Pediatr Blood Cancer. 2021; 68: e28894. https://pubmed.ncbi.nlm.nih.gov/33459500/
This cross-sectional observational study examined reproductive function in a nationwide cohort of female childhood acute lymphoblastic leukemia (ALL) survivors.
Self-reported reproductive characteristics (age at menarche, virginity status, desire for children, pregnancy rates, and adverse pregnancy outcomes) were assessed by a questionnaire in 357 adult 5-year ALL survivors, treated between 1964 and 2002, and 836 controls. Ovarian function was assessed by anti-Müllerian hormone (AMH), follicle-stimulating hormone (FSH), inhibin B and antral follicle count (AFC). ALL survivors were significantly more likely to have low AMH and low AFC than controls. However, ALL survivors treated with chemotherapy (CT) only had overall self-reported reproductive outcomes, pregnancy rates and ovarian function markers similar to controls. Whereas, ALL survivors treated with CT + radiotherapy (RT) had lower pregnancy rates.
Patients treated with cranial RT have an increased risk of neuropsychological sequelae, which potentially reduce the chances of becoming parents. However, the reduced pregnancy risks among ALL survivors treated with CT + RT could also result from hypothalamic-pituitary damage (after cranial RT) or ovarian damage (after TBI). A previous study of ALL survivors showed that risk of miscarriage is increased in patients treated with craniospinal RT, but not in patients treated with cranial RT only (1). Recent advances in ALL treatment have made the use of spinal RT obsolete (and RT is not included in standard risk protocols), therefore the risk of miscarriage is probably not increased in more recent ALL survivors. Female childhood ALL patients need to be informed of the late effects of treatment on fertility. In particular, survivors who were treated with RT should be advised not to delay childbearing due to their reduced reproductive lifespan. Survivors not treated with RT seem not at risk of a diminished reproductive function.
Strengths of this study include the large number of participants, but there are also some limitations. Participants who underwent the study of ovarian function markers were significantly younger than questionnaire-only participants. This could possibly have over- or underestimated the prevalence of impaired reproductive function. Additionally, the self-reported outcomes may have been influenced by recall bias. Finally, the study population included relatively young women, and data on menopausal status needs to be confirmed, because not all women with premature menopause may have been identified.
Reference: 1. Green DM, Whitton JA, StovallM, et al. Pregnancy outcome of female survivors of childhood cancer: a report from the Childhood Cancer Survivor Study. Am J Obstet Gynecol. 2002; 187: 107080.