On July 26, 1978, the world’s first “test-tube baby”, Louis Brown, was born in England. “Since then, 35 years have passed since the birth of IVF babies, many of whom have grown into adults. Brown also became the mother of a boy. Although Professor Robert G. Edwards was awarded the 2010 Nobel Prize in Physiology or Medicine for his invention of IVF, the controversy surrounding the technology from its inception has not been quelled by Edwards’ award. In October 2013, the annual meeting of the International Federation of Fertility Societies and the American Society for Reproductive Medicine was held in Boston, USA. At this meeting, the International Monitoring Committee on Assisted Reproductive Technology reported that there are now more than 5 million “test-tube babies” worldwide, which is comparable to the populations of countries such as Lebanon and Ireland. In terms of numbers alone, this is a great medical achievement. Studies by the International Monitoring Committee on Assisted Reproductive Technology show that in 1990 there were only about 95,000 IVF babies worldwide, but by 2000 there were nearly 1 million, and by 2007 there were 2.5 million. From 2007 to the present, IVF technology has added about 2.5 million more people to the world’s population, a clear trend of accelerated growth. This indicates that in vitro fertilization technology, represented by IVF, has become a major treatment for infertility. In March 1988, the first “test tube baby”, “Mengzhu”, was born in the Third Hospital of Peking University. In June of the same year, China’s first IVF baby, “Luo Youqun”, was born at CITIC Xiangya Hospital, and in 1996, China’s first “ICSI” baby was born at In 1999, fluorescence in situ hybridization technology was introduced into the preimplantation sex diagnosis of human embryos, and Zhongshan University successfully selected healthy baby girls from two cases of hemophilia A gene carriers, becoming the first case of “PGD” in China. IVF technology. At present, there are no accurate statistics on the number of IVF in China. Years ago, the Chinese Ministry of Health estimated that from 1988 to 2004, more than 10,000 IVF cases were born in mainland China. But by 2010, the CITIC Xiangya Reproductive and Genetic Hospital alone had performed 13,000 IVF procedures, and in 2011, that number rose to 18,000. By 2009, every province in China had established a reproductive center, and 138 institutions were qualified to do IVF. Therefore, it is conservatively estimated that the number of IVF cases in China is close to 100,000. The increase of IVF from one to three generations means the development and maturity of IVF technology. The in vitro fertilization-embryo transfer (IVF-ET) technique, invented by Edwards and often referred to as the first generation of IVF, involves placing sperm and eggs in the same medium and allowing them to combine naturally to form conventional fertilization. Subsequently, the second generation of IVF is the single sperm intracytoplasmic injection (ICSI) technique, in which a single sperm is injected directly into the egg cytoplasm; later, IVF technology evolved to pre-implantation genetic diagnosis (PGD), which aims to ensure the presence of a single genetic recessive gene. The aim is to ensure that infertile couples with single-gene genetic predispositions have healthy babies, hence the name third-generation IVF. In recent years, the medical community has improved the third generation of IVF technology by performing preimplantation genetic screening (PGS) of in vitro fertilized embryos through whole genome sequencing. This is a preimplantation genetic screening of individual embryo cells to increase the pregnancy rate and reduce the risk of miscarriage in women of advanced age, women with recurrent embryo implantation failure, and women with infertility such as habitual miscarriage. Both pre-implantation genetic diagnosis (PGD) and pre-implantation genetic screening (PGS) require embryo biopsy after 3 days for embryos successfully fertilized by in vitro fertilization and intracytoplasmic single sperm injection. Are IVF babies healthy? “One of the biggest issues facing IVF babies since their birth is the concern that they will be as healthy and normal as naturally conceived children, including physical, intellectual and emotional intelligence. For this reason, researchers have done numerous comparative studies. A follow-up study published by the European Union in 2003 showed that IVF children are as healthy as those born from natural conception, with normal physical, intellectual and psychological development and social skills. A larger study in the United States in 2009 also concluded, as did the European Union, that there were no substantial differences between IVF and naturally conceived children, and that they grew up and had as good a job and normal family life as anyone else. The world’s first “test-tube baby,” Louise Brown, tied the knot with bank security guard Wesley Mallinder on Sept. 4, 2004. After their marriage, Brown conceived naturally, without any scientific means, and gave birth to a healthy boy on December 20, 2006. This in itself shows that there is no difference between “test-tube babies” and naturally conceived children as adults. Other studies, however, are not as optimistic. Some of the more typical studies have even produced surprising results. This has raised concerns about possible problems with IVF technology. In 2008, epidemiologist Jennita Reefhuis of the Centers for Disease Control and Prevention and others published an article in the November issue of the journal Human Reproduction, saying that IVF is two to