“Uh… I was just wondering… Did the chemo make it so I won’t be able to have kids?”
As my physician readers all know, it’s the question that is asked as the patient is walking out the door that often reflects what is most on his/her mind.
This snippet happened as my 20 year old survivor of metastatic Hodgkin’s Lymphoma was leaving the clinic last week. It raises a very important point… now that pediatric oncologists are curing ¾ of our patients, we have to worry more and more about the harm we do in the process. One of the biggest concerns of my patients (those old enough to care or understand) and their families (no matter how young the patient is) is future fertility. I’ll talk about this in two parts: Part 1 - what the risks are, and Part 2 - what can be done about it.
Part 1: Risks of Infertility
Although we mostly think of chemotherapy and radiation therapy as the primary causes of infertility, there is evidence that some cancers can impair fertility even before treatment. For example, Hodgkin’s lymphoma is associated with impaired sperm production pretreatment in 2 of every 3 male patients. The mechanism for this finding is unclear.
Surgery, radiation, and chemotherapy can all result in reduced fertility in both men and women. Men who require extensive removal of abdominal lymph nodes (bilateral radical retroperitoneal lymph node dissection) universally have nerve damage that results in dry ejaculation (in other words, no ejaculate fluid). Fortunately, such procedures are now rare, and nerve sparing techniques have reduced this risk to less than 10%.
Radiation therapy to the pelvis can impair fertility in a number of ways. Irradiation of the testes is directly toxic to sperm, and doses of 4-20 Gy (the abbreviation for gray, a unit for measuring the amount of radiation delivered) or higher can cause permanent loss of sperm production. Lower doses will cause a transient decrease in sperm production that will recover with time. Interestingly, the Leydig cells, cells of the testis that produce testosterone, are relatively resistant to radiation, so testosterone production (and therefore sexual development and function) will be normal even if no sperm are produced. In women, pelvic radiation can impair fertility not only by killing oocytes (eggs), but also by damaging the uterus, making it difficult to become pregnant, to carry a pregnancy to term, or for the fetus to grow to a normal size (intrauterine growth retardation). Unfortunately, because girls are born with all of the oocytes they will ever have, as girls age, the dose of radiation that causes infertility falls steadily.
Chemotherapy is a major cause of fertility problems in survivors of childhood cancer. Not all chemotherapy is the same, though, which is an important point when counseling patients about their fertility risk. So-called alkylating agents (cyclophosphamide, ifosfamide, busulfan, procarbazine, and others) have the highest rate of gonadal toxicity. Cisplatin, carboplatin, and doxorubicin have an intermediate level of risk, and vincristine, vinblastine, dactinomycin and bleomycin carry a lower risk (see Table 2 here).
As with radiation therapy, in boys the cells that support sperm production (seminiferous epithelium) is very sensitive to chemotherapy, while Leydig cells are relatively resistant, so again, boys may develop normally but fail to produce sperm. Girls are less susceptible to the toxic effects of chemotherapy than boys. Although fertility may be less compromised, premature menopause is not uncommon in girls who receive chemotherapy. Byrne et al found that 42% of women who were treated with radiotherapy and alkylating chemotherapy drugs (such as ifosfamide, cyclophosphamide, and procarbazine) before age 20 had reached menopause by age 31.
All of that sounds pretty grim. It is important to keep in mind, though, that fertility difficulties don’t strike everyone. One of the first patients I took care of as a fellow was a teenaged boy diagnosed with Hodgkin’s Lymphoma, notorious for resulting in infertility both because of the disease and because of the treatment. We talked about his fertility risks, but I warned him not to count on the chemo as birth control. I’m not sure he heard that part, because two years later he came for a follow-up appointment with his girlfriend and their baby!
Next time… Part 2 - what we can do to preserve fertility.