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Life After Cancer A Roadmap for Cancer Survivors

Infertility
Mitchell Rosen, MD and Ernest H. Rosenbaum, MD

Introduction
Cancer Therapy and Reproduction
The Psychological Impact of Infertility



Introduction
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Infertility has been a common problem for those who have had cancer and cancer therapy. In recent years, improvements in cancer treatments have been developed to both prolong life and reduce the risk of infertility. New treatment options are making fertility a possibility for many cancer survivors.

There is evidence to suggest that pregnancy after cancer treatment does not increase a breast cancer survivor's risk of recurrence or shorten her life. It is wise for breast cancer patients to wait two years after completing their cancer treatment before trying to conceive a child, as that is the highest risk period for breast cancer recurrence. An infertility consultation should be considered.

If the proper steps are taken before treatment to preserve fertility, surgery and radiation therapy have not been shown to affect a breast cancer survivor's ability to conceive a child or to have a normal child. Chemotherapy, however, may cause amenorrhea (loss of periods) and an increased possibility of infertility. Breast cancer patients should consult with their physicians about their future pregnancy plans before starting cancer treatments.

The human reproductive system is complex and unique for both genders. The reproductive system is affected by many cancer related therapies with the end result of difficulty conceiving. Cancer therapy effects to fertility will depend on the patient's age, type of cancer, and method of treatment.

Reproduction system
The reproductive axis is made up of the pituitary gland (under the brain) the gonads (ovaries or testes), and the reproductive tract; vagina-uterus-fallopian tubes in women, and epididymis-vas deferens- penile urethra and glands in men. In the man, the seminal vesicles and prostate are the major glands responsible for semen production.

Women
A woman's oocytes (eggs) are completely formed during fetal development and are stored in a resting pool in her two ovaries. After birth, the oocytes do not regenerate but rather decline with age and when depleted result in ovarian failure (menopause). The oocytes continually leave the resting pool, enter the growth phase and die. When a woman reaches puberty, a complex cyclic process begins--the menstrual cycle--which rescues one of the oocytes from death and causes ovulation which culminates in either pregnancy or a menstrual period. The ovulatory cycle continues until menopause, which occurs on average at 51 years of age.

Men
In contrast to the female reproductive system, sperm production is initiated at puberty and continues throughout life. The testes contain stem cells which continually replenish the sperm pool. The ability to produce sperm is dependent on adequate amounts of hormones FSH, LH (from the pituitary gland) and testosterone from the testes. The sperm are stored in the epididymis glands (a reservoir near the prostate) until ejaculation. During intercourse, the sperm is transported through ducts along with secretions from the glands and is ejaculated through the penile urethra. The testes also produce testosterone which controls sex drive and the ability to achieve an erection.

Cancer Therapy and Reproduction

Cancer Therapy and Reproduction
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Cancer therapies can cause a spectrum of damage to the reproductive axis. The damage may be severe and result in sterility (ovarian/testicular failure) or partial injury resulting in early menopause and infertility (inability to conceive within 12 months). Symptoms of ovarian failure include absence of menses, hot flashes, and vaginal dryness. Testicular failure can lead to loss of sex drive and ejaculation or erection difficulties.
The treatments for cancer that can affect the reproductive system include:
surgery on the reproductive organs
chemotherapy
radiotherapy to abdomen and pelvis

Surgery
Operations for cancer that do not involve the functionality of the reproductive axis do not affect a woman's ability to achieve pregnancy. However, if the operation involves removing parts of the reproductive system it may cause sterility/infertility. For example, gynecological cancer may require the removal of the uterus (a hysterectomy); ovaries (a bilateral oophorectomy); or some portion of the reproductive tract such as the cervix, vulva or vagina. The surgery that is performed will depend on the type of cancer and whether it has spread to other organs.

For a man, surgery may involve removing both testicles (a bilateral orchiectomy), which will result in sterility.

Chemotherapy
Chemotherapy targets tissues with actively dividing cells'such as skin, hair, digestive tract and the ovaries and testes. The sperm and supporting cells of the oocyte are dividing during development. Therefore all chemotherapies are potentially damaging to the ovaries and testes, and may reduce the number of oocytes and sperm. Whether chemotherapy results in infertility depends on the patient's age, the type of chemotherapeutic drugs used, and the dosage of drugs given.

Alkylating chemotherapy agents are most harmful to oocytes. In one study, 42% of women treated with this type of chemotherapy were in premature menopause by the age of 31, although some returned to normal menses. However, having normal periods does not mean a woman is fertile.

