Fresh embryo transfer is performed at the blastocyst stage, or what is known as a “Day 5 transfer”. The embryologist will choose the best quality embryo, and this embryo will be transferred to the woman’s uterus. Blastocyst grade is determined by several factors.
How are my blastocyst embryos graded? First, the degree of expansion of the blastocoele (the inner pool of fluid) of the blastocyst is represented by a number 1-6, with 1 being the least expanded and 4 being the most expanded fluid pocket. The number 5 represents an embryo that is so expanded that it is starting to hatch out of its outer shell, known as the Zona Pellucida. A 6 score represents an embryo that has fully hatched.
Second, the Inner Cell Mass (ICM) is graded. The ICM goes on to become the fetus. The more cells we see, the better the score. ICMs with high cell number are graded “A”, moderate cell number is “B”, and few cells seen is a “C”. A represents the highest grade.
Finally the Trophectoderm is graded. The trophectoderm is the layer of cells on the outside of the embryo that go on to become the placenta. Again, the more cells we see, the better the score. Trophectoderms with high cell number are graded “A”, moderate cell number is “B”, and few cells seen is a “C”.
On Day 3, the embryologist will check the embryos. The best quality embryo on day 3 is between 6 cells and 8 cells, has even size cells or blastomeres, and no fragmentation (basically old cellular material that has been kicked out of the cells).
On Day 5, the embryologist will choose the best embryo for a fresh transfer. The best quality on day 5 embryo is well compacted ICM and even size trophectoderm with plenty of numbers of cells. Transferring at the blastocyst stage confers a significant increase in live birth rate per transfer.
The best quality embryo on day 3:
The best quality embryo on day 5:
Embryos which reach the blastocyst stage can be genetically tested in two ways.
PGT – A: The first and most common form of genetic testing is testing each embryo to determine if the embryo has a normal number of chromosomes. This is called PGT-A (Preimplantation Genetic Testing – Aneuploidy). An abnormal embryo will be one that has either more or less than the standard 46 chromosomes. For example, an embryo with 45 or 47 chromosomes is considered abnormal. Most of the time, if these embryos were transferred to the woman’s uterus, the embryo simply would be too abnormal to implant, and the result would be a negative pregnancy test. Sometimes, however, these abnormal embryos can implant and result in an early miscarriage. In fact, the most common cause of miscarriage among all women is chromosome number abnormality, or aneuploidy. PGT-A can also tell us other information about the embryo, such as the sex of the embryo. Finally PGT-A can find other chromosomal abnormalities including chromosome genetic deletion, duplication, inversion, and mosaicism.
PGT – M: The second form of genetic testing for specific genetic defects prior to possible transfer by PGT-M (Preimplantation Genetic Testing – Mutation). This type of testing requires more preparation. This type of testing is specifically for those in which the patient providing the sperm and/or the patient providing the egg have a known genetic mutation. For example if a heterosexual couple knows that they both carry the mutation for cystic fibrosis, an autosomal recessive disease, they have a 25% chance of having a child born with CF. By doing PGT-M, we can identify the normal unaffected embryos, those that simply carry the mutation, and those embryos with two copies of the mutation which would result in a child with the disease. This way couples can only put back normal embryos. This type of testing can also be used for couples who carry sickle cell trait, spinal muscular atrophy, musular dystrophy, neurofibromatosis, BRCA, and many other mutations which cause disease.
In order to test the embryos through PGT, embryologists must do an embryo biopsy. The embryo biopsy involves carefully removing 2-4 cells from the trophectopderm.
Embryologists can do the embryo biopsy on day 5 or day 6:
- The embryo should be at the expanded blastocyst stage (or beyond) at the time of biopsy.
- This stage is reached on day 5 to 6 after fertilization.
- Trophectoderm cell removal is much less traumatic compared to blastomere removal that happen on Day 3 biopsy.
These cells from each embryo will be tested, and the cells are sent to an offsite laboratory for PGT. The testing takes about 1 week after the biopsy. Because embryos cannot survive this length of time in the incubator, we freeze all embryos while we wait to get the PGT result back. The results come back two weeks after egg retrieval.
Frozen embryos generated in a preceding cycle, are thawed just prior to the transfer, which is then termed “frozen embryo transfer” (FET). The outcome from using cryopreserved embryos has uniformly been positive with no increase in birth defects or development abnormalities.
The embryologist will thaw the embryos on the day of transfer, and will choose the best quality embryo in hopes of achieving pregnancy. If the patient did PGT, the embryologist will review all test results, and choose the best embryo for transfer. All other remaining parts of the embryo transfer procedure are the same as fresh embryo transfer.
The patient returns to the clinic to have the embryos transferred. An ultrasound will be used to help guide the physician as he/she transfers the embryos. A predetermined number of embryos are loaded into a fine transfer catheter that passes through the vagina and cervix, into the uterus.
The embryo is deposited from the catheter into the uterus. Following this procedure, the patient usually instructed limited activity for 2 days, but not bed rest. The first pregnancy test will be 10 days later after the transfer.