The effects of radiotherapy and chemotherapy on female reproduction

Abstract

High dose chemotherapy and radiotherapy have radically increased long-term survival of young cancer patients, but major side effects of these treatments are ovarian failure and infertility. Knowledge of the risks and probabilities of ovarian failure caused by treatment is crucial for patients and physicians in order to make informed choices that will best serve patients' interests. This review presents data on ovarian damage and failure following exposure to radiotherapy, chemotherapy and ablative therapy. The risk is evaluated from the published literature according to patient's age, treatment protocol and also according to the diagnosis of some common malignancies. Many of these patients will not be sterilized immediately following treatment, but will suffer from premature menopause. In order to prevent sterilization, ovarian transposition before pelvic irradiation is mandatory. Besides cryopreservation of ovarian tissue and embryos before administration of chemotherapy, the possible protective effect of pituitary-ovarian down-regulation is discussed. The mechanism of primordial follicles damage induced by radio/chemotherapy is presented as well as the role of apoptosis signalling pathways underlying destruction. Increased knowledge of these mechanisms could help to identify potential effective inhibitors that can block the path of primordial follicles destruction and reduce ovarian failure rate.

Results from the survey for preservation of adolescent reproduction (SPARE) study: gender disparity in delivery of fertility preservation message to adolescents with cancer

“…Similarly, chemotherapy and radiation in female cancer patients can result in premature menopause and ovarian dysfunction secondary to ovarian toxicity. The risk of gonadotoxicity is related to the patient's age at the time of treatment, pre-existing gonad function, and the dose and duration of treatment [23]. In addition, the mechanism of action of agents determines their impact on gonad function.…”

IVF for fertility preservation in breast cancer patients—efficacy and safety issues

“…The extent of anthracycline-related ovarian toxicity is controversial. According to our previous findings, it is expected to be low [10].…”

“…With reference to agents commonly used for breast cancer, alkylating agents have the greatest gonadotoxic potential. Taxans cause an intermediate ovarian damage, whereas methotrexate and 5-fluorouracil are associated with a lower toxicity risk [8][9][10][11]. The extent of anthracycline-related ovarian toxicity is controversial.…”

Anticancer Gene Transfer for Cancer Gene Therapy

“…While chemotherapy and cytotoxic therapy has brought tremendous progress to cancer therapeutics it presents with detrimental side effects that hamper the benefits of the tumor shrinkage or destruction. Common practice so far has been the systemic administration of cytotoxic therapies that instead of affecting the tumor specifically they affect all the human tissues non-specifically and uncontrollably (Meirow and Nugent, 2001). A new era for cancer therapeutics has emerged through the use of targeted and rationale-based therapies using small molecular inhibitors of proteins or pathways that are specifically deregulated in certain cancers.…”