**6.2 Impact of RT on fertility and gestation in females with WT**

As noted for male patients, studies have also shown female patients to have primary gonadal failure following 15–30 Gy flank or WART at 0.5–4 years of age [31]. Another study showed atrophied ipsilateral ovary in half of those treated with 4–41 Gy to the flank and atrophied bilateral ovaries in all patients treated with 21–30 Gy WART prior to puberty [34]. In addition to potential impact on gonadal function, late effects of RT to the abdominopelvic region in young children may impair normal growth and development of the irradiated pelvic bones, vasculature and organs including the uterus that are essential for successful gestation. Early studies of pregnancy outcomes in irradiated female WT survivors have shown increased incidence of perinatal death, low birthweight, and birth defects compared with offspring of unirradiated female survivors, sibling controls or wives of male WT survivors, regardless of chemotherapy exposure [35, 36]. In an analysis of 309 female WT survivors treated on NWTS 1–4, flank RT >25 Gy was associated with significantly increased risk of preterm labor, fetal malposition and lower mean gestational age with odds ratio of 2.36, 6.26 and 4.07, respectively compared to unirradiated female survivors [37]. This effect was not observed for female survivors receiving chemotherapy only or for gestations fathered by male survivors. In a subset of 126 of these female WT survivors who received more than flank RT, only seven were able to conceive at least once. Five of these women received upper abdominal RT, with nine of 10 gestations resulting in live births; the remaining two women received WART, with the one receiving 10.5 Gy able to have a single viable birth and the other receiving 21 Gy having three non-viable pregnancies [38].
