Thyroid autoimmunity and infertility.

We aimed to study the prevalence of thyroid autoimmunity in infertile women; to assess whether thyroid autoantibodies were associated with non-organ-specific autoantibodies; and to investigate the influence of this dysfunction on the couples' chances of pregnancy. We assayed serum levels of thyroid stimulating hormone (TSH), free thyroxine, and microsomal and thyroglobulin autoantibodies in 149 infertile women. In patients with serum TSH levels in the hypothyroid or hyperthyroid range and/or with thyroid autoantibodies, we performed thyroid ultrasound examinations and assayed some non-organ-specific autoantibodies. We compared the duration of infertility in infertile patients with normal thyroid (control group), with thyroid abnormalities, and with thyroid autoantibodies in euthyroidism. Thirty infertile patients (20.1%) had thyroid abnormalities. The prevalence of thyroid autoantibodies was 17.4%. In infertile patients with thyroid autoantibodies, we found a poor association with non-organ-specific autoantibodies. Only the women with thyroid abnormalities and ovulatory dysfunction had a mean duration of infertility significantly longer than that of the control group. When the data were analyzed for euthyroid women with thyroid autoantibodies, we found no significant variation in the duration of infertility. Although we found a high prevalence of thyroid autoantibodies in infertile patients, the presence of these autoantibodies per se did not reduce the chance of pregnancy.     

Effect of autoimmune thyroid disease in older euthyroid infertile woman during the first 35 days of an IVF cycle

In this case-control study of euthyroid first-cycle IVF patients ≥ 38 years old with singleton baby, miscarriage, biochemical pregnancy, and no pregnancy outcomes from 2005-2008, we assayed frozen serum for autoimmune thyroid disease (AITD) and thyroid function at cycle start, trigger, and 4 and 5 weeks' gestation. AITD prevalence in older infertile women was similar across clinical outcomes, and although AITD was associated with a higher baseline TSH, TSH remained within acceptable ranges, suggesting that T(4) supplementation may not affect maternal outcomes in older euthyroid AITD patients through 5 weeks gestation.     

Screening for hypothyroidism in infertile women.

OBJECTIVE: To determine the frequency of an elevated thyroid-stimulating hormone (TSH) level in 704 patients seeking treatment for infertility. STUDY DESIGN: Sera from 704 women evaluated for infertility were assayed for TSH levels using radioimmunoassay (normal, 0.45-4.09 mIU/mL). All women had at least one year of infertility. Women with a known history of thyroid disease were excluded from the review. RESULTS: Sixteen of 704 patients (2.3%) had elevated TSH levels and were treated with levothyroxine to normalize TSH. None of these women had overt clinical signs or symptoms of hypothyroidism. Of these women, 11 of 16, or 69%, had ovulatory dysfunction, and 7 (64%) later became pregnant while on thyroid replacement. Five of 704 (0.7%) women with infertility who presented without a history of ovulatory dysfunction had elevated TSH levels, and none became pregnant with treatment. CONCLUSION: The prevalence of elevated TSH in 704 women with at least one year of infertility was 2.3%. The majority of women diagnosed with hypothyroidism (11 of 16, or 69%) had ovulatory dysfunction. With treatment for hypothyroidism, successful pregnancies resulted in 7 of 11 (64%) of patients. Women with infertility and ovulatory dysfunction should be screened for hypothyroidism. Screening for hypothyroidism as part of a routine infertility workup in women with normal ovulatory function will yield few abnormal tests.     

Subclinical hypothyroidism in infertile women: the importance of continuous monitoring and the role of the thyrotropin-releasing hormone stimulation test.

The aim of our study was to assess the prevalence of subclinical hypothyroidism (SH) after administering a thyrotropin-releasing hormone (TRH) stimulation test among women with normal serum thyroid-stimulating hormone (TSH) levels and various causes of infertility. Eighty-seven infertile women (39 with ovulation disorders and 48 with other causes of infertility) had a TRH stimulation test on day 3 - 7 of their cycle. Exaggerated TSH response (>30 mIU/l at 20, 40 or 60 min) following intravenous injection of 400 microg TRH was defined as SH. The TRH test was performed 2 - 4 months after the first visit to the clinic. We found that the prevalence of SH was significantly higher among women with ovulation disorders (20.5%) than among women with normal ovulation (8.3%). In addition, we found that although basal TSH levels were normal at recruitment, 2 - 4 months later these levels were abnormally high in 8% of the women. All these women had an abnormal TRH test. We recommend performing TRH stimulation testing in women suffering from ovulation disorders who have normal basal TSH levels, followed by repeat assessments of thyroid function to enable treatment with thyroxine in cases with abnormal results.     

