Day 3 verses Day 5 Transfer – What is Blastocyst Transfer?
Recent advances in the IVF lab allow routine culture of embryos to the blastocyst stage. The initial results for blastocyst transfer in selected patients were extremely encouraging with reported pregnancy rates exceeding 50%. The human embryo develops to the blastocyst stage five to six days after fertilization.
A blastocyst is a fluid-filled ball of 60-100 cells.
The cells that make up the surface of the ball will attach to the uterine lining, initiate implantation and later provide the sac in which the embryo will grow. Contained within this hollow ball are the stem cells that will become the fetus. During a natural cycle, the embryo develops to the early blastocyst stage within the Fallopian tube. The embryo must reach the blastocyst stage before it is capable of attaching to the uterine wall and implanting. Thus, the transfer of blastocyst stage embryos following IVF. is more “natural” since the embryos are placed in the uterus at the correct developmental stage.
“Weeding out” embryos with poor developmental capacity
When embryos are cultured to the blastocyst stage in the IVF laboratory, it is common to see about half of the embryos stop growing by the end of the third day. This rate of attrition is normal and is a result of the poor developmental potential of some of the embryos. Once an egg is fertilized, no genetic instructions are required for the embryo to reach the four-cell stage of development. However, on the third day, when the embryo is between the 4- and 8-cell stage of development, new genetic instructions are required for continued growth.
About half the time, the genetic information required for growth beyond the 8-cell stage is conflicting, garbled or missing and the embryo simply stops growing. At present, it is beyond the IVF laboratory’s capability to correct or improve the genetic potential of a developing embryo. It is important to also note that since the environment within the lab or the uterus cannot influence the genetic make up of the embryo, the same attrition is observed when the embryos are transferred to the uterus on Day 3. That is, transferring genetically compromised embryos to the uterus on Day 3 does not improve their chances of continued development.
Reduce Twins, Eliminate Triplets, Quads, etc.
To compensate for the attrition in embryo growth and the unknown developmental potential of Day 3 embryos, many programs transfer more than two embryos on Day 3. Although this improves pregnancy rates, the practice of transferring more than two embryos can also lead to high order multiple gestations (i.e., triplets, quadruplets, etc.). Triplets and quadruplets present a serious risk to the mother and babies. This raises a serious ethical question. Is it appropriate for IVF programs to continue the practice of transferring three or more embryos of unknown developmental potential on Day 3 when the technology is available (i.e. transfer of two blastocyst stage embryos) to prevent high order multiple gestations and yield the same (or better) pregnancy rates? Blastocyst culture and transfer can provide several advantages for the IVF patient. The most obvious advantage is that fewer embryos may be transferred since the embryos are pre-selected for superior developmental capacity. Most programs that perform blastocyst stage transfer will transfer two embryos. When transferring two embryos with superior developmental potential, the possibility of triplets, quadruplets, etc. can be eliminated. This is particularly important for younger patients or donor egg recipients who are at high risk for triplets or quadruplets following the transfer of three or more embryos.
Reduce “Chemical” Pregnancies and 1st Trimester Miscarriage
Another advantage to blastocyst stage transfer is that although some embryos technically reach the blastocyst stage, there may be too few stem cells to make a baby. These “embryos” are capable of initiating implantation, but result in “chemical pregnancies” or an “empty sac” on ultrasound a few weeks after implantation. When embryos are cultured to the blastocyst stage in the laboratory, these developmentally comprised embryos can be identified and their transfer avoided. Blastocyst transfer can significantly reduce “chemical” and “empty sac” pregnancies and the disappointment they bring.
Provide Important Diagnostic Information
In addition to providing therapeutic value, extended embryo culture can provide important diagnostic information. Patients frequently want to know “Are my eggs any good?” Routine diagnostic procedures such as hormone evaluation, the clomiphene citrate challenge test, hysterosalpingogram and laparoscopy do not address the question of egg quality. Extended embryo culture can answer this question by determining the rate of embryo growth and the percentage of embryos that reach the blastocyst stage. This information is useful to everyone undergoing IVF, but is particularly important for older patients with few eggs. If the embryos develop slowly or fail to reach the blastocyst stage, this information can be a deciding factor for patients willing to pursue the option of donor eggs.
Is Blastocyst Transfer for Everyone?
Many patients worry that they will end up without any embryos for transfer. Actually, this is quite rare and happens only about 5% of the time at our Center. In the rare case where no embryos reach the blastocyst stage by the sixth day of development, this information can be very useful in deciding the next course of action, particularly if the couple has had a previous IVF failure following a Day 3 transfer. Although the news of developmental arrest of all the embryos is never welcome, it does save the couple the anxiety of waiting two weeks for a negative pregnancy test. Admittedly, it can be unnerving to observe a significant number of embryos stop growing on the third day, but it is important to keep in mind that the point of extended embryo culture is to select only those embryos that have the ability to implant.