Mouse embryo assay for human in vitro fertilization quality control: a fresh look

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Mouse embryo assay for human in vitro fertilization quality control: a fresh look Navid Esfandiari 1 & Ashley Gubista 1 Received: 16 January 2020 / Accepted: 27 March 2020 # Springer Science+Business Media, LLC, part of Springer Nature 2020

Abstract The mouse embryo assay (MEA) has been used in the field of human in vitro fertilization (IVF) for multiple purposes such as developing embryo culture media, quality control within the laboratory, and procedural training and proficiency testing for embryology staff. In addition, manufacturing companies use the MEA as a means of quality control for the development of embryo culture media and medical devices and to meet the standards of testing for FDA approval of new products. It has long been considered by embryologists and laboratory scientists whether the MEA is an accurate or sensitive test in the quality assessment of culture media and medical devices or if use of this testing is more an obligation. There is no uniformly accepted gold standard method for IVF lab quality control or FDA approval. This review aims to revisit the role of the use of mouse embryos in the formulation of IVF media for clinical use and the different methods of employing the mouse embryo assay for quality control. In addition, we will review the use of the MEA as an important adjunct in the training for embryology staff and fellows in training in reproductive endocrinology and infertility (REI), as well as alternatives to the use of the MEA for these purposes. Keywords Mouse embryos . Quality control . Culture media . In vitro fertilization . Proficiency testing

Introduction and history of MEA Throughout the history of cell culture and in the development of formulations for IVF culture media, the use of mouse embryos have had a significant impact. In the early 1900s, Hammond was able to retrieve 4-cell and 8-cell mouse embryos by flushing uterine horns and then culturing these divided embryos to the blastocyst stage in a generally simplified media made of Krebs-Ringers bicarbonate with egg white [1]. Whitten later cultured 8-cell mouse embryos to blastocysts in a media with only nine ingredients including glucose, water, and egg white [2]. In 1958, McLaren and Biggers were able to achieve the first healthy mouse offspring from flushing 8-cell embryos from the oviduct, culturing them to blastocyst in a media that contained bovine serum albumin, and subsequently

* Navid Esfandiari [email protected] 1

IVF and Andrology Laboratories, Department of Obstetrics, Gynecology and Reproductive Sciences, University of Vermont Medical Center, Burlington, VT 05401, USA

transferring these cultured embryos to the mouse uterus [3]. Finally, in 1962, Biggers cultured 1-cell stage mouse embryos to the blastocyst stage using chemically defined BGJB medium in the presence of mouse fallopian tube cells [4]. In the 1960s, Brinster investigated further into the components of culture media to find out what exactly would be an optimal environment for pre-implantatio