Alterations in thyroid function among the different polycystic ovary syndrome phenotypes

Abstract

The study evaluates the prevalence of subclinical thyroid dysfunction in infertile PCOS patients, according to the different PCOS phenotypes and to examine whether insulin sensitizers in insulin resistant (IR) PCOS patients may improve thyroid function. The study population consisted of all PCOS patients, attending the infertility and IVF unit of Department of Pediatrics, Obstetrics and Reproductive Medicine of University of Siena, Italy, and compared them to regularly cycling, healthy, infertile controls. Upon admission, blood was drawn from all patients during the early follicular phase, for complete hormonal and metabolic profiles. In IR-PCOS patients treated with insulin sensitizers, blood was drawn again after 6 months. PCOS patients had a significantly higher prevalence of subclinical thyroid dysfunction compared to infertile controls. While no significant association was detected between TSH value and the presence of hyperandrogenism, overweight and obese PCOS patients, as well as IR PCOS patients showed significantly higher prevalence of subclinical thyroid dysfunction. Moreover, among IR PCOS patients, 6 months treatment with insulin sensitizers significantly reduces TSH levels. Infertile PCOS patients have a high prevalence of subclinical thyroid dysfunction, which may be successfully treated in IR PCOS patients by insulin sensitizers.     

Subclinical hypothyroidism in infertile women: The importance of continuous monitoring and the role of the thyrotropin-releasing hormone stimulation test

The aim of our study was to assess the prevalence of subclinical hypothyroidism (SH) after administering a thyrotropin-releasing hormone (TRH) stimulation test among women with normal serum thyroid-stimulating hormone (TSH) levels and various causes of infertility. Eighty-seven infertile women (39 with ovulation disorders and 48 with other causes of infertility) had a TRH stimulation test on day 3 – 7 of their cycle. Exaggerated TSH response (>30 mIU/l at 20, 40 or 60 min) following intravenous injection of 400 µg TRH was defined as SH. The TRH test was performed 2 – 4 months after the first visit to the clinic. We found that the prevalence of SH was significantly higher among women with ovulation disorders (20.5%) than among women with normal ovulation (8.3%). In addition, we found that although basal TSH levels were normal at recruitment, 2 – 4 months later these levels were abnormally high in 8% of the women. All these women had an abnormal TRH test. We recommend performing TRH stimulation testing in women suffering from ovulation disorders who have normal basal TSH levels, followed by repeat assessments of thyroid function to enable treatment with thyroxine in cases with abnormal results.     

Subclinical hypothyroidism and thyroid autoimmunity in women with infertility.

OBJECTIVE: To determine the prevalence of different subclinical hypothyroidism (SH) grades and thyroid autoimmunity (TAI) in infertile women. DESIGN: Retrospective study. Setting. Endocrinology division of a public hospital in Argentina. PATIENTS: Group I comprised 244 women consulting on infertility (>1 year without pregnancy); Group C (controls) comprised 155 healthy women with confirmed fertility. INTERVENTION: Thyroid-stimulating hormone and thyroid peroxidase antibodies were measured in all patients, and a thyrotropin-releasing hormone (TRH) stimulation test was performed in 71 patients to diagnose SH grade 1. The pregnancy rate in hypothyroid women on levothyroxine treatment was also evaluated. RESULTS: SH was diagnosed in 13.9% of the patients in Group I and in 3.9% of Group C (p < 0.002). The TRH stimulation test was useful to detect SH grade 1 in 12.7% of the infertile patients. Patients with precocious ovarian failure, tubal disturbances and ovulatory dysfunction presented higher SH rates (40.0, 18.2 and 15.4%, respectively) than control patients (p < 0.0001, p < 0.002 and p < 0.003). No significant difference in TAI prevalence was shown in Group I relative to Group C. Pregnancy rate of 44.1% was achieved under levothyroxine treatment. CONCLUSIONS: We observed a higher prevalence of SH, but not of TAI, in patients with infertility. Our results support thyroid screening in women with reproductive failure.     

