Effects of Levothyroxine Treatment on Fertility and Pregnancy Outcomes in Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials
An erratum to this article was published (Thyroid, Jul 2025 ↗)
Authors' conclusion
Pre-conceptional LT4 treatment for subclinical hypothyroidism does not improve fertility or decrease the incidence of miscarriages. However, further well-designed studies are needed for pre-conceptional treatment, especially in TSH >4.0 mU/L. LT4 treatment during pregnancy had a positive effect on preterm birth; nevertheless, this was only applicable to subclinical hypothyroidism with TSH >4.0 mU/L.
Study context
- Population
- Women with SCH (elevated TSH, normal free thyroxine), including TSH >2.5 mU/L, treated pre-conception or during early pregnancy; RCTs from inception to February 20235 pre-conception + 8 pregnancy RCTs
- Comparison
- Levothyroxine (LT4) vs no LT4 treatment in SCH, before and during pregnancy
- Outcome
- Main outcomes before pregnancy: live birth, pregnancy, miscarriage; during pregnancy: live birth, miscarriage, preterm birth
Methodological detailssubgroup analyses by TSH 2.5-4.0 and >4.0 mU/L, 888 studies identified; 27 full-text articles screened, Of 2 pre-conception studies with TSH >4.0 mU/L, one had high risk of bias, the other 64 participants
- Subgroup analyses by TSH 2.5-4.0 and >4.0 mU/L
- 888 studies identified; 27 full-text articles screened
- Of 2 pre-conception studies with TSH >4.0 mU/L, one had high risk of bias, the other 64 participants
Pooled result
As reported in the abstract
Main outcomes, pre-conception (5 studies, 768 participants) and during pregnancy (8 studies, 2622 participants)
LT4 vs ControlRelative risk (95% CI)
Pre-conception: live birth; not significant
1.41(0.84–2.36)
Pre-conception: pregnancy; not significant
1.73(0.88–3.39)
Pre-conception: miscarriage; not significant
0.46(0.11–2.00)
During pregnancy: live birth; not significant
1.03(0.98–1.09)
During pregnancy: miscarriage; not significant
1.01(0.66–1.53)
- Effect of LT4 during pregnancy on preterm birth differed by TSH values
- P = 0.04
Further pooled results
| Outcome | RR (CI) | |
|---|---|---|
| Preterm birth during pregnancy, subgroup TSH >4.0 mU/LPositive effect reported | 0.47 (0.20–1.10) | |
| Preterm birth during pregnancy, subgroup TSH 2.5-4.0 mU/LNo significant effect | 1.35 (0.79–2.31) | |
| 0.20.5125Relative risk (log scale) |
Original publication
Effects of Levothyroxine Treatment on Fertility and Pregnancy Outcomes in Subclinical Hypothyroidism: A Systematic Review and Meta-Analysis of Randomized Controlled Trials. Thyroid. Published 1 April 2024. doi:10.
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