What does the thyroid do and how does it work?
A major player in the endocrine system is the thyroid. The thyroid is a gland that is located in the front of the neck and produces hormones that regulate metabolism. The thyroid gland actually produces two groups of hormones, but for the purpose of discussion surrounding infertility, thyroxine (T4) and triiodothyronine (T3) are the hormones that matter. The amount of these hormones in the body is controlled in a classic system called negative feedback. The thyroid produces thyroid hormones which increase metabolism. The brain has been programmed genetically to maintain a certain level of metabolism. The brain then measures the metabolic rate and compares it to the rate that has been programmed. If the body’s metabolism rate is too high, the brain wants to lower that rate and if the rate is too low, it wants to raise it. The brain will tell the pituitary gland, which is a pea-sized glands that sits at the base of the brain, how much of the hormone TSH (thyroid- stimulating hormone) to release. TSH causes the thyroid gland to release the thyroid hormones. So if the metabolic rate is low (hypothyroidism), the brain increases TSH and if the rate is too high (hyperthyroidism), the brain decreases TSH.
What are the primary thyroid diseases involved with infertility?
There are three primary diseases that are of concern for female infertility: Graves’ disease (hyperthyroidism), Hashimoto’s thyroiditis (hypothyroidism) and subclinical hypothyroidism. Unquestionably, Hashimoto’s and Graves, influence fertility and need to be treated.
Graves’ disease is an autoimmune disease where the antibody LATS, stimulates the thyroid to produce thyroid hormone. Hyperthyroidism is characterized by an increase in metabolism that results in heat intolerance, irritability, sleeplessness, weight loss, increased heart rate, and bulging eyes.
Hashimoto’s is also an autoimmune disease where the immune system gradually destroys the thyroid gland. Some people will develop a goiter (enlarged thyroid gland) and many will develop hypothyroidism. The symptoms of hypothyroidism include tiredness, weight gain, and depression. The diagnosis often is made when anti-thyroid antibodies, called anti-thyroid peroxidase antibodies, are detected in blood tests.
The slow destruction of the thyroid gland by the peroxidase anti-bodies creates a clinical condition called sub-clinical hypothyroidism. This problem is diagnosed by measuring both TSH and serum free thyroxine (T4). In subclinical hypothyroidism, the TSH is elevated but less than 10 mIU/L and the T4 is normal. Normal values for TSH are 0.5 – 4.5 mIU/L. So a person who has a TSH of anything above 10 mIU/L, will be asked to take thyroid supplement to lower the TSH levels. For a number of years, patients with infertility who has a TSH > 2.5 mIU/ L were treated with thyroid replacement hormones to lower their TSH to less than 2.5 mIU/L. Recent evidence has called this treatment into question.
Why are normal TSH levels above 2.5 mIU/L of concern for infertility patients?
The American Society for Reproductive Medicine (ASRM) published guidelines in 2015 that recommended that the diagnosis of subclinical hypothyroidism is made when the T4 level normal and the TSH level is greater than 4.0 mIU/L. A recent article permits even better criteria for diagnosis. An article by Seungdamroung et al (Fertility Sterility (2017) 108:843) found that it was the presence of the anti-thyroid peroxidase antibodies that was associated with increased miscarriage rates and a decreased probability for a live birth. Based on this information, it is strongly suggested that women with a TSH greater than 4.0 mIU/L and positive anti-thyroid peroxidase antibodies, be treated with thyroxine, in order to improve their chances for conception and delivery.
There are a number of factors that can influence the successful conception, pregnancy and delivery in the patient population. Diagnosing, monitoring and treating Thyroid disease can be the key for women who suffer from these conditions even in the case where it is considered sub-clinical and may not be treated as part of non-fertility based medicine.