Cancer Treatment and Infertility
This page discusses whether cancer treatment can cause infertility.
See also the separate discussion of pregnancy and cancer.
Certain types of cancer treatment, including surgery, radiation therapy and chemotherapy, can cause infertility in cancer patients. This can range from a slight impairment of fertility, making it more difficult to conceive, to complete infertility. The duration of infertility may vary from temporary to permanent, with temporary infertility lasting from months to years.
Infertility can be caused by surgery involving the reproductive system and by certain types of adbominal surgery.
Surgery involving the reproductive system can affect fertility. Bilateral orchiectomy (removal of the testes) and bilateral oophorectomy (removal of the ovaries) eliminate the ability to produce sperm and ova. When only one testicle or ovary has been removed, the remaining organ is usually capable, assuming it was not affected by further treatment. (However, some studies in the literature suggest that unilateral oophorectomy may impair the function of the other ovary, but the risk of infertility seems to be pretty low.) A woman who had both ovaries removed but who retained the uterus may be able to carry a baby to term with medical assistance, but may want to consider surrogacy as an alternative. A women who has undergone a hysterectomy, where the uterus is removed, can no longer become pregnant.
Certain types of abdominal surgery can also cause infertility. These include:
Radiation therapy can cause infertility in both men and women.
Direct irradiation of the testes and ovaries can cause infertility. Permanent infertility can be caused by irradiation of the testes with fractionated doses of 2 Gy and higher and the ovaries at 6 Gy and higher, according to Howell [1998, 2002]. Wallace [2003, 2005] found that women over age 40 at the time of treatment may suffer from permanent ovarian failure at doses as low as 4 Gy.
Radiation therapy induces infertility in women by destroying immature oocytes. As such, any exposure to radiation therapy will permanently reduce the number of oocytes, with an exposure of 2 Gy cutting the number of oocytes in half. Since the number of oocytes declines with age, older patients will be more likely to become infertile from radiation therapy than younger patients.
Direct irradiation of the testes is normally only done to irradicate carcinoma-in-situ while preserving normal hormonal function. This is much more common in Europe than in the United States. In the US the main risk of infertility is from scatter radiation absorbed by the testes.
Temporary male infertility can be caused by fractionated doses as low as 0.1 Gy. Even when the testes are protected by a clamshell shield, scatter radiation can still cause infertility. However, in most cases the scatter radiation will be less than 0.09 Gy (para-aortic field) and 0.32 Gy (hockey stick/dog leg field), so any radiation-induced infertility is likely to be temporary in nature.
Recovery of spermatogenesis after low dose radiation exposure takes anywhere from 6 months to two years. The higher the dose, the longer the interval until recovery of spermatogenesis. Howell 2005 reports that it will take 1-2 years for recovery of spermatogenesis after exposure to a fractionated dose of between 0.2 Gy and 0.7 Gy. (Note that fractionated doses are more likely to cause infertility than the same total dose given as a single dose.)
Radiation therapy for prostate cancer can cause erectile dysfunction in as many as 70% of patients.
Certain chemotherapy drugs can cause infertility. This is especially true for chemotherapy used to treat testicular cancer, Hodgkin's disease, leukemia and lymphoma, sarcoma, lung cancer, breast cancer and ovarian cancer.
In men, chemotherapy can affect sperm motility and reduce the number of sperm cells to subfertile levels (less than 20 million sperm per mL). If the sperm are eliminated entirely, the infertility may be permanent.
The term 'azoospermia' is sometimes used to refer to a complete absense of sperm and sometimes to an extremely low sperm count, typically less than 500,000 sperm per mL. So if your doctor says you are azoospermic, ask him for your actual sperm concentration.
Chemotherapy and hormone therapy can also cause infertility in women by damaging the ovaries and affecting the levels of hormones produced by the ovaries. This can lead to irregular menstrual periods, amenorrhea or even premature menopause. The menopause may be temporary or permanent.
The greatest risk of infertility caused by chemotherapy is with alkylating agents, such as carmustine (BCNU, BiCNU, Bicnu, Gliadel), busulfan (Busulfex, Myleran), chlorambucil (Leukeran), cisplatin (Platinol), cyclophosphamide (Cytoxan, Neosar), cytarabine (ARA-C, Cytosar-U, DepoCyt), ifosfamide (IFEX), lomustine (CCNU, CeeNu), mechlorethamine (Mustargen, Nitrogen Mustard), melphalan (Alkeran, L-Pam), streptozocin (Zanosar), temozolomide, thiotepa (Thioplex) and vincristine. Other chemotherapy drugs, such as adriamycin (Doxorubicin, Rubex), procarbazine (Mutalane) and vinblastine (Velban), may also affect fertility. These drugs may be included in combination chemotherapy, such as MOPP (mechlorethamine, vincristine, procarbazine, and prednisone) for Hodgkin's Disease. Carboplatin has been found to be less toxic than cisplatin.
The risk of infertility from chemotherapy is generally dose-dependent. Among women, age may also be a risk factor for chemotherapy-induced infertility.
Relevant journal articles include:
Certain types of cancer are associated with a higher rate of infertility than in the general population even before treatment. For example, testicular cancer and thyroid cancer are often associated with impaired fertility.
