Blastocyst transfer, is it really good?

I often get questions from patients: Doctor, is it better for me to transfer oogenic embryos or blastocysts? Will it be risky to raise the blastocyst? The doctor will usually not give you a definite answer at this time, but will help you to weigh the pros and cons. Don’t blame him because this question is currently inconclusive in the reproductive medicine community. In conventional IVF treatment, a transfer protocol of 2 embryos transferred on the third day after egg retrieval is usually chosen, also known as oogenesis embryo transfer, when the embryos are usually developed to the 8-cell stage. If the embryos continue to be cultured until day 5-6, they can develop to the blastocyst stage, hence the term blastocyst transfer. With the advent of sequential culture media, culturing oogenic embryos to the blastocyst stage has become a very simple technique. Since 1991, when the first successful pregnancy with a healthy live birth was reported, the percentage of blastocyst transfers performed in fertility centers around the world has gradually increased, with data reporting an increase in the percentage of blastocyst transfers in UK fertility centers from 1% in 2000 to 34% in 2012. Data from fertility centers in recent years have shown that transferring blastocysts significantly improves implantation and clinical pregnancy rates compared to transferring oogenic embryos. This is why some fertility centers have adopted the strategy of fully culturing blastocysts and performing only blastocyst transfers. Blastocysts at hatching (origin of identical twins) Advantages of blastocyst transfer There are limitations in measuring the developmental potential of embryos using day 3 embryo (8-cell stage) morphology, and the later developmental potential of embryos transferred during this period is still unpredictable. When cultured in vitro, embryos become more viable if they transcend the developmental block at the 8-cell stage and become blastocysts. Embryos that have been screened to develop into blastocysts are usually of better quality and have a higher transfer success rate. In addition, blastocyst culture allows the embryo to be more synchronized with the development of the female reproductive tract and more in tune with the natural environment of reproductive physiology, offering a higher potential for implantation and pregnancy. In recent years, with the improvement of IVF laboratory technology, blastocyst in vitro culture system has been gradually optimized and blastocyst rate has gradually increased; meanwhile, blastocyst freezing technology has also gradually matured, thus making blastocyst transfer possible as a routine transfer technique. Why do most doctors still recommend day 3 embryo transfer? In the world’s first successful IVF pregnancy, the embryos transferred were blastocysts. However, for many years in IVF practice, most doctors still choose to perform the transfer at the oogenesis stage. The main reason for doing so is that there is no assurance that the embryos will be cultured to form blastocysts. In IVF practice, blastocyst culture requires high conditions and only good quality embryos can develop into blastocysts, while poor quality embryos can be naturally screened out due to their own developmental abnormalities during the process of growing into blastocysts. This is also a process of elimination of the best and the worst. If the embryos have poor developmental potential, they may stop developing and stagnate at the day 3 stage. This is the biggest risk of blastocyst culture. Typically, about 50-60% of day 3 embryos will develop to the blastocyst stage. Furthermore, according to the results of randomized controlled clinical trials published by many fertility centers, transfer of blastocysts, while significantly increasing clinical pregnancy and live birth rates compared to transfer of oogenic embryos, also raises a number of perinatal and fetal risks, such as increased preterm birth rates, increased risk of fetal older than gestational age, increased monozygotic twin birth rates, and increased sex ratio at birth compared to transfer of oogenic embryos. Why does transferring blastocysts increase the risk of adverse perinatal and fetal outcomes relative to oogenesis embryos? Embryologists believe it is primarily due to the fact that most fertility centers currently culture human embryos at atmospheric oxygen concentrations rather than physiological oxygen concentrations. Normally, the physiological oxygen concentration in the human reproductive tract is 5%, while the atmospheric oxygen concentration is 21%, a significant difference. Human embryos cultured at atmospheric oxygen concentrations are subjected to greater oxidative stress. Prolonging the in vitro culture time exposes embryos to greater oxidative stress and greater sensitivity to other negative factors in the culture system. Experimental studies of mammalian embryos, including humans, have found that excessive concentrations of oxygen have the following negative effects on embryos: altered transcriptomics, altered proteomics, altered genetics and epigenetics, altered physiological homeostasis, and induction of early X chromosome inactivation, with different effects on male and female embryos. These alterations may be responsible for the higher risk of perinatal and fetal adverse outcomes in transferred blastocysts relative to oogenic embryos. These alterations occur mainly within the cells and cannot be detected by the currently accepted methods of embryo morphological evaluation. In conclusion, before choosing blastocyst culture, you need to be very aware of the possibility of no blastocyst formation and cancellation of embryo transfer or embryo freezing, and if this is not acceptable or if you are still very concerned about the risks, you can choose day 3 embryo transfer.