Subclinical HypothyroidismLESINCT07257250
Levothyroxine Treatment and IVF Outcomes in Women With Subclinical Hypothyroidism: A Target Trial Emulation
An observational study of Subclinical Hypothyroidism and Infertility, run by Mỹ Đức Hospital at 2 sites in Vietnam.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 18 to 45 years, women only
- Conditions the study is for
- Subclinical Hypothyroidism, Infertility, Assisted Reproductive Technology
- How many people
- 900 participants
- Where
- 2 sitesVietnam
- Study dates
- 1 Jan 2019to 30 Mar 2026
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 45 years
- Women only
- No healthy volunteers
- Adult
Study population: Infertile women aged 18-45 years diagnosed with subclinical hypothyroidism (TSH 4.2-<10 mIU/L, normal FT4) who underwent IVF/ICSI with subsequent frozen embryo transfer (FET) at My Duc Hospital and My Duc Phu Nhuan Hospital, Ho Chi Minh City, Vietnam, between 2019 and 2024.
Who may be able to join
- 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).
Who cannot join
- 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).
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Vietnam2 sites, 1 recruiting
- Recruiting
My Duc Hospital
Ho Chi Minh City, Ho Chi Minh, 700000
Hoanh Kieu Tran, Doctor, +84 982 741 425, trankieuhoanh@myduchospital.vn
Lan Thi Ngoc Vuong, Assoc. Prof., +84 901 183 918, drlan@yahoo.com.vn
- Completed
My Duc Hospital
Ho Chi Minh City, Ho Chi Minh, 700000
About this study
Official title: Effectiveness of Levothyroxine Treatment on In Vitro Fertilization and Pregnancy Outcome in Women With Subclinical Hypothyroidism and Infertility: A Target Trial Emulation
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.
Read the detailed description
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
- Subclinical Hypothyroidism, Infertility, Assisted Reproductive Technology, In Vitro Fertilization (IVF), Intracytoplasmic Sperm Injection, Frozen Embryo Transfer (FET)
- Keywords
- Levothyroxine, Subclinical Hypothyroidism, Infertility, Thyroid Disorders, IVF, ICSI, Frozen Embryo Transfer, FET, Assisted Reproductive Technology, Live Birth, Miscarriage, Pregnancy Outcomes, Thyroid Autoimmunity
- Medical subject headings
- Infertility, Thyroid Diseases, Abortion, Spontaneous
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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. | |
| 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. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Live birth rate after the first frozen embryo transfer (FET) cycle
Delivery of a neonate showing any sign of life (heartbeat, umbilical cord pulsation, or movement) at ≥ 22 weeks' gestation after the nearest frozen embryo transfer cycle performed following levothyroxine treatment (or no treatment) in women with subclinical hypothyroidism undergoing IVF/ICSI.
Measured: At delivery (within approximately 9 months after embryo transfer)
Secondary outcomes (13)
Positive pregnancy test rate
Serum β-hCG ≥ 25 IU/mL after embryo transfer.
Measured: 10-14 days post-transfer
Clinical pregnancy rate
Ultrasonographic visualization of a gestational sac or embryo with cardiac activity.
Measured: 6 weeks post-transfer
Ongoing pregnancy rate
Presence of a fetus with heartbeat at ≥ 12 weeks' gestation.
Measured: 12 weeks post-transfer
Implantation rate
Number of gestational sacs divided by number of embryos transferred.
Measured: 3 weeks post-transfer
Miscarriage rate
Spontaneous loss of a clinical pregnancy before 22 weeks' gestation.
Measured: Up to 22 weeks post-transfer
Ectopic pregnancy rate
Pregnancy outside the uterine cavity confirmed by ultrasound or surgery.
Measured: Up to 6 weeks post-transfer
Multiple pregnancy rate
Detection of ≥2 gestational sacs on ultrasound.
Measured: 6 weeks post-transfer
Preterm birth rate
defined as a birth that takes place after 22 weeks and before 37 completed weeks of gestational age.
Measured: At delivery
Gestational hypertension/preeclampsia
Gestational hypertension/preeclampsia is defined as the development of hypertension with or without proteinuria after 20 weeks of gestation.