Basal hormone levels in women with recurrent pregnancy loss.

The potential role of endocrine abnormalities during the follicular phase in women with unexplained recurrent pregnancy loss was investigated in a retrospective study. Eighty women with recurrent pregnancy loss underwent routine work-up to exclude known associations with the condition. Following investigation, 58 women failed to reveal an identifiable cause, and were therefore classified as having unexplained recurrent pregnancy loss. The control group consisted of women with known causes of abortions, such as uterine septum and parental chromosomal abnormalities. Mean age, gravidity, parity, presence of infertility, previous number of miscarriages and duration of marriage were similar in both groups. Day-3 serum levels of follicle stimulating hormone (FSH), estradiol, luteinizing hormone (LH) prolactin, total testosterone, dehydroepiandrosterone sulfate (DHEAS) and thyroid stimulating hormone (TSH) were compared in the two groups. FSH, estradiol, LH, prolactin and DHEAS concentrations were significantly higher in the unexplained recurrent pregnancy loss group than in the explained recurrent pregnancy loss group, although serum concentrations of all hormones were within the normal range (p < 0.01). TSH and total testosterone levels were similar in the two groups (p > 0.05). There were no differences in the frequency of abnormal levels of hormones between the two groups (p > 0.05). We conclude that endocrine abnormalities in the follicular phase are not associated with recurrent pregnancy loss.     

Hypothyroidism among infertile women in Finland

The main aim of this retrospective study was to evaluate the occurrence of hypothyroidism among Finnish women with infertility. For this purpose, the records of 335 women presenting for the first time with infertility at the outpatient clinic of reproductive endocrinology at Turku University Central Hospital during a 3-year period (January 1992 to December 1994) were reviewed. Due to missing data, 36 women were excluded from the analysis. Thyroid function was screened by measuring serum thyroid stimulating hormone (TSH) levels in conjunction with serum prolactin using immunoradiometric assays. Prior to enrolment in the infertility examinations, ten out of 299 women had used thyroxine substitution for primary hypothyroidism. In the TSH screening test, 12 women (4%) exhibited elevated serum TSH levels ranging from 5.1 to 32 mU/l. Three of these cases were previously diagnosed with hypothyroidism and were using an inadequate dose of thyroxine. The prevalence of abnormal TSH levels was highest in the ovulatory dysfunction (6.3%) and unknown infertility (4.8%) groups and lowest in the tubal infertility (2.6%) and male infertility (1.5%) groups, although no statistically significant differences between the groups were observed. Oligo/amenorrhea was present in 101 (34%) women in the whole study population and in eight (67%, p < 0.5) women with elevated serum TSH at screening. The relatively high occurrence of abnormal TSH levels in infertile women with ovulatory dysfunctions or unknown infertility, as well as with oligo/amenorrhea, emphasizes the importance of TSH screening in these patient groups.     

Hypothyroidism among infertile women in Finland.

The main aim of this retrospective study was to evaluate the occurrence of hypothyroidism among Finnish women with infertility. For this purpose, the records of 335 women presenting for the first time with infertility at the outpatient clinic of reproductive endocrinology at Turku University Central Hospital during a 3-year period (January 1992 to December 1994) were reviewed. Due to missing data, 36 women were excluded from the analysis. Thyroid function was screened by measuring serum thyroid stimulating hormone (TSH) levels in conjunction with serum prolactin using immunoradiometric assays. Prior to enrolment in the infertility examinations, ten out of 299 women had used thyroxine substitution for primary hypothyroidism. In the TSH screening test, 12 women (4%) exhibited elevated serum TSH levels ranging from 5.7 to 32 mU/l. Three of these cases were previously diagnosed with hypothyroidism and were using an inadequate dose of thyroxine. The prevalence of abnormal TSH levels was highest in the ovulatory dysfunction (6.3%) and unknown infertility (4.8%) groups and lowest in the tubal infertility (2.6%) and male infertility (1.5%) groups, although no statistically significant differences between the groups were observed. Oligo/amenorrhea was present in 101 (34%) women in the whole study population and in eight (67%, p < 0.5) women with elevated serum TSH at screening. The relatively high occurrence of abnormal TSH levels in infertile women with ovulatory dysfunctions or unknown infertility, as well as with oligo/amenorrhea, emphasizes the importance of TSH screening in these patient groups.     

