Birth Rates After Radioactive Iodine Treatment for Well Differentiated Cancer in Female Patients With Reproductive Potentials: A Meta- Analysis

Abstract The association between radioactive iodine (RAI) therapy and reduced fertility has remained controversial, in part because no large-scale randomized clinical trials or prospective studies have been done in this regard. Hence, we performed this meta-analysis to investigate the association between radioactive iodine therapy and birth rates in female patients in their reproductive years diagnosed with well- differentiated thyroid cancer. Relevant articles were retrieved from PubMed Central and PubMed according to the established inclusion criteria, followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement. Each article was assessed by the Newcastle-Ottawa Scale (NOS). The overall relative risk (RR) and 95% confidence intervals (CI) were calculated to estimate the association between radioactive iodine (RAI) therapy and birth rates. Random effect or fixed-effect model was used to calculate the pooled OR, based on heterogeneity significance. Subgroup analysis was conducted based on different age groups (<25 years old vs. 25-34 years old vs. >35 years old). Sensitivity analysis and publication bias detection were also performed. All statistical analyses were performed using RevMan software (version 5.3; Cochrane library) and STATA 12.0 software (Stata Corp., College Station, TX), and all P values were two-tailed, the test level was 0.05. 105 articles were obtained from the database search, and 6 articles were obtained from other sources. Three articles involving 32237 participants were included. All studies were considered moderate to high quality. Overall, no statistically significant association was observed (RR 1.02; 95% CI: 0.71,1.48, p=0.91, I2=96%). In subgroup analysis, groups with age <24 y/o (RR 0.87; 95% CI:0.76,0.99,p= 0.04, I2=0%), and age >35 y/o (RR 0.71; 95%CI: 0.59, 0.85, p=0.0002, I2=0%), there was an associated reduction in birth rates in patients who received radioactive iodine treatment. In contrast, in the group between 25 and 34 years of age, no statistically significant observation was made (RR 0.99; 95% CI:0.79,1.22, p= 0.89, I2=82%). Sensitivity analysis confirmed the stability of the result. Egger’s test, and Begg’s test found no publication bias of analysis (p= 0.824; p=0.602). This meta-analysis demonstrated that overall, no statistically significant association between RAI treatment and birth rates in female patients within their reproductive ages diagnosed with well- differentiated thyroid cancer. However, in the subgroup analysis, an association was found between RAI treatment and reduced birth rates in females <25 years old and those >35 years old. In contrast, no association of RAI treatment with birth rates in females 25-34 years old was found. More highly powered prospective studies of this topic are needed in the future to further elucidate the impact of RAI treatment on birth rates and fertility.