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Cleavage Stage vs. Blastocyst

Embryo transfer

Once a decision has been reached on the number of embryos to transfer, and which embryos to transfer, the Embryologist will check your identity and then prepare your embryos for transfer. A second Embryologist will supervise to ensure that all checks are complete and satisfactory, before "signing out" the embryos. The embryos are loaded into a soft catheter that is passed through your cervix and into the uterus. The small catheter is made of silicone and most patients feel little or no sensation during the procedure. You can watch the transfer take place since the catheter can be observed passing into the uterus with the aid of abdominal ultrasound. You will also be given a picture of the transferred embryos and an Embryologist will be happy to talk to you and point out the features of your embryos.

Blastocyst stage embryo transfer

It is not necessary to transfer the embryos to the uterus after only 3 days in the laboratory. The embryos can be cultured for 5 days until they have 60-100 cells. By this time, the cells have begun to organize themselves into 2 groups and the embryo is now called a "blastocyst". On the outside of the blastocyst are the "trophectoderm cells" and these are the earliest cells of the placenta. Inside these cells is the "inner cell mass", from which the fetus will develop.

     
Figure 1. A human 4-cell embryo (48 hours old)   Figure 2. A 3-day old embryo (with 8 cells). Notice how the cells are beginning to flatten against one another, beginning the process of compaction   Figure 3. At 4 days old, this embryo has reached the morula stage. The cells are compacted together, but the embryo should have between 16 and 32 cells.   Figure 4. Late on the 4th day or early on the 5th day, the morula begins to form a fluid filled cavity or cyst. The morula is becoming a blastocyst. The cells are becoming organized into 2 distinct groups. The inner cells (IN) are round and will become the fetus. The outer (OUT) cells are flat and will become the placenta.

Embryo, day three transfer versus Blastocyst, day five transfer

Transferring embryos at the blastocyst stage may be an option for you in an IVF cycle. We encourage the majority of our patients to have their transfer earlier, on day 3, when the embryos have approximately 8 cells. For most patients, the best embryos are identifiable at this time and we like to transfer them into the uterus (their natural environment) as soon as possible. Embryos that are not transferred can be frozen for later use. However, if a patient has a large number of embryos and/or the best embryos are not clearly identifiable on day 3, we may suggest waiting 2 more days and doing a blastocyst stage transfer. Waiting gives us more information on how well the embryos are developing and may allow us to make a better choice for transfer. The downside of allowing embryos to grow to day 5 is that not all will develop to the blastocyst stage and therefore there may be fewer or no embryos to freeze after the transfer. In addition, blastocysts do not tolerate the freezing procedure as well as embryos frozen at earlier stages, so your chance of pregnancy with frozen embryos may be lower.

There are advantages and disadvantages to transferring embryos or blastocysts. You may discuss the options which best suit your case with your physician or the embryologist. Issues for you to consider are listed below.

A Brief History of IVF Embryo Transfer:

In the early days of IVF, embryos were transferred back to patients as soon as fertilization of the egg and development of the embryo had been confirmed. Tests on mouse embryos had shown that embryos grew more slowly in the lab than inside the uterus, so human embryos were not kept in the lab for longer than necessary. Embryos were placed in the uterus no more than 48 hours after a patient’s egg retrieval procedure. The problem with transferring embryos so early was that we had very little time to assess their viability. If the embryos failed to implant, it was not possible to determine if they were capable of developing or if the problem was with the patient or her uterus. Another issue was embryo selection. For patients with several embryos, it was very difficult to select the best embryos for transfer. The fertilized egg had usually only divided into 2 or 4 cells, therefore we were limited in our ability to choose the most advanced embryos. 4-cell embryos look very similar.

In the early 1990’s several researchers were working to improve the liquid media in which embryos are grown or cultured. The medium, a nutrient broth, in which embryos grow, was dramatically improved. This enhanced medium allowed embryos to be kept in the laboratory for a longer period of time. Embryo transfers could now be delayed by one day to give the embryologist more time to determine which embryos were growing the best. Three days after ER, a normal embryo has 8 cells. If none of the embryos reached the 8-cell stage we have useful information concerning embryo quality that may explain why a patient does not get pregnant. Additionally, if we observe that individual embryos are developing slowly, we can consider other procedures such as assisted hatching to increase the patient’s chance of pregnancy.

In the late 1990’s, embryo culture media had become so refined that embryos were growing well in the laboratory for 5 or even 6 days after egg retrieval. Keeping the embryos in the laboratory for almost a week like this, allowed us to observe them growing through the morula and blastocyst stages. An embryo that has eight cells on day 3 of life should make the transformation to blastocyst in about 48 hours. The cells compact together to form a morula, and then begin to pump fluid to the center of the morula forming a cyst. As the cyst inflates with fluid, the cells of the embryo organize themselves into 2 distinct groups. The inner cells are the first cells of the fetus, and the outer cells will become the placenta. The size of the embryo increases as more and more fluid is pumped into the cyst, and the blastocyst bursts out of its shell. Once out of the shell, it is ready to implant in the uterus.

 
Located in Northern California’s San Francisco Bay Area, Pacific Fertility Center® is a leading international destination for infertility treatment, including ICSI, IVF - in vitro fertilization, PGD - preimplantation genetic diagnosis, egg donation and embryo freezing. Our fertility specialists are among the Top Doctors in the United States for treating both female and male infertility. For Bay Area residents, PFC is easily accessible from Berkeley, Oakland, Marin, Santa Rosa, San Mateo, San Jose, Sacramento and Stockton.
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