Embryo Freezing (Cryopreservation)
Embryo freezing, or cryopreservation, adds an important dimension to assisted reproduction by:
- Extending the possibility for pregnancy when fresh cycles fail or when couples want additional children after a successful embryo transfer.
- Avoiding many ethical dilemmas by eliminating the need to dispose of embryos.
- Offering an alternative to couples that might transfer too many embryos and risk a multiple gestation pregnancy.
- Avoiding embryo wastage by freezing embryos individually for efficient use.
- Increasing pregnancies per retrieval cycle with normal outcomes by 10-30% more. Many studies have evaluated the children born from frozen embryos. The result has uniformly been positive with no increase in birth defects or development abnormalities.
We define embryo survival based on the number of viable cells in an embryo after thawing. An embryo has “survived” if >50% of the cells are viable. We consider an embryo to “partially survive” if <50% of its cells are viable, and to be “atretic” if all the cells are dead at thaw. Approximately, 65-70% of embryos survive thaw, 10% partially survive, and 20-25% are atretic. Our data suggests that embryos with 100% cell survival are almost as good as embryos never frozen, but only about 30-35% survive in this fashion.
Embryo morphology (appearance of the cells / percentage of fragmentation) is one of the most influential factors for embryo survival. Interestingly, embryos produced from intracytoplasmic sperm injection (ICSI) also seem to survive somewhat better than embryos produced from conventional insemination. The following graph illustrates these points. The embryo grade in the graph goes from worst (3.2) to best (1.0).
Embryos that are 2, 4, or 8 cells when frozen have about 5-10% greater survival than embryos with an odd number of cells. Donor egg embryos have a 2-5% greater survival rate than embryos from infertile women when compared by morphology score.
Pregnancy rates are similarly affected by complex relationships and like embryo survival only 7-10% of the predictive value can be observed and measured. Age is not a significant factor with frozen embryos but fewer older women have frozen embryos. From the approximately 20 factors reviewed, the most important factors predicting pregnancy rates are the number of surviving embryos transferred, the number of 100% surviving embryos transferred, and the morphology scores of the transferred embryos. The delivered pregnancy rates ranged from 5% (a single poor quality embryo) to 36% (4 high quality embryos) when the cycles from 1987 to 2001 were combined.
Blastocysts (embryos cultured for 5 days rather than 2-3) are a special case. The embryos are much larger and have special needs with regard to freezing without damage. Many centers have had trouble with blastocyst cryo-survival and pregnancy rates. A new protocol developed in our laboratory and implemented in December 2000 led to a transfer rate of 62% and a 35% pregnancy rate per transfer. This important change now makes blastocyst transfer more appealing since excess blastocysts can be expected to yield pregnancy rates comparable to embryos frozen two to three days after retrieval. Click here to learn more about blastocysts.
Embryo Storage at Fairfax Cryobank
Frozen Embryo Transfer Success Rates
History of Embryo Cryopreservation
Embryo cryopreservation has its roots in the accidental successful cryopreservation of fowl sperm in 1948. Scientists apparently mislabeled the experimental freezing solutions and used glycerol instead of another compound. The glycerol solution was highly effective and its use led to a new branch of science. Subsequently, several solutions have been identified that protect the cells or tissues during the freezing process. Interestingly, cryopreservation of biological material has had its greatest practical impact in the field of reproduction. Cells and tissues freeze successfully and for very long periods of time. The process of freezing cells and tissues involves cryoprotectants that prevent the build up of salts as water crystallizes during freezing. High concentrations of salts and perhaps the ice crystals themselves can mortally wound cells either during freezing or thawing. The cells (embryos in this case) are stored in liquid nitrogen after a controlled freeze by special machinery. Embryo freezing takes several hours while the thaw process takes about 30-45 minutes. Embryos have been successfully thawed after cryopreservation for as many as 13 years. Clinical pregnancies have been reported from embryos stored for 9 years.