Finns det någon annan som har sköldkörtel-antikroppar som orsakar missfall? Mina sköldkörtelvärden är bra (äter Levaxin, TSH ligger på 1 som högst) men det är tydligen antikropparna i sig som orsakar missfall.
Kan man göra något åt detta?! Läkarna har inte bra koll på det här känner jag.
Hej Vilaa! Som jag skrev så har läkarna dålig kolla på detta, mycket märkligt med tanke på hur vanliga sköldkörtelsjukdomar är bland kvinnor i fertil ålder!
Vem gick du på missfallsutredning hos? Vilken endokrinolog? Det finns flera vetenskapliga undersökningar som visar på att antikropparna i sig har betydelse, även om man ligger bra i TSH och T4 med Levaxin. Tyvärr, känner mig så rädd, ledsen och maktlös. Kan man inte göra någonting åt antikropparna?
Jätteroligt att höra att det ändå gått bra för dig nu, vecka 13 låter ju lovande! Mina 2 missfall har också varit tidiga, vecka 6 och 7.
Jag har gått hos min Endokrinolog i 3 år sen jag fick giftstruma efter att min son fötts. Hade heller aldrig fått missfall innan. "Bara" svårt att bli gravid (gör IVF), har hållt på i 8 år. Jag frågade om sköldkörteln kunde vara orsaken till missfall, och hon sa nej, inte om TSH är bra. Pratade med henne igen några dagar senare och då hade hon läst på och hittat studier som faktiskt visar på samband mellan missfall och antikroppar av olika slag.
Är det TPO-ak som du har? Det är jättejätteviktigt att du ligger riktigt lågt i TSH under hela graviditeten, du måste ta kontinuerliga prover av TSH och T4 och höja Levaxinet succesivt.
Jag ska också göra en missfallsutredning men det känns som att jag redan vet vad den kommer visa. Ledsen, arg, deprimerad!!!
Lite länkar till vetanskapliga studier för den som är intresserad:
http://onlinelibrary.wiley.com/doi/10.1111/j.8755-8920.2000.430404.x/abstract
http://ltarkiv.lakartidningen.se/2003/temp/pda26203.pdf
http://www.ejog.org/article/S0301-2115(97)00097-3/abstract
The incidence of thyroid antibodies in euthyroid women with recurrent pregnancy loss appears to be significantly increased compared with controls of reproductive age without previous abortions. No correlation between the presence of thyroid autoantibodies and non-organ specific autoantibodies could be established.
Detection of At-Risk Pregnancy by Means of Highly Sensitive Assays for Thyroid Autoantibodies
We screened 552 women who presented to their obstetrician in the first trimester of pregnancy using highly sensitive enzyme-linked immunosorbent assays for the presence of thyroglobulin and thyroidperoxidase autoantibodies and found an incidence of positivity of 19.6%. The tendency to secrete detectable levels of thyroid autoantibodies was significantly correlated with an increased rate of miscarriage. Thyroid autoantibody—positive women miscarried at a rate of 17%, compared with 8.4% for the autoantibody-negative women. Individual levels of thyroglobulin and thyroidperoxidase autoantibodies were similarly related to this increased miscarriage rate, with no evidence of autoantibody specificity in the relationship. Furthermore, the increase in miscarriages could not be explained by differences in thyroid hormone levels, the presence of cardiolipin autoantibodies, maternal age, gestational age at the time of maternal entry into the study, or previous obstetric history. We conclude that thyroid autoantibodies are an independent marker of "at-risk" pregnancy.
http://jama.ama-assn.org/cgi/content/abstract/264/11/1422
http://www.eje-online.org/cgi/content/full/162/4/643
Introduction
The association between spontaneous miscarriage and thyroid autoimmunity (TAI) defined as the presence of autoantibodies against thyroid peroxidase (TPOab) and/or thyroglobulin (TGab) was initially reported by Stagnaro-Green et al. (1), subsequently investigated in numerous studies and finally confirmed by two meta-analyses (2, 3). Causality remains unclear; co-presence of TAI with other autoimmune syndromes, direct action of anti-TPO and TGab on placenta, hampered adaptability of the thyroid gland to the increased demands of pregnancy in the presence of TAI and higher age of women with TAI have all been implicated. The obscure pathophysiology is probably one of the reasons why adequate treatment strategies have not yet been developed. A well-designed randomized controlled trial, in which sodium levothyroxine (L-T4) supplementation was associated with a risk of miscarriage similar to that observed in healthy controls (4), needs to be confirmed before L-T4 supplementation could be routinely recommended in the course of a TAI-positive pregnancy (5).
