Reduced Ovarian Function in Long-Term Survivors of Radiation- and Chemotherapy-Treated Childhood Cancer

Oncofertility and preservation of reproductive capacity in children and young adults

“…Larsen et al evaluated ovarian function in 100 childhood cancer survivors and 21 controls of similar age. 23 Survivors with spontaneous menstrual cycles (n ¼ 70) were found to have smaller ovarian volume per ovary compared with controls (median, 4.8 cm 3 vs 6.8 cm 3 ; P < .001) and a lower number of antral Cancer follicles (AFC) per ovary (median, 7.5 AFC vs 11 AFC; P < .001). A regression analysis was performed to predict the total AFC number per ovary, which demonstrated a reduced number in women who were treated with ovarian irradiation (b ¼ À.40; P < .001), alkylating chemotherapy (b ¼ À.25; P ¼ .01), older age at diagnosis (b ¼ À.25; P ¼ .01), and longer time period off treatment (b ¼ À.19; P ¼ .044).…”

“…10 The number of primordial follicles present at the time of treatment, together with the dose received by the ovaries, will determine the fertility ''window'' and influence the age of premature ovarian failure. Ovarian failure has been reported in 90% of patients followed long term after TBI (10-15.75 Gy) and in 97% of females treated with total abdominal irradiation (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30) Gy) during childhood. 11,12 Using our knowledge and understanding of the radiosensitivity of human oocytes, it is now possible to predict the estimated sterilizing dose after any given dose of radiotherapy at any given age based on the application of the mathematical solution to our model for natural oocyte decline (Fig.…”

“…It is interesting to note that early puberty is often reported, particularly in females treated with cranial radiation doses of < 24 Gy. 14 However, it has been shown that after lowdose cranial radiotherapy (18)(19)(20)(21)(22)(23)(24), there is a subtle decline in hypothalamic-pituitary-ovarian function as characterized by decreased luteinizing hormone (LH) secretion, an attenuated LH surge, and shorter luteal phases that are likely to herald incipient ovarian failure or be associated with early pregnancy loss. 15 …”

“…A regression analysis was performed to predict the total AFC number per ovary, which demonstrated a reduced number in women who were treated with ovarian irradiation (b ¼ À.40; P < .001), alkylating chemotherapy (b ¼ À.25; P ¼ .01), older age at diagnosis (b ¼ À.25; P ¼ .01), and longer time period off treatment (b ¼ À.19; P ¼ .044). 23 A recent study in women aged <40 years 24 has suggested that, compared with inhibin B and AFC, anti-Mullerian hormone (AMH) was more consistently correlated with the clinical degree of follicle pool depletion in young women presenting with elevated follicle-stimulating hormone (FSH) levels. Further evidence that AMH will be useful in the assessment of the young woman who has been treated for cancer comes from a study of women treated during childhood for HL.…”

Is transplantation of a few leukemic cells inside an artificial ovary able to induce leukemia in an experimental model?

“…For these young patients, recovery of ovarian function and reproductive potential after treatment have become important quality-of-life issues. Various chemotherapeutic agents, particularly alkylating agents, have been identified as gonadotoxic, and pelvic or total body irradiation (TBI) can cause irreversible gonadal damage [3][4][5], potentially leading to infertility problems and premature ovarian failure (POF) [3][4][5][6][7][8][9]. This risk depends on the patient's age and follicle reserve, as well as the type and dose of drug received, and is not always easy to predict.…”