Contents




#### **Section 4 Improving Embryo Cleavage Technology 97**

#### Chapter 7 **Improving ART Pregnancy Rate with Two Kinds of Media and Two Types of Incubators 99**

Bin Wu, Jinzhou Qin, Suzhen Lu, Linda Wu and Timothy J. Gelety

## Preface

**Section 4 Improving Embryo Cleavage Technology 97**

**Two Types of Incubators 99**

**VI** Contents

Chapter 7 **Improving ART Pregnancy Rate with Two Kinds of Media and**

Bin Wu, Jinzhou Qin, Suzhen Lu, Linda Wu and Timothy J. Gelety

Embryo cleavage is the division of cells in the early embryo. This division from one-celled zygote into two cells, four cells, eight cells, and sixteen cells, morula stage, and the final forming blastocyst stage until implanting in the uterus is called embryo cleavage. These stage embryos still do not implant in the uterus, and also they are called as preimplantation embryos. Preimplantation embryo development experiences a series of critical events and remarkable epigenetic modifications, and reprogramming of gene expression occurs to acti‐ vate the embryonic genome. The development of current assisted reproductive technology (ART) has created some new observations and novel discoveries in cleavage embryos. For example, in order to observe embryo morphology and assess embryo quality, time-lapse imaging and light-sheet microscopy have made it possible to visualize early mammalian de‐ velopment in greater detail and over longer time periods than ever before. Thus, this book will collect some new technologies and methods on the study of cleavage embryos to select high-quality embryos for transfer and improve embryo implantation and pregnancy.

Since the birth of the first in vitro fertilization (IVF or test-tube) baby, ART has been widely used in human infertility treatment and animal population reproduction and expansion. However, the success of assisted reproductive technology mainly depends on the production of viable embryos with high implantation potential. More importantly, choosing the best em‐ bryo for transfer has become the major challenge in IVF. In the early embryo culture, the embryo quality assessment was mainly based on the morphological criteria of transfer em‐ bryo. Thus, performing serial observation of embryo morphology is a common technique for embryologist to evaluate embryos and has been considered as key predictor of implantation and pregnancy. For a long term, embryologists perform embryo quality and morphology assessment by taking embryos out of incubator and placing under a microscope. However, although this is easily practiced, it frequently takes embryos out of incubator due to concerns for safety and stability of culture conditions. Also, some key points of embryonic develop‐ ment may be missed for observation. Recently, various time lapse microscopy incubators have started to be used in human IVF clinic to monitor all steps of embryo growth and devel‐ opment. Time-lapse imaging is another noninvasive, emerging technology that allows 24 hour monitoring of embryo development, offering the possibility of increased quantity and quality of morphological information without disturbing the culture condition. This techni‐ que has been able to improve transferred embryo implantation and pregnancy. Thus, in the second part of this book, some morphokinetic markers can be revealed in time-lapse system. The first is the time outline of embryo cleavage, and embryologists may clearly know what situation embryo should be at various time points. Thus, an optimal quality embryo or high potential implantation embryo may be selected for transfer to obtain a higher pregnancy rate. Secondly, some specific events (such as a four-dimensional video sequencing of embryos) of cleavage embryos may be observed by morphokinetic markers and spatiotemporal analysis and innovated computer hardware and software analysis to determine embryo developmen‐ tal speed, sex, etc. Simultaneous monitoring of molecular processes enables the study of con‐ nections between genetic expression and cell physiology and development.

Cleavage embryos experience a series of gene expression. In the early stages, maternal mRNAs direct embryonic development. New study showed that differential demethylation process results in differential parental gene expression in the early developing embryos that may have an impact on the correct development. Thus, Part III listed a review paper that showed different factors affecting gene expression during early embryo development, which included epigenetic factors, focusing on methylation profiles. The effects of noncod‐ ing RNAs on gene expression were thoroughly evaluated. Based on the products of gene expression, an available metabolic and proteomic approach as the noninvasive molecular assessment of embryo viability has been described. A new discovery, the alpha-1 chain of the human haptoglobin molecule, may be used as a quantitative biomarker of embryo via‐ bility. If this molecular composition of cultivation media can be used as an additional nonin‐ vasive procedure to choose an embryo for selective transfer, it will be very useful to improve human IVF pregnancy outcome.

Embryonic quality, cleavage speed, and gene expression have a close relationship with in vitro culture environment, including culture media, incubator type, and gas concentration. Thus, an optimum for embryo in vitro culture plays important roles in improving embryo quality and pregnancy rate. In the last part of this book, an interesting research report has been listed, which showed the favorable response of individual patient's embryos to media and incubators. Some patents' embryos grow very well in one kind of medium, but it does not grow well in the other medium. Thus, in human IVF clinic practice, using two media and two incubators for embryo culture could significantly improve IVF/ICSI embryo quality and increase pregnant rates.

I thank all authors who devoted their time and expertise to prepare these outstanding chap‐ ters included in this book.

> **Bin Wu, PhD, HCLD (ABB)** Arizona Center for Reproductive Endocrinology and Infertility Tucson, Arizona USA

**Section 1**
