Reproductive Health Outcomes among Adolescent and Young Adult Cancer Patients: A Systematic Review and Meta-Analysis

Abstract

Background: This systematic review and meta-analysis (SRMA) aimed to synthesize the current literature on the impacts of adolescent and young adult (AYA, ages 15-39 years) cancer on reproductive health outcomes.

Methods: EMBASE and Medline were searched from 1 January 2000 to 26 January 2022 for observational studies that included individuals with AYA cancer and controls which evaluated reproductive health outcomes. We used random effects models and 95% confidence intervals to obtain pooled measures of associations between AYA cancer, cancer treatment, and reproductive health outcomes.

Results: The search identified 8625 articles; 21 were included. 62 reproductive outcomes were assessed and classified according to a sex-based framework as fetal/neonatal (n = 26), maternal (n = 11), fetal/neonatal-maternal (n = 23), and maternal-paternal (n = 2). Meta-analyses of crude estimates showed significant associations between AYA cancer and outcomes including preterm birth (pooled odds ratio [pOR] 1.31; 95% CI: 1.22, 1.42), gestational diabetes (pOR 1.43; 95% CI: 1.03, 1.99), and fertility treatment (pOR 2.66; 95% CI 1.71, 4.11). We also found higher odds of preterm birth (pOR 1.65; 95% CI: 1.21, 2.26) and low APGAR score at birth (pOR 2.03; 95% CI: 1.32, 3.13) among AYA cancer patients who received radiation compared to controls.

Conclusions: Our SRMA quantified impacts of AYA cancers and treatments on several reproductive health outcomes.

Keywords: adolescent and young adult; cancer survivorship; cancer treatment; reproductive health.

Figure 1

PRISMA flow diagram.

Figure 2

Sex-based framework of AYA cancer reproductive health outcomes based on systematic review (N = 21).

Figure 3

Forest plots for significant fetal/neonatal outcomes reported by two or more studies (n = 4). (A). [27,28,29,31,34,35,36,39,40,42,43,44,45], (B). [31,42], (C). [27,28,29,31,36,39,40,42,44,45], (D). [27,29,31,32,33,36,37,40].

Figure 4

Forest plots for non-significant fetal/neonatal outcomes reported by two or more studies (n = 6). (A). [27,39,40,42,44,45], (B). [36,44], (C). [29,31,40], (D). [36,40], (E). [27,31,36,42], (F). [34,35].

Figure 5

Funnel plots of meta-analyses of AYA cancer and reproductive health outcomes (n = 17). (A). [27,28,29,31,34,35,36,39,40,42,43,44,45], (B). [31,42], (C). [27,28,29,31,36,39,40,42,44,45], (D). [27,29,31,32,33,36,37,40]. (E). [27,39,40,42,44,45], (F). [36,44], (G). [29,31,40], (H). [36,40], (I). [27,31,36,42], (J). [34,35], (K). [28,31,34,35,36,44], (L). [27,28,34,36,40,44], (M). [28,40], (N). [27,31,34,36,39,40,42,44], (O). [35,36,40], (P). [29,36], (Q). [26,29,30,31,36,44].

Figure 6

Forest plots for maternal health outcomes reported by two or more studies (n = 3). (A). [28,31,34,35,36,44], (B). [27,28,34,36,40,44], (C). [28,40].

Figure 7

Forest plots for fetal/neonatal-maternal health outcomes reported by two or more studies (n = 3). (A). [27,31,34,36,39,40,42,44], (B). [35,36,40], (C). [29,36].

Figure 8

Forest plot for maternal-paternal health outcome reported by two or more studies (n = 1) [26,29,30,31,36,44].

Figure 9

Forest plots of meta-analyses of chemotherapy and reproductive health outcomes (n = 5). (A). [39,42], (B). [36,39,42], (C). [36,39,42], (D). [39,42], (E). [36,42].

Figure 10

Forest plots of meta-analyses of radiation and reproductive health outcomes (n = 5). (A). [27,36,42], (B). [27,36,42], (C). [27,36,42], (D). [27,42], (E). [27,36,42].

Figure 11

Funnel plots of meta-analyses of cancer treatment (chemotherapy or radiation compared to controls) and reproductive health outcomes (n = 5). (A). chemotherapy: [39,42]; radiation: [27,36,42], (B). chemotherapy: [36,39,42]; radiation: [27,36,42], (C). chemotherapy: [36,39,42]; radiation: [27,36,42], (D). chemotherapy: [39,42]; radiation: [27,42], (E). chemotherapy: [36,42]; radiation: [27,36,42].