Thyroid dysfunction and the presence of thyroid antibodies increase the risk of infertility and miscarriage. The aim of the present study was to assess if patients with autoimmune thyroid disease undergoing assisted reproduction technologies are afflicted by poor pregnancy and/or delivery rate and if the outcome is conditioned by pre-ART thyroid status. Women who underwent assisted reproduction were tested for TSH, free T4, thyroid peroxidase antibodies (TPOAb) before and during pregnancy. A total of 416 euthyroid women were selected; 42 (10.1%) were TPOAb (+). Women >35 yr were excluded. The endpoints were pregnancy and delivery rates. RESULTS: no differences in pregnancy and delivery rates were observed between women with and without antibodies. In TPOAb (+), women who failed to become pregnant or miscarried displayed higher TSH values before assisted reproduction (2.8 mIU/l) compared to the ones who delivered (1.6 mIU/l) and compared to TPOAb (-) (1.1 mIU/l). CONCLUSIONS: in euthyroid women undergoing assisted reproduction the pregnancy and delivery rates are not affected by the presence of TPOAb. In TPOAb (+) high-normal TSH values are associated with increased risk of unsuccessful pregnancy or subsequent miscarriage. Further studies are required to ascertain possible benefits of levo-T4 (L-T4) in such patients.
http://www.ncbi.nlm.nih.gov/pubmed/17318015
Thyroid-stimulating hormone (TSH), free thyroxine (FT4), free triiodothyronine, anti-thyroperoxidase antibody, and anti-thyroglobulin antibody at 11-13 weeks of gestation were measured in 202 singleton pregnancies that subsequently resulted in miscarriage or fetal death, and the values were compared with the results of 4318 normal pregnancies. RESULTS: In the fetal loss group, compared to the unaffected group, there was an increase in median TSH multiple of the normal median (1.133 vs. 1.007 MoM), decrease in median FT4 MoM (0.958 vs. 0.992 MoM), and increase in the incidence of TSH above the 97.5th centile (5.9% vs. 2.5%) and FT4 below the 2.5th centile (5.0% vs. 2.5%). Logistic regression analysis demonstrated that in the prediction of fetal loss there were significant contributions from FT4 MoM, maternal black ethnic origin, history of chronic hypertension, and use of ovulation drugs. The prevalence of antithyroid antibody positivity was not significantly different in the fetal loss group compared to that of normal pregnancies (15.3% vs. 16.8%). CONCLUSIONS: Impaired thyroid function may predispose to miscarriage and fetal death. http://www.ncbi.nlm.nih.gov/pubmed/20718684
Of the 31 studies evaluating miscarriage, 28 showed a positive association between thyroid autoantibodies and miscarriage. Meta-analysis of the cohort studies showed more than tripling in the odds of miscarriage with the presence of thyroid autoantibodies (odds ratio 3.90). For case-control studies the odds ratio for miscarriage was 1.80). There was a significant doubling in the odds of preterm birth with the presence of thyroid autoantibodies (2.07). Meta-analysis of the 12 case-control studies also showed an increase in the odds of miscarriage in women with normal thyroid function and thyroid autoantibodies (1.80). The weighted mean difference for thyroid stimulating hormone was significantly higher in the thyroid autoantibody positive group compared with the negative group by 0.51 mIU/L. Two randomised studies evaluated the effect of treatment with levothyroxine on miscarriage. Both showed a fall in miscarriage rates, and meta-analysis showed a significant 52% relative risk reduction in miscarriages with levothyroxine (relative risk 0.48). One study reported on the effect of levothyroxine on the rate of preterm birth, and noted a 69% relative risk reduction (0.31). Conclusion: The presence of maternal thyroid autoantibodies is strongly associated with miscarriage and preterm delivery. There is evidence that treatment with levothyroxine can attenuate the risks.
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3089879/
A clear association between the presence of thyroid antibodies and miscarriage was found with an odds ratio of 2.73 in eight case-control and ten longitudinal (odds ratio, 2.30) studies. This association may be explained by a heightened autoimmune state affecting the fetal allograft, of which thyroid antibodies are just a marker. Alternatively, the association can be partly explained by the slightly higher age of women with antibodies compared with those without. A third possibility is mild thyroid failure, as thyroid-stimulating hormone levels in antibody-positive but euthyroid (normal thyroid function) women are higher than in antibody-negative women: difference, 0.81. Randomized clinical trials with l-thyroxine (aiming at TSH values between 0.4 and 2.0 mU/l) and with selenium (to decrease antibodies against thyroid peroxidase) are clearly needed to elucidate further the nature of this association.