Measured: After 20 weeks' gestation
Gestational diabetes mellitus
Gestational diabetes mellitus is diagnosed by 75-g Oral Glucose Tolerance Test (OGTT) with abnormal fasting or postload glucose at 24-28 weeks.
Measured: 24-28 weeks' gestation
Neonatal birthweight
Infant weight at delivery (low <2500 g; very low <1500 g; high >4000 g).
Measured: At delivery
Congenital anomalies
Congenital anomalies are defined as structural or functional disorders that occur during intra-uterine life and can be identified prenatally at birth.
Measured: at delivery
Neonatal death
Death of a live-born infant within 28 days of birth.
Measured: Up to 1 month after delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 Dec 2025
- Study start1 Jan 2019
- Primary completion30 Dec 2024
- Study completion30 Mar 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Subclinical HypothyroidismStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 900 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mỹ Đức Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07257250
- Sponsor's protocol ID
- 13/25/DD-BVMD
- Acronym
- LESI
- Status last verified
- Dec 2025
- First submitted
- 20 Nov 2025
- Last updated
- 14 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Poppe K, Glinoer D. Thyroid autoimmunity and hypothyroidism before and during pregnancy. Hum Reprod Update. 2003 Mar-Apr;9(2):149-61. doi: 10.1093/humupd/dmg012.
PubMed 12751777Zhang Y, Wang H, Pan X, Teng W, Shan Z. Patients with subclinical hypothyroidism before 20 weeks of pregnancy have a higher risk of miscarriage: A systematic review and meta-analysis. PLoS One. 2017 Apr 17;12(4):e0175708. doi: 10.1371/journal.pone.0175708. eCollection 2017.
PubMed 28414788Bein M, Yu OHY, Grandi SM, Frati FYE, Kandil I, Filion KB. Levothyroxine and the risk of adverse pregnancy outcomes in women with subclinical hypothyroidism: a systematic review and meta-analysis. BMC Endocr Disord. 2021 Feb 27;21(1):34. doi: 10.1186/s12902-021-00699-5.
PubMed 33639909Maraka S, Singh Ospina NM, O'Keeffe DT, Rodriguez-Gutierrez R, Espinosa De Ycaza AE, Wi CI, Juhn YJ, Coddington CC 3rd, Montori VM, Stan MN. Effects of Levothyroxine Therapy on Pregnancy Outcomes in Women with Subclinical Hypothyroidism. Thyroid. 2016 Jul;26(7):980-6. doi: 10.1089/thy.2016.0014. Epub 2016 May 16.
PubMed 27112035Kim CH, Ahn JW, Kang SP, Kim SH, Chae HD, Kang BM. Effect of levothyroxine treatment on in vitro fertilization and pregnancy outcome in infertile women with subclinical hypothyroidism undergoing in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2011 Apr;95(5):1650-4. doi: 10.1016/j.fertnstert.2010.12.004. Epub 2010 Dec 30.
PubMed 21193190
Study at a glance
From the registry record, last updated by the sponsor on 14 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effectiveness of Levothyroxine Treatment on In Vitro Fertilization and Pregnancy Outcome in Women With Subclinical Hypothyroidism and Infertility: A Target Trial Emulation
- ClinicalTrials.gov ID
- NCT07257250
- Acronym / sponsor ID
- LESI / 13/25/DD-BVMD
- Conditions
- Subclinical Hypothyroidism, Infertility, Assisted Reproductive Technology, In Vitro Fertilization (IVF), Intracytoplasmic Sperm Injection, Frozen Embryo Transfer (FET)
- Keywords
- Levothyroxine, Subclinical Hypothyroidism, Infertility, Thyroid Disorders, IVF, ICSI, Frozen Embryo Transfer, FET
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 900 participants (estimated)
- Lead sponsor
- Mỹ Đức HospitalUniversity, hospital or other
- Study start
- 1 Jan 2019 (actual)
- Primary completion
- 30 Dec 2024 (actual)
- Study completion
- 30 Mar 2026 (estimated)
- First posted
- 2 Dec 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 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. |
| 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. |
Who may qualify
- Ages
- 18 to 45 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
- Study population
- Infertile women aged 18-45 years diagnosed with subclinical hypothyroidism (TSH 4.2-<10 mIU/L, normal FT4) who underwent IVF/ICSI with subsequent frozen embryo transfer (FET) at My Duc Hospital and My Duc Phu Nhuan Hospital, Ho Chi Minh City, Vietnam, between 2019 and 2024.
