Since the birth of the first in vitro fertilized baby, Louise Brown, in 1978, approximately 5 million people have been born worldwide through IVF technology. Assisted reproductive technologies, including artificial insemination and in vitro fertilization-embryo transfer, and their derivatives, have developed rapidly over the past three decades, and as a result, the “father of IVF,” physiologist Robert Edwards of the University of Cambridge, England, has become one of the world’s leading experts on IVF technology. Edwards was awarded the Nobel Prize in 2010 for his outstanding contributions to IVF technology. Statistics show that about 10% of couples worldwide have fertility problems, and it is IVF technology that has solved the medical problem of infertility. However, while bringing happiness to infertile families, it also brings some potential problems. In addition to the ethical issues that are most blamed and feared by the religious and even scientific communities, the problem that the whole society is worried about is also the impact of assisted reproduction technology on the mother and the baby, whether it will produce a bad prognosis, especially the IVF baby malformation and intelligence problems, and the adverse effects on the IVF mother deeply troubled everyone! 1. An analysis of the different types of assisted reproductive technologies Conventional in vitro fertilization-embryo transfer technology, which we know best as “in vitro fertilization” (IVF-ET), is commonly known as “first generation IVF technology”. In fact, the baby is not actually grown in a test tube, but for those infertility cases that may be caused by obstruction of the fallopian tubes, cervical factors, immune factors, etc. The egg and sperm are grown together in a glass vessel to an early embryo of 4-8 cells, which is then transferred into the uterus to continue development until delivery. Intracytoplasmic single sperm injection (ICSI), commonly known as “second generation IVF”, is used for men with sperm problems or those who have failed in the first generation of IVF. The technique involves injecting sperm directly into the cytoplasm of the egg through a microscope and other techniques to fertilize the egg and develop it into an early embryo, which is then transferred into the uterus. Pre-implantation genetic diagnosis (PGD), commonly known as “third-generation IVF”, is mainly for people with single-gene related genetic disorders, chromosomal disorders, and those at high risk of having children with these disorders. The embryos are removed 1-2 cells prior to transfer, and specific techniques are applied to transfer the embryos diagnosed as free of a single bed disease into the uterus. Other assisted reproductive techniques, which also include immature egg culture techniques, natural cycle IVF techniques, egg freezing techniques, frozen embryo IVF techniques, and mitochondrial transfer techniques, but some involve greater ethical issues and are banned in the country. It is important to note here that the term one, two or three generations of IVF is not rigorous and is not generally referred to as such in academic circles. The terminology of generations can be ambiguous and can be misinterpreted by the public, including non-reproductive physicians, as a substitution between generations. In fact, it is necessary to make an individualized and comprehensive assessment of which transplantation modality to adopt, and it is possible to use a combined approach where several generations of technologies can coexist. 2. Adverse effects of assisted reproductive technology on pregnancy outcomes (1) Pregnancy outcomes Data show that assisted reproductive technology does not increase early pregnancy loss rates or spontaneous abortion rates compared to natural conception. However, the technique increases the incidence of ectopic pregnancy (commonly known as “ectopic pregnancy”), which may be associated with the transfer of multiple embryos into the uterine cavity, and increases the rate of stillbirth (about 2 or 3 per 1,000 live births and about 16 or 2 per 1,000 in vitro conceptions). In addition, assisted reproductive technologies significantly increase the incidence of multiple pregnancies, with approximately 20% of multiple pregnancies statistically associated with in vitro techniques. Furthermore, there is a consensus that this technique not only increases the incidence of preterm birth, low birth weight, and small for gestational age babies (approximately twofold), but also increases the incidence of adverse pregnancy outcomes including gestational diabetes, hypertensive disorders of pregnancy (commonly known as hyperemesis), intrahepatic cholestasis of pregnancy (ICP), placenta abruptio, placenta praevia, and postpartum hemorrhage. and adverse pregnancy outcomes such as postpartum hemorrhage. As for possible causes, there are so many confounding factors that it is not possible to clarify exactly which factor or factors have which effect on which adverse pregnancy outcome. The possible causes are more likely to be attributed to the presence of various adverse factors in the infertile couple itself, especially the effects of advanced age of the egg donor and multiple pregnancies cannot be underestimated. It is important to note that there is no significant difference in prognosis between naturally conceived twins and in vitro twins, whereas in vitro