Blastocyst culture is an important program in IVF clinical embryology. It relies on the fertility center’s stable and high-quality embryo culture system, skillful and sophisticated embryo culture techniques, and the practitioner’s deep knowledge of the patient’s clinical characteristics and embryo quality. What are the views of doctors and embryologists on the myth of blastocysts that has been circulating? What are the advantages and disadvantages of blastocyst culture? Who are the right patients for blastocyst culture? Let’s take a look at the international consensus on blastocyst culture. With the development of assisted reproduction technology, the continuous optimization of ovulation regimen and the improvement of embryo culture system, the success rate of IVF at home and abroad has been increasing in the past 20 years. Usually, two strategies are generally chosen for embryo transfer: in vitro embryos that have developed to day 3 or day 5. We call embryos that have developed to day 3 “cleavage stage embryos” and embryos that have developed to day 5 “blastocysts”. Physiologically, the development of the cleavage stage embryo, which is fertilized in vivo, occurs in the fallopian tube, and the blastocyst stage embryo moves into the uterine cavity and deposits in the uterus. The formation of blastocysts undergoes a process of cell fusion, the emergence and expansion of the blastocyst cavity, and the gene regulation undergoes a transition from maternal to embryonic regulation, so only “good” embryos have the potential to develop into blastocysts. So, how to select “good” embryos? Morphological evaluation of cleavage stage embryos is the most traditional and widely used method of embryo screening, but it has some limitations in predicting the developmental potential of embryos, i.e., even highly rated cleavage stage embryos may not always develop into blastocysts, while some low rated cleavage stage embryos may still develop into “good” blastocysts. Because embryos are screened at the blastocyst stage, good blastocysts have a higher implantation rate than cleavage-stage embryos, so selective single blastocyst transfers can reduce the multiparity rate without reducing the pregnancy rate. First, the main point of blastocyst culture: the advantages of blastocyst culture 1, blastocyst culture can screen more “vigorous” embryos, eliminating those seemingly transferable cleavage stage “embroidered pillows”. Embryos that have undergone blastocyst culture have a higher implantation rate. According to the report, the average live birth rate of one cleavage stage embryo transfer is about 30~35%, while the live birth rate of one blastocyst can reach 50~60%. 2, Blastocyst transfer is more physiologically synchronized with the development of endometrium. Under the action of progesterone, the synchronized development of the endometrium is a prerequisite for embryo implantation, and in IVF cycle, this window period is usually only about 1~2 days. IVF blastocysts do not enter the uterine cavity from the fallopian tubes as in natural conception, but are transferred directly into the uterine cavity by the doctor, so the blastocysts on day 5 of the transfer coincide with the endometrial implantation window. 3. Blastocyst transfer has a significantly lower incidence of ectopic pregnancy than cleavage stage embryo transfer. If the cleavage stage embryo is transferred to the uterine cavity on the 3rd day, the embryo should grow in the environment of fallopian tube at this stage, so the embryo will wander in the uterine cavity for 2~3 days until the blastocyst stage and the endometrium come into contact with the bed, during this period the embryo is likely to instinctively pursue to the fallopian tube. If the fallopian tube is incompletely blocked due to inflammation, or if the fallopian tube does not move well due to hormonal abnormalities, the embryo may be blocked in the fallopian tube and an ectopic pregnancy may occur, therefore, IVF still has a 2~5% ectopic pregnancy rate. Embryos are transferred into the uterine cavity in blastocyst stage, which is the stage of synchronization of endometrial stage, blastocysts will soon find their own position, which reduces the chance of wandering the fallopian tube, and the incidence of ectopic pregnancy is reduced. 4, single blastocyst transplantation reduces the incidence of multiple births. Because of the increase in the rate of implantation, the rate of twin fetus of transplanting two blastocysts is too high, which is what we should avoid. In case you meet a blastocyst and then split into two, there is a possibility of multiple pregnancy with 3 to 4 fetuses, which is too horrible. So single blastocyst transfer can reduce the occurrence of multiple pregnancy rate. 5.The embryo is resistant to freezing. The number of blastocyst cells is large (up to more than 100), especially the trophoblast ectoderm cells, and the ability to repair the damage after freezing and recovery is strong, which has little effect on the developmental potential of the embryo. Anti-freezing tolerance is exactly a test of embryo quality, and the survivor wins. 6. Facilitate pre-implantation genetic diagnosis of embryos. For PGD/PGS cycle, the number of blastocyst cells is large, we can take biopsy material in the trophoblast cells of blastocysts, we can obtain multiple points of cells to make genetic testing more accurate, and will not harm the inner cell mass of blastocysts, which is the foundation of embryo development. Limitations of blastocyst culture 1. It is difficult to accurately predict blastocyst formation. With the current technology, it is not possible to accurately predict what kind of morphology of cleavage stage embryos can form blastocysts, although embryologists have some empirical standards. Occasionally, all cleavage stage embryos fail to form blastocysts, resulting in a situation where no embryos are transferred, which is the last thing anyone wants. Failure of blastocyst formation may also indicate that the embryo quality is not good enough. 2.Misunderstanding of high success rate of blastocyst. It is an indisputable fact that blastocysts have a high success rate, but there is a concept that is easy to misunderstand. Blastocysts are the embryos that win after eliminating the weak partners on the basis of further cultivation of the embryos at the cleavage stage on the 3rd day, and of course, they will be favored by everyone. Would it be fair if the selected star players were to compete with the universally selected amateurs? So the so-called high success rate just refers specifically to this transfer cycle, you appointed the elite team members, many ordinary team members to do the bottom. 3. The in vivo environment is always better than the in vitro one. This is the biggest hesitation people have about blastocyst culture. Theoretically, the ideal environment for embryo development would be the mother’s uterus; do the unknowns of in vitro conditions work against the embryo? Does it alter epigenetic function? There have been some small sample studies that have found heavy birth weights in blastocyst-cultured offspring; could this have adult-onset disease implications? Of course these ideas are still controversial, research continues and it will take time to answer this question. 4. Genetic risk remains. It is generally accepted that blastocyst culture is an optimization of embryo quality, and theoretically embryos with chromosomal abnormalities are likely to be excluded. However, genetic testing has found that a certain percentage of highly rated blastocysts still have chromosomal abnormalities, and at this stage, we can’t conclude that those who form good blastocysts will definitely be “a good man”. 5. Increased rate of single egg and twin fetus. Although the rate of multiple births can be obviously reduced after blastocyst culture and transfer, the incidence of monozygotic twin-fetus is slightly higher than that of cleavage stage embryos, which is a problem that we should pay close attention to and study. International strategy of blastocyst culture In 2013, the American Society for Reproductive Medicine (ASRM) proposed the following strategy of blastocyst culture: for women with “good prognosis” of IVF outcome, that is to say, relatively young, with good ovarian reserve and sufficient number of eggs (>8 mature eggs), blastocyst culture can increase the rate of live births, and it is recommended to carry out Single blastocyst transfer; In patients with repeated failure of embryo implantation, blastocyst culture can reduce failure due to differences in embryo potential; In patients with a “poor prognosis” for IVF outcome, blastocyst transfer does not increase the live birth rate and blastocyst culture is not recommended.