Frozen Embryo Transfer

At our Northern California San Francisco Bay Area fertility center, we typically freeze embryos five or six days after an egg retrieval procedure, when they have reached the blastocyst stage. We can actually freeze embryos on any day after fertilization has occurred, but we normally wait until preimplantation development is complete so that we know that the embryo has made it through all the preceding stages successfully and is still developing well. The day we freeze embryos depends on the individual circumstances of a particular patient, how well embryos are developing in the laboratory, how many embryos we have, and when a patient is having her embryo transfer. About 60% of patients have a transfer on the fifth day after retrieval and we freeze surplus healthy embryos the same day, and some embryos the next day (day 6) if more have reached the blastocyst stage.  At this time, we can see how well the embryos are developing and choose the best embryos for transfer and freezing. Embryos tolerate freezing relatively well on day 5 or 6 and about 50% of patients become pregnant after a transfer using thawed embryos (see table below showing % clinical pregnancies per FET for 2010 and 2011).

  <35 35-37 38-40 >40 OD
2010 (%) n=311 48 48 41 2/12 36
2011 (%) n=369 55 53 49 7/13 49
We are now doing more and more transfers on day 5-post retrieval (blastocyst transfer). Delaying the transfer until day 5 allows us to get a much better picture of which embryos in a cohort are really strong and healthy. By day 5, the embryo should have reached the blastocyst stage, which is characterized by the presence of a fluid-filled cavity or cyst in the embryo. Embryos that reach the blastocyst stage by day 5 have a higher chance of implanting after transfer when compared to embryos transferred on earlier days. However, it is worth noting that not all embryos that look healthy and strong on day 3 will make a blastocyst. We estimate that we get one nice blastocyst for every 3 nice day 3 embryos. Therefore, blastocyst transfers are usually undertaken only by patients with many nice embryos on day 3. Also, patients at high risk for a multiple pregnancy and/or those wishing to transfer only one embryo often decide to do their transfer on day 5.It is not common to freeze embryos on day 1 after retrieval since at this time we have very limited information on their development, but embryos tolerate freezing and thawing very well on this first day. Patients that freeze embryos on D1 are usually those with very few embryos (<3) and who are not planning to do a fresh transfer. Also, patients that are trying to accumulate embryos for a cycle with genetic screening of the embryos sometimes freeze on Day 1. The rate of survival is over 90% for embryos frozen at any stage, so there is no particular advantage to freezing embryos very early in development. However, the lack of embryo development information on day 1 means that we could be freezing many embryos that have little or no chance of establishing a pregnancy. We therefore prefer to let the embryos grow for at least another 2 days, and preferably for another 4 or 5, to make sure that we only end up with good quality embryos in our freezer.

After a day 5 transfer, surplus blastocysts are to be frozen for later use. They can be frozen on day 5, or if they are developing a little more slowly, on day 6. Blastocysts have many more cells (up to 200 cells) than day 3 embryos (up to 12 cells) but they freeze just as well. All freezing techniques involve dehydrating the embryo, and specifically with blastocysts, the fluid-filled cavity (cyst) must be collapsed (i.e. the fluid evacuated) before the embryo is frozen (see figure below). When thawed and placed inside the incubator in the laboratory, the cavity will begin to re-expand and the blastocyst should be fully inflated about 2 hours later. Blastocysts that show little or no signs of re-expansion are unlikely to implant after transfer.

The technology that allows us to grow embryos to day 5 or 6 continues to improve, and in line with this, we are offering blastocyst transfer and freezing to more patients. Blastocyst transfer has the specific advantage of giving us the ability to better choose viable embryos from among a group, so patients that have more embryos than they want to transfer on Day 3, usually culture the embryos on to Day 5 and then pick the best blastocyst(s) for transfer. Individuals using donor oocytes almost always do a day 5 transfer, since we tend to have many embryos to choose from in these cases. Blastocyst transfer will not be an option for everybody, and not everyone will have enough blastocysts to transfer and to freeze. We freeze blastocysts every day in our lab and transfers with thawed blastocysts are a regular part of our laboratory routine. If one thinks they might be a candidate for a blastocyst transfer, they should talk to their physician for more information.

Figure 1.

 

 

 

 

Image 1: A small hole is made between 2 outer cells (5 o’ clock position in this picture) to allow the fluid in the blastocyst cavity to escape
Image 2: The blastocyst collapses in on itself and towards the hole
Image 3: When the embryo is fully collapsed, it is ready to be frozen. After thawing, the embryo will re-inflate in about 2 hours