scholarly journals Levothyroxine to increase live births in euthyroid women with thyroid antibodies trying to conceive: the TABLET RCT

2019 ◽  
Vol 6 (11) ◽  
pp. 1-72
Author(s):  
Rima K Dhillon-Smith ◽  
Lee J Middleton ◽  
Kirandeep K Sunner ◽  
Versha Cheed ◽  
Krys Baker ◽  
...  
Keyword(s):  
Confidence Interval ◽  
Thyroid Function ◽  
Live Birth ◽  
Birth Rate ◽  
Live Birth Rate ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Peroxidase ◽  
Controlled Trials ◽  
Thyroid Antibodies ◽  
Thyroid Peroxidase Antibodies

Background Thyroid autoantibodies, specifically thyroid peroxidase antibodies, have been associated with miscarriage and pre-term birth in women with a normal thyroid function. Small randomised controlled trials have found that treatment with levothyroxine may reduce such adverse outcomes in pregnancy. Objectives The Thyroid AntiBodies and LEvoThyroxine (TABLET) trial was conducted to explore the effects of levothyroxine in euthyroid women with thyroid peroxidase antibodies. A concurrent mechanistic study was conducted to examine the effect of levothyroxine on immune responses. Design This was a randomised, double-blind, placebo-controlled, multicentre study. Setting The TABLET trial was conducted in 49 hospitals across the UK between 2011 and 2016. Participants Euthyroid women who tested positive for thyroid peroxidase antibodies, were aged between 16 and 41 years and were trying to conceive either naturally or through assisted conception were eligible. Intervention Participants were randomised to levothyroxine at a dose of 50 µg daily or placebo. The intervention was commenced preconception and continued until the end of a pregnancy. Women were given a 12-month period to conceive from randomisation. Main outcome measures The primary outcome was live birth at ≥ 34 completed weeks of gestation. The secondary outcomes included miscarriage at < 24 weeks; clinical pregnancy at 7 weeks; ongoing pregnancy at 12 weeks; gestation at delivery; birthweight; appearance, pulse, grimace, activity and respiration (Apgar) scores; congenital abnormalities; and neonatal survival at 28 days of life. Methods Participants were randomised in a 1 : 1 ratio. Minimisation was implemented for age (< 35 or ≥ 35 years), number of previous miscarriages (0, 1 or 2, ≥ 3), infertility treatment (yes/no) and baseline thyroid-stimulating hormone concentration (≤ 2.5 or > 2.5 mlU/l) to achieve balanced trial arms. Women were followed up every 3 months while trying to conceive to check thyroid function and general well-being, and, once pregnant, were seen each trimester: 6–8 weeks, 16–18 weeks and 28 weeks. Any abnormal thyroid results were managed in line with clinical guidance at the time. Results Of the 19,556 women screened, 1420 women were eligible and 952 were randomised to receive levothyroxine (n = 476) or placebo (n = 476). Six women from each arm either were lost to follow-up or withdrew from the trial. A total 540 women became pregnant: 266 in the levothyroxine arm and 274 in the placebo arm. The live birth rate was 37% (176/470) in the levothyroxine group and 38% (178/470) in the placebo group, translating to a relative risk of 0.97 (95% confidence interval 0.83 to 1.14; p = 0.74) and an absolute risk difference of –0.4% (95% confidence interval –6.6% to 5.8%). A subset of 49 trial participants (26 in the levothyroxine arm and 23 in the placebo arm) were recruited to assess changes in their serum chemocytokine concentrations. Treatment with levothyroxine resulted in some changes in chemocytokine concentrations in the non-pregnant state and in early pregnancy, but these had no association with clinical outcome. Conclusions Levothyroxine therapy in a dose of 50 µg per day does not improve live birth rate in euthyroid women with thyroid peroxidase antibodies. Limitations Titration of the levothyroxine dose based on thyroid-stimulating hormone/thyroid peroxidase concentrations was not explored. Future work Future research could explore the efficacy of levothyroxine administered for the treatment of subclinical hypothyroidism. Trial registration Current Controlled Trials ISRCTN15948785 and EudraCT 2011-000719-19. Funding This project was funded by the Efficacy and Mechanism Evaluation programme, a Medical Research Council and National Institute for Health Research partnership.

