Oocyte cryopreservation

ICSI sperm injection into oocyte

Human oocyte cryopreservation (egg freezing) is a novel technology in which a woman’s eggs (oocytes) are extracted, frozen and stored. Later, when she is ready to become pregnant, the eggs can be thawed, fertilized, and transferred to the uterus as embryos.

Indications

Oocyte cryopreservation is aimed at three particular groups of women: those diagnosed with cancer who have not yet begun chemotherapy or radiotherapy; those undergoing treatment with assisted reproductive technologies who do not consider embryo freezing an option; and those who would like to preserve their future ability to have children, either because they do not yet have a partner, or for other personal or medical reasons.

Over 50,000 reproductive-age women are diagnosed with cancer each year in the United States. Chemotherapy and radiotherapy are toxic for oocytes, leaving few, if any, viable eggs. Egg freezing offers women with cancer the chance to preserve their eggs so that they can have children in the future.

Oocyte cryopreservation is an important option for individuals undergoing IVF who object, either for religious or ethical reasons, to the practice of freezing embryos. Having the option to fertilize only as many eggs as will be utilized in the IVF process, and then freeze any remaining unfertilized eggs can be a positive solution. In this way, there are no excess embryos created, and there need be no disposition of unused frozen embryos, a practice which can create complex choices for certain individuals.

Egg freezing can also be beneficial for women who, for the purpose of education, career or other reasons, desire to postpone childbearing. Freezing eggs at an early age may ensure a chance for a future pregnancy.

Additionally, women with a family history of early menopause have an interest in fertility preservation. With egg freezing, they will have a frozen store of eggs, in the likelihood that their eggs are depleted at an early age.

Method

The egg retrieval process for oocyte cryopreservation is the same as that for in vitro fertilization. This includes one to several weeks of hormone injections that stimulate ovaries to ripen multiple eggs. When the eggs are mature, final maturation induction is performed, preferably by using a GnRH agonist rather than human chorionic gonadotrophin (hCG), since it decreases the risk of ovarian hyperstimulation syndrome with no evidence of a difference in live birth rate (in contrast to fresh cycles where usage of GnRH agonist has a lower live birth rate). The eggs are subsequently removed from the body by transvaginal oocyte retrieval. The procedure is usually conducted under sedation. The eggs are immediately frozen.

The egg is the largest cell in the human body and contains a great amount of water. When the egg is frozen, the ice crystals that form can destroy the integrity of the cell. To prevent this, the egg must be dehydrated prior to freezing. This is done using cryoprotectants which replace most of the water within the cell and inhibit the formation of ice crystals.

Eggs (oocytes) are frozen using either a controlled-rate, slow-cooling method or a newer flash-freezing process known as vitrification. Vitrification is much faster but requires higher concentrations of cryoprotectants to be added. The result of vitrification is a solid glass-like cell, free of ice crystals. Vitrification is associated with higher survival rates and better development compared to slow-cooling when applied to oocytes in metaphase II (MII). Vitrification has also become the method of choice for pronuclear oocytes, although prospective randomized controlled trials are still lacking.

During the freezing process, the zona pellucida, or shell of the egg can be modified preventing fertilization. Thus, currently, when eggs are thawed, a special fertilization procedure is performed by an embryologist whereby sperm is injected directly into the egg with a needle rather than allowing sperm to penetrate naturally by placing it around the egg in a dish. This injection technique is called ICSI (Intracytoplasmic Sperm Injection) and is also used in IVF.

Success rates

The percentage of transferred cycles is somewhat lower in frozen cycles compared with fresh cycles (approx. 80% and 90%, respectively). Such outcomes are considered comparable.

Two recent studies showed that the rate of birth defects and chromosomal defects when using cryopreserved oocytes is consistent with that of natural conception.

