As cancer therapy continues to improve and more patients survive, they are experiencing more late adverse effects. Some of those—such as infertility—can be life altering.
Not long ago, I met with a young man who had a liver tumor. I explained to him that his therapy would involve three chemotherapy drugs that put him at moderate risk for future infertility. Although he was only 14 years old, this patient had an immediate and visceral response.
“No chemo without preservation,” he said.
Fertility was obviously an important topic to him. So, with his assent and his father’s consent, we arranged for the collection and banking of his sperm before treatment began.
We also had a 16-year old female with a sarcoma who was concerned about her fertility. She completed oocyte cryopreservation, with retrieval of 35 oocytes. We were able to address the fertility concerns for both of these patients without delaying their therapy.
Their risk of infertility was linked to the very therapy required to save their lives: chemotherapy, radiation and surgery. The latter can affect females’ fertility directly by removal of the reproductive organs or indirectly through damage to the pelvic nerves or adhesions affecting the ovarian and fallopian tube function. In males, spermatogenesis starts at age 12 to 14 and continues throughout life. The germinal epithelium has a high mitotic rate, which is sensitive to the effects of radiation and chemotherapy.
The chemotherapies that put patients at the highest risk for fertility issues are alkylating agents. Radiation risk depends on multiple factors, including the location and the dose. All doses of total body irradiation increase risk of infertility. Cranial radiation doses greater than 40 gray (Gy) are associated with an increased risk, as is radiation to the hypothalamus and pituitary.
Data from the Childhood Cancer Survival Study showed that male survivors, ages 15 to 44, were less likely to sire children than their healthy siblings. Those who received testicular radiation doses of more than 7.5 Gy were less likely to sire pregnancies compared with those who did not receive testicular radiation. Other reports even mentioned doses as low as .1 Gy causing low spermia and doses as low as .35 Gy causing reversible azospermia.
Females are also at risk for adverse effects. Women have a finite number of unrenewable germ cells, and some patients can have treatment that causes damage to the oocyte. As the radiation dose increases, the number of patients with acute ovarian failure increases, with doses greater than 20 Gy resulting in over 70% of patients developing acute ovarian failure. Premature menopause is another side effect of treatment that can lead to early and often unexpected loss of reproductive potential, as well as cessation of ovarian sex hormone production.
The Childhood Cancer Survival Study included 5,149 female participants and 1,441 of their female siblings. The relative risk for those survivors ever being pregnant was .81 compared with their female siblings. Survivors had a higher incidence of non-surgical, premature menopause at 8% versus siblings at .8%. Early menopause may lead to osteoporosis, death from cardiovascular disease and psychosexual dysfunction.
In light of these risks, the role of the oncologist and the health care team is crucial. Research indicates that patients are interested in discussing fertility preservation.
These conversations can ultimately reduce distress and improve quality of life. The discussions should happen as early as possible. If patients are experiencing any kind of distress about potential infertility, we should refer them to reproductive specialists and psychosocial providers. We should also encourage patients to take part in fertility-related registries and clinical studies. And then, we should encourage the use of established methods of fertility preservation—such as semen cryopreservation and oocyte cryopreservation—for postpubertal minor children. Fertility preservation for prepubertal patients are still under investigation.
Although there's much guidance advocating semen cryopreservation, the number of men who choose to store semen is low. And even for those who store a sample, the number of patients who subsequently use their sample is also low.
For postpubertal females who choose oocyte cryopreservation, the survival rate of the cryopreserved oocytes is around 90%. The clinical pregnancy rate from the thawed oocytes ranges from 5% to 10%. If they have a partner, as with some of our older patients, we may also suggest embryo cryopreservation. And then investigational options, which would be very invasive, are cryopreservation of ovarian tissue through ovarian cortical biopsies or oophorectomy.
By discussing these topics with patients and families, we can help them make informed decisions that can impact their quality of life for years to come.