Thyroid imbalance and subfertility

Introduction

An optimal level of thyroid hormones is needed for reproductive health. This has been proved clearly in women who have a higher chance of having “autoimmune thyroid diseases (Hashimoto’s thyroiditis and Graves’ disease)” compared to men. Both overt and subclinical thyroid disease and thyroid autoimmunity (TAI) have been shown to be associated with infertility. Thyroid dysfunction can adversely affect follicular development, spermatogenesis, fertilization rates, embryo quality, and live birth rates. The evidence of this association is clearer with hypothyroidism than hyperthyroidism. Overt hypothyroidism leads to menstrual cycle irregularity and ovulatory dysfunction. Through the negative feedback on hypothalamic–pituitary axis, it leads to hyperprolactinemia and ovulatory dysfunction resulting from interference with pulsatile release of GnRH. Thyroid dysfunction causes alteration in sex steroids and sex hormone-binding globulin (SHBG) levels; hyperthyroidism and hypothyroidism affect SHBG levels and thus can impact reproduction.

The classification of thyroid dysfunction is given in Table 9.1 .

Table 9.1

Diagnosis of thyroid dysfunction.

	TSH (0.4–4.2 mIU/L)	FT4 (0.89–1.76 ng/dL)
Euthyroid	Normal	Normal
Subclinical hypothyroidism	High	Normal
Overt hypothyroidism	High	Low
Subclinical hyperthyroidism	Low	Normal
Overt hyperthyroidism	Low	High

Thyroid imbalance and female subfertility

Association of thyroid dysfunction with menstrual irregularity

Both “overt hypothyroidism” and “overt hyperthyroidism” can entail menstrual irregularity like polymenorrhea, oligomenorrhea, and menorrhagia. As many as 22% of hyperthyroid women can have menstrual irregularity in comparison with 8% of euthyroid controls. Infertile women with menstrual irregularities were prone to have abnormal thyroid function. Among infertile women, 67% had menstrual irregularity, while only 29% fertile women had menstrual disorder. In another study including 171 women with TSH concentrations >15 mU/L, menstrual irregularity was reported in 68% while only 12% women had menstrual irregularities among euthyroid controls.

Association of thyroid dysfunction with subfertility

Thyroid dysfunction is frequently found in infertile women in contrast to fertile women. Infertile women had lesser chances to be euthyroid in comparison with fertile women in a study which reported that 62.6% of infertile women were euthyroid compared to 82.6% of fertile women. In a study on women of reproductive age, the frequency of infertility was 52.3% and 47% in women with Graves’ disease and Hashimoto’s thyroiditis, respectively. However, there are contradictory data as well that reported similar prevalence of subclinical or overt hyperthyroidism in both infertile and fertile women. A retrospective study on 200 subfertile women aged 17–40 years revealed that 14% of women had preexisting hypothyroidism, 14.5% had recently discovered hypothyroidism, while 21% had subclinical hypothyroidism (SCH). Hypothyroidism was significantly associated with higher LH (8.5 IU/L vs 6.8 IU/L) and infertility related to anovulation (47.8% vs 27%) in women with TSH above or below 4.2 mIU/L, respectively. ⁷ Thus, it provides an insight into altered gonadotropin levels with hypothyroidism.

Association of SCH with subfertility

Many studies have tried to answer this question, but the results are inconsistent. A cross-sectional study found a prevalence of SCH in 2.3% of 704 infertile women, but this prevalence was comparable to background general population. Similar results were reported by another prospective study in which infertile women did not have increased prevalence of SCH. Nevertheless, many studies have shown increased rates of SCH in subfertile women. Higher frequency of SCH (13.9%) was found in infertile women in contrast to 3.9% in fertile women in a retrospective study. Among 454 women presenting for subfertility, TSH > 4.5 mIU/L was found in 24%. Women with ovulatory disorders and “unexplained (UE) infertility” had the highest level of TSH, while it was lower among those women with either tubal disorders or infertility due to male factor. Even euthyroid women with UE infertility had higher TSH values within the specified normal range. {TSH (mIU/L): UE infertility—1.95 vs male factor infertility—1.66; P —0.003}. In addition, women with UE infertility had double the chance of having a TSH of ≥ 2.5 mIU/L in comparison with controls with male factor infertility.

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