The Impact of Thyroid Function on Human Reproduction: A Comprehensive Mini-Review
Francesco Maria Bulletti1, Romualdo Sciorio2, Antonio Palagiano3, Maurizio Guido4 and Carlo Bulletti5,6*
1Department Obstetrics and Gynecology Lausanne, Switzerland
2Edinburgh Assisted Conception Programme, Royal Infirmary of Edinburgh, UK
3Reproductive Science Pioneer, Assisted Fertilization Center (CFA), Italy
4University of L’Aquila, Italy
5Extra Omnes, Assisted Reproductive Technology, ART, Center in Cattolica, Italy
6Associate Adjunct Professor, Department of Obstetrics, Gynecology, and Reproductive Science, Yale University, USA
Submission: June 05, 2023; Published: June 20, 2023
*Corresponding author: Carlo Bulletti, MD, Extra Omnes, Via Gallinelli, 8- 47841 Cattolica, Italy, Email: carlobulletti@gmail.com
How to cite this article: Francesco Maria Bulletti, Romualdo Sciorio, Antonio Palagiano, Maurizio Guido and Carlo Bulletti*. The Impact of Thyroid Function on Human Reproduction: A Comprehensive Mini-Review. J Endocrinol Thyroid Res. 2023; 7(2): 555710. DOI:10.19080/JETR.2023.07.555710
Abstract
Thyroid disorders are common endocrine disorders affecting millions of individuals worldwide. The thyroid gland plays a crucial role in regulating various physiological processes, including reproductive health. This scientific article aims to provide a comprehensive review of the current understanding of the impact of thyroid function on human reproduction. We discuss the physiological role of thyroid hormones, the effects of thyroid dysfunction on fertility, pregnancy outcomes, and the management of thyroid disorders in the context of reproductive health. The effect of hypothyroidism on human embryo’s implantation as well as the replacement therapy efficacy in reversal detrimental effects are discussed.
Keywords: Thyroid; Thyroid dysfunction; Human reproduction; Fertility; Pregnancy outcomes; Thyroid hormones; Hypothalamic-pituitary-thyroid axis; Reproductive health; Preconception care; Pregnancy management; Embryo’s implantation
Thyroid and Human Reproduction
Introduction
The thyroid gland produces essential hormones, primarily thyroxine (T4) and triiodothyronine (T3), which are critical for maintaining overall metabolic homeostasis. These hormones have a profound impact on reproductive health, influencing ovarian function, gametogenesis, fertilization, implantation, and early embryonic development [1] .
Thyroid hormone physiology and regulation: provides a detailed overview of thyroid hormone synthesis, secretion, and regulation. It explains the role of hypothalamic-pituitary-thyroid (HPT) axis and feedback mechanisms involving thyroid-stimulating hormone (TSH) and thyroid hormone receptors (TRs). Additionally, the discussion covers the conversion of T4 to T3, the active form of thyroid hormone, and the role of deiodinase enzymes in this process.
Thyroid dysfunction and female fertility [1,2]:
a. Ovulation and menstrual irregularities: Thyroid disorders, such as hypothyroidism and hyperthyroidism, can disrupt the menstrual cycle, leading to anovulation, oligomenorrhea, or amenorrhea. The mechanisms underlying these effects are explored, including alterations in gonadotropin-releasing hormone (GnRH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) secretion [3].
b. Polycystic ovary syndrome (PCOS): The association between thyroid dysfunction and PCOS is discussed, highlighting the bidirectional relationship between these conditions and their shared pathophysiological mechanisms [4].
c. Thyroid autoimmunity and infertility: Thyroid autoimmunity, including Hashimoto’s thyroiditis and Graves’ disease, has been linked to impaired fertility and an increased risk of miscarriage. The underlying immunological mechanisms and potential therapeutic approaches are explored [5].
Thyroid dysfunction and male reproductive health: The influence of thyroid dysfunction on male fertility is discussed in this section. Thyroid hormone imbalance can affect sperm quality, motility, and concentration, leading to male infertility. The impact of hypothyroidism, hyperthyroidism, and thyroid autoimmunity on male reproductive health is examined [1,6]
Pregnancy and thyroid function: Optimal thyroid function is crucial during pregnancy for the development of the fetus and the maintenance of maternal health. This section focuses on the effects of maternal thyroid disorders on pregnancy outcomes, including gestational hypertension, preeclampsia, gestational diabetes, preterm birth, and fetal developmental abnormalities. It also highlights the importance of thyroid hormone requirements during pregnancy and the need for careful monitoring and appropriate management [7].
Management of thyroid disorders in reproductive health [8]:
a. Preconception care: The importance of preconception thyroid evaluation and management is emphasized, particularly in women with a history of thyroid disorders or those at high risk.
b. Pregnancy management: Optimal management of thyroid disorders during pregnancy, including appropriate medication dosage adjustments, is discussed to ensure maternal and fetal well-being [9].
c. Postpartum considerations: The potential impact of postpartum thyroiditis on lactation, maternal health, and subsequent pregnancies is outlined, along with recommendations for postpartum thyroid function monitoring.
