Levothyroxine dose adjustment in hypothyroid women achieving pregnancy through IVF

Objective: About one out of two women with primary hypothyroidism has to increase the dosage of exogenous levothyroxine (L-T-4) during pregnancy. Considering the detrimental impact of IVF on thyroid function, it has been claimed but not demonstrated that L-T-4 dose adjustment may be more significant in hypothyroid women who become pregnant after IVF. Design: Retrospective cohort study. Methods: Hypothyroid-treated women who achieved a live birth through IVF were reviewed. Women could be included if thyroid function was well compensated with L-T-4 before the IVF cycle (i.e., serum TSH <2.5 mIU/l and serum free T-4 within the normal range). Serum TSH and dose adjustment were evaluated at five time points during pregnancy. The trimester ranges for serum TSH considered as reference to adjust L-T-4 therapy were 0.1-2.5 mIU/l for the first trimester, 0.2-3.0 mIU/l for the second trimester, and 0.3-3.0 mIU/l for the third trimester. Results: Thirty-eight women were selected. During the whole pregnancy 32 women (84%; 95% CI: 72-96%) required an increase in the dose of L-T-4. In most cases (n=28), this occured within the first 5-7 weeks of gestation (74%, 95% CI: 58-85%). At 5-7 weeks of gestation, the median (interquartile range) increase of L-T-4 dose for the whole cohort was 26% (0-50%). At 30-32 weeks, it was 33% (14-68%). In order to identify predictive factors of dose adjustment, we compared women who did (n=28) and did not (n=10) adjust L-T-4 dosage at 5-7 weeks' gestation. Significant differences emerged for thyroid autoimmunity prevalence and for the distribution of hypothyroidism aetiology. Conclusions: The vast majority of hypothyroid-treated women who achieve pregnancy through IVF need an increase in the L-T-4 dose during gestation. This requirement tends to occur very early during gestation.