Most modern women agree that it is advisable to plan pregnancy. And in cases where a woman suffers from any chronic disease, planning a future pregnancy becomes especially important and necessary.
Is it possible to get pregnant with the most common thyroid disease among young women – hypothyroidism? Yes! With adequate treatment before and during pregnancy, a woman can become pregnant and give birth to a healthy baby.
Let's discuss how to prepare for pregnancy and how to behave during pregnancy with hypothyroidism. Hypothyroidism is a deficiency of thyroid hormones. It is most often caused by a disease called autoimmune thyroiditis, or by removal of the thyroid gland for various reasons.
When planning a pregnancy, a woman who was diagnosed with hypothyroidism before pregnancy must take a blood test for TSH and visit an endocrinologist with the result.
The endocrinologist will adjust the dose of levothyroxine (Eutyrox, L-thyroxine) you take so that your hormonal levels are closer to ideal for pregnant women.
For women planning a pregnancy, a normal TSH value is considered to be up to 2.5 µIU/ml, and not the figure indicated on the laboratory form as the upper limit of normal. Why are the standards more stringent?
In the first half of pregnancy, the fetal thyroid gland is still developing and does not work; the child receives these hormones from the mother. A normal level of thyroid hormones is necessary for the proper development of the fetal nervous system; it affects the future intelligence of the child. Therefore, it is so important that in the first trimester of pregnancy (when a woman may not yet know about her pregnancy), the mother’s hormones are sufficient to provide for the fetus.
How to prepare for research
It is very important to correctly complete all the preparatory steps before taking the hormone test. The following conditions will be mandatory:
- donate blood for the hormone only on an empty stomach (you need to understand this word correctly: on an empty stomach - this means that the last meal should be at least 8 hours and maximum 12 hours before the test);
- you can drink water, but any sweet or sweetened drinks, tea and coffee are strictly contraindicated;
- the day before the blood test for the hormone, there should be no feast or heavy consumption of fatty and spicy foods (any holiday is a reason to postpone the test for several days);
- You need to go for analysis in the morning from 8 to 10 o’clock, when the level of TSH in the blood is most optimal;
- If a woman is taking hormonal contraceptives or other medications, she should consult a doctor about the need to discontinue them.
Right before donating blood for TSH, you must do the following:
- do not smoke for at least 1 hour;
- refuse any physical activity (you cannot come after training or physical work);
- It is not advisable to donate blood for the hormone after X-ray examination;
- It is advisable to take your time so that you have the opportunity to sit and relax in the laboratory;
- You should not take the test after severe emotional stress.
Women who are not pregnant do not need to donate blood for TSH on a certain day - the menstrual cycle does not affect the result.
Usually the doctor will explain what to do and what not to do. The recommendations should be strictly followed. If a woman with thyroid disease takes thyroid hormone for therapeutic purposes, she will need to take another dose after the blood draw.
MEDICAL CENTER
A pituitary hormone that regulates the functions of the thyroid gland. One of the most important tests in the laboratory diagnosis of thyroid diseases. .
TSH is a glycoprotein with a molecular weight of about 28 kDa. Synthesized in the anterior lobe of the pituitary gland. Activates the production and secretion of thyroid hormones (thyroid hormones), initiates cell growth and mitotic activity of thyroid cells. Synthesis and secretion of TSH are stimulated by thyrotropin-releasing hormone of the hypothalamus in response to a decrease in the level of circulating thyroid hormones. The level of TSH is in an inverse logarithmic relationship with the concentration of T4: as the level of T4 increases, the production of TSH decreases; as the level of T4 decreases, the production of TSH compensatory increases, which helps maintain the concentration of thyroid hormones at the required height. TSH secretion is influenced by various neuronal mechanisms and changes during sleep, low temperature, and nonspecific stress. TSH is characterized by daily fluctuations in concentration: blood TSH reaches its highest values at 2-4 a.m., high levels in the blood remain until 6-8 a.m., and minimum TSH values occur at 5-6 p.m. The reference values for TSH levels given below are applicable for outpatients in the period from 8 to 18 hours. The normal rhythm of thyrotropin secretion is disrupted when awake at night.
With clinically pronounced primary hypothyroidism (i.e., damage at the level of the thyroid gland, which leads to a decrease in its function), there is a significant increase in the level of TSH against the background of low levels of thyroid hormones. Primary hyperthyroidism, in contrast, is associated with decreased or undetectable TSH levels and high thyroid hormone levels. Determination of TSH levels makes it possible to identify subclinical stages of thyroid diseases, when the concentration of thyroid hormones is still maintained by regulatory mechanisms within the reference values. Typically, when screening for thyroid function, TSH is used as the only test or in combination with the determination of free T4.
