Grand Rounds

POSTAL Study Results: Does Levothyroxine Improve Pregnancy Outcomes in Women with Thyroid Autoantibodies Undergoing IVF?

BACKGROUND AND PURPOSE: 

Overt hypothyroidism is associated with increased risk of spontaneous miscarriage
Most hypothyroidism in reproductive age women is caused by ‘thyroid autoimmunity’ defined as the presence of
- Thyroid autoantibodies
- Antithyroperoxidase antibody
- Antithyroglobulin antibody
Some previous research suggests increased miscarriage among women with thyroid autoantibodies, including in the setting of IVF
Conflicting data as to whether levothyroxine impacts miscarriage rates when thyroid function is intact but autoantibodies are present
Wang et al. (JAMA, 2017) sought to determine whether levothyroxine treatment improves pregnancy outcomes among women undergoing in vitro fertilization and embryo transfer (IVF-ET) who had otherwise normal thyroid function but tested positive for thyroid autoantibodies

Open-label, randomized clinical trial 
Pregnancy Outcomes Study in Euthyroid Women With Thyroid Autoimmunity After Levothyroxine (POSTAL) study conducted over the 4.5-year study period)
Patients: Women referred for their first or second fresh IVF-ET cycles
- 23-40 years of age
- BMI ≤35
- No known endocrinological disorders or ≥2 miscarriages
- Normal thyroid function (TSH normal) but positive for antithyroperoxidase antibody
Women were randomized to  
- Intervention group: 25 25-μg/d or 50-μg/d dose of levothyroxine at study initiation that was titrated according to the level of TSH during pregnancy 
- Control group: Not administered levothyroxine
Primary outcome
- Miscarriage rate: Pregnancy loss before 28 weeks of gestation
Secondary outcomes
- Clinical intrauterine pregnancy rate: Fetal cardiac activity seen at sonography observation on the 30th day after the embryo transfer
- Live-birth rate: At least 1 live birth after 28 weeks of gestation

565 women had IVF-ET and completed the study
- Mean age was 31.6 years  
Miscarriage rates
- 10.3% in the intervention group and 10.6% in the control group
  - Absolute rate difference (RD) of -0.34% (95% CI, -8.65% to 8.12%)
Clinical intrauterine pregnancy rates
- 35.7% in the intervention group and 37.7% in the control group
- Absolute RD of -2.00% (95% CI, -9.65% to 5.69%) 
Live-birth rates
- 31.7% in the intervention group and 32.3% in the control group
  - Absolute RD of -0.67% (95% CI, -8.09% to 6.77%) 
Subgroup analysis on TSH levels ≥2.5mIU/L and ≥4.0 mIU/L
- No levothyroxine benefit found

Authors recognize limitations of this study, including lack of placebo, however, outcomes (e.g., miscarriage) could not be impacted by the investigator
Levothyroxine treatment did not impact miscarriage or live-birth rates for women undergoing IVF-ET with normal thyroid function and presence of antithyroperoxidase antibody
This data supports the American Thyroid Association and Endocrine Society guidelines
There are ongoing trials to assess benefit of levothyroxine treatment in other non-IVF settings

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