Women who undergo chemotherapy for cancer during their reproductive years may experience accelerated loss of primordial follicles, failure of pubertal progression, premature ovarian failure and premature menopause. Exposure to gonadotoxic alkylating agents such as cyclophosphamide causes dose dependant depletion of primordial follicles with ovarian fibrosis. However recent studies suggest that a fraction of OR is lost following any chemotherapy, regardless of the agent used. Measurement of ovarian reserve using AMH as a marker has shown that although AMH frequently recovers post-chemotherapy, AMH concentrations in serum are consistently lower than pre-treatment, suggesting a shorter fertility window post chemotherapy, especially in the high-risk group. Hence determination of ovarian reserve for female cancer patients is advantageous for future family planning and fertility preservation. Current assessment of ovarian reserve depends on biophysical (antral follicle count) and biochemical (anti-Mullerian hormone) measurements. However the quest for an oocyte derived marker of “quality” as well as “quantity” continues.
A number of options for “fertility preservation” are available to both pre- and post-pubertal women before commencement of chemotherapy or radiotherapy. These include ovarian stimulation with cryostorage of oocytes or embryos, storage of ovarian tissue or “protection” of the primordial follicle pool using GnRH agonists for pituitary downregulation. Each approach has its advantages and disadvantages and none can guarantee a future successful pregnancy.
Future prospects include maturation of oocytes from primordial follicles from stored tissue, production of gametes from stem cells or, most realistically, in vitro maturation (IVM) of oocytes collected from unstimulated ovaries before start of chemotherapy. Ability to have a family remains at the top of the list of the most desired aspects of “returning to normal” for long term young survivors of cancer so efforts to improve outcomes of fertility preservation will bring significant long term benefit to this group of patients.