Increased pregnancy loss rate in thyroid antibody negative women with TSH levels between 2.5 and 5.0 in the first trimester of pregnancy.

Division of Endocrinology, V. Fazzi Hospital, 73100 Lecce, Italy. .
The Journal of Clinical Endocrinology and Metabolism (Impact Factor: 6.31). 09/2010; 95(9):E44-8. DOI: 10.1210/jc.2010-0340
Source: PubMed

ABSTRACT The definition of what constitutes a normal TSH during pregnancy is in flux. Recent studies suggested that the first trimester upper limit of normal for TSH should be 2.5 mIU/liter.
The objective of the study was to evaluate the pregnancy loss and preterm delivery rate in first-trimester thyroid peroxidase antibody-negative women with TSH values between 2.5 and 5.0 mIU/liter.
The present study is a component of a recently published large-scale prospective trial that evaluated the impact of levothyroxine treatment on maternal and neonatal complications in thyroid peroxidase-positive women with TSH levels above 2.5 mIU/liter. The present study evaluated 4123 thyroid peroxidase antibody-negative women with TSH levels at or below 5.0 mIU/liter. Women were divided into two groups based on their initial TSH: group A, TSH level below 2.5 mIU/liter, excluding hyperthyroid women defined as an undetectable TSH with an elevated free T(4), and group B, TSH level between 2.5 and 5.0 mIU/liter.
The study was conducted at two ambulatory clinics of community hospitals in southern Italy.
A total of 4123 women were evaluated.
There was no intervention.
The incidence of pregnancy loss and preterm delivery in group A as compared with group B was measured.
The rate of pregnancy loss was significantly higher in group B as compared with group A (6.1 vs. 3.6% respectively, P = 0.006). There was no difference in the rate of preterm delivery between the two groups.
The increased incidence of pregnancy loss in pregnant women with TSH levels between 2.5 and 5.0 mIU/liter provides strong physiological evidence to support redefining the TSH upper limit of normal in the first trimester to 2.5 mIU/liter.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: RESuMEN El hipotiroidismo se relaciona con problemas ovulatorios, de implantación e infertilidad, así como con abortos y complicaciones de embarazo. El hipotiroidismo se define como la hiposecreción de hormonas tiroideas por la glándula tiroides. Los estándares para el diagnóstico y el tratamiento del hipotiroidismo subclínico han cambiado conforme los estudios van demostrando que existe una alteración tiroidea en las mujeres con valores entre 2.5 y 5 μUI/mL, en las que el único síntoma perceptible sea probablemente la infertilidad-esterilidad no explicada por otros factores. Lo que sí es cierto es que la función tiroidea está sumamente relacionada con la reproducción femenina, por lo que es necesario hacer un tamizaje a todas las mujeres; deben mantenerse cifras por debajo de 2.5 μUI/ml, principalmente en las mujeres que deseen embarazarse o que estén en su primer trimestre de embarazo. Palabras clave: hipotiroidismo, fertilidad, tiroides. AbSTRACT Hypothyroidism has proven to be related with ovulatory problems, implantation and infertility, as well as miscarriages and pregnancy complications. Hypothyroidism is defined as a hyposecretion of the thyroid hormones from the thyroid gland. Standards for the diagnosis and treatment of subclinical hypothyroidism have changed according to some studies that demonstrate that there is an alteration of the thyroid gland in women with values between 2.5-5 μIU/mL, and that probably the only noticeable symptom is unexplained infertility-sterility. Thyroid function is highly related to human reproduction and the screening of every woman is necessary, maintaining figures lower than 2.5 μIU/mL, mostly in those who desire pregnancy or those who are in their first trimester of pregnancy.