Although devastating on a personal level, pregnancy loss could be regarded as a natural outcome of an inefficient process, considering that only 23% of conceptions result in live births (6). However, pregnancy outcome becomes a matter of copious and costly efforts in subfertile women undergoing artificial reproduction techniques (ART), where any factor that could potentially affect the outcome should be adequately analyzed and carefully considered. Currently, it is not clear whether there is an association between TAI and poor IVF outcome (5, 7). Several studies which examined the association between TAI status and miscarriage provided rather controversial results (8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18), although it appears that ‘TAI per se does not alter the implantation of embryo’ (19). Moreover, observations regarding TAI and miscarriage risk from the general population could not be applied to an IVF setting and vice versa, since women undergoing IVF are considered as a distinct subgroup, representing a ‘special population’ (20). An answer to whether the presence of thyroid autoantibodies is associated with an increased risk for miscarriage in IVF might assist the IVF counseling in women with TAI. For that purpose, a meta-analysis of observational studies evaluating this research question was performed.
In short, the ideal study should be prospective in design, include only first-time ART users and analyze only first cycle ART outcomes, measure both TPOab and TGab in all the subjects before ART procedure, control for the possible confounding effect of other autoantibodies and/or causes of spontaneous miscarriages and involve euthyroid, without TAI, age-matched women undergoing IVF as controls.
A well-designed randomized controlled trial, in which sodium levothyroxine (L-T4) supplementation was associated with a risk of miscarriage similar to that observed in healthy controls (4), needs to be confirmed before L-T4 supplementation could be routinely recommended in the course of a TAI-positive pregnancy (5).
Results: The offspring of TPO-Ab- and TG-Ab-positive mothers had higher perinatal mortality, which was not affected by thyroid hormone status. Unadjusted and adjusted (for maternal age and parity) risk for increased perinatal mortality was an odds ratio of 3.1 (95% confidence interval 1.4–7.1) and 3.2 (1.4–7.1) in TPO-Ab- and 2.6 (1.1–6.2) and 2.5 (1.1–5.9) in TG-Ab-positive mothers. TPO-Ab-positive mothers had more large-for-gestational age infants (2.4 vs. 0.8%, P = 0.017), as did mothers with low TSH and high fT4 concentrations vs. reference group (6.6 vs. 2.5%, P = 0.045). Significantly higher placental weights were observed among mothers with low TSH and high fT4 or high TSH and low fT4 levels as well as among TPO-Ab-positive mothers.
Conclusions: First-trimester antibody positivity is a risk factor for perinatal death but not thyroid hormone status as such. Thyroid dysfunction early in pregnancy seems to affect fetal and placental growth.
http://jcem.endojournals.org/cgi/content/full/91/7/2500
The fourth, and most novel and important, result of the study was that levothyroxine administration to TAI-positive women allowed for a significant decrease in the rate of obstetrical complications, with the miscarriage rate reduced by 75% (from 13.8 to ± 3.5%) and the frequency of premature delivery by 69% (from 22.4 to ± 7%). These results confirm entirely data produced previously by other authors showing an association between thyroid autoimmunity features and adverse obstetrical effects, even in the absence of thyroid dysfunction. They are important because, for the first time in a prospective, randomized study, they clearly show beneficial effects of levothyroxine administration on the outcome of pregnancy in women with thyroid autoimmunity and without an evident perturbation of thyroid function in early gestational stages (4, 5).
An association between the risk of a miscarriage and autoimmune thyroid disease (AITD) was first reported 15 yr ago (6, 7). Since then, the statistical strength of this association has been largely confirmed in several population studies, leading authors to conclude that AITD without overt thyroid dysfunction was significantly associated with a 3- to 5-fold increase in overall miscarriage rate (8). In a recent review, a more detailed classification was attempted by examining separately the association between AITD and miscarriage (five studies), AITD and recurrent miscarriage (seven studies), and finally AITD and early pregnancy loss after in vitro fertilization (five studies). Overall and with only a few exceptions, all studies documented a statistically significant relationship between AITD and increased pregnancy loss (9). Finally, a recent metaanalysis of all case-controlled and longitudinal studies published since 1990, after the association between miscarriage and AITD was first described, amply confirmed that the overall relative risk of miscarriage was increased approximately 3-fold in women with AITD (10).
