Clinical Thyroidology® for the Public

Summaries for the Public from recent articles in Clinical Thyroidology
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THYROID AND PREGNANCY
Lower egg quality and quantity were seen in women with infertility and TSH levels in the high-normal ranges.

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BACKGROUND
Thyroid disorders are common endocrine disease in young women. Abnormal thyroid hormone levels and autoimmune thyroid disease, such as Hashimoto’s thyroiditis or Graves’ disease, may have impact on fertility. These disorders may interfere with ovarian function and make it more difficult to get pregnant. This is especially true with overt hyperthyroidism and hypothyroidism. It is currently not clear whether mildly abnormal thyroid hormone levels cause infertility.

One of the measures evaluated in the workup for infertility is called diminished ovarian reserve (DOR). DOR indicates that there is either a lower amount or a decrease in the quality of eggs produced by women with infertility and may lead to difficulty getting pregnant. This study aimed to assess whether blood TSH levels in the upper half of the normal range are associated with DOR and infertility.

THE FULL ARTICLE TITLE
 Li N et al. 2022 The impact of moderately high preconception thyrotropin levels on ovarian reserve among euthyroid infertile women undergoing assisted reproductive technology. Thyroid 32:841–848. PMID: 35317605.

SUMMARY OF THE STUDY
The researchers reviewed medical records of 3501 women who were between 20 and 40 years of age and seen at the Shandong University Hospital infertility clinic in China between 2015 and 2020. All women had TSH levels in normal ranges and no history of thyroid disease or taking thyroid medications. About two-thirds (62.5%) of women had a TSH level in the lower half of the normal range (low-normal group) and about one-third (37.5%) of women had a TSH level in the higher half of the normal range (high-normal group).

Women in the low-normal TSH group had ovarian problems more frequently than women in the high-normal group. However, women in the high-normal group had lower levels of anti-műllerian hormone (AMH), an ovarian hormone that is important in egg development, and lower numbers of ovarian follicles, both measures of viable eggs, compared to women in the low-normal group. Women in the high-normal group more frequently had positive thyroid peroxidase (TPO) or thyroglobulin (Tg) antibodies, suggesting underlying autoimmune thyroid disease. Overall, women in the high-normal group more frequently had DOR compared to women in the low-normal group (5.1% vs. 3.5%), after taking account of age, BMI, and presence of autoimmune thyroid disease.

Women in the high-normal group also had a slightly lower number of live-births and slightly higher number of very early pregnancy loss compared to women in the low-normal group (54.3% vs. 57.4%, and 9.7% vs. 7.6%, respectively). Overall rates of pregnancy were not different between the two groups. Higher TSH levels were correlated with lower AMH levels or lower follicle counts. Women with thyroid autoimmunity (positive TPO or Tg antibody levels) were also noted to have lower AMH levels or lower follicle counts, regardless of TSH levels.

WHAT ARE THE IMPLICATIONS OF THIS STUDY?
In this study of women with infertility, women with blood TSH levels in the higher half of the normal ranges had lower AMH levels and less ovarian follicle counts, indicating lower egg quality and quantity, compared with women with blood TSH levels in the lower half of normal ranges.

Even though there have been many studies, potential impact of mild thyroid hormone abnormalities and thyroid autoimmunity on fertility has not been clear due to limitations in these studies performed using medical records and different definitions used for thyroid problems and measures of fertility. This study was also limited to Chinese patients, and same effects may not be seen in other races/ethnicity. The results of this study add to the findings of some previously published studies. However, it does not definitely answer the question of the impact of mild thyroid abnormalities on infertility because lower AMH levels or lower numbers of ovarian follicles do not always cause infertility. So far, trials have not shown clear benefit of using levothyroxine to treat mild thyroid abnormalities in improving fertility. Thus, it remains unclear who needs to be treated and at what TSH levels.

— Sun Y. Lee, MD,MSc

ABBREVIATIONS & DEFINITIONS

Autoimmune thyroid disease: a group of disorders that are caused by antibodies that get confused and attack the thyroid. These antibodies can either turn on the thyroid (Graves’ disease, hyperthyroidism) or turn it off (Hashimoto’s thyroiditis, hypothyroidism).

Hashimoto’s thyroiditis: the most common cause of hypothyroidism in the United States. It is caused by antibodies that attack the thyroid and destroy the gland.

Graves’ disease: the most common cause of hyperthyroidism in the United States. It is caused by antibodies that attack the thyroid and turn it on.

TSH: thyroid stimulating hormone — produced by the pituitary gland that regulates thyroid function; also the best screening test to determine if the thyroid is functioning normally.

TPO antibodies: these are antibodies that attack the thyroid instead of bacteria and viruses, they are a marker for autoimmune thyroid disease, which is the main underlying cause for hypothyroidism and hyperthyroidism in the United States.

Thyroglobulin antibodies: these are antibodies that attack the thyroid instead of bacteria and viruses, they are a marker for autoimmune thyroid disease, which is the main underlying cause for hypothyroidism and hyperthyroidism in the United States.

Anti-műllerian hormone (AMH): a blood test that are used to assess the number of remaining eggs that a woman has.

Levothyroxine (T4): the major hormone produced by the thyroid gland and available in pill form as Synthroid™, Levoxyl™, Tirosint™ and generic preparations.

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