Levothyroxine Treatment and IVF Outcomes in Women With Subclinical Hypothyroidism: A Target Trial Emulation

Recruiting now

Conditions studied: Subclinical Hypothyroidism, Infertility, Assisted Reproductive Technology, In Vitro Fertilization (IVF), Intracytoplasmic Sperm Injection, Frozen Embryo Transfer (FET)

In brief

Subclinical hypothyroidism (SCH) is defined by elevated thyroid-stimulating hormone (TSH) with normal free thyroxine (fT4) levels. It affects approximately 5-7% of women of reproductive age and may negatively influence outcomes of assisted reproductive technology (ART). During controlled ovarian stimulation, rising estradiol increases thyroxine-binding globulin and thyroid hormone requirements. These physiological changes, combined with increased metabolic demand in early pregnancy, may worsen SCH and contribute to adverse outcomes such as miscarriage, preterm birth, and hypertensive disorders of pregnancy. Although levothyroxine (LT4) is routinely used to treat overt hypothyroidism, evidence for its benefit in SCH, especially among infertile women undergoing In Vitro Fertilization (IVF) or Intra-Cytoplasmic Sperm Injection (ICSI) with frozen embryo transfer (FET), remains inconclusive. Some trials and meta-analyses have shown reductions in miscarriage and neonatal mortality, while others have found no improvement in ART or obstetric outcomes. This study aims to evaluate the effectiveness of levothyroxine therapy on IVF/FET outcomes and subsequent pregnancy results in women with subclinical hypothyroidism and infertility. This retrospective cohort study will emulate the target trial to evaluate whether LT4 treatment, titrated to achieve a pre-transfer TSH \< 2.5 mIU/L, improves implantation, live birth, and obstetric outcomes compared with expectant management.

Key facts

Study ID

NCT07257250

Run by

Mỹ Đức Hospital

People needed

900

Starts

2019-01-01

Expected to finish

2026-03-30

Last updated by the study team

2026-01-14

Who can join

Age: 18 and older, up to 45. Sex: female. Healthy volunteers: not accepted.

You may qualify if…

• Women aged 18-45 years.
• Diagnosed with subclinical hypothyroidism (TSH 4.2-<10 mIU/L with FT4 0.92-1.68 ng/dL).
• Undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) followed by frozen embryo transfer (FET).

You may not qualify if…

• Overt hypothyroidism (TSH ≥10 mIU/L and FT4 ≤0.92 ng/dL).
• Current or recent (within 1 month) use of drugs affecting thyroid function (levothyroxine, amiodarone, methimazole, propylthiouracil).

Where it is running

• My Duc Hospital — Ho Chi Minh City, Ho Chi Minh, Vietnam (enrolling)
• My Duc Hospital — Ho Chi Minh City, Ho Chi Minh, Vietnam

Full record on ClinicalTrials.gov

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