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: While there is a large body of evidence showing a significant impact of controlled ovarian hyperstimulation (COH) on thyroid function in euthyroid patients undergoing in vitro fertilization (IVF), information on the effect of this treatment on thyroid axis equilibrium in hypothyroid-treated patients is insufficient. The goal of this prospective study was to investigate serum thyroid-stimulating hormone (TSH) modifications in hypothyroid-treated patients during IVF. Methods: Hypothyroid-treated women selected for IVF between November 2010 and December 2011 were considered for study entry. They were eligible if serum TSH tested the month preceding the IVF cycle was 0.4-2.5 mIU/L. Additional inclusion criteria were as follows: 1) a certified diagnosis of clinical or subclinical hypothyroidism; 2) consumption of at least 25 µg of levothyroxine daily; 3) serum FT3 and FT4 tested the month preceding the IVF cycle within the reference range; 4) no previous IVF cycles; 5) regular menstrual cycles; and 6) day 3 serum follicle-stimulating hormone (FSH) < 12 IU/ml and anti-Müllerian hormone (AMH) > 0.5 ng/ml. Serum TSH was tested at three time points: between day 1 and day 8 of the cycle during the month preceding the start of controlled ovarian hyperstimulation (COH), at the time of hCG administration and at 16 days after hCG administration. Results: Seventy-two women met our selection criteria. The serum levels of TSH at basal assessment, at the time of hCG administration, and at 16 days after hCG administration were 1.7 ± 0.7, 2.9 ± 1.3, and 3.2 ± 1.7 mIU/L, respectively. All pairwise comparisons were statistically significant. Serum TSH exceeded the threshold of 2.5 mIU/L in 46 subjects at the time of hCG administration (64%, 95%CI: 53-75%), and in 49 subjects 16 days after hCG administration (68%, 95%CI: 57-79%). Conclusions: Serum TSH increased considerably during COH in adequately treated hypothyroid women undergoing IVF. We suggest strictly monitoring these women during IVF cycles and, if necessary, promptly adjusting the levothyroxine dose. This is the most pragmatic approach but, to date, it is not supported by clinical evidence. Further studies aimed at clarifying the most suitable therapeutic strategy are thus warranted.
    Thyroid: official journal of the American Thyroid Association 08/2014; · 2.60 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Context: Thyroid dysfunction is associated with adverse obstetric outcomes, but there is limited information on pregnancy outcomes in women established on levothyroxine. Objective: The objective of the study was to determine the relationship between TSH levels and pregnancy outcomes in levothyroxine-treated women in a large community-based database. Design: This was a historical cohort analysis. Patients: Individuals with a first prescription of levothyroxine from 2001 through 2009 (n = 55ü501) were identified from the UK General Practice Research Database (population 5 million). Of these, we identified 7978 women of child-bearing age (18-45 y) and 1013 pregnancies in which levothyroxine had been initiated at least 6 months before conception. Main Outcome Measures: TSH, miscarriage/delivery status, and obstetric outcomes were measured. Results: Forty-six percent of levothyroxine-treated women aged 18-45 years had a TSH level greater than 2.5mU/L (recommended upper level in the first trimester). Among pregnant women who had their TSH measured in the first trimester, 62.8% had a TSH level greater than 2.5 mU/L, with 7.4% greater than 10 mU/L. Women with TSH greater than 2.5 mU/L in the first trimester had an increased risk of miscarriage compared with women with TSH 0.2-2.5 mU/L after adjusting for age, year of pregnancy, diabetes, and social class (P = .008). The risk of miscarriage was increased in women with TSH 4.51-10 mU/L [odds ratio (OR) 1.80, 95% confidence interval (CI) 1.03, 3.14)] and TSH greater than 10 mU/L (OR 3.95, 95% CI 1.87, 8.37) but not with TSH 2.51-4.5 mU/L (OR 1.09, 95% CI 0.61, 1.93). Conclusions: The majority of levothyroxine-treated women have early gestational TSH levels above the recommended targets (>2.5 mU/L) with a strong risk of miscarriage at levels exceeding 4.5 mU/L. There is an urgent need to improve the adequacy of thyroid hormone replacement in early pregnancy.
    Journal of Clinical Endocrinology &amp Metabolism 07/2014; · 6.31 Impact Factor