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Table 1 Summary of included studies

From: Effect of levothyroxine supplementation on pregnancy outcomes in women with subclinical hypothyroidism and thyroid autoimmuneity undergoing in vitro fertilization/intracytoplasmic sperm injection: an updated meta-analysis of randomized controlled trials

Study Country Study population ART details Causes of infertility Patients age Patients BMI
Negro 2005 Italy 86 TPO-Abs-positive infertile women undergoing ART The first cycle of IVF/ICSI In treated group: 11, 10, 7 and 8 patients were due to ovarian dysfunction, tubal factors, endometriosis and idiopathic causes, respectively; In control group: the number was 13, 9, 9 and 5, respectively. Treated group:29.2 ± 4; Placebo: 30.1 ± 5 Unclear
Rahman 2010 Egypt 70 infertile women with subclinical hypothyroidism undergoing ART All patients underwent ICSI In treated group: 13, 9, 7 and 6 patients were due to ovarian dysfunction, tubal factors, endometriosis and idiopathic causes, respectively; In control group: the number was 12, 11, 5 and 7, respectively. Treated group:31.2 ± 4.7; Placebo: 30 ± 4.3 Unclear
Kim 2011 South Korea 64 infertile patients with subclinical hypothyroidism undergoing ART In both treated and control group: 18 and 14 patients underwent IVF and ICSI, respectively. In treated group: 10, 6, 13 and 3 patients were due to tubal factors, endometriosis, male factors and idiopathic causes, respectively; In control group: the number was 9, 7, 13 and 3, respectively. Treated group:36.0 ± 2.4; Placebo: 36.1 ± 2.2 Treated group:21.5 ± 1.9; Placebo: 21.7 ± 2.1
Wang 2017 China 600 TPO-Abs-positive infertile women undergoing ART The first or second fresh IVF cycle In treated group: 140, 37, 10, 15, 37, 128 and 21 patients were due to tubal factors, PCOS, endometriosis, Uterine malformation, Intrauterine insemination failure, male factors and idiopathic causes, respectively; In control group: the number was 142, 35, 14, 22, 27, 110 and 12, respectively. Treated group: 31.3 ± 3.9; Placebo: 31.7 ± 3.8 Treated group: 22.7 ± 3.3; Placebo: 22.8 ± 3.2
Study Reference values for thyroid status Thyroid status and thyroid hormone values in patients Intervention Pregnancy outcomes
Negro 2005 TSH 0.27–4.2 mIU/L fT4 9.3–18.0 ng/L (12–33.5 pmol/L) TPO-Ab 0–100 kIU/L For all patients:TPO-Ab (+). TSH and fT4 within normal range. Treated group: TSH 1.9 ± 0.7 mIU/L before treatment, fT4 11.2 ± 1.8 ng/L before treatment; TSH 1.1 ± 0.3 mIU/L after treatment, fT4 14.1 ± 2.5 ng/L after treatment; Conttrol group:TSH 1.7 ± 0.7 mIU/L, fT4 11.7 ± 2.1 ng/L Patients in treated group underwent LT4 1 μg/kg/day treatment, one month before ART, this treatment was maintained throughout pregnancy CPR, LBR, MR
Rahman 2010 TSH 0.27–4.2 mIU/L, fT3 2.56–4.4 pg/mL, fT4 0.9–2.59 ng/dL For all patients:TSH > 4 mUI/L, fT4 within normal range. Treated group: TSH 4.7 ± 0.5 mIU/L before treatment, fT3 2.85 ± 0.7 ng/L before treatment, fT4 1 ± 0.4 before treatment; Conttrol group:TSH 4.8 ± 0.7 mIU/L, fT3 2.79 ± 0.8 ng/L, fT4 1.04 ± 0.49 ng/L Patients in treated group underwent LT4 50–100 μg/day, one month before ART, this treatment was maintained throughout pregnancy CPR, LBR, MR
Kim 2011 TSH 0.27–4.0 mIU/L fT4 0.9–2.59 ng/dL For all patients:TSH>4.5 mUI/L, fT4 within normal range. Treated group: TSH 6.6 ± 1.7 mIU/L before treatment, fT4 1.2 ± 0.2 before treatment; Conttrol group:TSH 6.7 ± 1.8 mIU/L, fT4 1.2 ± 0.2 ng/L Patients in treated group underwent LT4 50 μg/day, from the first day of controlled ovarian stimulation, this treatment was maintained throughout pregnancy CPR, LBR, MR
Wang 2017 TSH 0.5–4.78 mIU/L TPO-Ab 0–60 IU/mL For all patients:TPO-Ab (+). TSH and fT4 within normal range. Treated group: TSH (mean (interquartile range)), 2.94 (2.04–3.74) mIU/L before treatment, fT4 (mean ± SD), 1.16 ± 0.13 before treatment; Conttrol group: TSH 2.12 (1.5–2.8) mIU/L, fT 4 1.19 ± 0.14 ng/L LT4 was supplemented between 2 and 4 weeks before the COS and continued through the end of pregnancy. For individuals with a TSH level ≥ 2.5 mIU/L, the starting dose was 50 μg/d; for those with a TSH level < 2.5 mIU/L, the starting dose was 25 μg/d. For individuals with body weight < 50 kg, the starting dose was decreased by 50%. The LT4 dose was titrated to keep the TSH level within 0.1 to 2.5 mIU/L in the first trimester, 0.2 to 3.0 mIU/L in the second trimester,and0.3 to 3.0mIU/L in the third trimester. CPR, LBR, MR, PBR
  1. TPO-Ab thyroperoxidase antibody; TSH thyrotropin; LT4 levothyroxine; CPR clinical pregnancy rate; LBR live birth rate; MR miscarriage rate; PBR preterm birth rate; COS controlled ovarian stimulation