THYROID AUTOIMMUNITY AND DISORDERS OF FEMALE REPRODUCTION

THYROID AUTOIMMUNITY AND DISORDERS OF FEMALE REPRODUCTION

Infertility

With regard to thyroid dysfunction, clinical hypothyroidism is clearly associated with female infertility and, in women in the reproductive age, autoimmune thyroid disease (AITD) is the most common cause of hypothyroidism (132,133). Although many of the studies relating to the association of thyroid antibodies and infertility are subject to selection bias, retrospective analysis, and different causes of infertility, they broadly confirm the association. Analysis of a large Danish population (11254 women) has shown that impaired fertility is associated with TSH, TPOAb and subclinical hypothyroidism (134). A previous large study employing control women study has documented an OR of 2.1 (1.7-2.6), p< 0.0001, in favour of the association of infertility and thyroid antibodies (135). Medically-assisted conception and onset of gestation is not hampered by AITD, but a successful outcome of the ongoing pregnancies is significantly reduced in those women with AITD due to greater early pregnancy loss (see Figure 14-23) (136)

The mechanism of the association between thyroid antibodies and infertility is not clear. A review has noted that thyroid hormone disorders and TPOAb are associated with disturbed folliculogenesis,spermatogenesis, fertilization and embryogenesis but the pathogenesis of TPOAb and reproduction is not well understood (137). It is of interest that there is an increase in infertility in women with endometriosis [RR 3.57] (138) which is known to have immune cell depression (NK cells), as well as decreased activity and cytotoxicity against autologous endometrium (139). The importance of NK cells has been emphasised (139) and impaired cellular and humoral response in women with unexplained infertility has been shown (140). The demonstration of antithyroid antibodies in ovarian follicles (141) may also suggest a critical role in infertility associated with autoimmune thyroid disease. These conclusions are strengthened by a study in mice in which it was noted that the anti TPO antibody may affect post-implantation embryo development leading to fetal loss (142). Lack of vitamin D was suggested as a predisposing factor to autoimmune diseases, and was shown to be reduced in patients with thyroid autoimmunity. In turn, its deficiency is also linked to infertility and pregnancy loss, suggesting a potential interplay with thyroid autoimmunity in the context of infertility (143)

The main practical question is whether one should give the benefit of thyroxine administration to infertile women who have positive thyroid antibodies with variable degrees of thyroid insufficiency.Screening for thyroid function in infertile women should be routinely performed (144,145) Obviously, overt thyroid dysfunction should be treated before conception or planned ART. Since SCH has a negative impact on the outcome of pregnancy after ART, thyroxine treatment should also be advised (146). It should be noted that in a study of 21 thyroxine treated women compared to 219 euthyroid women, women with hypothyroidism had a significantly decreased chance of achieving a pregnancy following IVF compared to euthyroid patients (147). The reasons are unknown and more data are required. Controlled ovarian hyperstimulation studied in 57 women led to significant elevations in TSH, often above pregnancy appropriate targets. These findings were particularly evident in women with preexisting hypothyroidism and may have important clinical implications for screening and thyroid hormone supplementation (148) Evidence on the treatment of isolated autoimmune features, but without thyroid dysfunction, was insufficiently documented until recently to advise prompt action (see later section on medical interventions).