Levothyroxine dose adjustment in hypothyroid women achieving pregnancy through IVF

Abstract

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 (nZ28), 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 (nZ28) and did not (nZ10) 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.

2021 European Thyroid Association Guideline on Thyroid Disorders prior to and during Assisted Reproduction

“…Women already treated with levothyroxine (LT4) should adapt the dose of LT4 at least 4 weeks before OS. Women with (subclinical) hypothyroidism should initiate LT4 to keep serum TSH levels <2.5 mIU/L [10].…”

Effect of levothyroxine supplementation on pregnancy outcomes in women with subclinical hypothyroidism and thyroid autoimmuneity undergoing in vitro fertilization/intracytoplasmic sperm injection: an updated meta-analysis of randomized controlled trials

“…[ 24 – 26 ]. These inconsistent conclusions may be attributable to the different time windows in which thyroid function testing was conducted and LT4 supplementation was initiated [ 27 ].…”

Cancer Risk in Women Treated with Fertility Drugs According to Parity Status—A Registry-based Cohort Study

“…Thus, confounding by indication may be driving some of the observed associations between fertility drugs and ovarian cancer. This may also be the case for thyroid cancer as, it has been demonstrated that thyroxin substitution treatment is used more frequently by ART pregnant women, than by those pregnant after natural conception (69). It may therefore be that the preexisting thyroid disease may be a common cause of both infertility and thyroid neoplasms.…”