Since it can take several years for fertility to return after cancer treatment, it is generally a good idea for men to bank sperm before any treatment that may affect fertility, such as abdominal surgery, abdominal/pelvic radiation therapy, and chemotherapy. Cryopreserved sperm can be stored indefinitely; the longest known interval before use resulting in a baby was 21 years (Horne 2004).
Likewise, women should discuss fertility with their oncologists before undergoing treatment, and may wish to consider cryopreservation of ova or fetuses or ovarian tissue or other methods of preserving fertility. Harvesting ova is a more complicated and time-consuming process than banking sperm, and is still somewhat experimental.
Often a decision about cryogenic preservation has to be made very quickly, before the start of chemotherapy or radiation therapy. Usually one does not want to delay the start of treatment, so there is a small window in which the samples can be collected.
Depending on the type of chemotherapy, it may be possible to safely collect sperm samples up to 2-3 weeks after the start of chemotherapy. It is, however, recommended that sperm banking be completed before the start of chemotherapy. It is usually not advisable to delay chemotherapy in order to complete sperm banking.
Unfortunately, only about half of oncologists discuss the risk of infertility with affected cancer patients, so many cancer patients aren't aware of the fertility risks until their options are more limited. Only about a quarter of at-risk male cancer patients bank sperm. The most common reasons for failing to bank sperm include:
Sperm banking typically costs around $1,000. Freezing embryos and ova can cost as much as $8,500. Annual storage fees for frozen sperm, embryos and ova range from $200 to $400.
Although many health insurance policies cover infertility treatment, most health insurance policies do not cover the cost of cryopreservation. The excuse given is that the policies are limited to treating an existing illness or injury, not a future condition, and cryopreservation is at best prophylactic in nature. (Fifteen states -- Arkansas, California, Connecticut, Hawaii, Illinois, Louisiana, Maryland, Massachusetts, Montana, New Jersey, New York, Ohio, Rhode Island, Texas and West Virginia -- require insurance companies to cover infertility diagnosis and treatment. In California, Connecticut and Texas, however, the insurance company is only required to offer coverage; your employer must ask for it to be included in the policy. None of these states, however, require insurance companies to cover cryopreservation.) If you are unable to afford the cost of cryopreservation, consider talking to your employer's human resources office, as they may be able to help.
Fertile Hope is a nonprofit organization that provides discounts on cryopreservation services for newly diagnoses cancer patients.
Cancer patients who pursue cryopreservation should have an attorney draft a document concerning the disposition of the preserved genetic material in the event of the cancer patient's death. If the cancer patient wishes to allow his or her spouse to use the genetic material posthumously, this must be explicitly addressed. There are several court cases in the literature in which the surviving spouse has been prevented from using the preserved sperm or ova because of questions about whether the deceased would have consented to the use. Only the individual who produced the cryopreserved gametes (sperm, ova, embryos) can consent to their use. Spouses have no rights to the banked specimens. In addition, the cancer patient's will should explicitly address the status of any children produced posthumously, as these children will likely be considered legal offspring of the deceased.
Cancer survivors may need to wait six months to a year after the end of treatment before trying to conceive, to give enough time for fertility to recover and for any residual chemotherapy to reach subtherapeutic levels. They should be patient, as it may take several years for recovery of spermatogenesis.
Various studies in the literature report intervals to recovery of spermatogenesis ranging from 6 months to 5 years. If spermatogenesis does not recover within 5 years, the infertility is likely to be permanent.
Generally, if a cancer survivor recovers fertility, there is no increased risk of birth defects so long as the survivor is not on any long-term medications such as hormonal therapy.
There have been some reports that hormonal therapy can help stimulate the recovery of spermatogenesis. Most of the research has focused on the use of gonadrotropin-releasing hormone (GnRH) and testosterone agonists to suppress intratesticular testosterone levels. (See Meistrich 2003.)
If fertility does not return after the end treatment, one can consider using AI (artificial insemination), IVF (in vitro fertilization), ICSI (intracytoplasmic sperm injection), fertility cycle enhancement, surrogacy and other common fertility treatments. ICSI allows even poor quality cryopreserved spermatozoa to result in pregnancy. ICSI has also be used to achieve pregnancies using spermatozoa retrieved by testicular biopsy from an azoospermic patient.
There is some concern that taking infertility drugs, such as clomiphene citrate, for more than a year may increase the risk of ovarian cancer. But it is not yet clear whether the risk is associated with the drug or with the subset of the general population that seeks fertility treatment. For example, one study found that only infertile women who failed to become pregnant had a significantly increased risk of ovarian cancer; women who used the drugs and became pregnant were not at increased risk. There are also several studies that contradict these results, finding that use of drugs to induce ovulation does not increase the risk of ovarian cancer.
If a male survivor is suffering from true azoospermia or a female survivor underwent bilateral oophorectomy, and did not pursue cryopreservation, using donated sperm and/or ova is a possibility. The donated gametes are usually matched to the prospective parents' ethnicity, hair and eye color.
If all else fails, the cancer survivor can consider adoption.
However, many adoption agencies will be reluctant to place a child with a cancer survivor because of concerns about the possibility of a relapse. Even cancer survivors who are more than five years since the end of treatment will face resistance.
For this reason, cancer survivors who are interested in adoption should hire an attorney to handle the adoption for them. This will distance the couple from any questions concerning health. Cancer survivors should also consider private placements or international adoption.
Copyright © 2005-2009 by Mark Kantrowitz. All rights reserved.
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