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

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

900 participants

Study Classification

OBSERVATIONAL

Study Start Date

2019-01-01

Study Completion Date

2026-03-30

Brief Summary

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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.

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Detailed Description

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This study is a target trial specified (a randomized controlled trial between the Intervention (Exposed) Group and the Control (Unexposed) Group).

* Intervention (Exposed) Group: Women treated with levothyroxine 25-50 µg/day initiated before the planned FET, titrated every 2-4 weeks to achieve TSH \< 2.5 mIU/L before transfer.
* Control (Unexposed) Group: Women managed expectantly without thyroid medication (Before 2020, LT4 use was at the discretion of clinicians; since 2020, the Reproductive Endocrinology Unit has standardized treatment for most SCH patients)

The target trial is emulated using observational data of infertile women aged 18-45 years diagnosed with subclinical hypothyroidism, defined as TSH 4.2-\<10 mIU/L and FT4 0.92-1.68 ng/dL, undergoing IVF/ICSI followed by FET in My Duc Hospital and My Duc Phu Nhuan Hospital (Ho Chi Minh City, Vietnam), using routinely collected medical records from January 1, 2019, to December 31, 2024.

Conditions

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

Study Design

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Observational Model Type

COHORT

Study Time Perspective

RETROSPECTIVE

Study Groups

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Levothyroxine-Treated Group

Women with subclinical hypothyroidism (TSH 4.2-\<10 mIU/L, normal FT4) treated with levothyroxine 25-50 µg/day before frozen embryo transfer (FET). The dose was adjusted every 2-4 weeks to achieve a pre-transfer TSH \<2.5 mIU/L. Outcomes including implantation, pregnancy, and live birth rates were assessed after the nearest post-treatment FET cycle.

No interventions assigned to this group

Non-Treated (Control) Group

Women with subclinical hypothyroidism (TSH 4.2-\<10 mIU/L, normal FT4) who did not receive levothyroxine treatment prior to frozen embryo transfer. Participants were managed expectantly according to clinical judgment. Outcomes were compared with those of the treated group for IVF/ICSI-FET success and pregnancy results.

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* 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).

Exclusion Criteria

* 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).

Minimum Eligible Age

18 Years

Maximum Eligible Age

45 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No