Women who face cancer treatment also face the real possibility of losing their fertility in the process. Damage from such treatments as radiation and chemotherapy can render the ovaries dysfunctional. Thus, women who undergo these treatments and want to have children in the future are very interested in ways to preserve their fertility in the meantime.1
Reproductive Options Following Cancer Therapy
There are various options for women who want to preserve their fertility, such as embryo freezing, in which eggs are removed from the patient, fertilized using standard in vitro fertilization (IVF) techniques, then frozen and stored for use sometime in the future. Using donor eggs might be another option, in which a patient uses eggs from an anonymous donor to be fertilized with her partner's sperm after cancer treatment.2
A more tentative, but potentially viable option is egg freezing. This method allows women undergoing cancer treatment to have her healthy eggs removed beforehand, then frozen for later use, but has "limited" value currently, experts say. That's because of the egg's delicate nature. Thawing an egg after freezing subjects it to potential damage, and the hardening of its outer wall (zona pellucida) has led to lower fertilization success.3 This is because it's more difficult for sperm to penetrate the egg.
Cutting Edge Technique Emerging
However, in a new analysis whose results were released this past May at an international medical conference,4 medical researchers at the University of Michigan evaluated the effectiveness of a technique known as vitrification. This process allows the eggs to be cooled fast enough that no potentially destructive ice crystals form.
So far, vitrification has only been used in studies involving animals,5 however the Michigan researchers are testing it in people in a new clinical trial.
"Vitrification goes back many, many years," explained the study's chief researcher, Gary Smith, PhD, an associate professor of Obstetrics and Gynecology, Urology, and Molecular and Integrative Physiology at the University of Michigan.
The technique was tested in mouse embryos as far back as 1985.6 But most of those studies involved freezing embryos. Testing vitrification as way to freeze eggs hasn't been investigated as thoroughly, Smith explained. But it definitely has advantages.
"With traditional slow-freeze techniques, just over half the eggs survive the thawing process," said Smith. "Using vitrification, we are getting 98% survival [of the eggs]. For a woman with cancer, these are the only eggs she's ever going to have, so it's important that as many as possible remain viable."
That survival rate compares to 70%, at best, with standard freezing, Smith said, in an interview with Priority Healthcare.
Vitrification doesn't involve ice crystals because eggs are warmed much faster. The transition from a liquid to solid state, and vice-versa, happens "almost instantaneously," Smith explained. "It's almost [like] forming a glass."
Research in Smith's lab often focuses on cell biology, and so he and his colleagues have been studying whether vitrification modifies egg cells detrimentally. But they've gone further than that, as well, assessing whether vitrification negatively impacts fertilization and subsequent embryo development, as well as its effect on pregnancy rates in mice.
Potential Value of Egg Freezing
While some women who undergo certain types of cancer treatment will regain their reproductive function afterwards, others will not, and will become infertile. That's why egg freezing may be an option for these women. It also circumvents ethical objections about embryo freezing, experts say.7
When a woman is ready to become pregnant after cancer treatment, her frozen eggs can then be warmed and fertilized using her partner's sperm. The resulting embryos would then be transferred to the uterus in the same way it's done after embryo freezing, Smith and his colleagues maintain.
To overcome difficulties that sperm have in penetrating the eggs outer wall during IVF, a procedure known as intracytoplasmic sperm injection (ICSI) is used as an alternative. In this technique, the doctor injects a single sperm into the egg, and it tends to have higher success rates, as has been reported in some studies.8
According to Smith, who is also director of the Fertility Counseling and Gamete Cryopreservation Program at the University of Michigan Comprehensive Cancer Center, some 80% of eggs previously vitrified were later successfully fertilized using ICSI. Thirty percent of those have resulted in healthy births. That's comparable, he says, to rates for eggs fertilized using IVF that were not previously frozen.
Hormone-Sensitive Cancers
There are some possible drawbacks to egg freezing, Smith and his associates warn. In order for it to work, only mature eggs must be used, meaning women would have to undergo at least two weeks of hormone treatments to stimulate the body to produce mature eggs. This may be risky for women with cancers fueled by the hormone estrogen, such as breast cancer, some experts contend. Thus, it may be necessary to use immature eggs in this event.8 This might involve harvesting immature eggs, then maturing them in vitro prior to freezing. At the University of Michigan, decisions about egg freezing for these women are discussed beforehand between the patient and her doctor, Smith said.
"There still is concern that we not do exogenous hormone stimulation in women with estrogen-sensitive cancers," he said. But, he says future medical research needs to be done to confirm the assumption that giving synthetic hormones to women with these types of cancers is detrimental.
The hormone treatments also require that the cancer treatment be postponed, which may not be an option for every patient.9
Guidelines Needed
As a result, guidelines about egg freezing for women facing cancer therapy should be established if and when it becomes routine in the clinical setting, Smith explained. "This is a very new technology, and it requires education both of patients and physicians," he said.
A clinical trial to test the feasibility and effectiveness of vitrification in egg freezing versus standard cryopreservation—what Smith terms "slow-rate freezing"—is already underway. University of Michigan investigators are collaborating with researchers in Brazil to test the two methods side-by-side, and involve a group of patients.
"The data hasn't been analyzed yet," Smith told Priority Healthcare. But it appears, so far, that vitrification holds some promise. "I think we have to say that with caution, though, because the study's not done."
1. Simon B, Lee SJ, Partridge AH, Runowicz CD. Preserving fertility after cancer. CA Cancer J Clin 2005 Jul-Aug;55(4):211-28. quiz 263-4.
2. Fertile Hope. Parenthood Options. Available at: http://www.fertilehope.org/resources/preservation_cat.cfm?CID=3#TID20. Accessed September 8, 2005.
3. Van der Elst J. Oocyte freezing: here to stay? Hum Reprod Update 2003 Sep-Oct;9(5):463-70.
4. 13th World Congress on In Vitro Fertilization, Assisted Reproduction, and Genetics. 2005 May 26-29. Istanbul Turkey.
5. Walker DL, Tummon IS, Hammitt DG, Session DR, Dumesic DA, Thornhill AR. Vitrification versus programmable rate freezing of late stage murine embryos: a randomized comparison prior to application in clinical IVF. Reprod Biomed Online 2004 May;8(5):558-68.
6. Rall WF, Fahy GM. Ice-free cryopreservation of mouse embryos at -196 degrees C by vitrification. Nature 1985 Feb 14-20;313(6003):573-5.
7. Tucker M, Morton P, Liebermann J. Human oocyte cryopreservation: a valid alternative to embryo cryopreservation? Eur J Obstet Gynecol Reprod Biol 2004 Apr 5;113 Suppl 1:S24-7.
8. Mavrides A, Morroll D. Bypassing the effect of zona pellucida changes on embryo formation following cryopreservation of bovine oocytes. Eur J Obstet Gynecol Reprod Biol 2005 Jan 10;118(1):66-70.
9. Holzer HE, Tan SL. Fertility preservation in oncology. Minerva Ginecol 2005 Feb;57(1):99-109.
John Martin is a long-time health journalist and an editor for Priority Healthcare. His credits include overseeing health news coverage for the website of Fox Television's The Health Network, and articles for the New York Post and other consumer and trade publications.