http://www.eje-online.org/cgi/reprint/150/6/751.pdf
A clear association between thyroid autoimmunity and miscarriage was observed with a pooled odds ratio of 2.55 in 8 case-control studies, and a pooled relative risk of 2.31 in 14 cohort studies. Women with thyroid autoimmunity were found to have slightly higher age [age difference, 1.29 years] and thyroid-stimulating hormone (TSH) levels [TSH difference, 0.61 mIU/l] compared with those without thyroid autoimmunity. Conclusion: Based on the currently available evidence, it appears that the presence of thyroid autoimmunity is associated with an increased risk of spontaneous miscarriage in euthyroid (normal thyroid function) women.
http://www.ncbi.nlm.nih.gov/pubmed/21198746
The mean basal TSH serum levels were higher in repeat miscarriage women [2.1 μIU/ml] compared with the controls (1.3 μIU/ml). Establishing serum TSH at an individual level, a large overlap was observed and the receiver operating characteristic curves did not allow us to find an optimal cut-off point with an adequate sensitivity/specificity ratio. Therefore, we suggest a novel statistical model, the 'iTSHa index' (available on www.afar.it/tsh-trh-miscarriage), that is capable of identifying women with repeat miscarriage due to transient thyroid function impairment of the early pregnancy, in particular when baseline serum TSH is less than 1.5 μIU/ml, i.e. well below the conventional upper cut-off indicated as 'safe' in those who want to conceive.
http://www.ncbi.nlm.nih.gov/pubmed/21429952
Women with overt thyroid dysfunction were excluded. The mean TSH and FT(4) level in the women with miscarriage was 1.48 mU/l compared with 1.11 mU/l in women without child loss. The incidence of child loss increased by 60% (OR=1.60) for every doubling in TSH concentration. This association remained after adjustment for smoking, age, parity, diabetes mellitus, hypertension, previous preterm deliveries, and previous preterm stillbirth/miscarriage (adjusted odds ratio=1.80). This was not true for FT(4) concentrations (OR=1.41).
http://www.ncbi.nlm.nih.gov/pubmed/19273570
Forty-five pregnant women with a clinical diagnosis of threatened miscarriage and a live fetus and 30 normal pregnant women were included in the study. The patients were divided retrospectively into two groups on the basis of outcome: 1) 31 women who did not miscarry (positive outcome) and 2) 14 women who miscarried (negative outcome). RESULTS: Human chorionic gonadotropin was significantly higher in women who did not abort (39.4 IU/mL) than in women who miscarried (17.6 IU/mL). Free thyroxine but not fT3 was lower in patients with negative outcome (1.25 ng/mL compared with 1.98 ng/mL) and IgG and IgM plasma levels were higher (780 ng/mL compared with 470 ng/mL and 930 ng/mL compared with 650, respectively). Plasma TSH levels were higher in patients with negative outcomes (1.72 mIU/mL compared to 1.01). Plasma concentrations of hCG and thyroid hormones were significantly correlated with peripheral blood lymphocyte and neutrophil counts only in the group of women who aborted. CONCLUSION: Our results indicate that maternal immune response, trophoblast function, and maternal thyroid function are somehow correlated. The presence of low concentrations of hCG and fT4 and high levels of TSH and gamma globulins in women with threatened abortion suggests a negative outcome for the pregnancy.
http://www.ncbi.nlm.nih.gov/pubmed/9699752
To evaluate a possible role of thyroid hormones in maintaining early pregnancy, serum levels of thyroid hormones, TSH and thyroxine-binding globulin in 32 patients with a clinical diagnosis of threatened miscarriage were compared between two groups of patients with favorable and unfavorable pregnancy outcome. Serum levels of T4, T3, free T4 and free T3 levels determined at the onset of clinical signs of threatened abortion were found to be significantly lower in patients (N = 11) who subsequently miscarried compared to patients (N = 21) who did not. Serum TSH levels did not differ between the two groups. Serum thyroxine-binding globulin levels in the patients who subsequently miscarriage were lower compared to patients with favorable pregnancy outcome. Furthermore, serum levels of T4 and T3 at the onset of threatened abortion in patients who subsequently did not abort were significantly higher compared to levels before pregnancy, whereas little increase in serum T4 and T3 levels relative to the pregnant levels was observed at the onset of clinical signs in the patients who subsequently miscarried. These data imply a possible role of thyroid hormones in maintaining early pregnancy, and suggest that maternal serum level of thyroid hormone may be one of the endocrine factors responsible for the outcome of threatened miscarriage.