Taking thyroxine preparations on the eve of taking blood for testing does not affect the concentration of TSH. Normalization of TSH levels during replacement therapy for hypothyroidism with L-thyroxine drugs occurs slowly (over several weeks and months), since in chronic severe hypothyroidism hyperplasia of thyrotrophs develops. The paradoxical combination - a high level of TSH and a high level of free T4 - during this period is an artificially induced (iatrogenic) condition. It is advisable to carry out repeated studies of TSH levels in order to monitor therapy no earlier than 6 weeks after changing the dose or type of drug.
In secondary and tertiary hypothyroidism associated with pituitary dysfunction due to pathology of the pituitary gland and hypothalamus, significantly reduced levels of T3 and T4 are combined with normal or slightly increased levels of TSH, which in these cases has reduced biological activity. Rare clinical cases of secondary hyperthyroidism may be due to TSH-secreting tumors.
Severe diseases not associated with thyroid pathology can cause a temporary change in TSH concentration. The cause may be the use of medications or the consequences of the disease itself. Typically, there is a decrease in TSH levels during the acute phase of the disease and a slight increase in levels during recovery. If necessary, in such cases, it is advisable to focus on the extended reference range of TSH (0.02-10 mU/l) and use a set of tests for TSH and T4 (or free T4).
Physiological changes in TSH concentrations are observed during pregnancy. High concentrations of human chorionic gonadotropin, which has a certain structural similarity to TSH, can have a stimulating effect on the synthesis of thyroid hormones. In the first trimester of pregnancy, a temporary increase in T4 levels and a decrease in TSH levels are observed. During the second and third trimesters, TSH levels return to normal. An elevated TSH level in early pregnancy may indicate latent maternal hypothyroidism, which is potentially dangerous for the development of the fetus.
Limits of determination: 0.0025 mU/l-100 mU/l
Who should have hormone levels assessed?
The procedure for determining the concentration of TSH in the blood allows you to obtain the necessary information about how the thyroid gland works. This endocrine organ greatly influences reproductive function, so if an examination is not carried out, there are no guarantees for normal conception and smooth gestation of the fetus. TSH must be taken in the following cases:
- against the background of prenatal preparation;
- for any manifestations of thyroid pathology in the past;
- after operations on endocrine organs;
- when diagnosing infertility;
- against the background of an irregular menstrual cycle;
- to identify the causes of miscarriage and prematurity;
- with a sharp increase in body weight in a short period of time;
- against the background of increased blood pressure or rapid pulse.
Any variant of endocrine ill health is a reason to take a blood test for the hormone. There is no need to evaluate the level of all thyroid hormones - it is quite enough to take a correct TSH test to see deviations in the functioning of the organ.
When preparing for conception or during pregnancy, it is necessary to evaluate the level of thyrotropin in order to notice problems in the thyroid gland in time. It is better to do this before pregnancy in order to restore the functioning of the endocrine system and prevent complications during pregnancy.
