Abstract
We thank Drs. Mintziori and Goulis for their letter regarding our article (1). They raise several concerns, which we address herein.
We found a significantly reduced pregnancy rate in overtly hypothyroid women treated with levothyroxine (LT4), which was reflected in the reduced live birth rate. The United States Preventive Service Task Force recommendation that women with subclinical hypothyroidism treated with LT4 have improved obstetrical outcomes (Level B), does not address the issue of actual pregnancy rates following in vitro fertilization (IVF) in treated hypothyroid women, which was the objective of our study.
Our retrospective study included 21 patients with hypothyroidism, which is a small number of patients upon which to draw definitive conclusions. However, our findings represent the largest study to date on the impact of treated hypothyroidism in IVF patients. We welcome a larger multicenter prospective study of LT4-treated women with hypothyroidism in IVF.
The Endocrine Society clinical practice guidelines on the treatment of hypothyroid women attempting to conceive, with the goal of maintaining thyrotropin (TSH) levels <2.5 μU/mL, had not been issued at the time of patient recruitment for this study (2). However, the mean baseline TSH level in our cohort was 2.5±1.3 μU/mL. We agree that some of our patients may have been undertreated, according to the 2007 clinical practice guidelines, and we have preliminary results indicating that aggressive LT4 treatment, with the aim of maintaining TSH levels <2.5 μU/mL, and close monitoring of TSH during ovarian stimulation (on day one, day of human chorionic gonadotropin trigger, and day of pregnancy test), may help improve IVF outcomes in these patients.
The role of thyroid autoimmunity is, at best, controversial. Although we did not measure thyroid autoimmunity in our IVF patients, there was no evidence of an adverse effect on early pregnancy outcomes, as demonstrated by the lack of miscarriages in the 21 patients who had LT4-treated hypothyroidism, which was significantly less than the 19% miscarriage rate in the 219 women without thyroid dysfunction. With respect to IVF outcomes, a recent large meta-analysis of seven eligible studies, found no association between the presence of thyroid antibodies and the clinical pregnancy rates after IVF (3).
Our study compared overtly hypothyroid women, treated with LT4, to women without thyroid dysfunction undergoing IVF. Nevertheless, it appears that subclinical hypothyroidism also significantly impacts IVF live birth rates in untreated women (4), emphasizing the need to optimize TSH levels before and during controlled ovarian stimulation for IVF.
Our study is the largest to date to document the impact of treated hypothyroidism in a young (age <37 years) IVF population, and the first to show that treated hypothyroidism can negatively affect implantation, clinical pregnancy, and live birth rates. However, due to its retrospective nature, prolonged recruitment time interval and heterogeneity of stimulation protocols, our study requires confirmation by a larger multicenter prospective trial.