In men, alkylating agents are similarly most harmful to sperm production. However, in contrast to women, the testosterone producing cells (Leydig cells) are more resistant to chemotherapy. Therefore, sterility may not be readily apparent.

Radiation
The gonads (testes/ovaries) can be temporarily or permanently damaged by radiation therapy. The severity of damaging effects relates to the dose of therapy, the number of treatments, location of the radiation field, and patient age. In contrast to chemotherapy, prepubertal age provides no protection against radiation effects to the reproductive system for men.

The factors of radiation therapy mentioned above affect the number of oocytes remaining in the resting pool and stem cells in the testes. The dose that causes ovarian failure is dependent on age. In younger women, more oocytes are present. Therefore, for a given dose of radiation young women will have less chance of menopause compared to older women. In several studies, the incidence of ovarian failure was over 70% regardless of doses over 2000 cGy. In other studies, this failure has occurred with doses as low as 300 cGy.


The Psychological Impact of Infertility
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Infertility can be an emotionally devastating experience for anyone, especially for premenopausal women as well as men. For survivors, the possibility of infertility adds an additional burden to the many challenges created by both the short- and long-term side effects of therapy, and the potential for recurrence or a new cancer.

Those fortunate enough to be able to conceive after cancer treatment experience a greater sense of a normal life. Fertility is a high priority despite the risks, making it possible to be a parent and watch one's progeny grow and develop, one of the most valued and coveted of life's experiences. Recent studies have shown that pregnancy does not increase the risk of stimulating breast cancer growth or cancer recurrence.

If success cannot be achieved, adoption is often considered, although this approach also presents costs, both fiscal and emotional, in the struggle to find a suitable baby. For many, adoption does not satisfy their desire to sustain the family/genetic life history.

Another option is the third-party approach using a gamete [fertilized ovum (egg)] and surrogacy with someone else carrying the baby. Alternatively, a cancer survivor may consider using a donated egg and/or sperm. Some religions, such as Roman Catholicism and Islam, are against third-party reproduction.

To have one's own biological child through use of current advanced technology is becoming a potentially more accessible approach.

To preserve fertility, the most important step is for the patient to discuss his or her concerns with their doctor. If possible, alternatives of treatment, such as different chemotherapeutic agents or radiation exposure, may help decrease the incidence of infertility. Before beginning treatment, discuss alternative options for fertility preservation. The most effective methods are prior to cancer treatment. ASCO has written guidelines for fertility preservation, available from your doctor or the ASCO website.

Males
Men have the well-established option of freezing (cryopreserving) sperm for later use. An experimental option for prepubertal boys is cryopreserving testicular tissue for future transplantation.
Females

For women, there are a number of strategies for preserving fertility.

1. Embryo cryopreservation
The most well established option is embryo cryopreservation. It is a common technique used with couples to overcome cases of infertility. It is only available for females that have experienced puberty and have a partner or are willing to use donor sperm. The success rate depends on the female's age and number of oocytes recovered from the ovary. The process entails a 2-6 week time commitment and should be performed prior to the initiation of cancer treatment. It begins with ovarian stimulation, which allows for multiple oocytes to be produced. The oocytes are collected by a minor surgical procedure, fertilized and stored (cryopreserved) for later use. When ready for pregnancy, the embryos are thawed and transferred into the uterus.
2. Oocyte preservation
If no partner is present, or the use of donor sperm is not preferable, oocytes may be cryopreserved. However, this is experimental and should only be performed under the supervision of an institutional review committee. The process of obtaining the oocytes is similar to undergoing embryo cryopreservation. However, the oocyte is not fertilized, and is stored for later use. When the patient is ready, oocytes are thawed, fertilized and the embryos created are transferred.
3. Ovarian cryopreservation (tissue freezing)
This procedure entails a surgical procedure to remove part or all of the ovary, and cryopreserving the tissue. It does not require ovarian stimulation or a partner, and is an option for prepubertal patients. However, it is experimental and should only be performed under the supervision of an institutional review committee. Therefore, it is not widely available or accessible to patients at this time.

If fertility preservation was not performed, and pregnancy was desired after treatment, spontaneous conception is possible depending on multiple factors (i.e., type and dose of chemotherapy, age, etc). Cancer survivors unable to use their own eggs may achieve pregnancy from eggs or sperm that are donated.
4. Ovarian suppression
Premenopausal women receiving chemotherapy may have some fertility (egg) preservation success by injections of GnRH agonists (lupron). This is still investigational.
5. Ovarian transposition
For patients receiving pelvic radiation, the ovaries can be surgically moved out of the radiation field.


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First appeared December 18, 2007; updated August 2, 2008