Fertility preservation by egg freezing
For many decades cryopreservation of sperm and embryos has been performed successfully using the slow-freeze method. In the traditional slow-freeze method the cell to be frozen is immersed in a special solution (cryoprotectant) that withdraws the water from the cell over many hours to minimize formation of ice crystals that can expand during thawing and destroys the mechanism that aligns the chromosomes. Unfortunately, due to the large size of the egg and its high water content, achieving a state of complete dehydration for egg freezing was very difficult. Although the first live birth from frozen eggs occurred in 1986, until recently, egg survival rates of 20% and pregnancy rates of 10% were too low to make egg cryopreservation practical.
In 2008 a new ultra-rapid freezing technology called vitrification was introduced to freeze human embryos. By taking cells from room temperature to -196 degrees C in a fraction of a second, vitrification completely avoids the formation of ice crystals. The results are higher rates of embryo survival and live births seen with frozen embryo transfer cycles.
The same vitrification process to freeze embryos was slightly modified to allow successful freezing of eggs. Preliminary studies have shown that the ultra rapid freezing process completely avoids formation of ice crystals to allow achievement of egg survival rate of 90% and pregnancy rates of 50% or higher in certain groups of patients. As of October 2012 the American Society of Reproductive Medicine has removed the “experimental” label and endorsed oocyte vitrification for medical indications.
How many eggs to freeze and and for how long?
At IVFMD we recommend that you freeze about 10 mature eggs for every pregnancy you plan to achieve. Assuming a 90% egg survival rate, thawing of 10 eggs would result in 9 viable eggs. With an average fertilization rate with ICSI of 70%, about 5-6 eggs would fertilize to eventually provide 2 blastocysts for transfer on day 5 of culture.
There is very limited data on long term storage of eggs. However, one study showed no difference in egg survival rate embryo quality, pregnancy rate, or live birth rate in eggs frozen up to 4 years compared to earlier thaws.
A large study published in 2016 from a prominent IVF program provided useful data on how many eggs a woman needs to freeze in order to have a certain number of children. The graphs below reflect some of the data from the study:
What is the cost of freezing eggs and using them later?
- The global cost of a cycle of an egg freezing cycle at IVFMD is $6,000. The global fee takes effect at the start of stimulation cycle and covers professional management, facility fee, monitoring sonograms, hormone monitoring, egg retrieval, anesthesia, cryopreservation and the first year of storage.
- Annual storage fee for subsequent years is $500.
- The global fee for an egg thawing cycle is $5,000. The global fee takes effect at the start of hormone replacement cycle and covers professional management, facility fee, monitoring sonograms, hormone monitoring, egg thawing, ICSI, embryo culture, laser hatching, embryo transfer and 2 pregnancy tests.
The egg freezing process
The entire process takes about 4-6 weeks from start to finish and is consisted of the following steps:
- Evaluation of ovarian reserve: Assessing your ovarian reserve is important. An antral follicle count of 12 or higher and an AMH level of 1.2 ng/ml or higher suggest normal egg reserve.
- Prestimulation cycle: During this cycle you will take birth control pills (BCP) to rest the ovaries and learn how to inject medications. This period can last 2-3 weeks. Patients with low egg reserve will not use BCP.
- Ovarian stimulation cycle: The stimulation protocol depends on how many eggs your ovaries can produce in a cycle and how many children you desire in the future. For about 10-12 days you will use injectable medications to stimulate your ovaries while undergoing close monitoring with a sonogram and hormone levels.
- Egg retrieval: You will undergo deep IV anesthesia for 20 minutes while eggs are aspirated from both ovaries using a thin needle that is on top of a vaginal ultrasound probe. You will not feel or remember anything during retrieval procedure. You will wake up instantly after the prodecure is completed. Mild cramping or discomfort may occur and can be treated by medications as needed. You will rest for about 30 min before being discharged. Due to the effects of anesthesia you will need to have someone available to drive you home after the procedure. You should be able to return to normal activity later that day. Over the next few days you may feel mild abdominal discomfort and bloating sensations but these will likely resolve within 1-2 weeks.
- Egg freezing and storage: In the laboratory the following process will take place:
- The eggs will first be stripped of attached cells and assessed for maturity. Only mature eggs will be frozen. Immature eggs are incubated in special media and observed for signs of maturity for later freezing.
- Mature eggs are immersed in cryoprotectant solution to remove water from the egg cells (dehydration).
- The ‘dehydrated’ eggs are put into specialized straws and flash frozen in milliseconds.
- The frozen straws are finally stored in a liquid nitrogen tank.
What is the process of using frozen eggs?
When you are ready to use your frozen eggs you will likely go through these steps:
- Preparation of the endometrium. The goal is to prepare the endometrium for the embryos. Estrogen is used for about 2 weeks to grow the endometrium before progesterone is added to mature the uterine lining for implantation.
- Egg thaw and fertilization. Eggs are thawed and injected with sperm (ICSI) to optimize fertilization since the freezing process can harden the zona (shell) of the egg.
- Fertilization check is performed the next day (day 1). Normally fertilized eggs are cultured further.
- Embryo culture progress is checked on day 3 and day 5 and you will be informed of the status of your embryos.
- Embryo transfer is performed on day 5 at the blastocyst stage. Up to 2 embryos can be transferred. Laser hatching of the zona may be performed to facilitate implantation.
- Pregnancy test is performed 10 days later.
Indications for egg freezing
The ability to freeze eggs safely has opened new opportunities for women who wish to preserve their fertility for the following reasons:
- Cancer: Women who are about to undergo chemotherapy or radiation therapies focusing on the pelvis can result in loss of eggs, sometimes years after treatment. In addition, the surviving eggs may have irreversible damage to their genetic materials that can lower the chance of successful conception in the future.
- Benign gynecological diseases such as endometriosis or ovarian cysts that necessitate removal of their ovaries.
- Family history of premature menopause
- Delaying childbearing– Many women desire to postpone having children for a variety of reasons (career, lack of suitable partner). Since egg quantity and quality decline with time, freezing her eggs enables a woman to arrest the effect of time on her reproductive potential.
- Objection to embryo freezing– Egg freezing avoids the ethical dilemma of discarding extra embryos. Instead of fertilizing all available eggs in an IVF cycle, some eggs can be frozen for future use. If the first treatment attempt is unsuccessful the frozen eggs can be thawed and fertilized to give the patient another chance to conceive.
How safe is egg freezing?
Since 1986 there have been more than 2,000 live births from frozen eggs worldwide. Studies on the safety of egg cryopreservation have revealed the following:
- There was no difference in chromosomal abnormalities in embryos from frozen eggs compared to those created from fresh eggs.
- A review of 900 births from slow freeze eggs revealed no increased risks of birth defects compared to general population.
- A review of 200 babies born from vitrified eggs showed no difference in birth defect rates compared to those conceived after fresh IVF.
- Overall, of the babies born from frozen eggs, only 1.3% birth defects, a rate not significantly different from that seen in naturally conceived infants.
How successful is egg freezing?
The success in producing a baby from egg freezing depends on the age of the woman. The risk of producing abnormal eggs increases significantly after age 35.
Studies have revealed an egg survival rate of 80-90% after thawed and a the fertilization rate of 70-80%, which is about the same as in fresh eggs.
Vitrification experience in Italy (182 couples) had shown similar survival rates after thawing among women of different age groups but clinical pregnancy rate was lower in women older than age 38. Pregnancy rates per transfer were 49% (age ≤ 34), 24% (age 35-37), 23% (age 38-40), and 22% (age 41-43%).