Huang Guoning: New Progress in Assisted Reproductive Technology in 2019

Since the comprehensive implementation of the "two child" policy by the government in 2016, reproductive medicine has faced more challenges, including exploration, discussion, research, and application in reproductive mechanisms, assisted pregnancy techniques, and reproductive ethics, such as the issue of reproduction for elderly couples, in vitro embryo culture and evaluation. These challenges have put forward higher requirements for reproductive medicine clinical doctors and embryology researchers in China. As the Chairman of the Reproductive Medicine Branch of the Chinese Medical Association, the author summarized and reviewed the new progress of assisted reproductive technology in 2019.           

China has a vast territory and a certain particularity in population distribution. Currently, there is a lack of accurate data on the incidence of infertility nationwide. According to data and literature reports from various regions, the incidence of infertility is estimated to be around 10%. According to the data analysis in the data reporting system of the branch, 80% of patients under the age of 37 who receive assisted reproductive technology (ART) assisted pregnancy treatment, with fallopian tube obstruction being the primary factor in the occurrence of female infertility, accounting for 40% of ART assisted pregnancy patients; Ovulation disorders and decreased ovarian reserve function have also become important causes of female infertility, accounting for 20% of assisted reproductive technology assisted pregnancy patients. In response to the issue of male infertility, the analysis of semen parameters from over 8000 healthy men in seven sperm banks across the country by the branch showed a downward trend in parameters representing male reproductive ability, such as sperm concentration, semen volume, and normal morphology rate, among normal men in China. This is consistent with recent reports abroad. However, there are no literature reports on this downward trend that have reduced fertility or shown any adverse effects on fertility.

In recent years, with the effective management and promotion of infertility diagnosis and treatment by the country, infertile patients have basically concentrated in reproductive centers of various medical institutions and received effective and standardized medication, surgery, and assisted reproductive technology treatment.

Assisted reproductive technology has a history of over 30 years in China. Under the standardized management of the National Health Commission, assisted reproductive technology has been steadily and orderly developing. The branch analyzed data from 217 reproductive centers nationwide from 2016 to 2017, and found that the average clinical pregnancy rate and average live birth rate of assisted reproductive technology were 51.84% and 42.51%, respectively; There is no statistically significant difference in the incidence of birth defects in offspring between natural pregnancy delivery and assisted reproductive technology.

China has a vast territory and a certain particularity in population distribution. Currently, there is a lack of accurate data on the incidence of infertility nationwide. According to data and literature reports from various regions, the incidence of infertility is estimated to be around 10%. According to the data analysis in the data reporting system of the branch, 80% of patients under the age of 37 who receive assisted reproductive technology (ART) assisted pregnancy treatment, with fallopian tube obstruction being the primary factor in the occurrence of female infertility, accounting for 40% of ART assisted pregnancy patients; Ovulation disorders and decreased ovarian reserve function have also become important causes of female infertility, accounting for 20% of assisted reproductive technology assisted pregnancy patients. In response to the issue of male infertility, the analysis of semen parameters from over 8000 healthy men in seven sperm banks across the country by the branch showed a downward trend in parameters representing male reproductive ability, such as sperm concentration, semen volume, and normal morphology rate, among normal men in China. This is consistent with recent reports abroad. However, there are no literature reports on this downward trend that have reduced fertility or shown any adverse effects on fertility.

In recent years, with the effective management and promotion of infertility diagnosis and treatment by the country, infertile patients have basically concentrated in reproductive centers of various medical institutions and received effective and standardized medication, surgery, and assisted reproductive technology treatment.

Assisted reproductive technology has a history of over 30 years in China. Under the standardized management of the National Health Commission, assisted reproductive technology has been steadily and orderly developing. The branch analyzed data from 217 reproductive centers nationwide from 2016 to 2017, and found that the average clinical pregnancy rate and average live birth rate of assisted reproductive technology were 51.84% and 42.51%, respectively; There is no statistically significant difference in the incidence of birth defects in offspring between natural pregnancy delivery and assisted reproductive technology.