four times more likely to have congenital defects than regular babies. For example, IVF babies are two to three times more likely to have a congenital heart defect, twice as likely to be born with a cleft lip, and four times as likely to have a congenital gastrointestinal defect. In 2013, HansenM of the University of Western Australia and others published an article in the journal New Advances in Human Reproduction in which they compared 92,671 “test-tube babies” born between 1978 and 2012 with 387,076 children conceived naturally and found that the former had a relatively high The RR was greater than 1, suggesting that birth defects were positively associated with IVF, and the RR was greater than 1. “If the RR is greater than 1, it means that birth defects are positively correlated with IVF, and the risk is higher as the value increases; if the RR is equal to less than 1, it means that birth defects are not related to IVF. In 2010, the Reproduction Group of the Obstetrics and Gynecology Branch of the Shanghai Medical Association published in the Chinese Journal of Obstetrics and Gynecology “Analysis of birth defects in the offspring of in vitro fertilization-embryo transfer in Shanghai from 1998 to 2007”, which initially confirmed that IVF-ET did not increase the incidence of birth defects in the offspring. Different insemination methods, embryo handling methods and sperm acquisition methods were also not associated with the incidence of offspring birth defects, while advanced maternal age and multiple pregnancies significantly increased the incidence of offspring birth defects. The slightly higher risk of autism in IVF is mainly related to the second generation of IVF technology, intracytoplasmic sperm injection (ICSI), and Lisa Yadan, head of the UK’s Human Fertility and Embryology Authority (HFEA), recently pointed out that ICSI has been used too often, making it likely that male babies born through the technique will have lower sperm counts. Now, people are willing to choose ICSI technology because it is easier in operation and procedure, and it has a higher success rate than the standard “in vitro fertilization” (IVF) technique, which has a success rate of about 30 percent, and the latter has a success rate of about 25 percent. Half of all infertile couples in the UK choose this technique, and the rate is as high as 90 to 95 percent in North America and Europe. However, the widespread use of the technique is a cause for concern. The concern is indeed well-founded. A paper published in the Journal of the American Medical Association in 2013 by Sven Sandin of the Institute of Psychiatry in London at King’s College London and others noted that the ICSI technique was associated with an increased risk of intellectual disability and autism in children. In this study, researchers analyzed the birth records of more than 2.5 million children from 1982 to 2007 and followed these children to see if they were clinically diagnosed with autism or intellectual disability, which continued through 2009. Of those more than 2.5 million children, 1.2 percent (30,959) were born through IVF technology; 103 of the 6,959 children diagnosed with autism were born through IVF technology; and 180 of the 15,830 children diagnosed with intellectual disability were born through IVF technology. However, in explaining their findings, Sandin said that when multiple IVF treatments were combined and looked at together, an overall increased risk of autism was not found, but a small increase in the risk of intellectual disability. When the different IVF treatments were looked at separately, conventional IVF was found to be safe, but when IVF involved ICSI, children were at increased risk for both intellectual disability and autism. What causes the increased risk of intellectual disability and autism in the offspring produced by the ICSI technique? The exact mechanism by which ICSI technology is associated with an increased risk of intellectual disability and autism in the offspring produced by the technology is not known. ICSI technology is used primarily in male infertility, and it is possible that if the father of the child has a genetic disorder, then the child may have a future fertility that is different from normal simply because of genetics, and not because of ICSI technology. In natural reproduction, tens of millions of sperm need to compete before one or two good sperm break through the difficulties and obstacles to unite with the egg, so as to fertilize successfully and conceive a fetus. Therefore, each life born through the natural reproductive process is one of the best in ten million, because the sperm of its parent is one of the successful ones out of ten million or billion, and such life is the best one that has passed the natural selection and competition, so it is strong, excellent and outstanding. However, the ICSI technique only selects a sperm at random to unite with the egg, which clearly violates the principle of “competition for the job” in the natural state. Since there is no competition and the selection is not natural, it is not a coincidence that problems occur after the formation of the embryo. It seems that with the development of technology and the birth of more and more “IVF” babies, more and more problems will arise from “IVF”. In the future, only through a deeper understanding of the process and laws of natural reproduction, so that assisted reproduction technology is closer to natural reproduction and more in line with the principles of natural selection in the evolution of life, will the offspring produced by assisted reproduction be more healthy and excellent.