Finding an association does not imply a causal relationship, and the etiology of increased pregnancy loss in women with AITD remains largely unknown. Three working hypotheses have been proposed. The first hypothesis holds that pregnancy loss is not directly related to the presence of circulating thyroid antibodies and, in this view, AITD could represent only a marker of an underlying, yet-to-be-defined, more generalized autoimmune imbalance that, in turn, would explain a greater rejection rate of the fetal graft. The second hypothesis holds that despite apparent euthyroidism, the presence of AITD could be associated with a subtle deficiency in thyroid hormone concentrations or a lesser ability of thyroid function to adapt adequately to the changes associated with the pregnant state because of a reduced functional reserve characteristic of the thyroid gland in chronic autoimmune thyroiditis. The third hypothesis holds that AITD could act by delaying the occurrence of a conception because of its known association with infertility. In this view, TAI-positive women would tend to become pregnant at an older age (3–4 yr older, on the average), and older women are more prone to pregnancy loss. These hypotheses do not contradict one another, and it remains plausible that the increased risk of pregnancy loss associated with AITD is multifactorial, resulting eventually from a combination of several independent deleterious factors (11, 12).
Until the present study by Negro et al. (1), only three studies have investigated whether medical intervention would benefit women with thyroid autoimmunity. In a prospective study by Vaquero et al. (13), 27 TAI-positive women with two previous first-trimester miscarriages were subdivided into 11 TAI-positive women who received iv Igs during pregnancy and 16 TAI-positive women who received levothyroxine, started before conception and continued during pregnancy. The pregnancy success rate was 81% in the thyroxine-treated group, compared with 55% in the other group. Despite its inherent limitations (small number of cases and absence of randomization, etc.), the study by Vaquero et al. (13) constituted the first intervention trial showing a positive effect of thyroid hormone administration in women who were habitual aborters. In 2005 Negro et al. (14) also reported the results of levothyroxine administration in euthyroid TAI-positive infertile women who underwent in vitro fertilization. The authors showed that the miscarriage rate was reduced to 33%, compared with 52% in untreated controls. The study, however, failed to reach statistical significance, perhaps because of the small number of cases (14). Finally, in a slightly different clinical setting, a study by Abalovich et al. (4) showed that it was not so much the diagnosis of overt vs. subclinical hypothyroidism that mattered in relation with pregnancy outcome but mainly the adequacy of levothyroxine treatment. The outcome of pregnancy was compared in 27 women with hypothyroidism already known before pregnancy and who received an adequate levothyroxine treatment with 24 women in whom levothyroxine treatment was not adequately adjusted during gestation and who, hence, did not reach euthyroidism. When the treatment was not adequate, pregnancy ended with abortion in 60 and 71% of overt and subclinical hypothyroid women, respectively, with an increased prevalence of preterm deliveries. Conversely, in hypothyroid pregnant women who received an adequate treatment, the frequency of abortions was minimal and pregnancies carried to term without complications.
First the facts, and then the interpretation and perspective will be discussed. In summary, what are the lessons to be learned from the study of Negro et al. (1)? First, there is a confirmation of previously known findings, namely that: 1) euthyroid women with thyroid autoantibodies tend to be older when they become pregnant; 2) even though euthyroid in early gestational stages, these women tend to have a reduced thyroid functional reserve; 3) they have an increased risk for obstetrical complications (miscarriage and premature delivery); and 4) when given the benefit of treatment with thyroid hormone, they normalize thyroid function tests and behave as control women. Furthermore, the study clearly showed the benefits of levothyroxine administration in pregnant women with AITD not only to correct maternal thyroid function but also to reduce markedly the rate of undesired obstetrical events and lower their prevalence down to that found in healthy controls. There is no reason to believe that levothyroxine administration played a role in altering underlying autoimmunity. Also, the age difference between TAI-positive and control women was not large enough to explain the different rates of miscarriage and premature birth and obviously even less the changes observed in such rates after treatment with levothyroxine. The present study therefore leads us to conclude that among the three hypotheses evoked above, the second one, i.e. a subtle deficiency in thyroid hormone concentration and/or a lesser ability of maternal thyroid function to adapt adequately in women with AITD, was the main reason for the beneficial effects of thyroid hormone administration. If confirmed by future studies, these results would constitute an additional argument to screen pregnant women systematically for the presence of asymptomatic chronic autoimmune thyroiditis and/or mild thyroid underfunction to give such women the benefit of thyroid hormone treatment.
http://jcem.endojournals.org/cgi/content/abstract/92/8_suppl/s1
http://jama.ama-assn.org/cgi/content/abstract/264/11/1422