In order to improve the technical and standardized level of assisted reproductive technology in China, the branch held multiple academic conferences at different levels in 2019. At the 13th National Reproductive Medicine Academic Annual Conference of the Chinese Medical Association held in Fuzhou, a branch venue for reproductive care was arranged for the first time; An academic conference on new advances in reproductive medicine was held in Shanghai with the aim of discussing new developments and trends in assisted reproductive technology; A consensus guidance seminar for grassroots medical personnel was held in Changchun. In response to the Health Poverty Alleviation Project of the Chinese Medical Association, in 2019, the branch continued to hold a series of reproductive medicine health border area activities in Jinzhai, Anhui, Yanbian, Jilin, and Taihang Mountains, Shanxi, respectively. At the same time, special technical training courses were held for assisted reproductive laboratories in grassroots and poverty-stricken areas, with a total of Fifty laboratory technicians from grassroots hospitals in Guangxi and Inner Mongolia have received technical training on semen preparation, routine in vitro fertilization, intracytoplasmic sperm injection, and embryo freezing and resuscitation for in vitro fertilization techniques. In addition, the branch has also held a speech and debate competition for young physicians aimed at improving and encouraging their academic level. The above work has effectively promoted the standardization and science popularization of assisted reproductive technology in China, improved the level of assisted reproductive technology in western and impoverished areas of China, and made more ordinary people understand assisted reproductive technology, increased their understanding of reproductive health, and laid a good foundation for the standardized development of assisted reproductive technology in China.

At the same time, the branch actively cooperates and exchanges academic knowledge with the International Union of Reproductive Medicine, the European and American Societies of Reproductive Medicine, and continues to hold a special session of the Reproductive Medicine Branch of the Chinese Medical Association at the American Reproductive Medicine Annual Conference, promoting China's reproductive medicine to step onto the international academic conference stage.

After more than 30 years of development, assisted reproductive technology in China has ushered in a booming opportunity for clinical application research and basic research to advance simultaneously. Clinical and scientific researchers continue to work hard and actively explore, and their academic level continues to improve. They have conducted a large number of clinical and basic research related to assisted reproductive technology. Every year, academic papers in China are published in high-level academic journals both domestically and internationally. In 2019, the New England Journal of Medicine, Lancet, Nature, Science Multiple clinical and basic research papers on assisted reproductive technology have been published in journals such as Nature Medicine and Cell Stem Cell. Our country's assisted reproductive laboratory technicians are also constantly exploring and innovating in laboratory technology and equipment intelligence and automation. Currently, we have completed the design of an intelligent laboratory for in vitro fertilization of embryos, and are conducting research on the automation of in vitro fertilization and embryo culture dish preparation. In 2019, we also obtained multiple national technology invention patents.

Several multicenter randomized controlled clinical studies in the field of reproductive medicine have been carried out nationwide, aiming to quickly apply new technologies and methods in the field of assisted reproductive technology to improve the efficiency of assisted reproductive technology treatment and benefit the vast number of infertile patients. Each reproductive center optimizes the current drug stimulated ovarian program to explore how to obtain high-quality eggs and improve treatment efficiency. At the same time, high-throughput gene sequencing technology is used to sequence genes related to endometrial receptivity in patients with recurrent embryo implantation failures, in order to explore the most suitable implantation timing.

Time difference microscopy has been used for a long time, accumulating a large amount of data in the field of embryonic development kinetics parameters and publishing multiple academic papers. However, due to the differences in technical conditions among different laboratories, the application of embryonic development kinetics parameters has certain limitations. In 2019, reproductive center laboratories in Chongqing, Hunan, and Hubei provinces discovered "real events" of in vitro embryonic development through the analysis of massive embryo images accumulated under time difference microscopes, such as "abnormal cleavage patterns" during embryonic division and "blastomere phagocytosis/exocytosis phenomenon, which may be one of the reasons for chromosomal aneuploidy of blastomeres due to nuclear embryo fragments being swallowed into the blastomeres, Revealing the difference between embryos with normal and abnormal morphology is expected to guide the correct evaluation of embryos in clinical practice. With the continuous development of artificial intelligence technology, Chinese scholars are also exploring how to apply artificial intelligence technology to the treatment of assisted reproductive technology, in order to improve the accuracy of assisted reproductive technology treatment.