Thyroid (dys-)function in normal and disturbed pregnancy

Introduction

During pregnancy, physiologic changes in maternal thyroid function take place especially due to hormonal as well as metabolic processes. Human chorionic gonadotropin activates the maternal thyroid gland leading to increased thyroid hormone production. A sufficient availability of maternal thyroid hormones is essential for fetal development, especially during the first trimester of pregnancy, when the fetal thyroid gland is not yet functional.

Materials and Methods

Current knowledge of thyroid dysfunction including thyroid autoimmunity, hypothyroidism or hyperthyroidism is summarized with special focus on miscarriage and pregnancy disorders. Therefore, a Medline research as well as an analysis of current guidelines on thyroid function and pregnancy was performed.

Results

A study focusing on TSH levels in normal and disturbed pregnancies, the risk of miscarriage in association with thyroid autoantibodies, and (subclinical) hypothyroidism in infertile and fertile women were included.

Conclusion

Maternal thyroid dysfunction negatively affects pregnancy outcome. Besides a routine iodine supplementation in pregnant women and treatment of hypo as well as hyperthyroidism, TSH levels should routinely be measured in women during childbearing years and adjusted to concentrations <2.5 mIU/l in order to optimize maternal health and fetal development.     

Thyroid function abnormalities and antithyroid antibody prevalence in pregnant women at high risk for gestational diabetes mellitus.

Both gestational diabetes mellitus (GDM) and thyroid dysfunction in pregnancy compromise maternal and fetal health. The aim of the present study was to determine the prevalence of abnormal thyroid function and antithyroid antibodies during early pregnancy in a population at high risk for GDM. Serum free triiodothyronine (FT3), free thyroxine (FT4) and thyroid-stimulating hormone (TSH) were measured in 301 pregnant women who underwent routine 'universal screening' for GDM. The antithyroid peroxidase antibody (antiTPOAb) was also quantified in 255 of these women. GDM was confirmed by a 75-g oral glucose tolerance test using World Health Organization criteria. No statistically significant difference was found between the 80 (26.6%) women with GDM and the 221 (73.4%) women without GDM for any of the thyroid function tests. In the cohort tested for antiTPOAb, the 51 (20.0%) women who were positive for antiTPOAb had higher mean TSH (1.57 +/- 2.49 mIU/l; p < 0.001) than the women negative for antiTPOAb. Seventeen (5.6%) women had low FT4 while 12 (4.0%) women had high TSH; 28 (9.3%) women had low serum TSH, among whom three (1.0%) also had high FT4. The significantly higher prevalence of hypothyroxinemia and antiTPOAb titers than generally reported warrants routine screening for thyroid abnormalities. This screening, which can be effectively and easily incorporated into screening practices already in place for GDM, would result in improved obstetric care.     

Thyrotropin-releasing hormone (TRH) and metoclopramide testing in infertile women.

Thyroid stimulating hormone (TSH) determinations before and after thyrotropin-releasing hormone (TRH) stimulation were obtained in 834 infertile women, from 1982 until 1985. Thyroid function disturbances were seen in 20% of the women, in accordance with the prevalence in South Germany. Postcoital tests were significantly poorer in women with subclinical hypothyroidism than in euthyroid patients. Spontaneous conception was more frequent in euthyroid (16%) than in hypothyroid (6%) women. During the same period, prolactin was determined after TRH stimulation in the early follicular phase and after metoclopramide stimulation in the luteal phase, in 759 women. The pregnancy rate was not improved by administration of dopamine agonists in women with an exaggerated response to TRH or metoclopramide. Our results suggest that subclinical hypothyroidism as well as disorders of prolactin secretion may play a role in infertility. The TRH test is proposed to rule out thyroid dysfunction. Neither the TRH nor the metoclopramide test was useful for the prognostic differentiation of prolactin secretion disorders.     

