In standard IVF or ICSI procedures, a woman’s ovaries are stimulated to produce the optimal number of eggs. After fertilization in the laboratory and embryo cultivation for 3-6 days, they are selected for embryo transfer and / or freezing and storage. Not all embryos are of sufficient quality to be frozen and stored. Only those who have the potential to survive the freezing and thawing process are selected. This assessment can only be made by a specialist embryologist after considering the entire period of embryonic development. In addition to quality, the survival of embryos depends on a well-performed freezing procedure and proper storage.

Embryo freezing (cryopreservation) is a method of preserving the viability of embryos for a long period of time at ultra-low temperature (-196oC). Embryos can be frozen at any stage of their development if they are of sufficient quality to survive the freezing and thawing cycle. Embryos are stored one by one or in a group of two, depending on the number of embryos planned for embryo transfer. In Sofia Specialized Hospital for Active Treatment in Obstetrics, Gynecology and Pediatric Medicine we offer vitrification of embryos at different stages of their development. Vitrification is a ultra fast cryopreservation technique, which creates a glass like condition in the alive cells, due to which there is no forming of ice crystals during freezing or thawing. The main advantages of vitification are the elimination of mechanical damage caused by intra- and extracellular formation of ice crystals and decreasing the risk of damage resulting in prolonged and slow exposure to steadily declining temperatures Vitrification combines the high speed of freezing and high concentration cryoprotectants. Due to its specifics, this method requires the presence of good technological skills and experience.  After thawing of embryos that were freezed with the vitrification method, more than 95% survivability of the embryos is achieved and the success rate of the embryotransfer is similar to the one using fresh embryos.

Embryo freezing is recommended for:

• Ovarian hyperstimulation syndrome (OHSS), when embryo transfer is not recommended in the current cycle;
• If the endometrium is not suitable for implantation in the current cycle;
• Remaining embryos of good quality after embryo transfer; thus, after the “fresh” transfer, they can be used if pregnancy does not occur or if there is a repeated desire for reproduction;
• Desire to reduce the risk of multiple pregnancy;
• Need to preserve fertility for the future.

Benefits of freezing embryos:

  1. Frozen embryos provide patients with additional transfer opportunities, which increases the chance of success from a single puncture..

If fresh transfer fails, the frozen embryos provide you with additional chances without the need for re-ovarian stimulation and a new follicle puncture.

  1. Frozen embryo transfers (FETs) are cheaper than fresh ones.

After a fresh IVF cycle, subsequent FET cycles become more accessible to patients. With the FET cycle, the cost of medication is lower. The difference in prices also comes from the fact that in FET cycles patients pay a smaller number of check-ups, and also do not go through re-puncture, fertilization procedure and embryo culture.

  1. The FET cycle is more gentle.

For most patients, FET cycles are more gentle due to the lack of hormonal stimulation, surgery (puncture) and anesthesia.

  1. Freezing embryos for future FET cycles overcomes the adverse effect on pregnancy outcome caused by elevated progesterone levels.

According to the most recent studies, elevated levels of progesterone during ovarian stimulation make the endometrium (the lining of the uterus) less resistant to embryo implantation and therefore the chances of becoming pregnant are significantly reduced. If progesterone levels rise above acceptable levels, it is recommended that all embryos be frozen instead of fresh transfer.The results of a number of studies show that frozen embryo transfers are associated with an increased chance of success, compared to fresh transfers, in cases of elevated progesterone levels.

  1. Frozen embryo transfer leads to a reduced risk of the so-called. ovarian hyperstimulation syndrome, while maintaining an excellent chance of a successful pregnancy.

The team of doctors of SBALAGRM “Sofia” carefully selects the protocols for stimulation in order to avoid triggering the syndrome. It is for this reason that in our practice this syndrome occurs in less than 1% of patients. However, if the doctor considers that the patient is at risk (has a large number of follicles and high estrogen levels, sudden weight gain, accumulation of fluid in the pelvic area, etc.), he may recommend freezing the available embryos instead of fresh transfer should be performed, as possible pregnancy may further increase the risk of developing the disease.

  1. Frozen embryos allow the creation of a family at a later stage.

Frozen embryos retain their reproductive potential far in time, thus allowing you to choose the most appropriate time to raise your children. This type of transfer can slow down your biological clock.

The team of In Vitro Clinic “Sofia” is convinced that the freezing of embryos has another purpose. Various studies have shown that embryo transfer of thawed embryos has a higher success rate than the embryo transfer of fresh embryos, especially in women over 38 years of age.Dr. Vladimirov and Dr. Tacheva are the creators of “Theory of cryo-treatment of embryos” – the first theory to provide a scientific explanation for the causes and mechanism of higher success in thawed embryo transfer. Freezing and thawing of preimplantation embryos can be considered as a way to stimulate their endogenous activity and affect their regenerative abilities. In an analysis of some studies and results in assisted reproduction that have not yet been satisfactorily explained, we have found evidence to support the thesis that the freezing and thawing procedure has a “therapeutic” effect on embryos.

    Embryos have the ability to adapt and develop in a wide range of cultivation conditions, showing different patterns of gene expression under different conditions. This process causes stress and is known as HORMESIS. If the embryo is placed in less adverse conditions, it has a stimulating effect on its development.

However, if the conditions are too unfavorable or toxic, then the embryo stops developing and dies. HORMESIS is the response of the embryo that induces protective signals. Freezing of embryos suppresses mitochondrial activity below a certain threshold required to initiate implantation. Upon thawing, there is a rapid recovery of mitochondrial activity in the embryo’s trofectodermal cells (the so-called “jumping effect”), which mimics the physiological processes in the embryo and has a beneficial effect on its implantation.

On the other hand, the freezing / thawing procedure has a “detoxifying” effect on the embryo, by removing cells from mutated forms of mitochondrial DNA and partially releasing free radicals (ROS).

“Theory of cryo-treatment of embryos” has been published in the Journal of Reproductive Medicine and Biology, an official publication of the Japanese Society of Reproductive Medicine.