High Dose Radioiodine Therapy Affects Ovarian Reserve in Women with Differentiated Thyroid Cancer

Presentation Number: OR22-6
Date of Presentation: April 2nd, 2016

Iris Yaish1, Foad Azem1, Merav Serebro1, Gabi Shefer2, Rona Limor1, Sivan Shamai1, Orit Gutfeld1, Naftali Stern3 and Karen Michele Tordjman*3
1Tel Aviv Sourasky Medical Center, Tel Aviv, Israel, 2Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel, 3Tel Aviv Sourasky Medical Center and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

Abstract

Women undergoing radioiodine  (RAI) therapy are advised to refrain from conceiving for 6-12 months following treatment as ovaries are exposed to radiation(1). It is unclear if this exposure carries a risk for reduced fertility, however earlier menopause has been reported in women undergoing RAI treatment (2). Given the finite number of primordial follicles women are endowed with at birth, radiation injury to germinal cells is not expected to be reversible. We sought to assess the effect of RAI  on ovarian reserve of women undergoing treatment for differentiated thyroid cancer (DTC) by prospectively examining blood levels of anti-Müllerian hormone (AMH), and accepted index of the size of this reserve.

Subjects and Methods: Thirty  premenopausal women (aged 33.3+1.4, 20-45 y), scheduled to undergo RAI treatment  for the first time after surgery for DTC, were enrolled in the study.  Subjects with prior pelvic surgery or irradiation were excluded. Blood levels of AMH were assessed by immunoassay at baseline, and every 3 months  for up to 1 year following RAI.

Results: All 30 women  reported regular menses prior to treatment. Nineteen had borne children. Baseline AMH levels were, as expected, inversely correlated with age ( r= -0.49, P=0.006).

To this date, 23 women all  AJCC Stage 1, have received treatment at a mean dose of 110.7±9.9 mCi (30-150). Of those, 18 have been reevaluated after treatment. Baseline AMH levels of these 18 women were 3.43 ±0.65 ng/ml. A  45% decrease in AMH levels was observed 3 months after treatment (1.9±0.4 ng/ml, P=0.001). The level improved somewhat afterwards, but it remained significantly lower than at baseline at 6, 9, and 12 months (2.4±0.5, 2.6±0.6, and 2.8±0.6, respectively). As most of these subjects had received high doses RAI of 100 and 150 mCi, we could not determine if there was a dose effect.  In order to examine this issue, we grouped the 4 subjects who had received an ablative dose of 30 mCi  for DTC with 5  women who had been treated with RAI for Graves' disease in doses ranging from 10-22 mCi. In these 9 subjects (aged 34.9±2.3, 22-43 y), baseline AMH levels were 2.5±0.7 ng/l and did not change after treatment. They were 2.4±0.8, 2.5±0.8, 3.0±1.0, and 2.6±0.8 ng/ml, at 3, 6, 9 and 12 months respectively.

Discussion and Conclusions: Large doses of RAI given as adjunct therapy to women with DTC appear to impair ovarian reserve as assessed by AMH levels. A nadir for this effect is seen 3 months after treatment, but  there is no complete recovery even after a year. In contrast, lower doses up to 30 mCi, such as those given for ablation of thyroid remnant of for hyperthyroidism, appear to be innocuous.  The question whether this effect translates in decreased fertility is outside the scope of this study, but this piece of data adds further weight to the precautions currently advocated with regards to RAI therapy in low risk DTC subjects.

 

Nothing to Disclose: IY, FA, MS, GS, RL, SS, OG, NS, KMT