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Oocyte Cryopreservation – Freezing Eggs for Future Use

Oocyte cryopreservation, the freezing of human eggs is an emerging bio-technology option that may one day replace the freezing of embryos.  While cryopreservation of embryos is more common, as of April 2009, 939 children worldwide are the result of using frozen eggs to achieve pregnancy.

WHAT IS EGG FREEZING?

Egg freezing is an advanced assisted reproductive technology (ART) which was developed for the purpose of fertility preservation for women.  Since a woman must supply a healthy egg to unite with sperm for a pregnancy to occur, egg freezing has emerged as a unique technology to harvest eggs and preserve them while still healthy before they are damaged.  Various factors can affect a woman's ovarian reserve and the ability of her ovaries and the eggs stored within the ovaries to lead to a viable pregnancy.  For instance, as a woman gets older, both the number and the quality of her eggs diminish.  Other factors such as exposure to chemotherapy or radiation therapy, and surgery to remove part or the entire ovary, can also lead to a rapid decrease in ovarian reserve.  When eggs are depleted, the chances for pregnancy decrease substantially.  Therefore, freezing eggs prior to advancing in age or any other potentially damaging factor, can "save" a woman's eggs from damage and preserve such eggs for future use.

WHO IS A CANDIDATE FOR EGG FREEZING?

The development of this medical technology was originally driven by the concern of women who faced cancer that their ability to have children after cancer treatment would be lost.  Because many types of cancers today can be completely cured, this remains a valid reason to consider oocyte cryopreservation.  Many cancer treatments involve chemotherapy and/or radiation therapy, which usually damage a woman's eggs and deplete her ovarian reserve, potentially rendering a woman completely sterile.  Although younger women may occasionally experience a recovery in their ovarian function several years after being treated with chemotherapy/radiation therapy, the vast majority of cancer survivors are not this fortunate.  If such women have not had children, or have had children but wished to have more, egg freezing prior to cancer treatment may be their best choice for allowing them to establish or extend their families in the future.

There are additional reasons for which a woman may want to consider oocyte cryopreservation.  A woman may feel for moral reasons that she should not have children without a partner, yet the man of her dreams has not yet come along.  Unfortunately, the passage of time and the "aging" of a woman's ovaries, decreases every woman's ovarian reserve and the well-being of her eggs.  If enough time has passed, when she finally does meet her life partner, a woman may no longer be able to get pregnant naturally using her "older" eggs, or even with advanced ART treatments such as in vitro fertilization (IVF).  However, if she was fortunate enough to preserve her eggs while she was younger, if she is significantly older when she does meet her life partner, a woman can have a very good chance of a successful pregnancy using her previously preserved eggs and her partner's sperm.

Other women, despite already being married or having found their life partners, may wish to delay childbearing for other personal, professional, or academic reasons.  As more and more women join the professional work force, having children and establishing families are being delayed as women complete their education and climb up the corporate and academic ladders.  Such women do not want to take the risk of not being able to get pregnant when they are finally ready to have children.

Moreover, not only is the risk of infertility higher at an older reproductive age, but also the risk for chromosomal defects, such as Down's syndrome, may increase.  For women who choose to delay child-bearing to later in life, egg freezing is an excellent way of obtaining "reproductive insurance".   Despite being potentially significantly older when they are finally ready to begin building their families, having had their younger eggs frozen in time, such women can improve their chances for a healthy pregnancy at an older age by using their previously preserved eggs.

In theory, any woman is a candidate for freezing eggs.  However, the technology is mostly offered to younger women because the viability of eggs depends profoundly on a woman's age.  This means that the likelihood that an egg will survive the freezing, and then the all-important thawing process, depends to a great extent on a woman's age.  The vast majority of medical studies on egg freezing, for this reason, have been performed on women younger than age 35 years.  This by no means excludes women older than 35 years of age from freezing their eggs.  If a woman who is older than 35 year of age wishes to freeze her eggs, she should have a consultation with a reproductive endocrinology/infertility specialist to determine what her ovarian reserve is and what the likelihood is that her frozen-thawed eggs will lead to a viable pregnancy when she is ready to use them.

HOW IS EGG FREEZING DONE?

In order to maximize the number of eggs frozen for future use, the egg freezing process relies on an ART technique called controlled ovarian hyperstimulation (COH).  In COH, a woman's ovaries are stimulated using hormone injections of medications called gonadotropins.  The injections are self-administered daily for a period of approximately 8-10 days, during which time the patient gets monitored by her doctor with blood tests and vaginal ultrasound exams for the growth of multiple follicles (each follicle, containing a microscopic egg).  Once follicles reach a mature size, another injection is given to mature the eggs inside the follicles, and the woman is prepared for the egg retrieval harvesting procedure.  The egg retrieval procedure is a minor surgical procedure done in the embryology laboratory under light sedation, and completed in most cases in 15-20 minutes.  In the process, each follicle is aspirated under ultrasound guidance and eggs are recovered.  The eggs are next carefully prepared for freezing.

One of the difficulties encountered in oocyte cryopreservation is the high level of water present in the ripe human ovum. Unlike sperm which have almost no water present, the oocyte's water forms ice crystals that can destroy the egg as it freezes.  This must be overcome by replacing the water with an antifreeze compound, a cryoprotectant.  This reduces the risk of damage to the oocyte during the freezing process.

After treatment with the cryoprotectant there are two methods used to freeze and thaw the oocytes.  The most common method involves freezing the egg slowly (slow freeze) then thawing it rapidly.  A newer technique, known as flash-freezing or vitrification, has shown promise because the faster freezing process can minimize or avoid ice crystal formation. Studies as to which one is the most effective are still needed, but the number of live births resulting from eggs frozen using the vitrification method is approaching the number seen from slow-frozen eggs.

HOW ARE FROZEN EGGS USED TO ACHIEVE PREGNANCY?

Once a woman is ready to get pregnant using her frozen eggs, various basic steps have to be done in order to achieve pregnancy.  First and foremost, a sperm source must be obtained.  This can be her partner's sperm or donor sperm.  Secondly, the uterus has to be prepared in order to receive embryos.

Preparing the uterus for the implantation of embryos is a simple process in which the uterine lining is stimulated with estrogen in order to achieve an optimal thickness.  After approximately 10-14 days of estrogen treatment, another hormone, progesterone, is added, and a date for the egg thawing, fertilization, and finally embryo transfer, is set.

The egg has a shell, the zona pellucida, which tends to harden during the freezing process. This makes it difficult for sperm to penetrate.  To overcome this obstacle, immediately upon thawing the eggs, embryologists use a special micro-needle to inject one single sperm into each thawed egg.  This technique, known as intracytoplasmic sperm injection (ICSI), has improved fertilization rates of thawed eggs significantly, improving the number of embryos available for transfer.  Fertilized eggs are next allowed to develop as embryos in the lab, and following a few days of incubation, are transferred into the woman's uterus in a short and simple procedure.

By the fall of 2009, the American Society for Reproductive Medicine (ASRM) reported that oocyte cryopreservation holds "great promise for applications in oocyte donation and fertility preservation."  New cryoprotectant formulas and new freezing and thawing techniques have improved the number of oocytes that survive the freezing then thawing process.

If you are considering egg freezing, make sure to consult with a board-certified reproductive endocrinology/infertility specialist to discuss your options in detail.

About the Author

Dr. Eliran Mor specialized in Obstetrics and Gynecology during his residency, then went on to spend three years pursuing his interest in Reproductive Endocrinology and Infertility at USC. As a specialist in fertility issues, he continues to instruct residents and junior fellows at USC as well as providing fertility services through the California Center for Reproductive Health

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