Why do we need new guidelines?
In recent years, there has been increasing evidence that the normal range of thyroid stimulating hormone values during pregnancy should be lowered compared to non-pregnancy and that a new standard range of values should be established. Since then, however, there have been few reviews of studies on thyroid stimulating hormone (TSH) values between 2.5 and 4.0 mIU/L (or above laboratory normal values).
In response to the recent publication of the American Society for Reproductive Medicine guidelines for the management of subclinical hypothyroidism in women with infertility, Medscape interviewed Professor Steril for this report and summarized it as follows.
What are the recommended standard values?
Abnormal thyroid function can be divided into hyperthyroidism and hypothyroidism, which can be further divided into clinical hypothyroidism (elevated TSH and low thyroid hormones) and subclinical hypothyroidism (elevated TSH and normal thyroid hormones).
Most laboratories currently use a TSH value greater than 4-4.5 mIU/L as the criterion for abnormality. However, some evidence suggests that the maximum standard TSH value during pregnancy should be lowered to 2.5 mIU/L (early pregnancy), 3 mIU/L (mid-pregnancy), and 3.5 mIU/L (late pregnancy).
Why do I need treatment? There is a difference between hypothyroidism and subthyroidism!
Clinical hypothyroidism is associated with infertility, miscarriage and poor pregnancy outcomes and may lead to delayed embryonic neurodevelopment. Therefore, this condition needs to be treated. However, the correlation between subclinical hypothyroidism and infertility and pregnancy outcome is not significant.
Subclinical hypothyroidism can be further classified into two types: TSH above the upper limit of normal and TSH values of 2.5-4.0 mIU/L. Subclinical hypothyroidism is more common in the population of infertile women (especially in unexplained infertility) than in the general population. Miscarriage rates are higher in women with subclinical hypothyroidism and a TSH greater than 4 mIU/L, but it remains unclear whether subclinical hypothyroidism is associated with miscarriage rates in women with TSH values between 2.5 and 4.0 mIU/L.
Placental abruption, preterm delivery, and premature rupture of membranes are more common in pregnant women with subclinical hypothyroidism with TSH values greater than 4 mIU/L, but studies of pregnant women with hypothyroidism with TSH values between 2.5 and 4.0 mIU/L remain inadequate.
There is sufficient evidence of delayed neurological development in subclinical hypothyroidism with TSH values greater than 4.0 mIU/L. However, whether subclinical hypothyroidism with TSH values between 2.5 and 4.0 mIU/L has adverse effects on the development of the central nervous system remains understudied.
In subclinical hypothyroidism with TSH values greater than 4.0 mIU/L, the use of levothyroxine sodium tablets may improve conception rates and pregnancy outcomes. However, there is still insufficient evidence on the effect of levothyroxine sodium tablets on conception rates and pregnancy outcomes in hypothyroidism with TSH values between 2.4 and 4.0 mIU/L.
Thyroid antibodies (mainly thyroid peroxidase antibodies) are the main cause of subclinical hypothyroidism and clinical hypothyroidism. Positive peroxidase antibodies can lead to a high rate of miscarriage. Treatment with levothyroxine sodium tablets can reduce the rate of miscarriage, especially in women with TSH values greater than 2.5 mIU/L.
In general, women with clinical hypothyroidism should receive appropriate thyroxine replacement therapy. subclinical hypothyroidism with a TSH value greater than 4 mIU/L should receive levothyroxine sodium tablets as replacement therapy. The goal of replacement therapy is to achieve a TSH control of 2.5 IU/L or less.
Women with TSH values of 2.5-4.0 mIU/L and positive anti-thyroid peroxidase may do better with levothyroxine replacement therapy. However, there is no evidence to suggest that thyroid hormone therapy in the presence of negative anti-thyroid peroxidase improves conception rates or pregnancy outcomes.
Hypothyroidism: Pregnancy or not is important
Hypothyroidism affects more than 5% of American women, and this number increases with age. Subclinical hypothyroidism, with a TSH marker of 4.5-5.0 mIU/L, affects 4-8.5% of Americans, and this number increases with age.
Even the management of subclinical hypothyroidism in women with non-pregnant states is controversial. However, there is a lack of scientific evidence regarding the treatment of pregnant or infertile women. Infertile women are more likely to have abnormal thyroid function, especially those with abnormal ovarian function, unexplained infertility, recurrent miscarriages, or poor pregnancy outcomes.
Many centers routinely test patients for TSH values to clarify the presence of subclinical hypothyroidism or clinical hypothyroidism. The management of clinical hypothyroidism is well defined. The development of the embryo in early pregnancy is dependent on maternal thyroid hormones, and the embryo’s own thyroid gland only just begins to have secretory activity at 11-13 weeks of gestation.
Hypothyroidism increases the risk of infertility, miscarriage, and has an impact on the embryo’s neurological development. Hormone replacement can improve all of these. women with a TSH of 2.5-4.0 mIU/L and positive thyroid peroxidase antibodies are more likely to benefit from thyroxine hormone supplementation. In this population, TSH values should be kept below 2.5 mIU/L. This way, even if the benefit is not significant, supplementation will at least not increase the risk.
Antibody-negative women do not benefit significantly with thyroxine therapy and therefore can be treated without it. For this population, TSH values should be tested once every 4-6 weeks and supplemental therapy should still be initiated if TSH begins to rise. In the meantime, we look forward to studies with larger samples to provide further guidance for these populations.