Thyroid autoimmunity and intracytoplasmic sperm injection outcome: a systematic review and meta-analysis.

BACKGROUND: Since 2010, three meta-analyses have been published on the impact of thyroid autoimmunity (TAI) on pregnancy outcomes in infertile women treated with assisted reproductive technology (ART). The initially observed high risk of miscarriage became very low in the most recent meta-analysis published in 2016. OBJECTIVE: To investigate whether the lower risk of miscarriage in the latest meta-analysis was associated with the increased use of intracytoplasmic sperm injection (ICSI) in recent studies. DATA SOURCE: MEDLINE was searched from January, 1990, to May, 2017. STUDY SELECTION: Data from case-control and cohort studies, on ART (IVF/ICSI) pregnancy outcomes in women with and without TAI. Only studies were included in which women were treated with ICSI. DATA EXTRACTION AND SYNTHESIS: Four studies were retained including 1855 ICSI cycles (290 with and 1565 without TAI). In women with a clinical pregnancy (114 ICSI cycles with TAI and 651 without), there was no difference in miscarriage or live birth rates: respective combined OR 0.95 (95% CI, 0.48 to 1.87) and 1.12 (95% CI, 0.62 to 2.03). There was no difference in age in women with and without TAI: combined mean difference of 0.13 years (95% CI, -0.51 to 0.76), but serum TSH was higher in women with TAI: combined mean difference of 0.20 mIU/L (95% CI, 0.07 to 0.33). CONCLUSION: Infertile women with TAI treated with ICSI had no increased risk of a first trimester miscarriage compared with women without TAI.

Pregnancy outcomes are not altered by variation in thyroid function within the normal range in women free of thyroid disease.

OBJECTIVE: In the recently revised guidelines on the management of thyroid dysfunction during pregnancy, treatment with thyroid hormone (LT4) is not recommended in women without thyroid autoimmunity (TAI) and TSH levels in the range 2.5-4.0 mIU/L, and in a recent study in that particular group of pregnant women, more complications were observed when a treatment with LT4 was given. The objective of the study was therefore to investigate whether variation in thyroid function within the normal (non-pregnant) range in women free of thyroid disease was associated with altered pregnancy outcomes? DESIGN: Cross-sectional data analysis of 1321 pregnant women nested within an ongoing prospective collection of pregnant women's data in a single centre in Brussels, Belgium. METHODS: Thyroid peroxidase antibodies (TPO-abs), thyroid-stimulating hormone (TSH), free T4 (FT4) and ferritin levels were measured and baseline characteristics were recorded. Women taking LT4, with TAI and thyroid function outside the normal non-pregnant range were excluded. Pregnancy outcomes and baseline characteristics were correlated with all TSH and FT4 levels within the normal range and compared between two groups (TSH cut-off < and ≥2.5 mIU/L). RESULTS: Tobacco use was associated with higher serum TSH levels (OR: 1.38; CI 95%: 1.08-1.74); P = 0.009. FT4 levels were inversely correlated with age and BMI (rho = -0.096 and -0.089; P < 0.001 and 0.001 respectively) and positively correlated with ferritin levels (rho = 0.097; P < 0.001). Postpartum haemorrhage (>500 mL) was inversely associated with serum FT4 levels (OR: 0.35; CI 95%: 0.13-0.96); P = 0.040. Also 10% of women free of thyroid disease had serum TSH levels ≥2.5 mIU/L. CONCLUSIONS: Variation in thyroid function during the first trimester within the normal (non-pregnant) range in women free of thyroid disease was not associated with altered pregnancy outcomes. These results add evidence to the recommendation against LT4 treatment in pregnant women with high normal TSH levels and without TPO antibodies.

Maternal thyroid parameters in pregnant women with different ethnic backgrounds: Do ethnicity-specific reference ranges improve the diagnosis of subclinical hypothyroidism?

