Preconceptional antithyroid peroxidase antibodies, but not thyroid-stimulating hormone, are associated with decreased live birth rates in infertile women

Seungdamrong, Aimee; Steiner, Anne Z.; Gracia, Clarisa R.; Legro, Richard S.; Diamond, Michael P.; Coutifaris, Christos; Schlaff, William D.; Casson, Peter R.; Christman, Gregory M.; Robinson, Randal D.; Huang, Hao; Alvero, Ruben; Hansen, Karl R.; Jin, Susan; Eisenberg, Esther; Zhang, Heping; Santoro, Nanette

doi:10.1016/j.fertnstert.2017.08.026

Cited by 48 publications

(38 citation statements)

References 39 publications

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“…A recent study of infertile women as part of two large randomised controlled trials showed no association between TSH ≥2.5 mU/L and miscarriage. 19 This result does not preclude an association, but it does show the well known TSH cut-off of 2.5 mU/L is not a discriminator for this outcome. The authors did find a significant association with miscarriage and the presence of anti-thyroid antibodies in direct contrast to the outcome of a recent meta-analysis, which concluded that there was no association.…”

Section: Subclinical Hypothyroidism and Spontaneous Abortionmentioning

confidence: 77%

“…One of the most accepted associations is between thyroid disease and miscarriage; however, even here the study findings are contentious. A recent study of infertile women as part of two large randomised controlled trials showed no association between TSH ≥2.5 mU/L and miscarriage . This result does not preclude an association, but it does show the well known TSH cut‐off of 2.5 mU/L is not a discriminator for this outcome.…”

Section: Introductionmentioning

confidence: 87%

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Subclinical hypothyroidism during pregnancy: the Melbourne public hospitals consensus

Hamblin

Sheehan

Allan

et al. 2019

Internal Medicine Journal

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Background Interest in potential adverse outcomes associated with maternal subclinical hypothyroidism (normal free T4, elevated thyroid‐stimulating hormone (TSH)) has increased significantly over recent years. In turn, the frequency of maternal thyroid function testing has risen, despite universal thyroid function screening not being recommended, leading to a marked increase in referrals to obstetric endocrinology clinics. In 2017 the American Thyroid Association revised their diagnostic and management guidelines. Although welcome, these new guidelines contain recommendations that may cause confusion in clinical practice. Aim To ensure uniform practice in the diagnosis and management of subclinical hypothyroidism in pregnancy across all Melbourne public hospitals. Methods Endocrinology and obstetric representatives from all Melbourne public hospital networks reviewed the 2017 American Thyroid Association guidelines and other relevant literature to develop a consensus for diagnosing and treating subclinical hypothyroidism during pregnancy in Melbourne. The consensus guidelines were then referred to the Endocrine Society of Australia for comment and endorsement. Results Consensus was achieved and the guidelines were endorsed by the Council of the Endocrine Society of Australia. Trimester and assay‐specific TSH reference intervals derived from healthy local populations should be used, where available. When unavailable, a TSH cut‐off of 4 mU/L (replacing the previously recommended 2.5 mU/L) should be used to initiate treatment, irrespective of thyroid auto‐antibody status. The recommended starting dose of levothyroxine is 50 μg daily, with a therapeutic TSH target of 0.1–2.5 mU/L. Levothyroxine should generally be ceased after delivery, with some exceptions. Hospitals will ensure smooth transfer of care back to the woman’s general practitioner with clear documentation of pregnancy thyroid management and a recommended plan for follow‐up. Conclusion Fewer women will be classified as having subclinical hypothyroidism during pregnancy, which is likely to lead to reductions in emotional stress, hospital visits, repeated blood tests and financial costs. Uniform clinical practice will occur across Melbourne.