Live-birth rate in euthyroid women with recurrent miscarriage and thyroid peroxidase antibodies

2015 ◽  
Vol 32 (2) ◽  
pp. 132-135 ◽  
Author(s):  
Rosa Vissenberg ◽  
Eric Fliers ◽  
Joris A. M. van der Post ◽  
Madelon van Wely ◽  
Peter H. Bisschop ◽  
...  
Keyword(s):  
Live Birth ◽  
Birth Rate ◽  
Recurrent Miscarriage ◽  
Live Birth Rate ◽  
Thyroid Peroxidase ◽  
Thyroid Peroxidase Antibodies

Thyroid Peroxidase Antibodies and Prospective Live Birth Rate: A Cohort Study of Women with Recurrent Pregnancy Loss

Thyroid ◽  
2019 ◽  
Vol 29 (10) ◽  
pp. 1465-1474 ◽  
Author(s):  
Sofie Bliddal ◽  
Ulla Feldt-Rasmussen ◽  
Åse Krogh Rasmussen ◽  
Astrid Marie Kolte ◽  
Linda Marie Hilsted ◽  
...  
Keyword(s):  
Cohort Study ◽  
Live Birth ◽  
Pregnancy Loss ◽  
Birth Rate ◽  
Recurrent Pregnancy Loss ◽  
Live Birth Rate ◽  
Thyroid Peroxidase ◽  
Thyroid Peroxidase Antibodies

scholarly journals Different Strategies of Preimplantation Genetic Testing for Aneuploidies in Women of Advanced Maternal Age: A Systematic Review and Meta-Analysis

2021 ◽  
Vol 10 (17) ◽  
pp. 3895
Author(s):  
Wei-Hui Shi ◽  
Zi-Ru Jiang ◽  
Zhi-Yang Zhou ◽  
Mu-Jin Ye ◽  
Ning-Xin Qin ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Live Birth ◽  
Maternal Age ◽  
Birth Rate ◽  
Live Birth Rate ◽  
Advanced Maternal Age ◽  
Controlled Trials ◽  
Preimplantation Genetic Testing ◽  
Randomized Controlled ◽  
Blastocyst Biopsy

Background: Preimplantation genetic testing for aneuploidies (PGT-A) is widely used in women of advanced maternal age (AMA). However, the effectiveness remains controversial. Method: We conducted a comprehensive literature review comparing outcomes of IVF with or without PGT-A in women of AMA in PubMed, Embase, and the Cochrane Central Register of Controlled Trials in January 2021. All included trials met the criteria that constituted a randomized controlled trial for PGT-A involving women of AMA (≥35 years). Reviews, conference abstracts, and observational studies were excluded. The primary outcome was the live birth rate in included random control trials (RCTs). Results: Nine randomized controlled trials met our inclusion criteria. For techniques of genetic analysis, three trials (270 events) performed with comprehensive chromosomal screening showed that the live birth rate was significantly higher in the women randomized to IVF/ICSI with PGT-A (RR = 1.30, 95% CI 1.03–1.65), which was not observed in six trials used with FISH as well as all nine trials. For different stages of embryo biopsy, only the subgroup of blastocyst biopsy showed a higher live birth rate in women with PGT-A (RR = 1.36, 95% CI 1.04–1.79). Conclusion: The application of comprehensive chromosome screening showed a beneficial effect of PGT-A in women of AMA compared with FISH. Moreover, blastocyst biopsy seemed to be associated with a better outcome than polar body biopsy and cleavage-stage biopsy.

Prevention of recurrent miscarriage in women with antiphospholipid syndrome: A systematic review and network meta-analysis

Lupus ◽  
2020 ◽  
Vol 30 (1) ◽  
pp. 70-79
Author(s):  
Ziyi Yang ◽  
Xiangli Shen ◽  
Chuqing Zhou ◽  
Min Wang ◽  
Yi Liu ◽  
...  
Keyword(s):  
Preterm Birth ◽  
Antiphospholipid Syndrome ◽  
Live Birth ◽  
Birth Rate ◽  
Recurrent Miscarriage ◽  
Live Birth Rate ◽  
Controlled Trials ◽  
Cochrane Central Register ◽  
Pharmacological Interventions ◽  
Significant Difference