Presence of autoantibodies in women with unexplained infertility

Serum samples from 41 patients suffering from unexplained infertility and 351 normal pregnant women were assayed for a range of autoantibodies by means of immunofluorescence, counterimmunoelectrophoresis, double immunodiffusion, Western blots, and enzyme-linked immunosorbent assays. The prevalence of autoantibodies to smooth muscle, phospholipid, and nuclear antigens, the latter when detected by immunofluorescence, was elevated in women with infertility compared with normal pregnant women (p less than 0.001, less than 0.001, and less than 0.05, respectively). Antiviral antibodies were not detected. The reason for the high level of autoreactivity in infertile women is unclear, but smooth muscle and antiphospholipid antibodies may actively interfere with the reproductive process.     

Increased prevalence of antithyroid antibodies identified in women with recurrent pregnancy loss but not in women undergoing assisted reproduction

OBJECTIVE: To assess the prevalence of antibodies to thyroglobulin and thyroid peroxidase (or microsomal) in women with recurrent pregnancy loss and women undergoing assisted reproductive techniques (ART) compared with healthy controls. DESIGN: Retrospective, two-centered study. SETTING: University-affiliated private patient centers. PATIENT(S): Included were 700 women with a history of two or more consecutive pregnancy losses, 688 women with a history of infertility who were undergoing ART, and 200 healthy, reproductive-aged female controls. INTERVENTION(S): Blood was collected before ART cycles, frozen, and assayed. MAIN OUTCOME MEASURE(S): Standardized ELISAs were used to measure antithyroid antibodies and TSH levels. Statistical analysis was performed with use of the two-tailed Fisher's exact test. RESULT(S): Antithyroid antibodies were identified in 29 of 200 (14.5%) of controls and 158 of 700 (22.5%) of women with recurrent pregnancy loss and 132 of 688 (19.2%) of women undergoing ART. Less than 20% of the women with antithyroid antibodies were clinically hypothyroid. CONCLUSION(S): Antithyroid antibodies are identified more frequently in women with recurrent pregnancy loss than in controls but not in women undergoing ART. These autoantibodies may be markers of autoimmune activation and have been associated with an increased risk of pregnancy loss and postpartum thyroid disease.     

Basal hormone levels in women with recurrent pregnancy loss

The potential role of endocrine abnormalities during the follicular phase in women with unexplained recurrent pregnancy loss was investigated in a retrospective study. Eighty women with recurrent pregnancy loss underwent routine work-up to exclude known associations with the condition. Following investigation ,58 women failed to reveal an identifiable cause ,and were therefore classified as having unexplained recurrent pregnancy loss. The control group consisted of women with known causes of abortions ,such as uterine septum and parental chromosomal abnormalities. Mean age ,gravidity ,parity ,presence of infertility, previous number of miscarriages and duration of marriage were similar in both groups. Day-3 serum levels of follicle stimulating hormone (FSH) ,estradiol ,luteinizing hormone (LH) prolactin ,total testosterone, dehydroepiandrosterone sulfate (DHEAS) and thyroid stimulating hormone (TSH) were compared in the two groups. FSH ,estradiol ,LH ,prolactin and DHEAS concentrations were significantly higher in the unexplained recurrent pregnancy loss group than in the explained recurrent pregnancy loss group ,although serum concentrations of all hormones were within the normal range (p < 0.01). TSH and total testosterone levels were similar in the two groups (p > 0.05). There were no differences in the frequency of abnormal levels of hormones between the two groups (p > 0.05). We conclude that endocrine abnormalities in the follicular phase are not associated with recurrent pregnancy loss.     

The impact of elevated thyroid stimulating hormone on female subfertility

Purpose

Hypothyroidism is known to have a negative impact on female reproduction even in subclinical form, subclinical hypothyroidism (SH). This study aimed to investigate the association between elevated TSH level and reproductive outcome.

