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。

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.

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