Female reproductive function after treatment of childhood acute lymphoblastic leukemia

Abstract

Background The aim was to evaluate self‐reported reproductive characteristics and markers of ovarian function in a nationwide cohort of female survivors of childhood acute lymphoblastic leukemia (ALL), because prior investigations have produced conflicting data. Procedure Self‐reported reproductive characteristics were assessed by questionnaire among 357 adult 5‐year survivors, treated between 1964 and 2002, and 836 controls. Ovarian function was assessed by serum levels of anti‐Müllerian hormone (AMH), follicle‐stimulating hormone (FSH), and inhibin B and by antral follicle count (AFC). Differences between controls and (subgroups of) survivors (total group, chemotherapy [CT]‐only group, CT and radiotherapy [RT] group) were analyzed. Results Survivors treated with CT only do not differ from controls regarding timing of menarche, virginity status, desire for children, or pregnancy rates. Compared to controls, the CT+RT group was at significantly increased risk of a younger age at menarche (P < .01), virginity, an absent desire for children, and lower pregnancy rates (odds ratio [OR] [95% CI]: 0.3 [CI 0.1‐0.6], 0.5 [0.3‐0.9], and 0.4 [0.2‐0.9], respectively). Survivors in the CT‐only group were significantly younger at the birth of their first child. Pregnancy outcomes were not significantly different between any (sub)groups. Survivors treated with total body irradiation (TBI) or hematopoietic stem cell transplantation (HSCT) are at increased risk of abnormal markers of ovarian function. Conclusion Reproductive function of ALL survivors treated with CT only does not differ from controls. However, survivors additionally treated with RT seem to be at an increased risk of certain adverse reproductive outcomes. Providing personalized counseling about (future) reproductive health risks in this group is imperative.

Serum Anti-Müllerian Hormone Levels and Risk of Premature Ovarian Insufficiency in Female Childhood Cancer Survivors: Systematic Review and Network Meta-Analysis

“…A total of 22 studies were assessed for full text, of which 3 were removed for not evaluating AMH levels, 4 were removed for being out of topic, and 7 trials were excluded because they did not include a control group. A total of 8 studies [ 8 , 22 , 23 , 24 , 25 , 26 , 27 , 28 ], including 1303 participants (663 female CCS and 640 age-matched healthy controls) were included in the quantitative synthesis and network meta-analysis ( Figure 1 ).…”

“…All participants fully recovered from the pathology with no signs of relapse at the enrolment. Four studies compared an unselected cohort of female CCS to age-matched healthy controls [ 22 , 25 , 26 , 28 ]. Of those, Nystrom et al [ 25 ] studied a mixed CCS population of women treated with different schemes of RT, without differences between groups, while Bath et al [ 22 ], Van der Kooi et al [ 28 ], and Harzif et al [ 23 ] analyzed women subjected to CT or CT plus RT.…”

“…The incidence of POI among survivors and controls was analyzed in five cohort studies [ 8 , 24 , 25 , 26 , 27 ]. Neuroblastoma, acute lymphoid leukemia, thyroid cancer, or unselected female CCS were directly compared to healthy controls and indirectly compared between each other, as shown in the network map ( Figure 3 a).…”

“…Similar to neuroblastoma survivors, there were reduced levels of AMH, inhibin B, and AFC when a TBI regimen was used. Otherwise, AMH levels and subsequent fertility were similar to the age-matched healthy controls [ 26 ].…”

“…Roshandel et al [ 26 ] found that female CCS treated with RT showed lower AMH and inhibin B levels with a reduced AFC compared to controls. Similar to neuroblastoma survivors, there were reduced levels of AMH, inhibin B, and AFC when a TBI regimen was used.…”