Egg Freezing (Vitrification)
The use of Vitrification technology, or rapid freezing, to cryopreserve or freeze eggs offers a new option for cancer patients looking to preserve their fertility, prior to treatment; and articles in the lay press have proclaimed that egg freezing, using vitrification is "a woman's emancipation" from age-related infertility.
Egg or oocyte freezing has been around for years, but up to a few years ago was only available as an experimental technique for fertility preservation, and with limited success. While embryo cryopreservation has been successful for the last two decades, freezing unfertilized eggs or oocytes is trickier. Eggs are more susceptible to damage from ice crystallization than embryos during the freezing process. Up to a few years ago, a young and/or single cancer patient who wanted to preserve her future fertility, only had the option of fertilizing her own eggs with donor sperm. Also, some couples were faced with the moral and/or religious beliefs in having to decide what to do with multiple unused embryos. A third concern, was from young women, either single or married, that wanted to delay childbearing but were concerned about "getting too old and/or having problems" with resulting increased difficulty with achieving pregnancy; or at being at increased risks of chromosome abnormalities and miscarriages if they delayed childbearing for too long.
As a result, there has been ongoing research over the last decade to develop newer cryoprotectants to better protect the egg from damage from the freezing process. Until recently, the only method for freezing oocytes (or unfertilized eggs) was a slow-freezing method. Unlike sperm, which has been frozen and thawed successfully years later; eggs contain a great deal of water, which makes freezing more difficult. When an egg is frozen, ice crystals can form within the cytoplasm or center of the egg. These ice crystals, known as ice crystallization, can act like razor shape daggers and damage the egg's internal structure.
To help minimize the amount of ice crystal formation, researchers would remove some of the water from the egg and replace it with a cryoprotectant or "anti-freeze", before it was slowly frozen. But it is impossible to remove all the water and thus, completely prevent ice crystallization and resulting damage from occurring to the egg. As a result of damage from the slow freezing of eggs, fertilization and pregnancy rates were poor; and only a handful of successful pregnancies and births were reported.
Vitrification is a newer technique where eggs undergo rapid freezing, not allowing time for ice crystals to form. Vitrification of eggs involves newer cryoprotectants that have high concentrations of "anti-freeze" like products. In order to do successfully, the technique involves a fair amount of experience and expertise. The oocyte is first placed in a bath with a lower concentration "anti-freeze-like" cryoprotectant, along with sucrose (sugar) to help draw some of the water out of the egg. Then, the egg is moved into a high concentration of cryoprotectant for less than one minute and immediately placed in a liquid nitrogen bath (minus 400 degrees fahrenheit) which instantaneously freezes the egg. When the woman is ready to attempt pregnancy, the egg is rapidly thawed and the cryoprotectant is washed away.
With these newer techniques of rapid egg freezing, or vitrification, it is now possible to cryopreserve the female egg (oocyte), as successfully as it has been to cryopreserve embryos. Egg freezing is still a new and mostly experimentally technology that has been shown to be highly effective in preliminary research.
There are now a number of babies born with the use of egg vitrification technology; and at Arizona Center for Fertility Studies, we have had good results with vitrification of eggs. To date, there have been no increase in birth defects related to this process. Survival rates for eggs (oocytes) can reach as high as 85% and pregnancy rates as high as 65%, depending on the woman's age.
Pregnancy rates with egg vitrification, with subsequent thawing and fertilization, should be similar to success rates with that of frozen-thawed embryos. Once thawed, the egg can be fertilized using ICSI, an assisted reproductive technology, that injects one sperm directly into an egg.
Vitrification of eggs is primarily used in young single cancer patients as a means of fertility preservation and not having to use donor sperm to produce embryos. Currently, there is not a huge demand for egg vitrification to prevent "age-related" infertility in younger women having to delay childbearing in order to pursue their careers or just "not ready to have children"; but at Arizona Center for Fertility Studies, we are starting to see a slight increase in the demand for this service. Vitrification is also being done to try to preserve ovarian tissue. Ovarian tissue preservation, also known as ovarian cryopreservation, is another experimental technique being used to preserve fertility in female cancer patients. It involves removing portions or the entire ovary, that undergo rapid-freeze, and later transplanting the ovarian tissue back into the woman's body after cancer treatment is completed.