OBJECTIVE: Guidelines on the management of thyroid dysfunction during pregnancy have recently been updated and, for the diagnosis of subclinical hypothyroidism (SCH), a thyroid-stimulating hormone (TSH) upper reference limit (cut-off) of 4.0 mIU/L has been proposed when no institutional values are available. It is also suggested that serum TSH and thyroid autoimmunity (TAI) may be different according to the ethnic background of the women. We therefore determined the prevalence of TAI and SCH in pregnant women with different ethnic backgrounds and, to define SCH, we used different first trimester TSH upper reference cut-offs (institutional, ethnicity-specific, 2.5 mIU/L [Endocrine Society] and 4.0 mIU/L [American Thyroid Association]). DESIGN: Cross-sectional data analysis of 1683 pregnant women nested within an ongoing prospective database of pregnant women. METHOD: The study was performed in a single centre in Brussels, Belgium. During the first antenatal visit, thyroid peroxidase antibodies (TPO-abs), TSH and free T4 (FT4) were measured and baseline characteristics recorded. Data from 481 women with sub-Saharan (SaBg; 28.6%), 754 North African (NaBg; 44.8%) and 448 Caucasian (CaBg; 26.6%) backgrounds were analysed. For the calculation of TSH reference ranges, women with TAI, outliers, twin and assisted pregnancies were excluded. RESULTS: The prevalence of TAI was significantly lower in the SaBg group than in NaBg and CaBg groups (3.3% vs 8.6% and 11.1%; P<.001, respectively). Median TSH was significantly lower in SaBg and NaBg groups as compared with the CaBg group (1.3 and 1.4 vs 1.5 mIU/L; P=.006 and .014, respectively). The prevalence of women with SCH was comparable between all groups when 2.5 mIU/L was used as cut-off, but when 4.0 mIU/L or the institutional cut-off (3.74 mIU/L) was used, it was significantly higher in the CaBg group vs the NaBg group (5.4% vs 2.1% and 7.1% vs 3.3%, P=.008 and .013, respectively). The use of ethnicity-specific cut-offs did not change the prevalence of SCH as compared to the use of institutional cut-offs. However, when these cut-offs were used, the prevalence of SCH reduced by >70% (4.5% instead of 16.7%; P<.001) relative to the 2.5 mIU/L cut-off. CONCLUSIONS: Pregnant women with a sub-Saharan African background had a lower prevalence of TAI and TSH levels as compared with women from other backgrounds. The use of ethnicity-specific TSH cut-offs in early pregnancy was not more specific for the diagnosis of SCH as compared to the use of the institutional cut-off.

Prevalence of thyroid dysfunction and autoimmunity in the older population and implications of age-specific reference ranges.

OBJECTIVE: To investigate the prevalence of thyroid dysfunction and autoimmunity (TAI) and to determine age-specific reference ranges in individuals <60 and ≥60-year-old. Furthermore we investigated the impact of the age-specific reference ranges on the prevalence of thyroid dysfunction. DESIGN: Retrospective analysis of laboratory data collected over six months in 2015, mainly from individuals consulting the outpatient clinic. METHOD: Data from 676 individuals were withheld, after having applied strict exclusion criteria to avoid confounders. After exclusion of individuals with TAI (TPO-abs >60kIU/L) and/or outliers, data of 547 individuals were used to determine age-specific reference ranges. The prevalence of subclinical hypothyroidism (SCH) and subclinical hyperthyroidism (sch) was determined according to the reference ranges from the commercial assay and also according to the calculated age-specific reference ranges. From our study population. RESULTS: From the 676 individuals included, 559 (83%) were <60year-old and 117 (17%) ≥60year-old. The prevalence of sch and TAI was comparable between both groups (8.6% vs. 13.7% and 15.4% vs. 20.5% respectively). The prevalence of SCH was significantly higher in individuals ≥60years, compared to that in individuals <60years (14.5% vs. 5.4%; p<0.001). The calculated 2.5 and 97.5 percentile for the age-specific TSH range was 0.24 and 4.4 mIU/L in individuals <60years and 0.15 and 8.2mIU/L in individuals ≥60years. When these the prevalence of sch and SCH was then determined on the basis of the age-specific reference ranges, the prevalence of SCH significantly decreased in individuals ≥60years (14.5% to 5%; p=0.027) and it then became comparable with that in individuals <60years (5% vs. 3%). CONCLUSIONS: The prevalence of SCH was higher in individuals ≥60years, compared to that in individuals <60years, but when age-specific TSH reference ranges were used, it was comparable between both study groups. In order to avoid misclassification in older individuals, it is important to use age-specific reference ranges in daily clinical practice.

Prevalence of thyroid autoimmunity and dysfunction in women with iron deficiency during early pregnancy: is it altered?

OBJECTIVE: Thyroid disorders and iron deficiency (ID) are associated with obstetrical and fetal complications. Iron is essential for the normal functioning of thyroid peroxidase (TPO-abs) and ID is frequent during pregnancy. The aim of this study was to compare the prevalence of thyroid autoimmunity (TAI) and dysfunction during the first trimester of pregnancy in women with and without ID. DESIGN: Cross-sectional data analysis of 1900 pregnant women nested within an ongoing prospective collection of pregnant women's data. METHOD: The study was performed in a single, tertiary referral center. During the first antenatal visit, ferritin, TPO-abs, thyroid-stimulating hormone (TSH) and free T4 (FT4) were measured and age and BMI were recorded. ID was defined as ferritin <15µg/L, TAI when TPO-abs was >60kIU/L, and subclinical hypothyroidism (SCH) when TSH was >2.5mIU/L. RESULTS: ID was present in 35% of women. Age and BMI were comparable between both groups. In the ID group, the prevalence of TAI and SCH was significantly higher, compared with that in the non-ID group (10% vs 6% and 20% vs 16%; P=0.011 and 0.049 respectively). Ferritin was inversely correlated with serum TSH (ρ=-0.076; P=0.001) and positive with FT4 levels (ρ=0.112; P<0.001). In the logistic regression model, ID remained associated with TAI after correction for confounding factors (P=0.017). The association with SCH was absent after correction for the confounders in the logistic regression model (P=0.082), but remained present in the linear regression model (P=0.035). CONCLUSIONS: ID was frequent during the first trimester of pregnancy and was associated with a higher prevalence of TAI, higher serum TSH, and lower FT4 levels.