Why consider extended embryo culture and blastocyst transfer?
Cutting edge laboratory technology is used at Michigan Reproductive Medicine, allowing embryos to grow in our incubators for an extended period of time–up to six days. By six days of laboratory growth, the embryo must either be transferred into the woman’s uterus or cryopreserved and stored in liquid nitrogen for transfer at some future time.
Survival of the Fittest – Persistence Wins!
Reproduction across all species on the planet is not very efficient. Not all eggs, sperm or embryos they form are normal. Errors of nature commonly occur in the formation and growth of embryos. If cars and cell phones were of equal efficiency as normal human reproduction, product performance failure would force the manufacturers out of business for the sake of customer dissatisfaction alone!
One of the common errors in embryo development is related to genetics. Not necessarily abnormal genetics of the parents, but rather abnormal genetics of the egg, sperm or the process of evenly cutting the genetic deck of 46 chromosomes within any one cell of an embryo with every cell division while growing. Errors in chromosome number within embryo cells account for about two thirds of embryos failing to implant or failing to sustain life beyond the first 8 weeks of pregnancy, resulting in miscarriage.
Here’s the typical day-by-day sequence of embryo development in extended laboratory culture:
- The egg is harvested and exposed to sperm called insemination.
- If about 12 eggs are harvested, usually about 9 eggs are of mature development, receptive to a sperm.
- Fertilization Report: about 7 of 9 eggs fertilize normally.
- The fertilized egg is called a zygote.
- The egg provides the energy resource for growth at this time.
- Fusion of the egg and sperm DNA has occurred forming an embryo including the first two cell divisions (4-cell embryo).
- 6 of 7 zygotes progress to form embryos.
- Additional cell divisions have occurred with the optimal number of 8 cells.
- Up through day 3, the genetics contributed by the egg are driving embryo development. This is termed the “maternal genome”.
- If preimplantation genetic testing of the embryo is planned on day-5 or day-6, then on day 3, a laser induced “coin slot” is created in the outer shell of the embryo.
- Embryo cells compact so tightly, that individual cells are indistinguishable when viewed under a microscope.
- Integration and activation of genetics from the sperm occur and now drive the future stages of embryo development. Embryo development is now directed by the “embryonic genome”.
- Many embryos fail to succeed in this transition. Although the root cause may be an egg or sperm issue, sperm with male factor infertility may contribute to arrest of embryo development at this stage: failing to integrate and activate its DNA resulting in failure to progress to the advanced blastocyst stage.
Extended culture and blastocyst formation.
- 3 of 6 embryos from day-3 will advance in development to a blastocyst stage.
- Cell division accelerates to about 120 cells.
- Fluid builds up within the embryo.
- The embryo actually expands and enlarges.
- Two distinct sets of cells separate:
- The majority of cells press outward against the interior of the embryo shell called the trophectoderm and will become the placenta.
- About 12-14 cells huddle together within the fluid space while still connected to the trophectoderm. These cells, called the inner cell mass, will become the fetus and baby at birth.
- If preimplantation genetic testing of the embryo is planned, you can imagine the fluid pressure building from within the embryo may cause some of the trophectoderm cells to push out through the laser induced “coin slot” created on day-3. These cells will extend outside the confines of the embryo shell like a hernia. About 5 of these cells are excised with a laser and undergo genetic testing. This is called a trophectoderm biopsy. These cells have a high reliability to represent the same genome as the inner cell mass that will form the fetus. Thus, the genetic test results of cells destined to form the placenta should be similar to the genetics of the cells that will form the baby. Only obtaining cells that push to the outside of the embryo shell, protects the embryo as a whole, still within the shell, from harm during this biopsy procedure.
- An embryo can be transferred fresh into the uterus this day, be cultured an additional day to day-6 if awaiting a genetic test result for fresh transfer, or be cryopreserved by vitrification and stored for a later month awaiting other genetic test results.
Extended blastocyst culture.
- Some embryos with delayed growth may achieve blastocyst development by day 6.
- Embryo transfer can be done on this day.
- There is uncertainty of whether an embryo that has delayed transformation to blastocyst by day 6 will provide as good of a prognosis as one that achieved this stage of development by day 5.
- An embryo must be transferred to the uterus by day-6 or is obligated to be cryopreserved by vitrification if a delay in transfer is planned.
- Trophectoderm biopsy for preimplantation genetic testing can be performed on a day-6 blastocyst. The embryo must be cryopreserved for later use because the genetic test results cannot be known the same day.
Advantages of Extended Embryo Culture and Blastocyst Transfer
- Precision in selection of a high quality embryo.
- Embryos that advance to blastocysts stage are more likely to be genetically competent.
- Opportunity to more reliably assess genetic competency through preimplantation genetic testing.
- Reduction in the probability of miscarriage.
- Avoiding selection and transfer of a genetically abnormal embryo with normal microscopic appearance on day 3, but is truly “fixed to fail” leading to failure to become pregnant or to remain pregnant- resulting in miscarriage.
- For women with advanced reproductive age and women with diminished ovarian reserve, time is of the essences. Extended embryo culture and transferring a blastocyst with normal preimplantation genetic testing results (if at least one embryo forms normally) reduces the possibility of miscarriage and the typical 4-month delay from known pregnancy to recovery from miscarriage needed before trying to become pregnant again.
Setting Expectations: There is hope!
Let’s Check Our Math: prognosis for having a baby.
- 1 in 4 eggs harvested will likely develop to the blastocyst stage.
- 1 in 2 blastocysts will likely have a normal result from preimplantation genetic testing (PGT).
- That means about 1 in 8 eggs will be genetically competent to become a baby.
- There is about a 60% chance that a single embryo with genetically normal PGT result will result in the birth of a baby.
Please make-an-appointment with one of MRM’s fertility expert physicians to learn more about blastocyst culture and transfer and to discuss your specific needs and hopes for building your family.