Recently some fertility clinics have been marketing vitrification to women who want to delay childbearing, or don't have partners yet and "don't want to worry about their biological clocks". Marketing and offering vitrification to women wanting to avoid age-related fertility problems is controversial. The American Society of Reproductive Medicine (ASRM) is against the idea, saying that the technique is too new, and does not have enough research to prove it will be successful enough to be worth it. Only a few hundred pregnancies have resulted from vitrified egg freezing, and none of those included eggs frozen for more than a few years. There is no data, for or against, that shows that vitrified eggs can be stored for years at a time, then successfully thawed, fertilized and produce a healthy normal offspring. The risk in these younger women who want to delay childbearing is that when they decide that now is "the right time" and thaw their eggs, the eggs may not survive the thaw, not fertilize and not result in a successful pregnancy; and all along they thought that they had "all the time in the world" because they had frozen eggs from when they were "28 years old". On the other side of the coin, some fertility programs, who are marketing egg vitrification, claim that the latest research shows that the technique is successful, and it's time to release the new technology to those that want to try it. Arizona Center for Fertility Studies definitely recommends and does egg vitrification for fertility preservation in young cancer patients; but as far as using it for delaying childbearing in younger women, these women need to proceed with caution and at their own risk; that with future thawing, their eggs may not be usable. Once a woman completely understands these "potential" risks, Arizona Center for Fertility Studies will proceed with egg vitrification. Arizona Center for Fertility Studies will also do egg vitrification for couples who are facing a moral and/or religious dilemma as to what to do with potential multiple extra embryos obtained for an IVF cycle. One solution is to pick only a few of the "best" eggs from the cycle and have them undergo fertilization with ICSI, and cryopreserve the rest, to use on subsequent attempts. This eliminates the difficult decision about what to do with extra embryos, once they are finished with their families. As technology in this field advances, even newer cryoprotectants will be able to safeguard the egg for extended periods of time and more data will be available from cancer patients who use their vitrified eggs years after successful treatment.
Stages of Oocyte Cryopreservation Procedure
Oocyte cryopreservation procedure comprises several different stages:
The first stage entails stimulation of the ovary(s) to obtain multiple follicle growth and egg production (IVF). During the stimulation phase, follicular grow this carefully monitored with transvaginal ultrasound and testing for estradiol and LH, the hormones produced by follicles during their growth phase, in order to determine the appropriate time to harvest the eggs.
When a sufficient number of follicles have achieved satisfactory growth, the final, follicular maturation phase is induced with a trigger shot of hCG.
The next stage is the retrieval of the eggs from the follicles. This is done by needle aspiration through the vaginal wall under ultrasound guidance. The procedure is performed under intravenous anesthesia. Usually the patient is discharged approximately 30-60 minutes after the procedure.
Several hours after the procedure, oocytes that show a proper grade of maturation (metaphase II) are cryo-stored by vitrification (rapid freeze) and stored in liquid nitrogen.
After thawing of the frozen eggs, fertilization will be carried out by ICSI (intracytoplasmic sperm injection), irrespective of the quality of the semen.
The survival rate of the oocytes after thawing is reported as high as 85%. Egg freezing is still a developing technique. Women should be informed that vitrification of oocyte(s) is considered an experimental technique at this time and the rate of congenital anomalies or malformations in the offspring is unknown, although current data suggests that it is extremely low. This is due to the lack of data regarding damage that could be structural, biochemical, or genetic.
While oocytes may survive vitrification, the potential for sub-lethal permutations can influence subsequent normal fertilization, normal embryo development, and normal healthy live births must be considered.
Assessing the risk of fetal anomalies, malformations, and other complications is very difficult since there are several issues to be taken into account including a higher than average maternal age and factors linked to the cause of infertility, as well as oocyte vitrification being a relatively new technique. Moreover there is no consensus on how to assess various pathologies that are certainly more carefully monitored for a considerably longer time among children born as a result of medically assisted reproduction techniques. Taking all of this into account, it is reasonable to presume that the incidence of chromosomal anomalies and malformations are similar to that of children born after ICSI without vitrification.
Few reports exist in the literature concerning the probability of successful conclusion of this technique and these present an insufficient number of clinical cases for reliable conclusions to be drawn.
