). Although the use of microfluidic technologies for ARTs and EV isolation/characterization has grown in the past years, the use of microfluidics specifically for embryonic EV isolation has yet to be established.…”

Perspectives in Gamete and Embryo Cryopreservation

“…In attempting to pursue the same goal, such as standardization, cryopreservation may be conducted with a machine performing the automatic replacement of cryomedia by means of robotic arms, guaranteeing consistent volume pipetting and precise incubation timing. [141][142][143] Furthermore, the instruments might be operated with a micromanipulator device able to recognize the material and move it onto a specific point of the cryopreservation support. 142 Unfortunately, beyond the considerable financial investment required, very little evidence is currently available about the effective clinical advantages of using automated vitrification devices and further studies are needed before promoting this implementation for routine use.…”