Subclinical hypothyroidism and pregnancy
To determine the indications for the treatment of subclinical hypothyroidism, it is necessary to take into account the effect of different TSH levels on the course of pregnancy and its outcomes. Unfortunately, not all studies identify groups of pregnant women with varying degrees of increased TSH and take into account the titer of antithyroid antibodies, which also affect the course of pregnancy. A study by N. Benhadi [17] revealed a positive correlation between TSH levels, starting from normal values, and spontaneous abortion: with each doubling of TSH, the probability of miscarriage increased by 80%. An increase in TSH in the range of 2.5–5.0 mU/l in women without antithyroid antibodies is accompanied by an approximately 2-fold increase in the risk of miscarriage, both in early and late pregnancy [18, 19]. It should be noted that the effect of subclinical hypothyroidism on pregnancy increases when using local TSH standards. A study conducted in Australia showed that the risk of miscarriage increases by 3.66 times with TSH>95 percentile in early pregnancy, although TSH>95 percentile combines subclinical and overt hypothyroidism, which may affect the results of the study [20]. The risks of spontaneous abortion increase with a combination of elevated TSH and high titres of antibodies to thyroid peroxidase (TPO). In a study by C. Lopez-Tinoco et al. [21] demonstrated that the presence of antibodies to TPO in pregnant women with subclinical hypothyroidism increases the risk of miscarriage by more than 10 times. Researchers from China received similar data. The highest risk of miscarriage was identified in the group of pregnant women with subclinical hypothyroidism (TSH 5–10 mU/l) and elevated titer of antibodies to TPO (odds ratio (OR) 9.56; p<0.001). In a study by Y. Zhang [19], the risk of miscarriage at less than 20 weeks. pregnancy increased by 2.47 times with elevated TSH>2.5 mU/l and a high titer of antithyroid antibodies. However, not all studies have confirmed the negative effect of TSH>2.5 mU/l on the course of pregnancy. Thus, in a study by H. Liu [22], no statistically significant differences in the rate of abortion were found in the groups of pregnant women with TSH<2.5 mU/l and TSH in the range of 2.5–5.22 mU/l, although there was an increasing trend was observed in the group with elevated TSH (3.3% versus 2.2%, p=0.083). A Cochrane review compared pregnancy outcomes between total screening for thyroid dysfunction and screening based on risk factors. When TSH>2.5 mU/l, pregnant women received replacement therapy with levothyroxine. In the universal screening group, hypothyroidism was detected much more often (OR 3.15) and pharmacotherapy was prescribed more often, but despite better detection of hypothyroidism in the total screening group, no differences were found in pregnancy complications and outcomes. The authors concluded that total screening does not improve pregnancy outcomes [23]. However, the influence of weight cannot be excluded in this study, since healthy pregnant women significantly outnumbered patients with hypothyroidism in both groups. Conflicting data have been obtained from studies of the association of subclinical hypothyroidism and preterm birth. In a study by Casey et al. [24] revealed a connection between subclinical hypothyroidism and birth before 34 weeks. gestation, but no such association was found for periods less than 32 or less than 36 weeks. Subsequently, similar studies obtained conflicting data, partly due to the combination of pregnant women with subclinical and overt hypothyroidism into one group, as well as the inclusion in the study of pregnant women with antithyroid antibodies. As shown by T. Korevaar et al. [25], the complicated course of pregnancy depends on the degree of increase in TSH. Pregnant women were divided into groups depending on their TSH level: 2.5–4.0 mU/L or more than 4.0 mU/L. With TSH below 4.0 mU/L, no increase in the incidence of preterm birth was detected, while with TSH>4.0 mU/L the risk of delivery before 37 weeks. increased by 1.9 times, and earlier 34 weeks. - 2.5 times. But the primary analysis was carried out without taking into account the titer of antibodies to TPO. When pregnant women with elevated anti-TPO antibodies were excluded from the analysis, the difference between the groups disappeared, and even an isolated increase in TSH >4 mU/L did not affect the incidence of preterm birth. This study once again demonstrated the importance of distinguishing between pregnant women with normal and elevated titers of antibodies to TPO, since they are an independent risk factor for complicated pregnancy. The influence of subclinical hypothyroidism on the development of pregnancy-associated hypertension and preeclampsia appears to be questionable at this time. Previous cohort studies have found an association between subclinical hypothyroidism and preeclampsia, but only if screening for hypothyroidism was performed late in pregnancy. If thyroid function was studied before 20 weeks. pregnancy, no dependence was detected [26, 27]. It is assumed that in the initial stages of the development of preeclampsia, the placenta may produce factors that affect the function of the thyroid gland [28]. With elevated TSH (>2.15 mU/l) in the first trimester of pregnancy, there was no increase in the frequency of pregnancy complications, including preeclampsia, developing after 20 weeks. [29]. When studying moderately elevated TSH, from 2.5 mU/L to 97.5 percentile, and the population norm, an