Effect of levothyroxine supplementation on pregnancy loss and preterm birth in women with subclinical hypothyroidism and thyroid autoimmunity: a systematic review and meta-analysis

Rao, Meng; Zeng, Zhengyan; Zhou, Fang; Wang, Huawei; Liu, Jiang; Wang, Rui; Wen, Ya; Yang, Zexing; Su, Cunmei; Su, Zhenfang; Zhao, Shuhua; Li, Tang

doi:10.1093/humupd/dmz003

Cited by 101 publications

(94 citation statements)

References 109 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These results might indirectly show benefits of L-T4 treatment for infertile women with TSH levels above 2.5 μIU/mL. We speculate that appropriate treatment for infertile women with SCH alleviated the adverse effects on pregnancy, as previously reported [12,14]. Randomized controlled trials are needed to directly clarify the effect of L-T4 treatment, but we did not perform such trials owing to consideration of ethical issues, such as the possible risk of miscarriage.…”

Section: Discussionmentioning

confidence: 83%

“…It was still unclear whether L-T4 treatment decreases the effects of TAI on fertility and pregnancy outcome in infertile women. We therefore evaluated the effects of TAI on pregnancy under treatment with L-T4 for infertile women with TSH levels Recently, some benefits of L-T4 supplementation for SCH women with TSH levels above 2.5 μIU/mL have been reported; miscarriage and premature birth are reportedly decreased [21,22], and others have reported reduction of miscarriage in infertile women with ART [14]. In 2017 ATA guidelines, L-T4 supplementation for women undergoing ART with TSH levels above 2.5 μIU/mL is recommended [10], but the risk factors of miscarriage under L-T4 treatment had not been explored.…”

Section: Discussionmentioning

confidence: 99%

“…TAI is associated with hypothyroidism, so it is unclear whether TAI itself or the subsequent thyroid dysfunction adversely affects pregnancy. L-T4 treatment for euthyroid women with TAI undergoing ART is therefore widely debated [11,14,17,19].…”

mentioning

confidence: 99%

See 2 more Smart Citations

The influence of thyroid autoimmunity on pregnancy outcome in infertile women: a prospective study

et al. 2020

View full text Add to dashboard Cite

Thyroid dysfunction and thyroid autoimmunity (TAI) have been reported to be linked to infertility, pregnancy loss and preterm birth. Infertile women undergoing assisted reproductive technology are recommended to maintain thyroid stimulating hormone (TSH) levels below 2.5 μIU/mL. It is unclear, however, whether levothyroxine (L-T4) treatment decreases the effects of TAI on fertility and pregnancy outcome in infertile women. We therefore aimed to clarify the influence of TAI on pregnancy undergoing L-T4 treatment for hypothyroidism. Prospectively recruited to this study were the 595 infertile women who visited the Utsunomiya Ladies Clinic between January 2013 and December 2015. Five patients with Graves' disease were excluded. Clinical profiles of 590 women were as follows: proportion of SCH = 19.6%, thyroid peroxidase antibody (TPOAb) positivity = 10.4%, and thyroglobulin antibody (TgAb) positivity = 15.1%. Fertility was not affected by any thyroid-associated factors. Regarding pregnancy outcomes, TPOAb titers were significantly higher in women who had miscarriage than in those progressed to delivery (46.4 ± 114.1 vs. 18.9 ± 54.6 IU/mL, p = 0.039), notably in those undergoing intrauterine insemination (p = 0.046) and in vitro fertilization (p = 0.023). Multivariate logistic regression analysis revealed that higher age (odds ratio 26.4, p < 0.001) and higher TPOAb titer (odds ratio 11.8, p = 0.043) were risk factors for miscarriage. Higher TPOAb titer should be considered as one of the risk factors for miscarriage in infertile women, even if they have been treated with L-T4 for hypothyroidism.

show abstract

Section: Discussionmentioning

confidence: 83%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

The influence of thyroid autoimmunity on pregnancy outcome in infertile women: a prospective study

et al. 2020

View full text Add to dashboard Cite

show abstract

“…The hypothesis that autoimmunity may contribute to a tendency for pregnancy loss is plausible and supported by robust data showing an association between certain markers of autoimmunity and miscarriage. The most widelyrecognized and accepted autoimmune associations with pregnancy loss are those of aPL antibodies (68) and anti-thyroid peroxidase antibodies (69). It has become common practice on the part of some clinicians and clinical centers to test women presenting with recurrent miscarriage for these and other autoantibodies, including antinuclear antibodies (ANAs), the subject of this commentary.…”

Section: Treating Rheumatologic Aspects Of Recurrent Pregnancy Lossmentioning

confidence: 99%

“…Moreover, a tendency to miscarry is associated with factors such as advanced maternal age and obesity (86,87), both of which are known to be associated with a higher prevalence of ANA positivity (88,89). Also, autoimmune thyroid disorders are associated with recurrent miscarriage (69). A positive ANA result is found in 50% of individuals with evidence of thyroid autoimmunity (90), raising the distinct possibility that a positive ANA in a woman with recurrent miscarriage may be a reflection of an autoimmune thyroid condition.…”

Section: Treating Rheumatologic Aspects Of Recurrent Pregnancy Lossmentioning

confidence: 99%

Immunologic and rheumatologic causes and treatment of recurrent pregnancy loss: what is the evidence?

Odendaal

Quenby

Sammaritano

et al. 2019

Fertility and Sterility

View full text Add to dashboard Cite

show abstract

Levothyroxine in Pregnancy

Poppe

2021

70 Years of Levothyroxine

View full text Add to dashboard Cite

Thyroid hormone homeostasis changes markedly during pregnancy, and first trimester-specific reference ranges for thyrotropin (thyroid-stimulating hormone, TSH) are needed to diagnose hypothyroidism. Treatment consists in levothyroxine (LT4) in this setting (triiodothyronine or desiccated thyroid preparations have no role here). Severe hypothyroidism is associated with infertility, and levels of TSH above 4.0 IU/mL signal an increased risk of adverse pregnancy outcomes. All pregnant women (and women planning a pregnancy) with overt hypothyroidism must be managed effectively with oral LT4. Thyroid autoimmunity increases the risk of adverse pregnancy outcomes and is associated with certain causes of infertility. Current European and US guidelines recommend a role for patients with subclinical hypothyroidism and thyroid autoimmunity, not least to guard against progression to overt hypothyroidism during the pregnancy. Women with hypothyroidism undergoing assisted reproduction technology to become pregnant appear to be strong candidates for LT4-based therapy.

show abstract

Effect of levothyroxine supplementation on pregnancy loss and preterm birth in women with subclinical hypothyroidism and thyroid autoimmunity: a systematic review and meta-analysis

Cited by 101 publications

References 109 publications

The influence of thyroid autoimmunity on pregnancy outcome in infertile women: a prospective study

The influence of thyroid autoimmunity on pregnancy outcome in infertile women: a prospective study

Immunologic and rheumatologic causes and treatment of recurrent pregnancy loss: what is the evidence?

Levothyroxine in Pregnancy

Contact Info

Product

Resources

About