The Effect of Radioactive Iodine Therapy on Ovarian Function and Fertility in Female Thyroid Cancer Patients: A Systematic Review and Meta-Analysis

Introduction: Thyroid cancer is one of the most common carcinomas diagnosed in adolescents and young adults, with a rapidly rising incidence for the past three decades. Surgery is the standard treatment for patients with differentiated thyroid carcinoma (DTC), and when indicated, followed by radioactive iodine (RAI) treatment. The aim of this study was to evaluate the possible effects of RAI therapy on ovarian function and fertility in women. Methods: The PubMed, Embase, and Web of Science databases were systematically searched up to January 2020. In addition, a meta-analyses were performed for anti-Mullerian hormone (AMH) levels after RAI, comparison of AMH levels prior and 1 year after RAI, and pregnancy rates in patient with thyroid cancer receiving RAI compared with patients with thyroid cancer who did not receive RAI. Results: A total of 36 studies were eligible for full-text screening and 22 studies were included. The majority of the studies had a retrospective design. Menstrual irregularities were present in the first year after RAI in 12% and up to 31% of the patients. Approximately 8-16% of the patients experienced amenorrhea in the first year after RAI. Women who received RAI treatment (median dose 3700 MBq [range 1110-40,700 MBq]); had menopause at a slightly younger age compared with women who did not receive RAI treatment, 49.5 and 51 years, respectively (p < 0.001). Pooled AMH of the seven studies reporting AMH concentrations after RAI was 1.79 ng/mL. Of these, four studies reported AMH concentrations prior and 1 year after RAI. The mean difference was 1.50 ng/mL, which was significant. Finally, meta-analysis showed that patients undergoing RAI were not at a decreased risk of becoming pregnant. Conclusions: Most of the studies indicate that RAI therapy for DTC is not associated with a long-term decrease in pregnancy rates although meta-analyses show a significant decrease in AMH levels after RAI therapy. Prospective studies are needed to confirm these results. We recommend counseling patients about the possible effects of I-131 and incorporate today's knowledge in multidisciplinary counseling.