increase in the incidence of preeclampsia was detected only in pregnant women with highly normal free T4; in the rest, a highly normal TSH level did not affect the incidence of preeclampsia [11]. However, some studies did find an association between elevated TSH and high blood pressure during pregnancy. For example, a study by LM Chen [30] revealed an increased risk of gestational hypertension, as well as low fetal weight in pregnant women with subclinical hypothyroidism. That is, at first glance, diametrically opposite results were obtained. But in this study, subclinical hypothyroidism was diagnosed when TSH >3.47 mU/L, which was defined as the upper limit of normal in this laboratory, which is significantly higher than 2.5 mU/L. It is likely that it is the TSH level used to diagnose subclinical hypothyroidism that affects the results of studies of its effect on the course of pregnancy. Typically, when there is conflicting data, meta-analysis is used to identify the truth. A recent meta-analysis of 18 cohort studies found that subclinical hypothyroidism is associated with several adverse pregnancy outcomes, such as miscarriage (OR 2.01; 95% confidence interval (CI) 1.6–2.44), placental insufficiency (OR 2.14). ; 95% CI 1.23–3.7) and increased neonatal mortality (OR 2.58; 95% CI 1.41–4.73). There was no association with other adverse outcomes, such as preeclampsia [31]. It should be noted that the studies included in the meta-analysis used different TSH cutoff values for the diagnosis of subclinical hypothyroidism. In only 6 of 18 studies, the threshold TSH value was 2.15–2.5 mU/L. Moreover, three studies included pregnant women with TSH≥2.5 mU/l and normal free T4 levels. That is, the degree of increase in TSH could be different, from 2.5 to 10 mU/l. And as we see from other studies, different degrees of TSH elevation have different effects on pregnancy outcomes. In most meta-analysis studies, subclinical hypothyroidism was diagnosed when TSH >3.5 mU/L. And this is precisely the upper limit of the TSH norm recommended today for pregnant women, if modified general population norms are used. The effect of TSH from 2.5 to 4 mU/l on the psychoneurological development of the fetus and other indicators of fetal health has not been identified [31, 32]. Taking into account the currently obtained data, it can be considered that TSH>2.5 mU/l is associated with spontaneous termination of pregnancy. Other adverse pregnancy outcomes are associated with higher TSH threshold values. Pregnant women with elevated TSH and antithyroid antibodies deserve special attention. In this case, the adverse effect on the course of pregnancy increases. But it is necessary to understand whether the situation will change for the better if we compensate for the function of the thyroid gland during subclinical hypothyroidism in pregnant women. Many researchers support the idea of treatment, since it is quite safe and can have a positive effect on pregnancy [32]. Pregnancy outcomes did not differ between women taking levothyroxine sodium for overt or subclinical (TSH>2.5 mU/L) hypothyroidism and euthyroid women. This indicates the safety of treatment with sodium levothyroxine, at least regarding pregnancy [33]. Prescription of levothyroxine sodium to pregnant women with TSH above the norm determined in the local laboratory led to an overall decrease in pregnancy complications. Moreover, the effect depended on the timing of the start of treatment and the time spent to achieve the target TSH level. The incidence of complications decreased if treatment was started before 12 weeks. pregnancy and the treatment goal was achieved in less than 4 weeks. [34]. In a study by S. Maraka et al. [35] showed that the prescription of replacement therapy at TSH 2.5–5 mU/l reduces the risk of intrauterine growth restriction and low Apgar score of the fetus at birth. There were no differences in other pregnancy outcomes, including spontaneous abortion. In other studies, the positive effect of treatment with levothyroxine was detected only in groups of pregnant women with TSH>4.0–5.0 mU/l. However, one study showed a significant reduction in the incidence of preterm birth (OR 0.38; 95% CI 0.15–0.98). In pregnant women with TSH 2.5–4.0 mU/L, replacement therapy did not improve pregnancy outcomes [36–38]. Thus, at present, the positive effect of replacement therapy with levothyroxine sodium at a TSH level of 2.5–4.0 mU/l, especially with normal levels of antithyroid antibodies, has not been proven. However, with a more pronounced increase in TSH, the positive effect of treatment is beyond doubt. Perhaps the positive effect is manifested only when using local TSH norms, which increases the importance of their determination. Based on the latest data, it can be concluded that during pregnancy it is better to use local TSH norms to make decisions about prescribing treatment with levothyroxine sodium. In the absence of local norms, or with TSH>2.5 mU/l in pregnant women with antithyroid antibodies, or TSH>3.5 mU/l in women without antibodies, the appointment of replacement therapy at least reduces the likelihood of spontaneous abortion, and possibly has other positive effects, especially if initiated early in pregnancy. Subclinical hypothyroidism and fertility