Recent modifications in protocol regarding cryoprotectant composition, temperature and storage methods have had a large impact on the technology, and while it is still considered an experimental procedure, it is quickly becoming an option for women. Slow freezing traditionally has been the most commonly used method to cryopreserve oocytes, and is the method that has resulted in the most babies born from frozen oocytes worldwide. Ultra-rapid freezing or vitrification represents a potential alternative freezing method.

In the fall of 2009, The American Society for Reproductive Medicine (ASRM) issued an opinion on oocyte cryopreservation concluding that the science holds “great promise for applications in oocyte donation and fertility preservation” because recent laboratory modifications have resulted in improved oocyte survival, fertilization, and pregnancy rates from frozen-thawed oocytes in IVF. The ASRM noted that from the limited research performed to date, there does not appear to be an increase in chromosomal abnormalities, birth defects, or developmental deficits in the children born from cryopreserved oocytes. The ASRM recommended that, pending further research, oocyte cryopreservation should be introduced into clinical practice on an investigational basis and under the guidance of an Institutional Review Board (IRB). As with any new technology, safety and efficacy must be evaluated and demonstrated through continued research.

In October 2012, the ASRM lifted the experimental label from the technology, citing success rates in live births, among other findings.

In 2014, a Cochrane systematic review about this topic was published. It compared vitrification (the newest technology) versus slow freezing (the oldest one). Key results of that review showed that the clinical pregnancy rate was almost 4 times higher in the oocyte vitrification group than in the slow freezing group, with moderate quality of evidence.

Cost

The cost of the egg freezing procedure (without embryo transfer) is between $5,000 and $8,000. This does not include the fertility medications which can cost between $4,000 and $5,000. Egg storage can vary from $100 to several hundred dollars or more per year.

History

Cryopreservation itself has always played a central role in assisted reproductive technology. With the first cryopreservation of sperm in 1953 and of embryos thirty years later, these techniques have become routine. Dr Christopher Chen of Australia reported the world’s first pregnancy in 1986 using previously frozen oocytes. This report stood alone for several years followed by studies reporting success rates using frozen eggs to be much lower than those of traditional in vitro fertilization (IVF) techniques using fresh oocytes. Then recently, two articles published in the journal, Fertility and Sterility, reported pregnancy rates using frozen oocytes that were comparable to those of cryopreserved embryos and even fresh embryos. These newer reports affirm that oocyte cryopreservation technology is advancing.

Almost 42,000 'slow frozen' (as opposed to 'vitrified') human embryo transfers were performed during 2001 in Europe (Andersen et al. 2005). In addition, it is estimated that between 300,000 and 500,000 successful human births have resulted worldwide from the transfer of previously ‘slow frozen’ embryos performed from the mid-1970s to 2006.

See also

• Semen cryopreservation
• In vitro fertilization

External links

• New Egg Freezing Technology Eases Women's Career Family Angst, Bloomberg Businesssweek
• How egg freezing works, Human Fertilisation and Embryology Authority
• World Association of Reproductive Medicine
• American Society for Reproductive Medicine
• National Cancer Institute – Sexuality and Reproductive Issues
• Motherhood On Ice, Style Magazine story on the pros & cons of egg freezing, Cavanaugh Simpson
• Harrison, K.; et al. (April 2, 2007). "Oocyte cryopreservation as an adjunct to the assisted reproductive technologies". The Medical Journal of Australia. 186 (7): 379. {{cite journal}}: Explicit use of et al. in: |author2= (help); Unknown parameter |displayauthors= ignored (|display-authors= suggested) (help)
• Gook, D. A.; Edgar, D. H. (1999). "Cryopreservation of the human female gamete: Current and future issues". Human Reproduction. 14 (12): 2938–40. doi:10.1093/humrep/14.12.2938. PMID 10601074.
• Women Hedge Bets By Banking Their Eggs, Washington Post
• Human egg-freezing gets a stamp of approval, Philadelphia Inquirer
• We Need to Talk About Our Eggs, New York Times