http://www.ncbi.nlm.nih.gov/pubmed/1529657
Direct effects of T3 or T4 on the trophoblast function were investigated in vitro using an organ culture system of human placental tissues. Addition of T3 resulted in the maximum increase in daily secretion of progesterone, estradiol-17 beta as well as hCG alpha, hCG beta, hCG and hPL by cultured early placental tissues. Increases in progesterone and estradiol-17 beta secretion caused by the addition of T3 were further augmented in response to concomitant addition of pregnenolone and testosterone, respectively, suggesting that T3 enhances 3 beta-hydroxysteroid dehydrogenase and aromatase activity in the placenta. These stimulatory effects of T3 on the trophoblast endocrine function were also found with the use of T4. Addition of higher or lower concentrations of T3 or T4 gave attenuated effects. These results suggest that the optimal concentration of thyroid hormone is needed for it to exert its maximally stimulatory action on trophoblast endocrine function. Unlike early placental tissues, cultured term placental tissues did not respond to the addition of T3 or T4 with increased endocrine activity. Thus, the frequent occurrence of miscarriage in early pregnancy during the state of hypothyroidism or hyperthyroidism may represent a direct consequence of inadequate thyroid hormone availability at the level of placental trophoblasts, followed by diminished expression of trophoblast endocrine function.
http://www.ncbi.nlm.nih.gov/pubmed/1872126
Oocyte fertilization, grade A embryos, and pregnancy rates were lower in women with thyroid autoimmunity than in negative controls, while early miscarriage rate was higher. Anti-thyroid antibodies were measurable in follicular fluid in all affected women and were strongly correlated with serum levels. No significant changes in thyroid hormone levels were recorded in any women. Conclusion: The presence of anti-thyroid antibodies in ovarian follicles, as demonstrated for the first time in this study, may play a critical role in female infertility related to thyroid autoimmunity.
http://www.ncbi.nlm.nih.gov/pubmed/21241400
Women were divided into two groups based on their initial TSH: group A, TSH level below 2.5 mIU/liter (excluding hyperthyroid women), and group B, TSH level between 2.5 and 5.0 mIU/liter. The rate of miscarriage was significantly higher in group B as compared with group A (6.1 vs. 3.6% respectively). 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.
http://jcem.endojournals.org/cgi/content/abstract/95/9/E44
According to our algorithm for thyroid screening in pregnancy, if thyroid-stimulating hormone (TSH) exceeded 1 mU/l in TPOAb+ women, 50 µg of levothyroxine (Synthroid) was prescribed. Results: The miscarriage rate was significantly higher in the 47 nontreated TPOAb+ women compared with the 49 treated women (16 vs. 0%, p=0.02). Compared to the control group, TSH in TPOAb+ patients was higher at the first prenatal visit prior to levothyroxine treatment, while free thyroxine was higher than in the control group after the 20th week. Conclusions: Our study supports the potential benefit of universal screening and levothyroixine treatment for autoimmune thyroid disease during pregnancy. Efforts are still needed to further decrease miscarriage rates.
http://www.ncbi.nlm.nih.gov/pubmed/23147711
Recurrent miscarriage was not associated with abnormal thyroid function test.
http://www.ncbi.nlm.nih.gov/pubmed/11192102
Clinical hypothyroidism was associated with increased miscarriage, low birth weight, and congenital circulation system malformations; the adjusted odds ratios were 13.45, 9.05, and 10.44, respectively. Subclinical hypothyroidism was associated with increased fetal distress, preterm delivery, poor vision development, and neurodevelopmental delay; the adjusted odds ratios were 3.65, 3.32, 5.34, and 10.49, respectively. Isolated hypothyroxinemia was related to fetal distress, small for gestational age, and musculoskeletal malformations; the adjusted odds ratios were 2.95, 3.55, and 9.12, respectively. Isolated hyperthyroxinemia was associated with miscarriage; the adjusted odds ratio was 6.02. Clinical hyperthyroidism was associated with hearing dysplasia; the adjusted odds ratio was 12.14. Conclusions: Thyroid dysfunction in the first 20 wk of pregnancy may result in miscarriage and dysplasia and some congenital malformations.