An important question is what is the impact of subclinical hypothyroidism on a woman’s fertility. And this question gives rise to two more: 1) at what TSH level should treatment be started when planning pregnancy and 2) what is the target TSH level at the stage of pregnancy planning. If a woman at the planning stage of pregnancy has a TSH higher than the general population norm, the prescription of treatment is not in doubt. It is more difficult to decide on the need for treatment when TSH levels are normally high. Recently, more and more data have emerged on the effect of moderately elevated TSH on fertility. Indeed, it was found that in case of infertility, a woman’s TSH level is higher than in the control group, especially if the cause of infertility was ovarian dysfunction or the cause was unknown. [39]. In one study, the administration of levothyroxine sodium to infertile women with TSH>3 mU/l was accompanied by pregnancy in 84.1% of women, and spontaneous pregnancy in some women [40]. But earlier studies did not find an association between elevated TSH and decreased fertility in women [41]. A one-time elevated TSH level >2.5 mU/l at the stage of pregnancy planning can independently decrease after pregnancy. One small study showed that in 50% of pregnant women with TSH>3 mU/L at the planning stage after pregnancy, the TSH level independently normalized and became less than 2.5 mU/L. Unfortunately, this study did not examine differences between groups with elevated and normal TSH levels after pregnancy [42]. A larger study of 482 women undergoing in vitro fertilization (IVF) assessed the likelihood of pregnancy and pregnancy retention based on baseline TSH. In 55% of pregnant women, after pregnancy, TSH decreased from the initial level of 2.5–4.0 mU/l to 2.5 mU/l. The onset of pregnancy did not depend on the initial TSH level. The authors concluded that treatment for TSH levels between 2.5 and 4.0 mU/L may be delayed until pregnancy, when this level is confirmed [43]. On the other hand, a population-based study conducted in China revealed a dependence of the outcomes of spontaneous pregnancy on the TSH level determined within 6 months. before pregnancy. In women with TSH 2.5–4.28 mU/L, when compared with women with TSH below 2.5 mU/L (0.48–2.49 mU/L), a slight but still statistically significant increase in the frequency of spontaneous miscarriages (OR 1.1) and premature births (OR 1.09). More severe pregnancy complications, such as perinatal mortality, intrauterine fetal death, and cesarean section, were observed only with TSH levels >4.0 mU/L [44]. Many studies have assessed the impact of subclinical hypothyroidism and its treatment on the success of various assisted reproductive technologies (ART). Particular attention to this group of women is explained by the use of high doses of estrogens during stimulation, which can cause compensated thyroid insufficiency. There was no negative effect of TSH levels from 2.5 to 4.9 mU/L on the results of insemination. One study in euthyroid women found an inverse association between TSH levels at pregnancy and the rate of spontaneous miscarriage [45]. Another similar study did not find an association between elevated levels of antithyroid antibodies and/or TSH >2.5 mU/L on the rate of birth in women after insemination [46], although in a retrospective study the effectiveness of insemination increased when replacement therapy was prescribed to women with TSH levels >2 .5 mU/l [47]. The success rate of IVF with a TSH level <2.5 mU/L was even higher and the quality of the embryos was higher than in women with a higher TSH [48–50]. But not all studies have the same data. Thus, M. Aghahosseini et al. [51] did not reveal statistically significant differences in the incidence of pregnancy as a result of ART depending on the TSH level. A prospective study showed that prescribing replacement therapy to women with subclinical hypothyroidism (TSH 4.2–20.0 mU/L and free T4 normal) before IVF improves outcomes and they are comparable to euthyroid women. But in this study we are talking about a TSH level above the population norm, but not about a highly normal TSH. After prescribing replacement therapy, no differences in pregnancy outcomes were found depending on the target TSH level (0.5–2.5 or 2.5–4.0 mU/L); only its normalization was sufficient [52]. Thus, the prescription of replacement therapy at the stage of pregnancy planning, including for women planning ART, is indicated only when the TSH level increases above the general population norm. The use of standards for pregnant women at this stage is not justified. There is also an interesting question about the long-term risks of women with subclinical hypothyroidism detected during pregnancy. A study conducted in India showed that 2 years after pregnancy, 17.8% of women developed subclinical or overt hypothyroidism. Risk factors for the disease were age (23.6–25.5 years), goiter, degree of increase in TSH during pregnancy (7.9–5.1 mU/l), and increased titer of antibodies to TPO [53]. Thus, in the presence of such risk factors, periodic testing for hypothyroidism should be carried out; however, the frequency of testing has not been determined.
Conclusion
The data accumulated to date confirm the need to determine the local TSH norm for pregnant women. When deciding whether to prescribe treatment during pregnancy, it is necessary to take into account not only the increased level of TSH, but also the level of antibodies to TPO, since it is this group of pregnant women who has the greatest risk of a complicated pregnancy. At the pregnancy planning stage, treatment if TSH exceeds the general population reference values is mandatory. But the advantage of replacement therapy in women planning pregnancy, including through reproductive technologies, with highly normal TSH levels has not been proven.
