Early Menopause and Infertility in Females after Treatment for Childhood Cancer Diagnosed in 1964-1988 in Ontario, Canada

Abstract

This study was conducted to determine the risk of menopause and infertility in female childhood cancer survivors who received abdominal-pelvic radiation and/or chemotherapy with alkylating agents in comparison with those who were treated by nonsterilizing surgery only. Females who were diagnosed in 1964-1988 before age 20 years with a histologically confirmed malignancy and who had survived for at least 5 years, had attained age 18, and were alive at time of study were identified through the Ontario Cancer Registry. Reproductive outcomes were ascertained by a telephone-administered questionnaire, and treatment data were abstracted from medical records for 830 subjects aged 18-49 years; 719 survivors who were nonmenopausal at the end of treatment were included in the analyses. Survivors who received both alkylating agents and abdominal-pelvic radiation were more likely to be postmenopausal than were those who underwent surgery (risk ratio = 2.58; 95% confidence interval: 1.14, 5.80). Women treated with abdominal-pelvic radiation alone had a fertility deficit of 23% compared with those in the surgery group; the deficit was restricted to women diagnosed postpuberty. Risks of menopause and infertility increased with increasing dose of abdominal-pelvic radiation and amount of alkylating agent.

Whole sheep ovary cryopreservation: evaluation of a slow freezing protocol with dimethylsulphoxide

“…The combined 5 years relative survival rate for children with cancer has improved from around 63% for patients diagnosed during the period 1975-1979 to 79% for those diagnosed 1995-1999 [2]. Several chemotherapeutic agents [3] and radiotherapy used in cancer treatment are toxic to the ovaries [4].…”

Exposure to radiation therapy is associated with female reproductive health among childhood cancer survivors: a meta-analysis study

“…The included studies were published between 1999 and 2014, and all of them were cohort studies [4,[6][7][8][9][10][11][12][13][14][15][16][17][18]. A total of 10,717 women with radiation therapy and 11,128 women without radiation therapy from 13 studies were evaluated [4, 6-15, 17, 18].…”

“…In fertility factors, 5 studies were described about infertility [6,9.12,14, 18], 2 studies were based on AMH values [4,17], 2 studies on AOF [10,16], 3 studies on stillbirth or neonatal death [7,8,13], 2 studies on spontaneous abortion [7,12], 2 studies on congenital anomaly [7,15], 2 studies on low birth weight [7,11] and 1 study on preterm birth [11]. In radiation therapy methods, 4 studies were performed in radiation therapy without specific description [10,12,16,2], 2 studies on abd-pelvic radiation [6,7], 2 studies on ovarian radiation [8,15] and each of the 6 last studies were performed on pelvic radiation [4], abdominal or total body radiation [17], hypothalamic or pituitary radiation [14], nasopharyngeal radium irradiation [9], uterus radiation [11], uterus and ovarian radiation [13].…”

“…Conversely, as another aspect of the ability of female fertility, the proportion of abortion in cancer survivors was similar to the population from control subjects. Moreover, the risk of low birth weight and stillbirth increased among the offspring of females who received radiotherapy during childhood [6]. Untill now, no evidences have suggested the role of childhood radiotherapy on congenital malformation.…”

The influence of amifostine administration prior to cyclophosphamide on in vitro maturation of mouse oocytes

“…Long term side effects of this alkylating agent have been the main concern [5]. It was shown that CP treatment caused ovarian follicle damages and administration of high doses may induce reproductive failure in females [6]. In addition injuries of germ cells along with induction of transmissible genetic damages were observed in mouse model treated with CP [7].…”