In terms of basic research, in 2019, the research team of the First Affiliated Hospital of Zhengzhou University established an improved small number of cell ATAC-seq technology. A study published in Science magazine found that the establishment of histone modification I before the activation of the zygotic genome is closely related to the sequence characteristics of DNA, and with the opening of chromatin, histone reprogramming in early human embryonic development has high species specificity, This difference may be related to the differential expression of related modifying enzymes between species, thus proposing the "epigenome restart" model. The research published by Academician Qiao Jie from Peking University Third Hospital and Researcher Jiang Changtao from the School of Basic Medicine of Peking University Department of Medicine in the journal Nature focuses on the mechanism of gut microbiota metabolites regulating the body's intestinal immunity, delving into the key role of the gut microbiota bile acid IL22 axis in the pathogenesis of polycystic ovary syndrome, and elucidating the new mechanism by which gut microbiota and bile acid regulate the secretion of IL-22 by intestinal ILC3 cells, This provides a new perspective for the prevention and treatment of polycystic ovary syndrome. The research published in Nature by Chen Zijiang, an academician of Shandong University, and the team of Beijing Institute of Genomics, Chinese Academy of Sciences, found that the chromatin regulator CTCF plays a key role in the establishment of 3D chromatin structure during human embryogenesis. The research published by the team of Yunnan First People's Hospital and the Primate Transformation Medicine Research Institute of Kunming University of Science and Technology in the journal Nature has for the first time drawn a panoramic map of the development of human pregut embryos.

The development trend of assisted reproductive technology As an emerging discipline, assisted reproductive technology is currently in a stage of rapid development, with the main characteristics of new technologies constantly emerging and new theoretical knowledge constantly developing. Medical personnel engaged in assisted reproductive technology continuously learn and introduce these new technologies. With the development and transformation of intelligent technology, its application in the field of assisted reproductive technology is becoming increasingly widespread. For example, in the management and communication of infertility treatment, the establishment of embryo laboratories, and the assessment of embryonic development potential, it will be the future development direction of assisted reproductive technology treatment; At the same time, interdisciplinary approaches also contribute to the treatment of assisted reproductive technology, such as reducing the impact of psychological stress, depression, and anxiety on treatment outcomes in infertility patients in the field of psychology, and reducing comorbidities through weight regulation in the field of nutrition. In addition, the efficiency and safety of assisted reproductive technology treatment, especially the effectiveness and safety of cryopreservation technology applied to gamete/embryo cryopreservation, will be a key research area.

While carrying out assisted reproductive technology, we must comply with relevant national technical norms and medical ethical principles. Obtaining healthy infants under the premise of safety is the ultimate goal of reproductive medicine workers nationwide. Assisted reproductive technology, as an emerging discipline, is currently in a stage of rapid development, characterized by the continuous emergence of new technologies and the development of new theoretical knowledge. Medical personnel engaged in assisted reproductive technology continuously learn and introduce these new technologies. With the development and transformation of intelligent technology, its application in the field of assisted reproductive technology is becoming increasingly widespread. For example, in the management and communication of infertility treatment, the establishment of embryo laboratories, and the assessment of embryonic development potential, it will be the future development direction of assisted reproductive technology treatment; At the same time, interdisciplinary approaches also contribute to the treatment of assisted reproductive technology, such as reducing the impact of psychological stress, depression, and anxiety on treatment outcomes in infertility patients in the field of psychology, and reducing comorbidities through weight regulation in the field of nutrition. In addition, the efficiency and safety of assisted reproductive technology treatment, especially the effectiveness and safety of cryopreservation technology applied to gamete/embryo cryopreservation, will be a key research area.

While carrying out assisted reproductive technology, we must comply with relevant national technical norms and medical ethical principles. Obtaining healthy infants under the premise of safety is the ultimate goal of reproductive medicine workers nationwide.

For more information on assisted reproductive technology, please follow the WeChat official account of Jinan Yingli Technology Co., Ltd.