The freezing of embryos and sperm has long been recognized as a means of pursuing fertility treatments later in life. However, new techniques involving the freezing of eggs have recently resulted in greater success. As a result, the American Society for Reproductive Medicine (ASRM) no longer considers egg freezing to be an experimental procedure.
Candidates for egg freezing
Women who wish to put off childbearing
It is known that fertility declines with advancing age in women. In addition, women in their twenties or thirties have lower rates of miscarriage and of babies with birth defects compared to older women. This is largely due to the increase in the percentage of embryos with chromosome abnormalities that occurs with age. Because of the problems associated with reproductive aging, many women have chosen to use donor eggs to increase their chances of having a child. While this method has proven to be very effective, it is often a hard choice as it entails the greatest sacrifice. With the advances in cryopreservation, freezing of eggs at a younger and more fertile age would potentially allow women to be their own egg donors later in life.
Egg Freezing for Cancer patients
Egg freezing may be especially useful for cancer patients. Health data in the United States from 2001 shows that 8% of women diagnosed with cancer were under the age of 40. In 2007, an estimated 180,000 women were diagnosed with invasive breast cancer. Approximately 5% of those women were under the age of 40 at the time of the diagnosis and therefore potentially interested in maintaining their fertility. In fact, about 30% of women under age 40 have never been pregnant. Many of these women are single. For breast cancer, 81% of these young women who undergo treatment with chemotherapy and radiation will be alive and free of disease after 5 years. Unfortunately, less than 5% of women diagnosed with breast cancer under age 40 will go on to deliver a live born child.
Unfortunately for these women of childbearing age, treatments such as chemotherapy and radiation have been shown to cause damage to maturing follicles in the ovaries. These treatments are used to kill rapidly dividing cells but may cause damage to the eggs stored in the ovaries as well. In many cases, women who undergo chemotherapy or radiation will enter menopause prematurely and be unable to ever have children using their own eggs.
Currently, the recommendation for men who are going to undergo treatment with chemotherapy or radiation is to collect several semen specimens so that they can be frozen before treatment begins. The frozen semen can later be used for intrauterine insemination or in vitro fertilization if the man becomes sterile as a result of his cancer treatment. This method is easy, inexpensive and highly effective. The man is not required to have a current partner and so it can be performed on young men.
If a woman who is diagnosed with cancer has a male partner with whom she wishes to conceive, but is not ready to attempt pregnancy, the best option for them is create embryos through IVF and freeze the embryos (embryo cryopreservation). Embryo cryopreservation has been performed successfully for many years and is currently considered the gold standard in fertility preservation.
Some women may not have a partner that they want to have children with or are too young to have partner. These women are ideal candidates for egg freezing.
Egg freezing for soldiers
Soldiers tend to get overlooked as possible candidates for fertility preservation. Unfortunately, troops are vulnerable to pelvic injuries that damage their reproductive systems. Military records show that since 2003, more than 1,800 service members in Iraq and Afghanistan — the majority of them Army troops — have suffered such wounds. In some cases, these injuries or chemical exposure will leave a soldier unable to have children.
Failure to obtain sperm for IVF
Occasionally, a male partner of a couple undergoing IVF is unable to collect a semen sample on the day of egg retrieval. In the past, this presented an insurmountable obstacle which resulted in the recently eggs to be disposed. This resulted in much emotional as well as financial distress. Now eggs can be frozen and fertilized later after sperm has been collected. Two studies have reported successful outcomes in such situations.
Reluctance to freeze embryos
Some couples have personal religious beliefs that make them uncomfortable freezing embryos. In the past, in order to reduce the risk of having extra embryos, physicians would decrease the dose of fertility medications and/or attempt to fertilize less eggs. Unfortunately, this would sometimes result in an inadequate number of embryos and the couple’s chance for pregnancy would be reduced. Furthermore, women would then be subjected to another ovarian stimulation and egg retrieval in order to collect more eggs. These couples usually do not have religious objections to the freezing of unfertilized eggs. Therefore, a usual number of eggs can be collected.
Fertility medications for egg freezing?
Normally, when performing in vitro fertilization , the eggs are matured inside the body using fertility drugs. The eggs are removed after it is thought they are mature. An egg must be mature in order to be fertilized with sperm. These mature eggs can also be frozen.
If there is an urgency to begin cancer treatments on a woman who wishes to freeze her eggs, or if her cancer makes ovarian stimulation risky, the eggs can be retrieved while still immature and frozen. It may then be possible to mature the eggs later after thawing. This technique, known as in vitro maturation, or IVM, involves maturing eggs outside of the body in a laboratory setting. This procedure does not require hormone containing fertility medications and thus may be a better choice for women who want or need to avoid stimulation with fertility drugs .
