Infertility is a well documented side effect of treatment for childhood cancer1-3
Cancer treatments like chemotherapy, radiation and surgery can all cause infertility by damaging the pituitary or hypothalamus, by damaging the uterus or Fallopian tubes, or by affecting eggs or sperm quantity or production.
If egg quantity is depleted completely the female will enter premature menopause (menopause before the age of 40). If sperm quantity is depleted the male will have few or no sperm in his ejaculate.
The risk of becoming infertile after cancer treatment depends on the following factors:
- Age at diagnosis or treatment
- Pre-treatment fertility status
- Type and dose of chemotherapy
- Location and dose of radiation
- Surgical area
The gonads are very sensitive to cytotoxic therapy. Generally alkylating agents are the most damaging to egg and sperm production.
In males chemotherapy can damage/destroy sperm producing cells rendering the male infertile and can damage/destroy hormone producing cells (Sertoli and Leydig cells) affecting androgen production.
In females chemotherapy can damage/destroy eggs causing insufficient egg numbers or completely depleting egg reserve (aka ovarian reserve). If there is complete loss of ovarian reserve the female enters the menopause.
Other problems may occur which do not involve direct damage to the reproductive system or pituitary axis. For example, Adriamycin chemotherapy can cause cardiomyopathy as a long term side effect. This problem can make pregnancy very dangerous. During pregnancy the blood volume increases and sometimes this will precipitate cardiac failure in a patient who was previously treated with Adriamycin.
Radiation Therapy (RT)
Depending on the location and dose, RT can affect fertility. Abdomino-pelvic radiation and total body radiation can destroy eggs and sperm. In some instances sperm producing cells can recover but it depends on the location, dose and duration of treatment. Radiation to or near the hypothalamus or pituitary can affect sperm and eggs by damaging the endocrine stimulus (FSH, LH) to their production. Radiation on the uterus can affect the health of the lining (endometrium) increasing a female’s risk of miscarriage or can affect the wall (myometrium) such that it cannot expand to accommodate a growing pregnancy, leading to premature birth.
Surgery can cause infertility in males and females.
In girls: Tumors arising from or involving the ovaries may require oophorectomy as part of their therapy and this surgery can obviously be associated with infertility. Surgery on or around the Fallopian tubes can disrupt their function or block them completely and surgery involving the uterus or cervix can cause infertility or obstetrical complications like premature birth or miscarriage.
In boys: Orchiectomy for treatment of testicular cancer can cause infertility and decreased testosterone production. Radical retroperitoneal lymph node dissection can cause erectile dysfunction and low or absent ejaculatory fluid volumes. Radical prostatectomy causes erectile dysfunction in 30-80% of patients and can reduce sperm counts in the ejaculate.
Fertility can sometimes be preserved before treatment by freezing sperm, eggs, embryos or ovarian tissue, ovarian transposition.
The damage to fertility can be mitigated during treatment by shielding the testes or ovaries during radiation treatment or suppressing ovarian function in hopes of rendering the ovaries less sensitive to gonadotoxic treatments.