singleton pregnancies have a poorer prognosis than naturally conceived singletons. The reason for this is currently believed to be that approximately 10% of IVF singletons arise from vanishing twin or multiple pregnancies. The increased risk of twin pregnancies is consistently recognized across the literature evidence, and government departments such as health are now trying to find ways to reduce the incidence of twin pregnancies, but also trying to improve the success rate of single embryo transfers. in 2015, studies concluded that the occurrence of some adverse pregnancy outcomes should be controlled in addition to multiple pregnancies while minimizing the use of gonadotropins, which is not significantly related to the use of progestins relationship. (2) What are the effects on the IVF baby/mother? Neurological development: In 2013, a systematic review analyzed 80 studies on the neurological development of IVF babies and found no differences between IVF and naturally conceived babies, including the incidence of psychiatric, cognitive, behavioral, motor, socioemotional, and psychiatric disorders such as mental retardation, autism, and ADHD. Most of the available evidence also supports this view, except for the bias of the studies to be considered, for example, the studies were not followed up long enough to meet the requirements of many aspects of the assessment. And some studies have small sample sizes and many confounding factors, etc. Further studies with large samples are needed to confirm exactly how much of an impact IVF technology, which is currently so widely used, has on the mother and child! Congenital anomalies: Assisted reproductive technology appears to increase the risk of congenital structural defects in the offspring, but the reasons for this remain unknown. This is because the premise is that infertile couples may have many problems of their own, and it is difficult to judge how much risk is posed by assisted reproductive technology. It is reassuring, however, that the absolute risk, or incidence, of congenital malformations is still relatively low. The rate of birth defects is reported to be 2-5%, of which assisted reproductive technology may increase the risk by 1/3. A meta-analysis of 46 studies containing 124,468 IVF/ICSI infants concluded that the rate of structural birth defects in the offspring, including major organ defects, increased approximately 2-fold. An article published in the New England Journal concluded that IVF in vitro techniques did not significantly increase the rate of birth defects after correcting for some confounding factors in infertile couples. On the other hand, the IVF technique was also not found to significantly increase the risk of congenital chromosomal abnormalities compared to natural conception. Regarding birth defects in the offspring of in vitro fertilization-embryo transfer, data from seven reproductive centers in Shanghai during 1998-2007, with a total of 6551 cases and 8507 of their offspring, showed a birth defect rate of 1.08% (92/8507) in the offspring, with the highest rate of circulatory abnormalities, accounting for 34% of all birth defects. It was concluded that “IVF-ET did not increase the incidence of birth defects in the offspring, and different fertilization methods, embryo processing and sperm acquisition methods were not associated with the incidence of birth defects in the offspring, whereas advanced maternal age and multiple pregnancies significantly increased the incidence of birth defects in the offspring”. However, some studies have come to different conclusions, especially that the rate of congenital defects in twin pregnancies is three times higher than in singleton pregnancies. For intracytoplasmic single sperm injection (ICSI), although itself an invasive technique, there is no evidence that microscopic manipulation of oocytes can lead to an increased incidence of congenital malformations. the increased incidence of chromosomal and structural abnormalities in ICSI offspring, such as aneuploidy, chromosomal structural abnormalities, risk of genetic mutations, microdeletions and incidence of hypospadias in male fetuses, may The reasons for this are more related to the genetic background of low male fertility. Therefore, for post-ICSI pregnancies, we still recommend further prenatal diagnostic techniques such as amniocentesis. Cancer: A 2013 systematic review and meta-analysis concluded that various ovulation and egg retrieval techniques and assisted reproductive technologies, including IVF and ICSI, slightly increase the risk of developing some cancers in the offspring, such as hematologic cancers and neurologic tumors. Although the risk is mildly increased, it is true that there may be some correlation. It is just that this causal relationship cannot be clearly defined. Fortunately, the absolute risk of cancer development is still relatively low, with an RR of about 1.3. Of course, it is not conclusive whether ovulation promotion techniques increase the risk of ovarian and breast cancer in the mother. In any case, assisted reproductive technology has brought untold happiness to millions of families! It’s just that we health care professionals have to work together with everyone for a better management of pregnancy and delivery, and only by understanding the possible risks of IVF mothers and babies, a better mother-child outcome is possible!