Techniques for egg freezing
Slow egg freezing method
Cryoprotectant is a substance used to protect biological tissues from freezing damage. The slow freeze method of freezing eggs relies on low initial concentrations of cryoprotectant. This low concentration of cryoprotectant is introduced when the egg is still at a relatively warm temperature and is still experiencing the normal functions of a living cell. The cryoprotectant will permeate and fill the egg, replacing most of the water in the egg. The egg is inserted into a small plastic container and placed into a cooling chamber. By injecting tiny amounts of liquid nitrogen into the cooling chamber, the temperature is then lowered slowly to around –6°C. A computer controls the cooling process.
The purpose of these techniques is to prevent ice crystals from forming in the egg. If ice crystals are present when thawing, they can lead to damage of the egg and the egg may not survive the thawing process. The temperature is further lowered to around –32°C. By now, the metabolic rate of the egg is quite slow. The egg container is then plunged into liquid nitrogen, creating a solid.
Thawing of these eggs required a fast approach. They are rapidly warmed up to prevent ice crystal damage.
Rapid egg freezing method (vitrification)
During rapid freezing of eggs, the concentration of the initial cryoprotectant is quite high while the cell is at room temperature. The egg cannot stay at this temperature for long and is immediately plunged directly into the liquid nitrogen. An extremely rapid rate of thawing is used once again to prevent ice-crystal damage. Vitrification is a newer method for freezing eggs. Recent studies have found that vitrification of eggs significantly improves the chance for survival after thawing and the pregnancy rates. IVF1 uses the vitrification method for freezing of embryos and eggs.
A 2012 study compared several parameters using fresh eggs versus eggs frozen with vitrification from the same patient. The survival rate of eggs after thawing was 81%. The fertilization in thawed eggs was lower than that of fresh eggs (79% vs 90%). The percentage of fertilized eggs that went on to divide was also lower with frozen-thawed eggs (90% vs 99%). This became important as the percentage of eggs that reached blastocyst stage was lower in the thawed group (35% vs 51%). The good news is that the percentage of blastocysts with chromosome abnormalities was the same in both the thawed and fresh egg groups. Most importantly, the ongoing pregnancy rate per embryo transferred was the same in both groups.
The bottom line from this study is that it may take many more frozen eggs to get the same number of blastocysts but if blastocysts are available for transfer, the pregnancy rate after thawing seems the same as would be seen with fresh blastocysts.
Ovarian tissue freezing
Another alternative to freezing of eggs is the freezing of strips of ovaries or the freezing of entire ovaries. The majority of the eggs are located near the surface of the ovary in what is called the ovarian cortex.
For example, in women who are going to undergo cancer treatment, it is now possible to surgically remove a portion of the ovarian cortex and freeze it for later use. After cancer treatment has ended, if a woman has developed ovarian failure, surgery can be performed to transplant a portion of the cortex back onto the ovary.
In a small series of women, cortical “grafts” were performed after the development of ovarian failure. Some of these women saw the function of the ovarian tissue grafts return. Based on these subjects, it is estimated that in most women, ovulation should return in three to four months. The lifespan of these grafts is about three years or less.
Egg Freezing Outcomes
Comparison with Embryo Cryopreservation
While embryo cryopreservation is still the method of choice for most couples, it has many limitations for single women. These include discomfort with choosing a sperm donor, paternity and legal obligations in the case of a known sperm donor, and the disposition of frozen embryos when marriage occurs. With frozen eggs, on the other hand, in the case of divorce, separation, or abandonment, the disposition of eggs rather than embryos may be easier to handle. In the end, if pregnancy rates after egg cryopreservation continue to increase, the rate of multiple pregnancies could decrease with the use of more conservative practices such as fertilizing fewer eggs and transferring fewer embryos.
Egg Freezing Rates
Data has shown that egg freezing has shown a gradual improvement in efficiency over time with better survival, better pregnancy rates and lower miscarriage rates. Recent slow freeze studies have reported a miscarriage rate that is comparable to the rate seen in naturally conceived pregnancies. Live birth rates upon thawing, fertilization and transfer of cryopreserved eggs by either the slow freeze method or by vitrification are comparing favorably to the rates seen with frozen embryos in many programs. However, those programs that have very high frozen embryo pregnancy rates (such as at IVF1), egg freezing is still not as good as embryo freezing.
As noted above, eggs thawed after rapid freezing which become blastocysts, seem to have an equal chance of producing an ongoing pregnancy. A recent study from Canada showed that the rate of birth defects was 2.5 per cent in babies conceived after freezing of eggs. This is comparable to the rate seen in babies conceived naturally and from IVF. Other reports have found that the incidence of chromosome abnormalities in human embryos derived from frozen eggs is no different than the rate seen in fresh embryos. A study of 200 babies born from vitrified eggs also failed to find any difference in birth weight.
Conclusions regarding egg freezing
As of October 2012, the American Society for Reproductive Medicine (ASRM) concluded that, there is now ample high quality data that proves that fertilization rates and pregnancy rates are similar to IVF using fresh eggs in young infertility patients and egg donors. In addition, there has been no increase noted in chromosome abnormalities, birth defects or developmental defects in the children born from frozen eggs. Therefore, the freezing of eggs should no longer be considered experimental.