Fertility Preservation

Fertility preservation is the effort to help cancer patients retain their fertility, or ability to procreate. Research into how cancer affects reproductive health and preservation options are growing, sparked in part by the increase in the survival rate of cancer patients.

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Infertility

Infertility, the inability to achieve or maintain pregnancy after one year of intercourse, can decrease sense of self-worth and satisfaction with life. Causes include (in men) the cessation of sperm production, (in women) the cessation of egg release by ovaries, or other maladies with the reproductive organs and hormone release.

Treatment-related reproductive insufficiency

Chemotherapy and radiation treatments for cancer and other serious illnesses can affect reproductive health. Radiation to the pelvic area and chemotherapy containing alkylating agents, such as cyclophosphamide, ifosfamide, nitrosoureas, chlorambucil, melphalan, busulfan, and procarbazine, threaten ovarian and testicular function. These regimens attack rapidly dividing cells in the body, including healthy cells like sperm and those belonging to the ovarian follicle (egg). Depending on the dose and duration of administration, these therapies can have varying effects on reproductive health. Surgery involving reproductive tissue affects reproductive function and fertility.

The ovary holds a finite number of follicles, each of which contains the female germ cell, the oocyte. Both a pool of follicles selected for maturation and a reserve of dormant immature follicles can be found in the ovary. Immature follicles carry the potential to be matured and fertilized and, thus, determine a woman’s reproductive capacity. Every month, a mature egg is released from an ovary into the fallopian tube, where it can be fertilized in the presence of sperm. A change in the number of available follicles that can undergo this process can significantly impact reproductive function. Acute ovarian insufficiency, which affects the reservoir of maturing follicles without damaging the dormant, immature follicle pool, is a temporary condition after which the woman may regain normal ovarian function. Chronic ovarian insufficiency affects the dormant reserve of immature follicles, effectively damaging cells that can be matured and fertilized; this condition frequently leads to infertility.

Males have testes that store male germ cells, or sperm. Unlike in the ovary, however, the male germ cell pool is constantly regenerating. Men who experience reproductive insufficiency may have reduced sperm cell counts and impaired sperm cell motility.

For many cancer patients, the decrease or loss of reproductive function is temporary; many men and women, however, do not regain fertility after cancer treatment. Patients undergoing serious radiation, chemotherapy, or surgery sometimes experience symptoms resembling menopause (in women) or andropause (in men), which indicate reproductive damage. In women, decreased estrogen levels as a result of ovarian deficiency lead to weakened bone, changes in temperature control, altered mood, and decreased sexual desire. Men with testicular insufficiency also experience similar symptoms.

Symptom management

Reproductive insufficiency can affect health. Thus, it is particularly important for patients experiencing temporary or permanent treatment-related reproductive damage to maintain a healthy lifestyle that includes a balanced diet, regular exercise, and a network of social support. Some men and women experiencing the symptoms of early menopause or andropause consider hormone replacement therapy (HRT) as a method for compensating for the drop in androgen or estrogen levels, respectively. Current research is focused on finding the most effective combinations of hormones for the management of symptoms related to these disorders.

Research

New research has been launched to improve methods for preserving the fertility options of cancer patients, striving to provide any person diagnosed with a fertility-threatening disease the option of saving his or her reproductive ability before treatment. The goal of this research and scholarship is to develop technologies for storing patients' reproductive tissue, which can later be used to begin pregnancy. Additionally, these new methods may provide reproductive options to patients with other fertility-impairing diseases in the future.

Options

Men hoping to preserve their fertility before undergoing treatment for cancer or another fertility-threatening disease can cryopreserve, or freeze, their sperm, which can be obtained through masturbation in post-pubescent boys and men. This is the most established fertilty preservation method for males. For pre-pubescent boys, sperm can be obtained through testicular aspiration or electrostimulation and then stored for future use. Researchers are also looking at methods for cryopreserving testicular tissue samples so that they can be re-implanted into the body after treatment.

Fertility preservation options for women are more limited than for men. Some female patients choose to have mature eggs extracted and fertilized outside of the body with sperm from a partner or donor. The resulting embryo is then frozen until the woman is in remission from disease. When the woman is ready to initiate pregnancy, the embryo is thawed and implanted into the uterus for maturation and birth. While this option is the most common fertility preservation method in women, it is not available to pre-pubescent girls, who do not have mature eggs that can be fertilized. Women who do not have a partner will need to use donor sperm. Additionally, because this procedure requires a two-week period of hormonal stimulation to encourage egg maturation, it is not optimal for female patients who are diagnosed with hormone-sensitive cancers (such as breast cancer, ovarian cancer, etc) or those who cannot delay cancer treatment. Alternative methods of hormonal stimulation using letrozole or tamoxifen may be used for women with hormone-sensitive cancers.

New fertility preservation techniques are being developed that will allow women undergoing fertility-threatening treatment to store their unfertilized eggs or strips of their ovarian tissue containing unfertilized eggs, which can later be retrieved for the intiation of pregnancy. Currently, frozen mature eggs have a low survival rate but over 500 babies have been born worldwide from frozen eggs. Immature eggs are more tolerant of cryopreservation conditions but still cannot be effectively matured outside of the body. Thus far, this has generated two live births in mice, and scientists are working to translate these methods to humans. Strips of cortical ovarian tissue can also be cryopreserved, but it must be re-implanted into the body to allow the encapsulated immature follicles to complete their maturation. Furthermore, ovarian tissue is fragile under hard freezing conditions and putting it back into the body carries the risk of re-introducing cancerous cells. While this procedure has generated 5 live human births, techniques for the storage of this tissue are still being perfected.

Third-party reproduction

Many patients diagnosed with a malignancy or another disease requiring treatment that may impair their fertility consider alternatives to bearing biological children, such as assisted reproductive technology (ART) using in vitro fertilization (IVF) with donor eggs or donor sperm. The resulting embryo can be implanted into the woman's uterus after her endometrium (the lining of the uterus) is stimulated with hormones to prepare for the development of the embryo.

References

• Bahadur, G. (2000). "Fertility Issues for Cancer Patients". Molecular and Cellular Endocrinology 169: 117-122.

• , American Society for Reproductive Medicine, 1996

• Howell, S.J.; S.M. Shalet (2005). "Spermatogenesis After Cancer Treatment: Damage and Recovery". Journal of Natural Cancer Institute Monographs 34: 12-17.

• Lawrence, N.M. (2004). "What is the best approach to ovarian failure?". Contemporary OB/GYN: 46-55.

• Lee, S. J.; Leslie R. Schover, Ann H. Partridge, Pasquale Patrizio, W. Hamish Wallace, Karen Hagerty, Lindsay N. Beck, Lawrence V. Brennan, Ktuluk Oktay (2006). "American Society of Clinical Oncology Recommendations on Fertility Preservation in Cancer Patients". Journal of Clinical Oncology 24: 1-11.

• Mayo Foundation for Medical Education and Research (2007), , MayoClinic.com,

• Magelssen, H.; M. Brydoy, S.D. Fossa (2006). "The effects of cancer and cancer treatments on male reproductive function". Nature Clinical Practice Urology 3: 312-322.

• Petak, S. M. (2002). "American Association of Clinical Endocrinologist Medical Guidelines for Clinical Practice for the Evaluation and treatment of Hypogonadism in Adult Male Patients - 2002 Update". Endocr Pract 8: 440-456.

• Woodruff, Teresa Kaye; Karrie Ann Snyder (2007). Oncofertility: Fertility Preservation for Cancer Survivors (Cancer Treatment and Research). Chicago: Springer. ISBN 978-0387722924.