Response to Letter: Are We Really Sure that Subclinical Hypothyroidism and Thyroid Autoimmunity Are Not Associated With Fecundity, Pregnancy Loss, or Live Birth?

We appreciate Paparodis' thoughtful comments regarding our research. Although it is possible that patient self-report can be incorrect, questionnaires can collect personal or risk factor data that often are not included in hospital records. Additionally, questionnaires offer a method for collect data in a standardized fashion (1). Further, although a visit with a gynecologist could rule out current issues (ie, active pelvic inflammatory disease), it would be of little use in diagnosing a prior episode of pelvic inflammatory disease. Many of the disorders we used as exclusion criteria cannot be diagnosed without surgery or an invasive procedure (ie, tubal disease and endometriosis), and a simple visit to the gynecologist is a poor proxy for diagnosis of these disorders. Furthermore, infertility cannot be diagnosed without a careful history, and we must rely on our patients to provide this important information. However, although possible that some women in this population had undiagnosed or unreported endocrinopathy, we believe this actually improves the generalizability of our findings, because they apply to a broader population of women with a history of 1–2 prior losses and have not been diagnosed with these gynecologic conditions.

The clinical impact of both thyroid peroxidase (TPO) and thyroglobulin antibodies has been disputed in the literature, and in fact some evidence seems to point to the particular importance of anti-TPO (2, 3). We too were interested in the possible differences in these antibodies and did examine our data based on presence of anti-TPO antibodies vs presence of anti-thyroglobulin antibodies separately and did not observe any differences. However, it is possible that this subanalysis was underpowered; therefore, we combined the antibody positive women into 1 group. In addition, comparison of the mean titer levels between TSH groups yielded similar results.

There are certainly some limits to our study, which were noted in our original article. However, to date, this study offers the most insight on the relationship of subclinical hypothyroidism markers and fecundity and early pregnancy loss among a population of generally healthy women with a history of prior losses. We encourage other researchers to further our attempt to address these important clinical questions.

Funding Statement

This work was supported by the Intramural Research Program of the Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda, MD (Contract Nos. HHSN267200603423, HHSN267200603424, HHSN267200603426).