Objectives To compare and rank currently available pharmacological interventions for the prevention of recurrent miscarriage (RM) in women with antiphospholipid syndrome (APS). Methods A search was performed using PubMed, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, CNKI, ClinicalTrials.gov, and the UK National Research Register on December 15, 2019. Studies comparing any types of active interventions with placebo/inactive control or another active intervention for the prevention of RM in patients with APS were considered for inclusion. The primary outcomes were efficacy (measured by live birth rate) and acceptability (measured by all-cause discontinuation); secondary outcomes were birthweight, preterm birth, preeclampsia, and intrauterine growth retardation. The protocol of this study was registered with Open Science Framework (DOI: 10.17605/OSF.IO/B9T4E). Results In total, 54 randomized controlled trials (RCTs) comprising 4,957 participants were included. Low-molecular-weight heparin (LMWH) alone, aspirin plus LMWH or unfractionated heparin (UFH), aspirin plus LMWH plus intravenous immunoglobulin (IVIG), aspirin plus LMWH plus IVIG plus prednisone were found to be effective pharmacological interventions for increasing live birth rate (ORs ranging between 2.88 to 11.24). In terms of acceptability, no significant difference was found between treatments. In terms of adverse perinatal outcomes, aspirin alone was associated with a higher risk of preterm birth than aspirin plus LMWH (OR 3.92, 95% CI 1.16 to 16.44) and with lower birthweight than LMWH (SMD −808.76, 95% CI −1596.54 to −5.07). Conclusions Our findings support the use of low-dose aspirin plus heparin as the first-line treatment for prevention of RM in women with APS, and support the efficacy of hydroxychloroquine, IVIG, and prednisone when added to current treatment regimens. More large-scale, high-quality RCTs are needed to confirm these findings, and new pharmacological options should be further evaluated.

Thyroid evaluation of children and adolescents with Williams syndrome in Zhejiang Province

2017 ◽  
Vol 30 (12) ◽  
Author(s):  
Wei-Jun Chen ◽  
Chai Ji ◽  
Dan Yao ◽  
Zheng-Yan Zhao
Keyword(s):  
Children And Adolescents ◽  
Thyroid Function ◽  
Williams Syndrome ◽  
Subclinical Hypothyroidism ◽  
Thyroid Stimulating Hormone ◽  
Zhejiang Province ◽  
Overt Hypothyroidism ◽  
Thyroid Peroxidase ◽  
Thyroid Antibodies ◽  
Free Triiodothyronine

AbstractBackground:The objective of the study was to describe the prevalence of abnormal thyroid function and volume in children and adolescents with Williams syndrome (WS) in Zhejiang Province, China.Methods:Thyroid function, including thyroid-stimulating hormone (TSH), free triiodothyronine (fT3), free thyroxine (fT4), and thyroid antibodies (thyroid peroxidase and thyroglobulin) were measured in 83 patients with WS, aged 0.2–16.5 years. Twenty-three patients were followed for an average of 1.7 years (0.4–4.1), and multiple TSH determinations were considered. Thyroid ultrasonography was performed on 49 patients.Results:One patient was diagnosed with overt hypothyroidism, and 23 patients (27%) had subclinical hypothyroidism (SH). Thyroid antibodies were absent in all patients. In five age groups (0–1 years, 1–3 years, 3–6 years, 6–9 years, 9–18 years), the prevalence of patients with subclinical hypothyroidism was 25%, 28.5%, 44.4%, 16.7% and 4.7%, respectively. Through ultrasound examination, 21 patients (42%) were observed to have thyroid hypoplasia (TH), and there were no cases of thyroid haemiagenesis. The incidence rate of TH increased with age, rising from 20% in the youngest group to 66% in the oldest.Conclusions:SH and TH is common in children and adolescents with WS. Yearly evaluation of thyroid must be performed in all patients in this population, regardless of the result of the neonatal screening. Age under 6 years and existing thyroid abnormalities are risk factors for developing SH, and a shorter follow-up interval is needed for screening in these individuals, SH is often self-limiting, and clinicians should be alert to overt hypothyroidism.

