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).
The American Society for Reproductive Medicine recently published guidelines for the management of subclinical hypothyroidism in women with infertility, and Medscape interviewed Prof. Steril for this report, which is summarized below.
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 standard maximum 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 should I be treated? 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 infertile women than in the general population (especially in cases of unexplained infertility). 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 hypothyroidism in pregnant women with TSH values between 2.5 and 4.0 mIU/L remains understudied.
There is sufficient evidence of delayed neurodevelopment in subclinical hypothyroidism with TSH values greater than 4.0 mIU/L. However, whether subclinical hypothyroidism with a TSH value of 2.5-4.0 mIU/L has a detrimental effect on the development of the central nervous system has not been adequately studied.
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, which can be reduced by treatment with levothyroxine sodium tablets, 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 TSH values greater than 4 mIU/L should be treated with levothyroxine sodium tablets. The goal of replacement therapy is to achieve a TSH control of 2.5 mIU/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.
The management of subclinical hypothyroidism is controversial even for women in non-pregnant states. 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 identify 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 is only just beginning to secrete at 11-13 weeks of gestation.
Hypothyroidism increases the risk of infertility, miscarriage and has an impact on the neurological development of the embryo. Hormone replacement can improve all of these.
Women with TSH in the range of 2.5-4.0 mIU/L and positive for 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. In this population, TSH values should be tested once every 4-6 weeks and supplemental therapy should still be initiated if TSH begins to rise.