Preserving fertility in cancer survivors

Of the estimated 1.5 million men and women in the United States who will receive a diagnosis of cancer this year, 10 percent are younger than 45 years and 1 percent are less than 20 years of age. Overall five-year relative survival rates for this group are excellent — nearly 80 percent — and ongoing improvement in cancer treatment likely will continue to increase survivorship.

Jani R. Jensen, M.D., of the Division of Reproductive Endocrinology and the Department of Obstetrics and Gynecology at Mayo Clinic in Rochester, Minn., says: "Future fertility is often a primary concern for those newly diagnosed with cancer. More than 75 percent of patients who are less than 35 years of age and childless at the time of their cancer diagnoses desire children in the future. Although cancer therapy can be lifesaving, treatment sequelae can be considerable and may include premature gonadal failure or infertility, thus creating an important quality-of-life issue for these individuals."

Fertility preservation refers to therapies that promote or retain fertility for patients undergoing medical treatments that otherwise could jeopardize future childbearing ability. Dr. Jensen explains that conditions where fertility preservation may be considered include:

• Malignancies
• Autoimmune disorders such as lupus erythematosus
• Certain hematologic disorders such as vasculitis or aplastic anemia
• Any other medical condition where the disease itself or its long-term management may impair fertility

Risk of permanent reproductive damage varies with the type, dose and site of therapy rendered, as well as the patient's age at the time of treatment.

In general, noncell cycle specific types of chemotherapy, such as alkylating agents (for example, cyclophosphamide), have the highest risk of causing permanent gonadal damage. Likewise, pelvic irradiation poses a greater risk of gonadal damage than does irradiation to distant sites.

Options for fertility preservation vary by age and sex. Dr. Jensen continues: "Prepubertal males and females have limited options, primarily the collection and cryopreservation of gonadal tissue. The goal for later use is to autologously transplant the tissue or thaw it and perform in vitro maturation of immature gametes for use with in vitro fertilization."

Both of these approaches should be considered experimental. Although there are rare case reports of births after partial or whole ovary transplantation, to date there are no reported live human births from immature gametes retrieved from cryopreserved gonadal tissue.

One of the most familiar and long-standing fertility-preservation strategies is sperm banking for postpubertal males. Cryopreserved sperm can be used years — even decades — after initial storage, for either insemination into a female partner or with in vitro fertilization.

Embryo or oocyte cryopreservation

Cryopreservation of oocyte or embryo

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Postpubertal females may elect to undergo embryo or oocyte cryopreservation, processes that require two to three weeks to complete. Dr. Jensen notes: "Preserving unfertilized oocytes is a relatively new technique and may be an attractive option for single women who choose not to use donor sperm to create embryos."

Although the first human birth from cryopreserved oocytes was in the mid-1980s, it was not until the past decade that the technique was improved enough to make it a viable treatment option. Initial work with oocyte cryopreservation was hampered by technical difficulties, such as cytoplasmic rupture during freezing and artificial activation of the mitotic spindle, causing the oocyte to act as if it were already fertilized and thus be resistant to actual sperm fertilization.

With recent technical improvements, more than 70 percent of oocytes can now survive the cryopreservation process, and pregnancy rates — although lower than with conventional in vitro fertilization — are reasonable.

For cryopreservation of either the oocyte or the embryo, exogenous human gonadotropins (typically, a combination of follicle-stimulating hormone and luteinizing hormone) are administered for approximately 10 to 12 days.

During this time, growth of ovarian follicles is monitored with serial estradiol determinations and ultrasonography to measure follicular growth. When follicles are large enough to contain mature oocytes, human chorionic gonadotropin is given to mimic the natural preovulatory surge of luteinizing hormone, which causes the maturing oocytes to resume meiosis and prepare for ovulation.

Shortly before the anticipated ovulation, the oocytes are retrieved under light anesthesia with a needle attached to a vaginal ultrasonographic probe. For oocyte cryopreservation, the mature eggs are cryopreserved immediately; for embryo creation, mature oocytes are combined with sperm.

After fertilization is confirmed by the presence of two pronuclei (representing the genetic material of the sperm and egg), the embryos are cryopreserved. In either case, the oocytes or embryos can be used months or even years in the future.

Dr. Jensen concludes: "For patients facing certain serious medical conditions, fertility preservation may provide a way to create future genetic children, a goal that may otherwise be unattainable."

Patients considering fertility preservation should be counseled that time is of the essence and, where possible, fertility preservation should be initiated before receiving chemotherapy or any other fertility-jeopardizing treatment.

The experimental nature of some fertility-preservation strategies also should be explained to patients, and individualized risk-benefit counseling that takes patient prognosis into account should be performed before making a final decision regarding fertility preservation.