Abortion, Habitual
Conditions
Keywords
recurrent pregnancy loss, isolated maternal hypothyroidism, levothyroxine, adverse pregnancy outcomes, live birth, neonatal complications
Brief summary
The goal of this randomized, double-blind, placebo-controlled clinical trial is to evaluate whether levothyroxine supplement improves pregnancy outcomes in women with recurrent pregnancy loss (RPL) and isolated maternal hypothyroidism (IMH). The main questions it aims to answer are: Does levothyroxine increase the live birth rate after 24 weeks of gestation? Does levothyroxine improve secondary outcomes such as ongoing pregnancy rates, reduce the incidence of pregnancy loss, or influence maternal and neonatal complications? Researchers will: Compare the levothyroxine treatment group (50 µg/day) to the placebo group to assess the impact of the intervention on live birth rates and other pregnancy outcomes. Participants will: Be randomly assigned to receive either levothyroxine or a placebo. Take the assigned treatment daily starting from enrollment until the end of pregnancy. Undergo routine follow-up visits to monitor pregnancy progress and outcomes. This trial seeks to determine whether routine levothyroxine supplementation can improve pregnancy outcomes for women with RPL and IMH.
Detailed description
Investigators will perform a multi-center, randomized, placebo, double-blind clinical trial of levothyroxine (LT4) in patients aged between 18 years and 40 yearls who are diagnosed with isolated hypothyroxemia (defined as lower FT4 level with normal TSH) and have a previous history of recurrent miscarriages (defined as two or more pregnancy loss). Investigators will assess the effects of standard dose of 50ug/d levothyroxine therapy from the day after randomization to the day of delivery on the pregnancy outcomes, including live birth, neonatal complications, and adverse pregnancy outcomes, etc.
Interventions
DRUGLevothyroxin
Levothyroxin 50ug/d from randomization until delivery
DRUGPlacebo
Placebo to levothyroxin
Sponsors
Zhejiang Provincial People's Hospital
Women's Hospital School Of Medicine Zhejiang University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Participants and Investigators Both participants and investigators are blinded to the group assignments. Participants receive either levothyroxine (50 µg/day) or a placebo in identical tablets that are indistinguishable in appearance, color, shape, and weight. Investigators administering treatments and assessing outcomes remain unaware of the treatment allocation. Randomization and Allocation Randomization is conducted using a secure web-based system, ensuring a 1:1 allocation ratio to either the levothyroxine or placebo group. The randomization process is stratified by study centers to maintain balance across locations. Packaging and Labeling Study drugs, including the placebo, are packaged and labeled uniformly to prevent any visual or informational clues. Each package contains a unique identification code that corresponds to the randomization list, ensuring proper allocation without revealing the treatment group.
Intervention model description
This is a multi-center, randomized, double-blind, placebo-controlled trial
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* women with singleton pregnancy * women with a history of recurrent pregnancy loss (defined as two or more pregnancy loss before 20wks) * women diagnosed with isolated maternal hypothyroidism (defined as isolated lower level of FT4 with normal TSH levels) in the current pregnancy before 20wks
Exclusion criteria
* patients with known thyroid disorders * patients with antiphospholipid syndrome or other autoimmune conditions * patients with contraindications to levothyroxine (e.g., acute cardiac arrest, acute pancreatitis, acute myocarditis) * patients attending other ongoing clinical trials or unwilling to participate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Live birth after 28 weeks of gestation | From the enrollment to the day of delivery after 28+0 weeks of gestation | Live birth following spontaneous labor or iatrogenic delivery after 28+0 weeks of gestation (196 days from the participant's last menstrual period) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Ongoing pregnancy at 7 weeks of gestation | From the day of randomization to the 7 weeks of gestation | ultrasound diagnosis of ongoing pregnancy at 7 weeks of gestation |
| Ongoing pregnancy at 12 weeks of gestation | From the day of randomization to the 12 weeks of gestation | ultrasound diagnosis of ongoing pregnancy at 12 weeks of gestation |
| Ongoing pregnancy at 24 weeks of gestation | From the day of randomization to the 24 weeks of gestation | ultrasound diagnosis of ongoing pregnancy at 24 weeks of gestation |
| Miscarriage | From enrollment to 19+6 weeks of gestation | pregnancy loss before 20 weeks of gestation |
| Stillbirth | From enrollment to the day of delivery of the dead fetus from 20+0 weeks onward | fetal death delivered beyond 20 weeks of gestation |
| Ectopic pregnancy | From enrollment to the end of treatment up to 20 weeks | ultrasound diagnosis of ectopic pregnancy |
| Abortion | From enrollment to the day of termination of pregnancy up to 27+6 weeks | personal request the termination of pregnancy without medical conditions |
| Need for cervical cerclage | From enrollment to the day of cervical cerlage performed up to 27+6 weeks | medically indicated cervical cerclage up to 27+6 weeks of gestation |
| Gestational age at delivery | up to delivery | Gestational age at delivery |
| Antepartum complications | From enrollment to the day of delivery, up to 42+0 weeks | including: preeclampsia, gestational diabetes, fetal growth restriction |
| Intrapartum complications | up to delivery | including: fetal distress, dystocia, fever |
| Postpartum complications | up to 42 days after childbirth | including: postpartum hemorrhage, infection, fever |
| Neonatal birthweight | up to delivery | the birthweight of the neonate: unit (kg) |
| Neonatal APGAR score | up to 5 minutes after delivery | Neonatal APGAR score at 1 and 5 minutes |
| Neonatal complications | up to 7 days after delivery | include neonatal breathing disorders, neonatal infections, neonatal asphyxia, neonatal jaundice, NICU admission for any other causes |
| Preterm birth | From enrollment to the day of preterm birth between 28+0 and 36+6 weeks | live birth between 28+0 and 36+6 weeks of gestation |
Other
| Measure | Time frame | Description |
|---|---|---|
| Adverse outcomes related to levothyroxine treatment | From enrollment to the end of treatment, up to 40 weeks | unexpected medical event in a patient or clinical trial participant receiving a pharmaceutical product, which may not necessarily be causally related to the treatment |
Countries
China
Contacts
Primary ContactQiong Luo, Ph.D.
Backup ContactZixing Zhong, MSc
Outcome results
None listed