Future directions and conclusion: The field of thyroid and human reproduction continues to evolve, with ongoing research shedding light on the intricate relationship between thyroid function and reproductive health. Several areas warrant further investigation.
a. Mechanistic insights: Future studies should delve deeper into the underlying mechanisms by which thyroid hormones influence reproductive processes at the molecular and cellular levels. This could involve exploring the interactions between thyroid hormones, sex steroids, and other signaling pathways involved in gametogenesis, implantation, and embryonic development.
b. Biomarkers and diagnostic tools: The development of reliable biomarkers and diagnostic tools for assessing thyroid function in the context of reproductive health would aid in early detection and appropriate management of thyroid disorders. This could involve exploring novel biomarkers in blood, urine, or tissue samples, as well as the use of advanced imaging techniques to assess thyroid gland function [10].
c. Individualized management: Tailoring treatment approaches to individual patients based on their specific thyroid status and reproductive goals is an important area for future research. Precision medicine approaches, including the identification of genetic markers or other predictors of response to treatment, could optimize outcomes for individuals with thyroid disorders and reproductive concerns [11].
The Role of Hypothyroidism and Hyperthyroidism on Embryo Implantation: Implications for Implantation Rate and Thyroxine Restoration Embryo implantation is a crucial step in human reproduction, and successful implantation relies on a complex interplay of various physiological factors. Thyroid hormones, primarily thyroxine (T4) and triiodothyronine (T3), play a vital role in regulating reproductive processes, including embryo implantation [1]. In this chapter, we explore the impact of hypothyroidism [12]and hyperthyroidism on embryo implantation and examine the potential for restoring thyroxine levels to revert any reduction in implantation rates.
Hypothyroidism and embryo implantation [13]:
Hypothyroidism, characterized by insufficient thyroid hormone production or action, has been associated with impaired embryo implantation. Several mechanisms contribute to this negative effect:
a. Endometrial receptivity: Hypothyroidism can lead to alterations in endometrial receptivity, resulting in reduced implantation rates. Thyroid hormone receptors present in the endometrium play a role in regulating the expression of genes involved in endometrial receptivity and embryo implantation [14].
b. Altered hormonal milieu: Hypothyroidism disrupts the delicate hormonal balance necessary for successful implantation. Thyroid hormones modulate the production and release of reproductive hormones such as estradiol, progesterone, and gonadotropins, all of which are critical for preparing the endometrium for implantation [9].
c. Impaired embryo development: Hypothyroidism can adversely affect embryonic development, leading to suboptimal embryo quality and reduced implantation potential. Thyroid hormone imbalance during early embryogenesis may compromise cell division, differentiation, and implantation-related gene expression [15].
Hyperthyroidism, characterized by excessive thyroid hormone production or action, also has implications for embryo implantation:
a. Endometrial receptivity: Hyperthyroidism can disrupt endometrial receptivity, potentially leading to reduced implantation rates. Elevated levels of thyroid hormones can alter the expression of genes involved in endometrial receptivity and disrupt the coordinated interaction between the embryo and the endometrium.
b. Abnormal uterine contractility [16]: Hyperthyroidism may lead to increased uterine contractility, impairing the window of implantation and reducing the chances of successful embryo attachment [17].
c. Altered immune response: Hyperthyroidism can impact the immune system, leading to an altered immune response in the endometrium. This dysregulation may impair the acceptance of the embryo by the maternal immune system, potentially compromising implantation.
Thyroxine restoration and implantation rates [13,18]
Restoring thyroxine levels in individuals with hypothyroidism has shown promising results in improving implantation rates. Several studies have investigated the effect of thyroxine supplementation in assisted reproductive technologies (ART) and have reported positive outcomes [19,20]:
a. Improved endometrial receptivity: Thyroxine supplementation has been shown to restore endometrial receptivity by modulating gene expression patterns involved in implantation [9].
b. Enhanced hormonal balance: Thyroxine replacement therapy can restore the hormonal milieu necessary for successful implantation by optimizing the levels of reproductive hormones involved in endometrial preparation [21].
c. Improved embryo development: Thyroxine supplementation in hypothyroid individuals has been associated with improved embryo quality and development, potentially leading to higher implantation rates [5].
Conclusion
In conclusion, the thyroid gland plays a critical role in human reproduction, with thyroid hormone imbalance exerting significant effects on fertility, pregnancy outcomes, and overall reproductive health. Thyroid dysfunction can disrupt ovarian function, impair sperm quality, and contribute to adverse pregnancy outcomes. Thus, understanding the complex interplay between thyroid function and human reproduction is essential for appropriate diagnosis, management, and counseling of individuals seeking to conceive or maintain a healthy pregnancy. It is important to note that the effectiveness of thyroxine restoration in reverting implantation rate reduction may vary depending on individual factors, including the underlying cause and severity of thyroid dysfunction.
Continued research and advancements in this field will undoubtedly improve our understanding and guide clinical practices to optimize reproductive outcomes in individuals with thyroid disorders.
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