Introduction
Recent research indicates that a slightly underactive thyroid could impact a woman's fertility, even if the gland functions within the normal range's lower end. According to the study, women with unexplained infertility were almost twice as likely to have elevated thyroid levels of TSH (thyroid stimulating hormone), a hormone that stimulates the thyroid gland. In contrast, women facing infertility issues due to known problems with their male partner's sperm count did not show such elevated TSH levels. The pituitary gland produces TSH, and high levels indicate an underactive thyroid.
What Is the Role of Thyroid Hormones in Pregnancy?
Thyroid hormones play a crucial role in the normal development of a baby's brain and nervous system during pregnancy. In the first trimester, the baby relies on the mother's supply of thyroid hormone through the placenta. Around 12 weeks, the baby's thyroid starts functioning independently, but it takes 18 to 20 weeks to produce sufficient thyroid hormone.
During pregnancy, two hormones, hCG and estrogen, can cause higher thyroid hormone levels in the mother's blood. The thyroid may slightly enlarge, but it is usually not noticeable during a physical exam.
Diagnosing thyroid problems during pregnancy can be challenging due to elevated hormone levels and similar symptoms in both pregnancy and thyroid disorders. However, certain symptoms may raise concerns, leading the doctor to test for hyperthyroidism or hypothyroidism.
After childbirth, there is also a condition called postpartum thyroiditis that may occur.
How Does an Underactive Thyroid Affect Fertility in Women?
The connection between thyroid function and female fertility is significant. Pregnancy affects the thyroid gland, and thyroid issues have been linked to female fertility. Both obstetric and fetal outcomes are well-documented in relation to this connection.
Hypothyroidism:
The most common reasons for hypothyroidism during pregnancy are iodine deficiency in certain regions and chronic autoimmune thyroiditis in areas with sufficient iodine levels. While the link between overt hypothyroidism and infertility and poor pregnancy outcomes is clear, the connection with subclinical hypothyroidism is more controversial.
In women with hypothyroidism, there are hormonal changes affecting androgens and estrogen. These changes are characterized by lower metabolic clearance of androstenedione and estrone, leading to a higher rate of peripheral aromatization. Although free fractions of testosterone and estradiol increase, the total hormone levels decrease due to decreased SHBG concentrations. This condition may also increase prolactin and TSH levels in response to elevated hypothalamic thyrotropin-releasing hormone (TRH).
As a result, around 80% of women with hypothyroidism experience menstrual disturbances or irregularities. Elevated TSH levels have been linked to poor ovarian reserve, indicated by high follicle-stimulating hormone (FSH) levels, antral follicle count below five, and a poor response to previous ovarian stimulation. Studies have shown that women with unexplained infertility tend to have higher TSH levels, with twice as many cases having TSH above 2.5 mlU/L compared to women with infertility due to a male factor.
Overt hypothyroidism is linked to an increased risk of pregnancy and obstetric complications, including hypertension, preeclampsia, abruption placentae, miscarriage, preterm delivery, postpartum hemorrhage, low birth weight, neonatal respiratory distress, and stillbirth. If overt hypothyroidism is not adequately treated during pregnancy, there is an estimated risk of 60% fetal loss, along with the potential for stunted intrauterine growth and mild deficits in neurodevelopment. When this condition occurs during early gestational age, it may lead to changes in behavior and decreased cognitive abilities in the offspring, as well as delayed psychomotor development and intellectual impairment.
Spontaneous Conception Impact of Hypothyroidism:
Dosiou et al. demonstrated TPO expression on mature granulosa cells, indicating a possible connection between thyroid autoimmunity (TAI) and impaired fertility. Three hypotheses have been proposed to explain this link:
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TAI may trigger a general autoimmune response, enhancing natural cytotoxicity.
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TAI may directly affect ovarian tissue.
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TAI could lead to deterioration of thyroid function, eventually resulting in overt hypothyroidism, affecting reproductive health.
Another model suggests that in early stages, autoimmunity affects the ovary, and levothyroxine has no impact on outcomes, but instead, antioxidants, immunomodulators, and inositol may prove beneficial. As TAI progresses, impaired thyroid response to hCG stimulation may occur, leading to further difficulties adapting to the increased demands during pregnancy, creating a vicious circle. Regardless of thyroid function, TAI has been associated with unexplained subfertility, suggesting that it could be a significant cause of fertility and low ovarian reserve, and high TPOAb (thyroid antibodies) are observed in cases of unexplained infertility, supporting this idea.
What Is the Prevalence of Hypothyroidism in Infertile Women?
Hypothyroidism affects two to four percent of the reproductive age group and has been linked to infertility and habitual abortion. Detecting hypothyroidism is simple through TSH level assessment in the blood. A slight increase in TSH with normal T3 and T4 indicates subclinical hypothyroidism, while high TSH levels with low T3 and T4 indicate clinical hypothyroidism. Subclinical hypothyroidism is more common and can lead to anovulation directly or by elevating PRL levels. In infertile women with hypothyroidism, hyperprolactinemia is often present due to increased production of thyrotropin-releasing hormone (TRH) in ovulatory dysfunction. To address this, it is recommended to prioritize the treatment of hypothyroidism first if raised PRL is detected. As part of the infertility workup, routine measurement of TSH and PRL is done.
What Are the Recommended Treatment Guidelines?
The treatment guidelines for hypothyroidism during pregnancy are well-defined for overt cases. Still, for subclinical or underactive thyroid function or hypothyroidism, there's no consensus on whether to treat it or not. The latest ATA guidelines recommend measuring TPOAb in all pregnant women with TSH > 2.5mU/L.
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Treatment is advised for TSH > 10.0mU/L, regardless of FT3 or Ft4 levels.
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TPOAb-positive women should be treated if their TSH is above the pregnancy-specific reference range and may be treated with TSH more than 2.5mU/L and below the upper line of the reference range.
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TPOAb-negative women may be treated if their TSH is above the pregnancy-specific reference range and below 10.0mU/L, but not if their TSH is within the normal range.
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TPO/TgAb+ euthyroid women should be monitored regularly during pregnancy.
ATA and ETA guidelines agree that isolated hypothyroxinemia, characterized by low fT4 levels within the reference range of TSH, should not be routinely treated during pregnancy.
Conclusion
Infertility is a widespread issue affecting millions of people of reproductive age worldwide. Thyroid hormones play a significant role in reproduction and pregnancy, affecting various aspects of reproductive health. Thyroid dysfunction is linked to various reproductive disorders, including abnormal sexual development, menstrual irregularities, and infertility. Thyroid dysfunction is often linked to female infertility, and there is growing evidence of its impact.
