The systematic review and network meta-analysis, led by Eloise Fraison and colleagues from the University Hospital of Lyon, France, examined whether cancer treatments administered before the age of 25 impact later pregnancies. While survival rates for childhood and young adult cancers have improved, the long-term reproductive health consequences remain insufficiently understood.
For this purpose, the researchers analyzed data from studies published between 1990 and April 2023 using MEDLINE, Embase, and the Cochrane Library. Eligible studies included women who received chemotherapy or chemoradiotherapy before age 25 and later became pregnant. The primary outcome evaluated was live-birth rate, while preterm birth was among the key secondary outcomes. A random-effect frequentist network meta-analysis was performed, and sensitivity analyses addressed potential biases.
Key Results
Eight studies contributed to the live-birth rate analysis, covering 3,997 pregnancies resulting in 2,878 live births. Findings showed no significant difference in live-birth rates between those exposed to cancer therapy and controls.
However, analysis of six studies reporting on 1,976 pregnancies revealed a substantial impact on preterm birth risk:
- Chemoradiotherapy increased the likelihood of preterm birth by more than threefold compared to controls (Risk Ratio 3.44).
- Compared to chemotherapy alone, chemoradiotherapy nearly doubled the risk (RR 1.93).
- Chemotherapy alone still raised the risk by 78% compared with controls (RR 1.78).
Although live-birth rates remained unaffected, the heightened risk of prematurity highlights the need for careful obstetric monitoring in this population.
The authors caution that evidence quality was low to very low for most outcomes, as no randomized controlled trials were included, and several confounding variables—such as parity, hormone replacement therapy, and type or dose of chemotherapy—could not be adjusted. Additionally, definitions for preterm birth and other outcomes varied across studies, and reasons for prematurity were often not documented.
Despite these limitations, the findings raise concerns about the uterine effects of cancer treatments, possibly linked to structural or vascular changes. “Until more precise data are available, clinicians should consider prior chemotherapy or chemoradiotherapy during youth as a risk factor for prematurity and plan enhanced pregnancy surveillance,” the authors concluded.
Reference:
E. Fraison, S. Huberlant, M. Cavalieri, A. Gueniffey, J. Riss, C. Rousset-Jablonski, B. Courbiere, Increased risk of preterm birth in pregnant women exposed to chemotherapy during childhood, adolescence, or young adulthood: A systematic review and a network meta-analysis, European Journal of Obstetrics & Gynecology and Reproductive Biology (2025), doi: https://doi.org/10.1016/j.ejogrb.2025.114665
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