CancerPoints

Cancer Treatment and Infertility

 

This page discusses whether cancer treatment can cause infertility. See also the separate discussion of pregnancy and cancer.

Can Cancer Treatment Cause Infertility?

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 Caused By Surgery

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:

  • Abdominal Perineal Resection (APR), where part of the colon and rectum are removed.
  • Prostatectomy, where the prostate is removed.
  • Retroperitoneal Lymph Node Dissection (RPLND), where the lymph nodes at the back of the abdomen are removed.
  • Radical Cystectomy, where the bladder and prostate are removed.
  • Pelvic Exenteration, where the entire female urogenital system is removed, including the uterus, cervic, ovaries, vagina and bladder.
For example, a RPLND for testicular cancer can cause retrograde ejaculation, preventing the sperm from traveling in the right direction. A prostatectomy for prostate cancer can also cause impotence (erectile dysfunction) by injuring nerves and arteries. Infertility can be caused by any surgery involving the urogenital system and the nerves around the rectum, pelvic floor and abdominal aorta. Modern nerve-sparing surgical techniques can minimize the risk, but there is still a risk, especially if the surgery is performed after chemotherapy or radiation therapy.

Infertility Caused By Radiation Therapy

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.

Infertility Caused By Chemotherapy

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:

  • Huddart 2005 reports that among testicular cancer survivors, 77% were successful at fathering children without infertility treatment, and an additional 5% with infertility treatment, for an overall success rate of 82%. Among testicular cancer patients undergoing chemotherapy, the overall success rate was 71%, and among those undergoing both chemotherapy and radiation therapy, the overall success rate was 67%. These compare with overall success rates of 82% for just radiation therapy and 85% for surveillance.
  • Huyghe 2004 reports that 91.2% of testicular cancer patients who had tried to get their partners pregnant prior to diagnosis succeeded, while only 67.1% succeeded after treatment (with three years of follow-up). Conception rates were lower for radiation therapy than for chemotherapy.
  • Spermon 2003 reported that before treatment for testicular cancer, 66% of couples were able to conceive within one year, while after treatment 43% succeeded in conceiving within one year. There was no increase in birth defects among pregnancies.
  • Ferreira 1991 reported that of men undergoing unilateral orchiectomy, approximately half had subfertile sperm counts, regardless of the reason for the orchiectomy.
  • Jacobsen 2001 reports that it can take a year after orchiectomy for spermatogenesis to improve.
  • According to Rustin 1984, 79% of women receiving cyclophosphamide for gestational trophoblastic tumours succeeded in having a live birth, compared with 88% of those receiving agents other than cyclophosphamide. All received methotrexate.
  • Pryzant 1993 reported dose-dependent impairment of spermatogenesis among men receiving cyclophosphamide for non-Hodgkin's lymphomas.

Does Cancer Cause Infertility?

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.

Preserving 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:

  • Lack of knowledge about the fertility risks and the availability of cryopreservation.
  • Misinformation about the costs of sample collection and storage fees.
  • Confusion concerning the number of samples required to make cryopreservation worthwhile.
  • Embarrassment.
  • Insufficient time to collect samples before the start of therapy.
  • Lack of facilities for cryopreservation.

Cost of Cryopreservation

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.

Legal Considerations Associated with Cryopreservation

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.

Recovery and Restoration of Fertility

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.

  • Ragni 2005 reported recovery of spermatogenesis in 82% of men who were azoospermic at the time of cancer diagnosis.
  • Howell 2005 reported that cisplatin-based chemotherapy results in temporary azoospermia, with 50% recovering spermatogenesis in 2 years and 80% after 5 years. (Lampe 1997 reported 48% by 2 years and 80% by 5 years.) They also indicated that recovery after radiation therapy is dose dependent.
  • Dubey 2000 found that among patients treated for Hodgkin's disease with chemotherapy followed by radiation therapy, 96% recovered normal spermatogenesis within 18 months. Other studies reported permanent impairment of spermatogenesis, depending on the type of chemotherapy.
  • Pedrick 1986 reported 66% recovering fertility within 18 to 26 months following pelvic irradiation, and 88% recovering fertility after 26 months.
  • Kreuser 1989 reported recovery of spermatogenesis in 77% of testicular cancer patients treated with chemotherapy within 25-60 months after the end of treatment.
  • Kader 1991 found that FSH levels were predictive of recovery of spermatogenesis (i.e., a fall in FSH levels during the second year after the end of treatment among patients with initially elevated levels).
  • Hansen (Petersen and Hansen 1994, Hansen 1990) found that FSH levels were elevated in 86% of patients receiving chemotherapy, but only 11% of patients on surveillance; LH was elevated in 59% and 11%, respectively.

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.)

Ferility Treatments

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.

Adoption

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.

Cancer/Infertility Resources

References

Web Sites

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