http://www.ncbi.nlm.nih.gov/pubmed/21832110
Direct effects of L-triiodothyronine(T3) on placental endocrine function were investigated in vitro with an organ culture system for human placental tissues. The addition of an optimal concentration of T3 stimulated daily secretion of progesterone and estradiol from cultured early placental tissues, together with the enhancement of hCG(alpha, beta) and hPL secretion. The addition of higher or lower concentrations of T3 gave attenuated effects and the addition of an excessive concentration of T3 resulted in remarkable inhibition of progesterone and estradiol secretion by cultured early placental tissues. These results suggest that the optimal concentration of thyroid hormone acts as a biological amplifier of endocrine function of cultured trophoblasts obtained from early placentas. Unlike the early placental tissues, cultured term placental tissues did not respond to the addition of graded doses of T3 with increased endocrine function. Thus, the frequent occurrence of spontaneous abortion in early pregnancy during the state of hypothyroidism or hyperthyroidism may represent a direct consequence of inadequate thyroid hormone availability at the level of the trophoblast, followed by diminished endocrine function of early placental trophoblasts.
http://www.ncbi.nlm.nih.gov/pubmed/1940550
The present study compared maternal and neonatal adverse outcomes in 245 women who were euthyroid (TSH < 2.5 mIU/liter normal thyroid hormone levels ) but thyroid peroxidase positive in the first trimester to 3348 women who were euthyroid and thyroid peroxidase negative in the first trimester. Results: The main result was an increase in very preterm delivery (<34 wk gestation at delivery) (4.5 vs. 1.8%) and respiratory distress (3.3 vs. 1.2%) in women who were thyroid antibody positive. Conclusions: The present study provides further evidence of an association between thyroid antibody positivity and very preterm delivery in euthyroid women. The association with respiratory distress should be considered preliminary and awaits further study.
http://www.ncbi.nlm.nih.gov/pubmed/21411559
Background: about 10% of women in childbearing age are positive for thyroid antibodies. The presence of such antibodies has been associated with adverse obstetrical outcomes, in particular miscarriage and pre-term delivery, even though the strength of these associations varies widely from one to another study. Aim: to evaluate from the available data of the literature, the association between thyroid autoimmunity and pre-term delivery. Results: seven studies, collecting about 23,000 patients were selected. Meta-analysis of the studies showed an association between thyroid autoimmunity and pre-term delivery (odds ratio =1.67). Conclusions: the results of meta-analysis confirmed the association between thyroid autoimmunity and pre-term delivery.
http://www.ncbi.nlm.nih.gov/pubmed/21422804
Overall and spontaneous pregnancy rates were highest in women with normal basal and stimulated TSH, high T4 and low microsomal antibodies. Women with normal thyroglobulin antibodies or high thyroxine binding globulin experienced the highest delivery rate (77 versus 30%), while in women with low thyroglobulin antibodies or high microsomal antibodies miscarriage and tubal pregnancies were most frequent.
http://www.ncbi.nlm.nih.gov/pubmed/1955537
The prevalence of thyroid autoimmunity in women with unexplained infertility and implantation failure was significantly increased in comparison to those with recurrent miscarriage. There was also a trend towards a higher prevalence of thyroid autoimmunity in the unexplained infertility and implantation failure groups than in the control group.Thyroid autoimmunity is strongly related to unexplained infertility and implantation failure.
http://www.ncbi.nlm.nih.gov/pubmed/18070829
Children born to mothers who test positive for thyroid antibodies have a 10.5 point lower IQ
In a prospective study of a cohort of 293 pregnant women, the occurrence of TPO-Ab during gestation, thyroid dysfunction, and depression was investigated. Five years after delivery, child development was assessed in 230 children of the original cohort using the Dutch translation of the McCarthy Scales of Children's Abilities. Children of women with TPO-Ab during late gestation (n = 19, with normal thyroid function) had significantly lower scores (by t test) on the McCarthy Scales of Children's Abilities than antibody-negative women. The difference on the General Cognitive Scale, which reflects IQ scores, was substantial (10.5 points; t = 2.8). After correction for possibly confounding variables, maternal TPO-Ab during gestation was found to be the most important factor related to the scores on the General Cognitive Scale (odds ratio = 10.5). We conclude that children of pregnant women who had elevated titers of TPO-Ab but normal thyroid function are at risk for impaired development.
T3 has profound effect upon the developing embryo and infants. It affects the lungs and influences the postnatal growth of the central nervous system. It stimulates the production of myelin, the production of neurotransmitters, and the growth of axons. It is also important in the linear growth of bones.
http://en.wikipedia.org/wiki/Triiodothyronine