Obstetrics and Gynecology International shortly after the completion of cancer therapy, or premature menopause, deﬁned as menopause younger than 40 years in survivors who retain ovarian function following treatment [28, 33]. The speciﬁc risk of premature ovarian failure after direct radiation to the ovaries is site and dose-dependent [28, 34]. Stillman et al. [35] reported ovarian failure in none of 34 survivors who had both ovaries outside of the ﬁeld of abdominal radiation, in 14% of 35 survivors whose ovaries were at the edge of the radiation ﬁeld, and in 68% of 25 survivors who had both ovaries entirely within the ﬁeld of irradiation. Previous studies have demonstrated ovarian doses >10 Gy to be linked to a high risk of AOF, especially doses >20 Gy which are associated with the highest rate, with over 70% of a study cohort of 3390 survivors developing AOF [34]. Recently, doses as low as 5 Gy to the ovaries have been identiﬁed as a signiﬁcant risk factor for not having a pregnancy, presumably due to ovarian failure [17]. The LD50 (the radiation dose required to kill 50% of oocytes) of the human oocyte has been estimated at <2 Gy [25, 28]. 5. Chemotherapy Factors aﬀecting the risk of ovarian injury in children treated with chemotherapy include the speciﬁc agent, the number of agents, and the cumulative dose [4]. Several chemotherapeutic agents when given at high doses are recognised as toxic to young ovaries including alkylating agents, cisplatin procarbazine, and the nitrosoureas (CCNU and BCNU) [2, 36]. There is currently no data on threshold doses to cause ovarian failure, although it has been noted that exposures to procarbazine at any age or cyclophosphamide between 13 and 20 years are independent risk factors for AOF [34]. Additionally, cyclophosphamide and CCNU have been associated with a lower risk of pregnancy, with fertility rates decreasing with increasing doses of these agents [17]. Increasing alkylating agent score (based on the number of alkylating agents and cumulative doses) has also been identiﬁed as a risk factor for both nonsurgical premature menopause [34] and decreased fertility, with one study of 5149 survivors demonstrating that alkylating agent scores of three and four were associated with a lower observed risk of pregnancy compared to patients who had no alkylating agent exposure [17]. 6. Combination Radiotherapy and Chemotherapy A combination of radiation to the ovaries and chemotherapy poses the greatest risk of ovarian failure [25, 28, 37–39]. Amongst patients who are treated with alkylating agents plus abdominopelvic irradiation, 30–40% are estimated to develop non-surgical premature menopause [37, 39]. 7. Assessment of Ovarian Reserve 7.1. Hormonal Markers. A slow and steady compensatory rise in early follicular phase follicle-stimulating hormone 3 (FSH) has traditionally been used as marker of peri- menopause and ovarian reserve [28, 40]. Unless signiﬁcantly elevated however, early follicular phase FSH as an isolated test is not a sensitive early marker of diminished ovarian reserve [28]. Some women may experience transiently elevated FSH unrelated to their pool of follicles, which can add to potential erroneous presumptions of premature menopause. Inhibin-B is another hormonal marker which has been proposed to assess ovarian reserve. It is produced by follicles following recruitment during the early follicular phase and has been shown to decrease with age and during premature ovarian failure [40, 41]. However, it is a fairly late marker of reduced follicle reserve as levels do not decrease gradually with age [40]. Levels of antimullerian hormone (AMH) are more reﬂective of the number of preantral follicles and are thus a marker of oocyte pool [28, 40, 42, 43]. AMH levels in women of reproductive age appear to have a greater sensitivity and speciﬁcity for ovarian reserve over FSH and inhibin-B [40, 44]. Levels are independent of the phase of the ovarian cycle and should not vary signiﬁcantly between menstrual cycles as levels are not dependent on the feedback mechanisms of the HPO axis [28, 40, 42–44]. Importantly, AMH levels decrease steadily over time and often fall before other markers of ovarian ageing occur [42]. There is a demonstrated age- dependent decrease after 30 years, with a decline in AMH levels below 0.086 µg/L signalling menopause [45]. Although a promising marker for ovarian reserve, its eﬃcacy in assessing premature menopause and chance of pregnancy in young patients after cancer treatment is not well established, and more data are required. 7.2. Ultrasonographic Markers. Transvaginal ultrasound as- sessments of total ovarian volume and antral follicle count (AFC) are noninvasive and accurate tests of ovarian reserve as both exhibit an age-related decline [28, 40]. Mean pre- menopausal ovarian volumes of 4.9 cm3 compared to mean postmenopausal volumes of 2.2 cm3 have been determined [46]. The mean AFC is 15 at 25–34 years of age and decreases to 4 at 41–46 years of age [47]. AFC has also been shown to correlate tightly with plasma levels of AMH [48]. 8. Options for Fertility Preservation There are two main approaches to preserving fertility in female childhood cancer survivors, namely, cryopreservation of ovarian tissue, oocytes, and embryos, and interventions to minimise the eﬀects of cancer therapies on the ovaries [49]. Within these approaches, there are established practices and experimental strategies. 8.1. Cryopreservation. Embryo cryopreservation is the main established method of fertility preservation, with delivery rates per embryo transfer ranging between 10–40% depend- ing upon the age of the female partner and quality of oocyte [49, 50]. However, this option is of limited value in children as the patient must be postpubertal and have a partner or use donor sperm. This process also requires at least one