Role of hypothyroidism and associated pathways in pregnancy and infertility: Clinical insights

Thyroid disorders are the most common endocrine problems in women. In most of the cases, thyroid can lead to infertility or miscarriages. The etiology of infertility is multifactorial with thyroid disorders as the most common presenting factor, hypothyroidism in particular. Infertility in women can lead to emotional and psychological stress. The prevalence of hypothyroidism during pregnancy is estimated to be 0.3%–0.5%. Hypothyroidism and hyperthyroidism can result in menstrual irregularities and anovulatory cycles, thus affecting the fertility. There is a significant high prolactin (PRL) level in infertile women with hypothyroidism when compared to euthyroid patients, indicating the relation between hypothyroidism and hyperprolactinemia. The amount of thyrotropin releasing hormone (TRH) from the hypothalamus is markedly increased by inhibition of pyroglutamyl peptidase II, the enzyme catalyzing TRH. The increased TRH in hypothyroidism causes increased thyroid-stimulating hormone and PRL secretion by pituitary, leading to infertility and galactorrhea. In recent years, a neuropeptide called kisspeptin, encoded by Kiss1 gene, a potent stimulus for GnRH secretion, has been recognized, which suggests a future direction of treatment with kisspeptin and benefits the fertility induction among hyperprolactinemic infertile patients. Untreated hypothyroidism during pregnancy can lead to subfertility, fetal deaths, premature deliveries, and abortions. Therefore, women planning for pregnancy and infertile women should be assessed for thyroid hormones and serum PRL.