Methods

We retrospectively evaluated a total of 203 infertile women who first visited our infertility treatment division from January 1, 2009 to August 31, 2012, including 13 patients with TSH above 4.5 mIU/l (elevated-TSH patients), 11 of whom were diagnosed as SH, and 190 patients with normal TSH (normo-TSH patients). We evaluated them according to reproductive outcome, including clinical pregnancy, miscarriage, and live birth until April 31, 2014. We also aimed to redefine the upper limit of normal serum TSH level.

Results

Multivariate analysis showed significant influence of elevated TSH on clinical pregnancy, although miscarriage and live birth were not affected. In addition, we revealed that the rate of decreased ovarian reserve and unexplained infertility was increased in patients with elevated TSH levels.

Conclusions

We found an association between elevated TSH and the decreased rate of clinical pregnancy. This might be related to an ovulatory disorder and pathophysiology of unexplained infertility. These results may reinforce the usefulness of TSH screening in infertility population.

     

自身免疫性甲状腺疾病对妊娠结局和女性生育功能的影响

甲状腺自身免疫性疾病是育龄妇女的常见病,包括妊娠期甲状腺功能亢进症、甲状腺功能减退症及产后甲状腺炎。抗甲状腺过氧化物酶抗体(TPOAb)、甲状腺球蛋白抗体(TGAb)及促甲状腺激素受体抗体(TRAb)是机体自身免疫功能紊乱的重要标志。甲状腺功能紊乱对妊娠妇女及胎儿可产生诸多不良影响。甲状腺功能正常但甲状腺自身抗体阳性的妊娠妇女在妊娠期发生甲状腺功能减退、分娩后发生产后甲状腺炎的危险性增高,应注意监测甲状腺功能。甲状腺自身免疫的存在可能与不孕不育以及自然流产等相关。对高危人群进行筛查、早期诊断并及时给予治疗,可有效降低妊娠不良结局的发生。     

Detection and significance of serum zona pellucida antibodies in sterile females

Sera of 100 infertile women and of 100 patients with early pregnancy as control group were investigated for antibodies to zona pellucida by the indirect immunofluorescence. Zonae of oocytes from pigs were used for the procedure. A positive control serum with a high titer was produced by immunization of rabbits with an antigen from pig zonae. The frequency of antibodies to zona pellucida was 29% for infertile patients and 18% in the control group. The titers of these autoantibodies were higher in infertile than in fertile women. There was no increase of these antibodies if the age increased and no relation to the menarche and the ovulation. Antibodies to zona pellucida were demonstrated frequently in patients with disturbances of cycle, free Fallopian tubes, secondary infertility, and ovarian and unknown origin of infertility.     

早孕期甲状腺过氧化物酶抗体阳性对甲状腺功能的影响

目的：探讨妊娠8~12周甲状腺过氧化物酶抗体(TPOAb)阳性对甲状腺功能的影响。方法：对2010年9月至2011年6月北京友谊医院产科门诊行产前检查的611例无甲状腺疾病高危因素的健康初产妇,于妊娠8~12周进行甲状腺功能[促甲状腺激素(TSH)、游离四碘甲状腺原氨酸(FT4)]和TPOAb的检测,通过制定早孕期甲状腺功能正常参考区间,分析TPOAb阳性切割值、阳性率及对TSH、FT4的影响。结果：(1)妊娠8~12周TPOAb中位数值及变化范围为38.9(6.4~>1300)mU/L。(2)通过建立妊娠8~12周人群特异参考标准,以第90百分位计算TPOAb阳性切割值为206.77 mU/L,TPOAb阳性率为10.8%(66/611)。(3)回归分析显示：TPOAb滴度与TSH呈正相关,与FT4呈负相关,P值均为0.000。妊娠8~12周TPOAb阳性妇女TSH中位数值较TPOAb阴性者升高0.4 mU/L,前者TSH异常升高的风险是后者的4.4倍。结论：妊娠8~12周TPOAb阳性率为10.8%,通过建立妊娠期人群特异甲状腺功能参考标准和TPOAb阳性切割值,可避免过高估计TPOAb的阳性率。TPOAb阳性孕妇发生TSH异常升高的风险明显增加。