Key inclusion criteria (3 listed)
- 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).
Key exclusion criteria (2 listed)
- 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).
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Live birth rate after the first frozen embryo transfer (FET) cycle
Time frame: At delivery (within approximately 9 months after embryo transfer)
Delivery of a neonate showing any sign of life (heartbeat, umbilical cord pulsation, or movement) at ≥ 22 weeks' gestation after the nearest frozen embryo transfer cycle performed following levothyroxine treatment (or no treatment) in women with subclinical hypothyroidism undergoing IVF/ICSI.
13 secondary outcomes
Positive pregnancy test rate
Time frame: 10-14 days post-transfer
Clinical pregnancy rate
Time frame: 6 weeks post-transfer
Ongoing pregnancy rate
Time frame: 12 weeks post-transfer
Implantation rate
Time frame: 3 weeks post-transfer
Miscarriage rate
Time frame: Up to 22 weeks post-transfer
Ectopic pregnancy rate
Time frame: Up to 6 weeks post-transfer
Multiple pregnancy rate
Time frame: 6 weeks post-transfer
Preterm birth rate
Time frame: At delivery
Gestational hypertension/preeclampsia
Time frame: After 20 weeks' gestation
Gestational diabetes mellitus
Time frame: 24-28 weeks' gestation
Neonatal birthweight
Time frame: At delivery
Congenital anomalies
Time frame: at delivery
Neonatal death
Time frame: Up to 1 month after delivery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jan 2026.
- Background: PubMed 12751777Poppe K, Glinoer D. Thyroid autoimmunity and hypothyroidism before and during pregnancy. Hum Reprod Update. 2003 Mar-Apr;9(2):149-61. doi: 10.1093/humupd/dmg012.
- Background: PubMed 28414788Zhang Y, Wang H, Pan X, Teng W, Shan Z. Patients with subclinical hypothyroidism before 20 weeks of pregnancy have a higher risk of miscarriage: A systematic review and meta-analysis. PLoS One. 2017 Apr 17;12(4):e0175708. doi: 10.1371/journal.pone.0175708. eCollection 2017.
- Background: PubMed 33639909Bein M, Yu OHY, Grandi SM, Frati FYE, Kandil I, Filion KB. Levothyroxine and the risk of adverse pregnancy outcomes in women with subclinical hypothyroidism: a systematic review and meta-analysis. BMC Endocr Disord. 2021 Feb 27;21(1):34. doi: 10.1186/s12902-021-00699-5.
- Background: PubMed 27112035Maraka S, Singh Ospina NM, O'Keeffe DT, Rodriguez-Gutierrez R, Espinosa De Ycaza AE, Wi CI, Juhn YJ, Coddington CC 3rd, Montori VM, Stan MN. Effects of Levothyroxine Therapy on Pregnancy Outcomes in Women with Subclinical Hypothyroidism. Thyroid. 2016 Jul;26(7):980-6. doi: 10.1089/thy.2016.0014. Epub 2016 May 16.
- Background: PubMed 21193190Kim CH, Ahn JW, Kang SP, Kim SH, Chae HD, Kang BM. Effect of levothyroxine treatment on in vitro fertilization and pregnancy outcome in infertile women with subclinical hypothyroidism undergoing in vitro fertilization/intracytoplasmic sperm injection. Fertil Steril. 2011 Apr;95(5):1650-4. doi: 10.1016/j.fertnstert.2010.12.004. Epub 2010 Dec 30.
- ClinicalTrials.gov registration (once approved)Link provided by the sponsor.
- University of Medicine and Pharmacy at Ho Chi Minh City - Reproductive Endocrinology UnitLink provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Subclinical Hypothyroidism and Infertility, run by Mỹ Đức Hospital at 2 sites in Vietnam.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 14 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Vietnam. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Hoanh Kieu Tran, Doctor (+84 982 741 425, trankieuhoanh@myduchospital.vn), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Live birth rate after the first frozen embryo transfer (FET) cycle (time frame: At delivery (within approximately 9 months after embryo transfer)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07257250, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jan 2026.