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Section: Subclinical Hypothyroidism and Spontaneous Abortionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 87%

Subclinical hypothyroidism during pregnancy: the Melbourne public hospitals consensus

Hamblin

Sheehan

Allan

et al. 2019

Internal Medicine Journal

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“…The incidence of miscarriage, mainly occurs in the first trimester, was found to be higher (6%‐15%) in patients with hypothyroidism compared to normal population (2.2%) with a higher risk of miscarriage as a result of the increase in maternal TSH concentrations. Apart from thyroid function, TPOAb were found to be associated with an increased miscarriage rate up to 43.9% …”

Section: Introductionmentioning

confidence: 99%

“…Apart from thyroid function, TPOAb were found to be associated with an increased miscarriage rate up to 43.9%. 2 Many mechanisms have been studied to explain the cause of infertility and subfertility in hypothyroid patients including associated hyperprolactinemia, gonadotropins ovarian axis effects, 3 direct ovulatory dysfunction, 4 and endometrial dysfunction (endometrium-blastocyst interaction). 5 However, the underlying pathological mechanisms remain unclear.…”

Section: Introductionmentioning

confidence: 99%

A hidden cause of infertility in hypothyroid patients

Allam

El‐Zawawy

Barakat

et al. 2020

Clinical Case Reports

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“…AIT is the most prevalent autoimmune state that affects up to 5-20% of reproductive-age women [1]. Patients with anti-thyroid antibodies, even in the presence of euthyroidism, may be at a higher risk of adverse reproductive outcomes, including miscarriage and preterm birth [2][3][4][5]. e most common and severe adverse pregnancy outcome caused by AIT with euthyroidism is miscarriage; however, the mechanism has not been elucidated.…”

Section: Introductionmentioning

confidence: 99%

Analysis of Blimp-1 and PD-1/PD-L1 Immune Checkpoint in an Autoimmune Thyroiditis Animal Model

Zhang

Chen

et al. 2020

International Journal of Endocrinology

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Objective. B lymphocyte-induced maturation protein 1 (Blimp-1) and programmed cell death protein 1 (PD-1) have opposing roles in the development of T cells; however, the mechanism of autoimmune thyroiditis-(AIT-) associated abortion is unclear. e present study investigated the expression of Blimp-1 and PD-1/PD-ligand 1 (PD-L1) in AIT-associated pregnancy loss and elucidated the related signaling pathway involving in the inflammatory response. Methods. An experimental fetal loss model with autoimmune thyroiditis was established after murine thyroglobulin-(mTg-) immunized CBA/J female mice mating with Balb/c males. ELISA was employed to investigate the TgAb level in the serum of CBA/J female mice. e expression of Blimp-1, PD-1/PD-L1, mammalian target protein rapamycin (mTOR), and Foxp3 proteins in the placenta and spleen was detected through immunofluorescence staining and western blotting. Results. ELISA indicated that the serum TgAb level in the mTg group was higher than that in the control group (P < 0.001). Fetal resorption rates increased in the mTg group compared with those in the control group (45.63% vs. 3.1%, P < 0.05). Blimp-1 levels in the placenta and spleen were higher in the AIT-related miscarriage group than in the control group. However, the expression of PD-1/PD-L1 and Foxp3 was significantly decreased in the placenta and spleen in the AIT-related miscarriage group. Conclusion. Blimp-1 participates in the pathogenesis of autoimmune thyroid disease-associated pregnancy loss through the inflammatory immune response, which is potentially mediated through the PD-1/PD-L1 signaling pathway.

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Preconceptional antithyroid peroxidase antibodies, but not thyroid-stimulating hormone, are associated with decreased live birth rates in infertile women

Abstract: PPCOS II NCT00719186; AMIGOS NCT01044862.

Cited by 48 publications

References 39 publications

Subclinical hypothyroidism during pregnancy: the Melbourne public hospitals consensus

Subclinical hypothyroidism during pregnancy: the Melbourne public hospitals consensus

A hidden cause of infertility in hypothyroid patients

Analysis of Blimp-1 and PD-1/PD-L1 Immune Checkpoint in an Autoimmune Thyroiditis Animal Model

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