Recurrent Pregnancy Loss and Thyroid Disease

Early Phase 1

• Conditions: Recurrent Pregnancy Loss
• Interventions: Drug: Levothyroxine

• Registration Number: NCT03106935
• Lead Sponsor: Second Affiliated Hospital of Soochow University

Brief Summary

The present study is divided into two groups ,one is the patients with subclinical hypothyroidism who has TPO antibody positive women with TSH concentrations \> 2.5 mU/L and below the upper limit of the pregnancy specific reference range ,another is TPO antibody negative with TSH concentrations greater than the pregnancy specific reference range and below 10.0 mU/L.The two groups are randomized into either the LT4 treatment group or control group by the use of a computer-generated list.

The aim of our study is to determine whether the use of levothyroxine is beneficial in patients with subclinical hypothyroidism in two groups。

Detailed Description

Many studies have stratified the risk imparted by hypothyroidism according to TPOAb status, and consistently show that this risk is higher in TPOAb positive women. Some data also suggest that the adverse impact associated with maternal TSH levels is apparent at lower TSH elevations in women known to be TPOAb positive compared to women who are TPOAb negative. Furthermore, studies suggest a reduction in pregnancy loss when TPOAb positive women are treated with levothyroxine, even when biochemically euthyroid. Intervention trials have not been performed in TPOAb negative women. A etiology analysis process,from June 2010 to June 2015 in The Second Affiliated Hospital of Soochow University, were showed that 22.2% of total 917 cases who had RPL history present as abnormal serum TSH level or positive TPOAb, while 36.6% of 523 cases who repregnancy present as abnormal.This present study is divided into two groups ,one is the patients with subclinical hypothyroidism who hasTPO antibody positive women with TSH concentrations \> 2.5 mU/L and below the upper limit of the pregnancy specific reference range ,another is TPO antibody negative with TSH concentrations greater than the pregnancy specific reference range and below 10.0 mU/L.The two groups are randomized into either the LT4 treatment group or control group by the use of a computer-generated list.For the LT4 treatment group, 50μg LT4 (Merck Serono, Geneva,Switzerland) was administered every morning from the first day of diagnosed as subclinical hypothyroidism and continued up to the day of serum β-HCG measurement.If pregnancy was confirmed, levothyroxine dose need to increase 25-30% and be adjusted according to the pregnancy specific reference range ( T1 0.1-2.5mIU/L,T2 0.2-3.0mIU/L, T3 0.3-3.0mIU/L).For the control group ,women with subclinical hypothyroidism are not given any drugs . The aim of our study is to determine whether the use of levothyroxine is beneficial in patients with subclinical hypothyroidism who has TPO antibody positive women with TSH concentrations \> 2.5 mU/L and below the upper limit of the pregnancy specific reference range or TPO antibody negative with TSH concentrations greater than the pregnancy specific reference range and below 10.0 mU/L.

Study Timeline

• Study Start: 2015-07
• Study First Submitted: 2017-02-27
• Status Verified: 2017-04
• Study First Submitted QC: 2017-04-04
• Last Update Submitted: 2017-04-10
• Study First Posted: 2017-04-11
• Last Update Posted: 2017-04-12
• Primary Completion: 2017-12
• Study Completion: 2018-06

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Female
• Target Recruitment: 300

Inclusion Criteria

1. having a diagnosis of RPL (two or more consecutive or non-consecutive first-trimester losses)
2. be.ing aged 18-39 years at randomisation
3. trying to conceive naturally
4. willing and able to give informed consent

Exclusion Criteria

1. they were unable to conceive naturally (as confirmed by urinary pregnancy tests) within 1 year of recruitment or before the end of the randomisation period in the trial, whichever came earlier
2. they had antiphospholipid syndrome [lupus anticoagulant and/or anticardiolipin antibodies (immunoglobulin G or immunoglobulin M)]; other recognised thrombophilic conditions (testing according to usual clinic practice) l they had uterine cavity abnormalities (as assessed by ultrasound, hysterosonography, hysterosalpingogram or hysteroscopy)
3. they had abnormal parental karyotype
4. they had other identifiable causes of RPL (tests initiated only if clinically indicated) such as diabetes or systemic lupus erythematosus
5. they had any contraindications to Levothyroxine use

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Obstet Gynecol,SecondSoochowU	Levothyroxine	Levothyroxine is an orodispersible tablet.For the LT4 treatment group, 50μg LT4 (Merck Serono, Geneva,Switzerland) was administered every morning from the first day of diagnosed as subclinical hypothyroidism and continued up to the day of serum β-HCG measurement.If pregnancy was confirmed, levothyroxine dose need to increase 25-30% and adjusted according to the pregnancy specific reference range ( T1 0.1-2.5mIU/L,T2 0.2-3.0mIU/L, T3 0.3-3.0mIU/L) .

Primary Outcome Measures

Name	Time	Method
Gestational week at delivery	28 weeks	The research doctor site telephoned every participant 2 weeks after the expected date of delivery to obtain pregnancy outcome data.
Newborn birth weight	at birth	The research doctor site telephoned every participant 2 weeks after the expected date of delivery to obtain newborn birth weight.
APGAR Score at birth	at birth	The APGAR (Appearance, Pulse, Grimace, Activity, Respiration) scale is determined by evaluating the newborn baby on five simple criteria on a scale from zero to two, then summing up the five values thus obtained. The resulting APGAR score ranges from zero to 10.

Secondary Outcome Measures

Name	Time	Method
Number of clinical pregnancy at 6-8 weeks (defined as the presence of a gestational sac, with or without a yolk sac or fetal pole)	8 weeks	The research doctor site telephoned every participant at between 6 and 7 weeks of gestation, to ensure there were arrangements for an ultrasound appointment with her usual carers, before 8 weeks of gestation. If an appointment had not been booked, the research doctor assisted with booking. The research doctor telephoned each participant again between 3 and 5 days after the scheduled date of the ultrasound appointment, to obtain details of the observations of a gestational sac.
Number of ongoing pregnancy at 12 weeks (defined as the presence of a fetal heartbeat)	12weeks	The research doctor site telephoned each participant between 10 and 12 weeks of gestation, to ensure there were arrangements for an ultrasound appointment with her usual carers, at between 12 and 14 weeks of gestation. As previously, the research doctor assisted with booking an appointment if necessary, and telephoned the participant afterwards to obtain details of variables such as fetal heartbeat. The research doctor also recorded the expected date of delivery at this stage.
Number of miscarriage (defined as loss of pregnancy before 28 weeks of gestation).	28 weeks	The research doctor site telephoned each participant before28 weeks of gestation, to obtain their pregnancy outcomes such as miscarriage.

Trial Locations

Locations (1)

Second Affiliated Hospital of Soochow University; 🇨🇳 Suzhou, Jiangsu, China