Preserving fertility in female cancer patients: A snapshot of the options
ABSTRACTWith the odds of surviving cancer improving, many young women facing chemotherapy or radiotherapy may first wish to take steps to ensure that they will still be able to bear children afterward. The options depend on the type of disease, the treatment required, the age of the patient, whether she has a long-term partner, and whether cancer treatment can be delayed. This paper is an overview of current and experimental strategies for preserving fertility in female cancer patients.
KEY POINTS
- Chemotherapy and radiotherapy are toxic to the ovaries, although the damage can be attenuated in some cases.
- The standard option for preserving fertility has been oocyte retrieval after controlled ovarian stimulation, followed by in vitro fertilization and subsequent cryopreservation of the resulting embryos.
- Unfortunately, controlled ovarian stimulation takes time, may delay needed cancer therapy, and may worsen estrogen-dependent cancers. Alternatives are being explored.
- Cryopreservation of unfertilized oocytes is an option for women who do not have a partner, although oocytes are more susceptible to damage during freezing than embryos are.
OVARIAN TRANSPOSITION
When a woman of childbearing age needs radiation treatment for a pelvic malignancy, transposition of the ovaries above the pelvic brim outside the radiation field (oophoropexy) should be considered before starting therapy. It is indicated in patients diagnosed with malignancies that require pelvic radiation but not the removal of the ovaries. It can be performed during surgical treatment of the tumor or as a separate laparoscopic procedure. The radiation dose that the transposed ovaries receive is considerably less than that in ovaries left in place.
Laparoscopic ovarian transposition is highly effective. However, the risk involved in the surgical procedure should not be underestimated. The most important complications are vascular injury, infarction of the fallopian tube, and ovarian cyst formation.44
PHARMACOLOGIC PROTECTION
Some drugs induce a state of ovarian quiescence similar to menopause. Can they be used during chemotherapy to protect the ovaries, allowing restoration of normal ovarian function and natural fertility after cancer treatment and preventing premature ovarian failure?
GnRH analogues slow the cellular activity of the gonads, in theory making them less sensitive to damage by cytotoxic agents. Initially, the release of gonadotropins is stimulated (flare-up effect), but after 10 to 15 days pituitary GnRH receptors are down-regulated by internalization of receptors. Since chemotherapy affects mainly actively dividing cells such as mature ovarian follicles, the use of the analogues is based on the assumption that by reducing FSH levels, follicles will remain quiescent, decreasing their sensitivity to the gonadotoxic effect of chemotherapy.
In a randomized study of 281 patients with early breast cancer, Del Mastro et al45 reported a reduction in the occurrence of early menopause in those treated with a GnRH analogue during chemotherapy after 1 year of follow-up. However, the debate regarding the effect of GnRH analogues on the fertility of cancer patients is still open and needs further investigation.
In recent years, research has focused on imatinib, a new, potentially protective drug,46 but a lot of work still needs to be done. To date, the use of GnRH analogues is not recommended outside of clinical studies, and it should be offered only after careful counseling about other options to preserve fertility.
