Development and validation of an automated robotic system for preparation of embryo culture dishes

Abstract

Objective: To study the development and clinical validation of the ART Pipetting Robot for the IVF Laboratory (APRIL), a liquid-handling robot customized for the precise preparation of microdroplet culture dishes in the field of in vitro fertilization (IVF).

Design: A prospective randomized study conducted at an academic IVF center comparing mouse and human embryo outcomes and quantitative measures of accuracy in embryo dishes prepared using APRIL compared with standard manual preparation.

Setting: Academic IVF center.

Subjects: The study involved the assessment of the automated culture dish preparation system, APRIL, compared with manual preparation methods in the context of IVF treatment.

Intervention: ART Pipetting Robot for the IVF Laboratory is an enclosed liquid-handling robot equipped with custom three-dimensional-printed adapters and designed to dispense embryo culture media and mineral oil into microdroplet culture dishes.

Main outcome measures: The study evaluated the precision and consistency of APRIL in culture dish preparation by looking at droplet mass, pH of prepared media droplets, and mouse and human embryo development rates. Clinical implementation was assessed by comparing embryo development and outcomes in dishes prepared by APRIL and human embryologists.

Results: Compared with embryo culture dishes prepared using standard manual procedures, embryo culture dishes prepared using APRIL demonstrated a greater than 10-fold improvement in consistency (coefficient of variation, 0.46% vs. 6%-7%), maintained optimal pH levels (pH range, 7.281-7.33 vs. 7.275-7.311), and had a greater mouse embryo blastocyst rate (100% vs. 90%-91%). Human embryos cultured in dishes prepared by APRIL had a higher rate of development on days 3 (92.4% vs. 82.6%) and 5 (19.75% vs. 15.57%), and a total number of usable embryos (50.3% vs. 46.1%) compared with manually prepared dishes, although the last two outcomes did not reach statistical significance.

Conclusion: The results suggest that the use of an automated robotic system for preparation of embryo culture dishes may improve accuracy and outcome measures while reducing the need for trained laboratory personnel to prepare the dishes manually.

Keywords: IVF; automated system; culture dish preparation; embryo development; robotics.