A Systematic Review Examining the Effects of Therapeutic Radioactive Iodine on Ovarian Function and Future Pregnancy in Female Thyroid Cancer Survivors

Anna M. Sawka; Deepak C. Lakra; Jane Lea; Bandar Alshehri; Richard W. Tsang; James D. Brierley; Sharon Straus; Lehana Thabane; Amiram Gafni; Shereen Ezzat; Susan R. George; David P. Goldstein


Clin Endocrinol. 2008;69(03):479-490. 

In This Article


We assembled a multidisciplinary panel of clinical content and methodology experts and developed a series of key questions for this scoping review (series of systematic reviews). To be eligible for inclusion in the scoping review, a study was required to answer one or more of the following questions, relating to RAI treatment of women with well-differentiated thyroid carcinoma (DTC):

  1. What is the effect of therapeutic RAI on sex steroid (oestradiol, oestrone, progesterone) and gonadotrophin (FSH, LH) levels in women?

  2. What is the effect of therapeutic RAI on ovarian function, menses, ovulation, fertility or the age of menopause? A secondary question was to examine whether any effect (if present) was different in women treated with oral contraceptives at the time of RAI treatment.

  3. What is the effect of therapeutic RAI for DTC on future fertility, pregnancy outcomes and offspring (including live births, spontaneous abortions, induced abortions, stillbirths, preterm birth, infant mortality and congenital defects)?

A requirement for inclusion in the review was a control group comparison (either external comparison or comparison to measures prior to RAI treatment) for one or more of the relevant outcomes listed above. The review was restricted to papers published in the English language. Data from the following types of studies were eligible for inclusion: cohort studies, cross-sectional studies, cancer registries, administrative datasets, meta-analyses, or case series of more than five patients. Studies examining outcomes after RAI for diagnostic purposes or for treatment of benign thyroid diseases (such as hyperthyroidism) were not eligible for inclusion. With respect to the control group comparisons, we considered the use of historical or referenced published controls acceptable if there was some numerical description of event rates in the control study or a quantitative comparison with the study population. Studies examining outcomes of women who inadvertently received RAI during pregnancy were not included.

We conducted an electronic search of the following databases for relevant studies examining the RAI effects on gonads or offspring (duration from inception of electronic dataset to 21 November 2007: Ovid Medline, Ovid Medline-in-Process and nonindexed citations, Cochrane database of systematic reviews, ACP Journal Club, Evidence-Based Medicine Reviews (including Database of Abstracts of Reviews of Effects and Cochrane Central Register of Controlled Trials), Embase, Cumulative Index to Nursing and Allied Health Literature, and Ovid Healthstar. A preliminary electronic search was originally restricted to papers on humans published in the English language with no gender restriction (July 2007).[5] In the updated search from 21 November 2007, search terms relating to male sex steroids, spermatozoa or testes were not included as the update was restricted to female gender. The electronic search was supplemented with papers recommended by content experts as well as relevant cross-referenced citations.

Two reviewers independently examined all abstracts and citations and any abstract or citation deemed potentially relevant was retrieved in full-text form. Subsequently, all full-text papers were reviewed by two independent reviewers and consensus was required for study inclusion in the review. Two abstractors independently abstracted data from the included studies. If duplicate publications examining data from the same patient population were identified, we included only the largest or more complete relevant study for the outcome of interest.

The methodological quality of included papers was appraised based on the following criteria: (a) longitudinal follow-up or cross-sectional sampling of participants, (b) the type of control group [i.e. internal (measurements prior to RAI treatment), contemporaneous external controls or historical external controls], (c) any description of losses to follow-up for longitudinal studies (yes, no), and (d) the presence of a statistical comparison for the outcome of interest (as reflected by the presence of a P-value or 95% confidence intervals).

Descriptive data from individual studies were tabulated using means or medians and standard deviations (SD) or ranges for continuous data and numbers with percentages for categorical data. We quantified agreement between reviewers for relevance of abstracts as well as inclusion of full-text papers using Kappa statistics (Confidence Interval Analysis (CIA) software, BMJ Books, 2000).


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