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- Akram, Frida Hosseini
(author)
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The importance of thyroid function for female reproduction
- 2019
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Licentiate thesis (other academic/artistic)abstract
- Background: Thyroid dysfunction is one of the most common endocrine disorder. Thyroid dysfunction affects the female reproductive system and can be manifested by menstrual irregularities, pregnancy loss and infertility. Unexplained infertility has an incidence of 10 to 15 % worldwide. Aim: The general objective of this thesis was to explore the importance of thyroid function for reproduction Material and method: Serum levels of thyroid stimulating hormone (TSH) were compared in three groups of women in early pregnancy, one high-risk group (n = 88), one low-risk group (n = 511) and a general screening group (n = 699). Serum levels of TSH, free thyroxine (fT4) and thyroid peroxidases antibodies (TPO Ab) in fertile women (n = 67) were compared to women with unexplained infertility (n = 147). By using immunohistochemistry, the protein staining of thyroid hormone receptors (TRα1 and TRβ1), TSH receptor (TSH R), mono carboxylate transporter-8 (MCT8), and type 2 iodothyronine deiodinases (DIO2)] in endometrial biopsies were compared between fertile women (n = 19) and women with unexplained infertility (n = 28). Thyroid related proteins in different part of Fallopian tube during the menstrual cycle in fertile women (n=13) were analyzed. Additionally, embryo development until day 6, in 38 human embryos cultured in standard media with T4 added were compared to development of 36 embryos cultured in standard media. Results: The incidence of subclinical hypothyroidism and hypothyroidism was almost the same in all three study groups (almost 10 %). Hypothyroid women on levothyroxine (LT4) supplementation had in almost 50 % of cases an inadequate treatment. Women with unexplained infertility had significantly higher serum level of fT4, and lower protein staining of TRα1 and MCT8, in the endometrium. Supplementation of thyroid hormone in vitro culture media improved the blastocyst development. Additionally, we showed thyroid related proteins in the Fallopian tube. Conclusion: It can be concluded that a general screening for thyroid dysfunction during early pregnancy, by use of TSH levels, is optimal. Furthermore, the imbalance in the thyroid system in women with unexplained infertility highlights the importance of thyroid hormone for female fertility. The improvement of blastocyst development by adding thyroid hormone in early embryo cultures and the presence of proteins related to thyroid in Fallopian tubes suggest involvement of thyroid hormone in early embryo development.
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| 2. |
- Hosseini Akram, Frida
(author)
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Endocrine and paracrine factors related to pregnancy and infertility
- 2019
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Doctoral thesis (other academic/artistic)abstract
- Unexplained infertility, one of the common gynecological disorders, affecting 10 to 15 % of women worldwide. Recurrent pregnancy loss affects approximately 1 to 3 % of pregnant women with an unknown etiology in 50 % of cases. Endocrine dysfunctions, including thyroid dysfunction, are one of the related factors to female reproductive disturbances. The aim of the thesis was to explore the importance of thyroid function and endometrial factors for implantation and pregnancy. Three groups of pregnant women, one group with high risk (n = 88) was compared to a low-risk (n = 511) and a general screening group (n = 699) to study the incidence of subclinical hypothyroidism and hypothyroidism, defined as TSH < 2.5 mIU/L. Women with recurrent pregnancy loss, (n = 165), and controls, (n = 289), were included in genetic analysis and gene expression array of endometrium, (n = 4 and n = 5 respectively). Infertile women (n = 19) and fertile women were included to study thyroid-related proteins in endometrium (n = 28) and Fallopian tube (n = 13). Human embryos, (n= 36), were used to study the effect of thyroid hormone on embryo development. Thyroid stimulating hormone (TSH), free thyroid hormone (fT4) and TPO antibodies (TPO-Ab) levels were analyzed by use of immunological methods. Genetic variations in the HABP2 gene was performed by use of TaqMan SNP Genotyping Assays. Gene expression array was used to study mRNA in endometrium of women with recurrent miscarriage at the time of implantation. Immunohistochemistry was used to analyze the presence and distribution of thyroid related proteins in endometrium. Additionally, influence of thyroid hormone (T4) on the early embryo development was analyzed. Approximately 10 % of all pregnant women, regardless of risk, had elevated TSH levels. Furthermore, hypothyroid women on levothyroxine supplementation had in almost 50 % of cases inadequate treatment. There were no significant differences in the presence of polymorphism in HABP2 genes in comparison to fertile controls. In total, 124 genes were differently expressed in women with recurrent miscarriage mainly related to immunological processes, particularly shown by upregulation of IL8 in women with recurrent miscarriage. The infertile women showed lower protein staining of TRα1 and MCT8 in endometrium compared to the fertile women. Staining of thyroid related proteins was observed in all different parts of Fallopian tube. T4 supplementation showed improvement of blastocyst development in T4 added media. In conclusion, general screening for thyroid dysfunction during first trimester of pregnancy is needed to find all women in need to LT4 supplementation. Inflammatory events, especially IL8, might offer a clue to recurrent pregnancy loss while variations in the HABP2 gene does not seem to be associated with recurrent miscarriage. The expression and distribution of thyroid-related factors in endometrium seem to be related to unexplained infertility. The presence of thyroid-related proteins in fallopian tube and the improvement of embryo development after T4 treatment suggest that a functional thyroid system is important form achievement of a normal pregnancy.
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