The role of maternal prenatal thyroid function on offspring depression: Findings from the ALSPAC cohort

2019 ◽  
Vol 32 (1) ◽  
pp. 189-196 ◽  
Author(s):  
Dagnachew Muluye Fetene ◽  
Kim S. Betts ◽  
Rosa Alati
Keyword(s):  
Thyroid Function ◽  
First Trimester ◽  
Thyroid Stimulating Hormone ◽  
Thyroid Peroxidase ◽  
Child Depression ◽  
Depression And Anxiety ◽  
Thyroid Peroxidase Antibodies ◽  
First Trimester Of Pregnancy ◽  
Maternal Thyroid ◽  
Stimulating Hormone

AbstractMaternal thyroid dysfunction during pregnancy may contribute to offspring neurobehavioral disorders. In this paper, we investigate the relationship between maternal thyroid function during pregnancy and offspring depression and anxiety. Data were taken from the Avon Longitudinal Study of Parents and Children. A total of 2,920 mother-child pairs were included. Thyroid-stimulating hormone levels, free thyroxine (FT4), and thyroid peroxidase antibodies were assessed during the first trimester of pregnancy because maternal supply is the only source of thyroid hormone for the fetus during the first 12 weeks of gestation. Child symptoms of depression and anxiety were assessed using the Development and Well-Being Assessment at ages 7.5 and 15 years. The odds of presenting with depression and anxiety were estimated using the generalized estimating equation. The level of FT4 during the first trimester of pregnancy was associated with child depression combined at ages 7.5 and 15 (odds ratio = 1.21, 95% confidence interval [1.00, 1.14]. An increase of 1 standard deviation of FT4 during pregnancy increased the odds of child depression by 28% after adjustment made for potential confounders. No association was found among maternal levels of thyroid-stimulating hormone, FT4, and thyroid peroxidase antibodies and childhood anxiety. In conclusion, increased levels of FT4 during the first trimester of pregnancy appear be linked to greater risk of offspring depression.

scholarly journals A Comparison of the Miscarriage and Live Birth Rate for Frozen Embryo Transfer According to Two Endometrial Preparations: Natural or Primed with Estrogens

2019 ◽  
Vol 01 (01) ◽  
pp. 43-49
Author(s):  
S. Mubarak ◽  
S. Acharyya ◽  
V. Viardot-Foucault ◽  
H. H. Tan ◽  
J. W. L. Phoon
Keyword(s):  
Confidence Interval ◽  
Live Birth ◽  
Odds Ratio ◽  
Birth Rate ◽  
Adjusted Odds Ratio ◽  
Live Birth Rate ◽  
Miscarriage Rate ◽  
Natural Group ◽  
Endometrial Preparation ◽  
Vaginal Progesterone

Objective The primary objective is to compare miscarriage rates in frozen-thawed embryo transfer (FET) cycles, according to the endometrial preparation used either artificial through the administration of exogenous estrogen and progesterone or natural without any treatment, during a spontaneous ovulatory cycle. The secondary objective is to compare the live birth rates between the two endometrial preparations. Study design This is a retrospective study done at KK Women’s and Children’s Hospital Singapore. We included women who underwent FET cycles either with hormone replacement treatment (HRT) or no treatment (natural) for the endometrial preparation, regardless of their cycle number, from 1 January 2011 till 31 December 2015. Results A total of 2,752 FET cycles were included in our analysis. The natural cycle followed by vaginal progesterone support was used in 1,221 cycles and the HRT cycle with estrogen and vaginal progesterone was used in 1,531 cycles. There is a significantly higher miscarriage rate in the HRT group (38.4%) compared with the natural group (22.3%). The live birth rate is significantly higher in the natural group (22.8%) compared with the HRT group (17.3%). The multivariate analysis further shows that the HRT therapy is independently associated with an increased risk of miscarriage (adjusted odds ratio 2.05; 95% confidence interval 1.45–2.90; [Formula: see text] <0.001) and hence lower odds of live birth (adjusted odds ratio 0.69; 95% confidence interval 0.56–0.84; [Formula: see text] <0.001) after adjusting for the patient’s age at which the embryo was cryopreserved, race, body mass index, main indications for in vitro fertilization, number of embryos transferred and type of embryo transferred. Conclusion We have shown in this study that the miscarriage rate is higher in the HRT FET group and that this increased miscarriage rate translates into a lower live birth rate in the HRT group. Thus, we conclude that patients with regular menstrual cycles should be offered a natural FET cycle to achieve better outcomes in terms of live birth rate and reducing the miscarriage rate.

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