The importance of thyroid function for female reproduction

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.

List of scientific papers

I. Frida Hosseini Akram, Bengt Johansson, Gunnar Möllerström, Britt-Marie Landgren, Anneli Stavreus-Evers, Lottie Skjöldebrand Sparre. Incidence of subclinical hypothyroidism and hypothyroidism in early pregnancy. Journal of Women's health. 2017, 26, 1231–1235.
https://doi.org/10.1089/jwh.2016.6111

II. Frida Hosseini Akram, Lottie Skjöldebrand-Sparre, Britt-Marie Landgren, Fatma Gulen Yaldir, Lusine Aghajanova, Kjell Wånggren, Anneli Stavreus-Evers. Thyroid hormone receptors in endometrium, Fallopian tubes and human blastocysts in women with unexplained infertility compare to fertile controls. [Manuscript]