Informed Consent for Egg Freezing (Vitrification)
Arizona Center for Fertility Studies informed consent for egg freezing or vitrification:
Possible medical side effects of the technique:
It may happen that after a course of ovarian stimulation, the decision is taken not to proceed with egg retrieval on account of inadequate response. The literature reports this as occurring in 5 to 20% of all cases. The causes include the age and specific clinical characteristics of the patient. I have also been informed of the possibility that no eggs may be retrieved even after apparently normal ovarian stimulation. The incidence reported in the literature varies from 0.1 to 0.9%
Possible risks for the woman as a result of medically assisted reproductive treatment:
There are reports of a 0.6% incidence of ovarian hyper stimulation syndrome or OHSS among women undergoing treatment. The literature reports values ranging from 0.2 to 1%. The condition can lead to abnormal increase in the size of the ovaries, fluid in the abdomen (ascites) and other complications that may require admission to the hospital. Arizona Center for Fertility Studies has not had a single case of severe OHSS in the last 10 years.
Complications following ultrasound-guided retrieval of eggs are very low. They include, however, pelvic infections (0.6%), abdominal bleeding (0.07%), and perforation of the iliac vessels (0.04%)
Invasiveness of the technique:
The technique is only minimally invasive, i.e. when the eggs are retrieved from the woman's ovaries. This is done through the vagina under ultrasound guidance. The procedure is done in a day-surgery facility under intravenous anesthesia.
Costs for the whole procedure:
The cost of the standard procedure including the freezing procedure and the preservation of the oocytes for a period of one year from the date of freezing has been discussed with us. At the anniversary of the freeze I/we will receive a letter requesting whether I/we would like to keep the oocytes frozen and stored for another year ($500) or would like that they be donated (given that all FDA guidelines are met), discarded, used for research or practice.
Arizona Center for Fertility Studies reserves the right to update this amount in line with any increase in cryopreservation and storage cost.
Should treatment be discontinued on account of failure to respond to stimulation and/or failure to recover any eggs, the woman shall be liable only for an itemized amount of the total charges instead of the full charge for the treatment.
In addition to the cost of the treatment indicated above, we shall be liable for the fee of the anesthesiologist/RN sedation.
I agree to absolve, release, and hold harmless Arizona Center for Fertility Studies, its officers, directors, physicians, agents and employees from any and all liability for any adverse outcome, however remote, arising from the retrieval and storage of the oocytes.
In the case of oocyte donation, confidentiality and anonymity will be maintained. The prevailing legal opinion is that any offspring will carry the legal status of adopted children, and have no legal ties to the genetic parents.
If under any circumstances the Arizona Center for Fertility Studies-ART program is terminated and oocyte(s) remain in storage, Arizona Center for Fertility Studies will make all reasonable efforts to contact the woman for a period of one year and document that effort, and arrange for disposition of the oocyte(s) in accordance with her desires at such time. I/we understand that failure to make contact or failure to provide current addresses and contact numbers will result in disposal of the oocyte(s), according to Arizona Center for Fertility Studies policies, if no contact after one year of the announcement.
I/we understand we are voluntary participants in this program, and are free to withdraw our consent as to the disposition of our oocytes and to discontinue participation by requesting in writing relocation of our oocyte(s) to another suitable location at any time without prejudice, as long as there are no financial obligations to Arizona Center for Fertility Studies.
If I/we or any of our offspring should require any medical treatment as a result of physical injury arising from our participation in this program, financial responsibility will be ours. Payment of all medical costs associated with our participation will be our responsibility.
In the event of injury resulting from this procedure, Arizona Center for Fertility Studies is not able to offer financial compensation or absorb the costs of medical treatment. However, necessary facilities, emergency treatment and professional services will be recommended. My/our signature(s) below acknowledges my voluntary participation in this procedure, but in no way releases the medical staff from their professional and ethical responsibilities to me.
I/we shall indemnify Arizona Center for Fertility Studies for any attorney's fees, court costs, damages, judgments, or any other losses or expenses incurred by the Center or for which they may be responsible with respect to any claim, legal action or defenses arising out of the cryopreservation process. This includes but is not limited to any claim or legal action brought by the child or children resulting from the vitrification process or any confidentiality of the data will be maintained within legal limits.
I/we understand that final disposition of oocytes will require an original notarized consent signed by both partners (if applicable).