Our study results show that women with HT have a lower AMH levels compared with age-matched healty women. Thyroid hormone disorders are associated with menstrual irregularities, anovulation, disturbed folliculogenesis and infertility. Menstrual regularity and ovarian reserve play a critical role in achieving pregnancy in reproductive-age women. Premature ovarian failure (POF) is gonadal failure defined by clinical and laboratory findings before the age of 40. AMH is accepted as a reliable marker for the quantitative evaluation of ovarian reserve, and serum AMH concentration varies with ageing of the female. Ovarian expression of AMH starts in fetal life, reaches a peak at puberty, starts to decline in adulthood and does not occur after menopause. In women with normal menstrual cycles, levels of serum AMH have been shown to decrease before FSH rises .
Cellular immunity and autoimmune process abnormalitiesplay a role in the autoimmune etiology of POF. There has been stated to be a personal or family history of autoimmune diseasein 80% of females with idiopathic POF, high titers of thyroid autoantibodies in 50%, and anti-ovary antibodies in 20%. HT is the most frequently seen disease accompanying POF in adult women [13-16].
The hypothesis of this study was that thyroid autoimmunity may suppress follicle development and will therefore reduce the ovarian reserve in patients with HT. The results of this clinical trial showed that serum AMH concentration in the HT patients was lower than in the control group. It was assumed that when antithyroid antibodies are present, they may cause antibody-mediated cytotoxicity in the growing ovarian follicle and damage to the maturing oocyte, thereby leading to diminished quality and developmental potential. In the hypothesis of cross-reactivity, it has been suggested that thyroid autoantibodies alter fertility by targeting zonapellucida, human chorionic gonadotropin receptors and other placental antigens . Weghofer et al reported that thyroid autoimmunity was 11.1% and serum AMH concentration was 1.3+2.0 ng/mL in 225 women who underwent IVF. In that study, the mean AMH levels were determined to be significantly higher in women with TSH <3.0 μIU/mL compared to those with TSH ≥3.0 μIU/mL ( p = 0.02). It was concluded that there was robust statistical evidence that thyroid function in the euthyroid range has a more significant role in the effect on the ovarian reserve than thyroid autoimmunity. However, in the current study, median TSH was 2.8 mIU/L (IQR 25-75;1.56-4.65) in patients with euthyroid HT. In the 2012 American Association of Clinical Endocrinologists (AACE) and America Thyroid Association (ATA) co-sponsored guidelines, it is stated that the upper limit of a third generation TSH should be considered as 4.12 mIU/L in iodine-sufficient areas. Morover, approximately 20 –26% of the population could be considered hypothyroid if the upper limit of the normal range were decreased to 2.5–3.0 mIU/L .
Kurado et al showed that AMH levels in women with Hashimoto’s thyroiditis were improved with LT4 treatment, but there was no correlation between thyroid antibody titers and serum AMH levels during LT4 supplementation. In contrast in the current study, no differences were determined in serum AMH concentrations of HT patients using or not using levothyroxine (euthyroid HT) (p=0.734). In a study of euthyroid HT adolescents, Pirgon et al demonstrated that AMH levels were significantly higher in the HT group than in the control group . In another study, serum AMH levels were determined to be significantly higher in women with HT than in the control group. From this result, it was suggested that there could be a common etiological link in HT and polycystic ovary syndrome (PCOS). Therefore, PCOS patients were not included in the current study.
As expected, there was determined to be a negative correlation between serum AMH levels and age in this study (r= -0.489 p=<0.001). However, there was no significant correlation of AMH concentration with the levels of TgAb or TPOAb and TSH. Similarly, Chen et al. demonstrated relationship between positive TPOAb and idiopathic low ovarian reserve in Chines women, but this influence was not related TPOAb levels . Osuka et al reported that thyroid autoantibodies are not likely to affect ovarian reserve in euthyroid women with a normal range TSH level, but elevated TSH levels may be involved in decreasing serum AMH levels. Saglam et al. reported lower AMH levels in euthyroid women with HT compared to an age- and BMI-matched healthy control group (1.16 ± 0.17 vs 1.28 ± 0.25, p=0.001 . The results of the current study demonstrated that statistically significantly more HT patients had AMH concentration <1 ng/mL compared to the control group (35.2% vs 23.8;p=0.04).
Several studies have shown a correlation between subclinical hypothyroidisim and adverse pregnancy outcomes. The results of the meta-analysis showed that the prevalence of miscarriage in patients with subclinical hypothyroidism with autoimmune thyroiditis was significantly higher compared to those with subclinical hypothyroidism only. However, the effect of subclinical hypothyroidism on the risk of miscarriage is unclear. In the current study the miscarriage rate was statistically significantly higher in the patients with HT, compared to the control subjects (p=0.041), but there was no difference in AMH levels between the subjects who had had or had not had a miscarriage (p=0.366). This suggests that autoimmunity itself may increase the risk of miscarriage. Glinoer et al. reported that thyroid autoantibodies indicate abnormal immune function, which induces miscarriage by unstable placenta implantation . This was explained with 3 hypotheses;
The first stated that pregnancy loss is not directly linked to the presence of circulating thyroid antibodies, but rather to a more general autoimmune imbalance, which would therefore explain the higher rejection rate of fetal graft. In the second hypothesis, it is assumed that even if there is apparent euthyroidism, the presence of autoimmune thyroid disease could be related tothe decreased thyroid function capacity to adapt sufficiently to the changes of pregnancy with a reduced functional reserve of thyroid gland. The third hypothesis stated that there was a tendency for pregnancy at an older age in thyroid autoantibody positive women and older women are more prone to pregnancy loss . However, further studies on this matter may be needed to reveal the mechanisms.
There were some limitations to this study, primarily the retrospective design and that antral follicle count could not be evaluated. Most studies of thyroid autoimmunity and ovarian reserve have been conducted on infertile women. This study can be considered to contribute to the limited available literature on ovarian reserve in patients with autoimmune thyroiditis.This is the first study to have evaluated AMH concentrations in women with HT who are euthyroid with levothyroxine treatment and in those who do not use levothyroxine. The women included in this study were not patients who had presented because of infertility.