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ASRM Guidelines on Blastocyst Culture and Transfer
March 11, 2013
From the fertility patient perspective, it is sometimes difficult to understand the reason a fertility doctor would recommend a day three versus a day five embryo transfer during an in vitro fertilization (IVF) cycle. Typically, healthy embryos that are cultured until day five reach the blastocyst stage. Embryos transferred on or around day three are cleavage stage embryos. The American Society for Reproductive Medicine (ASRM) has released updated guidelines on blastocyst culture and transfers in the March 1, 2013 edition of Fertility and Sterility to help fertility doctors and patients understand the current recommendations.
Understanding Blastocyst Stage Embryos
Samantha Pfeifer, M.D., Director of Reproductive Surgery at the University of Pennsylvania says there are several important factors to keep in mind when considering blastocyst development and transfer. “We have very few ways to assess the quality of embryos other than to let them grow out to blastocyst stage. On day three, we look at the cells and characteristics of an embryo. If we have two good looking embryos, we can’t tell if they are truly good or bad. If an embryo makes it to a day five blastocyst, it has jumped through hoops and is still kicking,” she states. Embryologists and fertility doctors can get a better sense of the embryo’s quality if it has overcome the day three hurdle and reached blastocyst stage. Success rates are much higher with a blastocyst transfer than a cleavage stage embryo transfer as they are more likely to develop into healthy pregnancies, Dr. Pfeifer apprises.
Despite the evidence that blastocyst transfers seem to yield superior results to cleavage stage embryo transfers, there are conflicting views in the field of reproductive medicine as to which is the best time to transfer an embryo. Some fertility doctors believe that all embryos should be cultured until they reach blastocyst stage. If they do not survive until day five, it is believed that they were not good quality embryos to begin with. Pfeifer states: “The big argument is if an embryo doesn’t make it to blastocyst stage, is it still a good embryo? Some say if it is not a blastocyst then we shouldn’t put it back, but it may be that embryos do better if they are put back rather than left in a dish. There is no definitive data. Some embryos transferred on day three don’t look good, but they turn into beautiful children.” Given that plenty of pregnancies have resulted from day three embryo transfers, many fertility doctors encourage a day three embryo transfer if the embryos are not likely to survive to day five. These doctors believe that the safest place for an embryo to be is inside the uterus rather than in a culture in the lab.
Should You Opt for a Day Three or Day Five Embryo Transfer?
Dr. Pfeifer advises that a fertility patient should first talk to their doctor about the clinic’s expertise before deciding on a day three or pushing for a day five embryo transfer. “Some labs don’t grow embryos out to blastocyst stage and some clinics only do a blastocyst transfer, so it really depends on the clinic’s expertise. A patient would want to do the transfer with which their clinic is most experienced. Younger patients under the age of 35 have a better chance of growing their embryos out to blastocyst stage and picking the best one. Older women with good looking embryos could also do a blastocyst transfer if the clinic allows,” says Pfeifer.
The added benefit is that with blastocysts, a single embryo transfer (SET) could be done to minimize the risk of a multiples gestation. A day five embryo transfer would also give patients the opportunity to have genetic screening of their embryos via Preimplantation Genetic Diagnosis (PGD) where the results of the screening are available in time for a day five transfer.
The primary risk of pushing an embryo transfer out to day five is that the embryos may not survive to day five, leaving no embryos to transfer or freeze. Another theorized risk is that by leaving the embryos to culture for longer periods of time, they might be predisposed to epigenetic phenomena (genetic changes that are not inherited, but cause genes to express themselves differently), though there is not strong evidence to support this.
Fertility patients should talk to their doctor about success with day three versus day five transfers. Where clinically indicated, a blastocyst transfer may be most beneficial for achieving a successful pregnancy. Patients who have experienced previously failed IVF cycles, or those who are not expected to have healthy blastocyst development should opt for a cleavage stage embryo transfer.