Schilddrüse und Schwangerschaft

Management of thyroid diseases during pregnancy requires special considerations because pregnancy induces major changes in thyroid function. Both overt and subclinical hypothyroidism have adverse effects on the course of pregnancy and development of the fetus. Hypothyroidism should be diagnosed and corrected before initiation of pregnancy. If hypothyroidism is diagnosed during pregnancy, thyroid function should be normalized as rapidly as possible. Adequate iodine intake is important. By hyperthyroidism differentiation of Graves’ disease from gestational thyrotoxicosis is possible by evidence of autoimmunity (morphologic change of goiter and TSH-receptor antibodies). For overt hyperthyroidism due to Graves’ disease or hyperfunctioning thyroid nodules antithyroid drug therapy should be either initiated or adjusted to maintain the maternal thyroid hormone levels for free T4 in the upper reference range for nonpregnant women. TSH screening should be obtained of patients who are at increased risk (such as miscarriage, preterm deliver miscarriage or history of thyroid disease, Age >?30 years, goiter, autoimmune disease such as diabetes mellitus type 1).     

Immunological abortion: the thyroid factor

Spontaneous miscarriage (SM) is a multifactorial problem involving several couples. Recent studies investigated the correlations between the presence of antithyroid antibodies (ATA) and pregnancy loss, and found that many women with a previous history of recurrent miscarriage, showed high levels of ATA circulating in their blood. Further-more, the thyroid function disorder may also affect the course of pregnancy. Basically, two theories can explain the reasons of the spontaneous termination of pregnancy in presence of ATA: the first theory suggests that the hypofertlity or infertlity of these subjects may be due to a subtle degree of hypothyroidism which is difficult to detect by routine serum hormone determinations; the second theory supports that the presence of thyroid antibodies reveals a more generalized underlying abnormal stimulation of the immune system. Therefore, the thyroid function should be tested before conception and during pregnancy to avoid the pregnancy loss and neuropsychological deficits in infants. Actually, some papers suggest that treatments reserved to women with thyroid antibodies could decrease the miscarriage rate. Unfortunately, there is not agreement about the most effective therapy. We need more large, randomised, placebo controlled, double blind studies.     

Autoimmune thyroid disease and pregnancy--challenge or routine

TSH or Thyroid Stimulating Hormone, is responsible for regulating the amount of thyroid hormones released by the body. The TSH is produced by the pituitary gland. If there is a thyroid problem or the thyroid gland is diseased, it may result in excess or reduced production of thyroid hormone, and these conditions are called hyperthyroidism and hypothyroidism respectively. Normal thyroid function is needed for a successful pregnancy. In the general population, a TSH level between 0.45 and 4.5 mIU/l is considered normal and indicates euthyroidism. Studies, however, have suggested that the normal TSH level during pregnancy should be lower than this and have suggested using 2.5 mIU/l as the upper range cutoff. The risk for miscarriage and preterm delivery were increased when the level was higher. The presence of thyroid antibodies may further complicate this situation. Women with positive antibodies are at a 2-fold increased risk for miscarriage.     

Effect of antithyroid antibodies on ICSI outcome in antiphospholipid antibody-negative euthyroid women

Antithyroid antibodies (ATA) are found in 5–15% of women at reproductive age and are not necessarily accompanied with thyroid dysfunction. ATA are associated with adverse effects such as spontaneous miscarriage, recurrent miscarriages, preterm delivery and maternal post-partum thyroiditis in women with normal thyroid hormone concentrations. The role of ATA on the outcome of IVF cycles remains to be investigated. This study evaluated the impact of ATA on the outcome of intracytoplasmic sperm injection (ICSI)–embryo transfer cycles in euthyroid women. A total of 253 women undergoing ICSI–embryo transfer cycles were prospectively enrolled in this study. Women positive for at least one of the thyroid antibodies, with normal thyroid-stimulating hormone (TSH) and free T4 concentrations and negative for anticardiolipin antibodies and lupus anticoagulant were included. ICSI was performed for fertilization in all cycles. Of 253 women, 219 were ATA negative and 34 ATA positive. Implantation rates (19.1% versus 18.4%), miscarriage rates (9.0% versus 8.3%) and ongoing pregnancy rates (37.0% versus 32.4%) did not differ significantly between the ATA-positive group and the ATA-negative group, respectively. The presence of antithyroid antibodies in euthyroid and antiphospholipid antibody-negative women was not found to significantly affect the outcome of ICSI–embryo transfer cycles.Antithyroid antibodies (ATA) can interact with thyroid hormone receptors located on the human oocyte and impair the chance of fertilization and healthy pregnancy. They are found in 5–15% of women at reproductive age and are not necessarily accompanied with thyroid dysfunction. ATA have been reported to be associated with adverse effects such as spontaneous miscarriage, recurrent miscarriages, preterm delivery and maternal post-partum thyroiditis in women with normal thyroid hormone concentrations. The role of ATA on the outcome of IVF cycles remains to be investigated. The objective of our study was to evaluate the impact of ATA on the outcome of intracytoplasmic sperm injection (ICSI)–embryo transfer cycles in euthyroid women. A total of 253 women undergoing ICSI–embryo transfer cycles were prospectively enrolled in this study. Women with at least one of the thyroid antibodies positive and normal TSH and free T4 concentrations were included in the study. Since other immunological disorders might affect the results, antiphospholipid antibodies (APA), which are the markers of antiphospholipid antibody syndrome, were also screened in all women prior to study. Women with positive for APA were excluded in the final analysis. Of 253 women, 219 (86.6%) were ATA negative and 34 (13.4%) ATA positive. Implantation rates (19.1% versus 18.4%), biochemical pregnancy rates (9.2% versus 14.3%), miscarriage rates (9.0% versus 8.3%) and ongoing pregnancy rates (37.0% versus 32.4%) did not differ significantly between the ATA-positive group and the ATA-negative group, respectively. In conclusion, presence of antithyroid antibodies in euthyroid and antiphospholipid antibody-negative women does not affect the outcome of ICSI–embryo transfer cycles.     

Infertility and thyroid disorders

PURPOSE OF REVIEW: This review highlights the 'gap' in knowledge regarding the contribution of thyroid dysfunction in reproduction. Thyroid dysfunction, which is quite prevalent in the population affects many organs including the male and female gonads, interferes with human reproductive physiology, reduces the likelihood of pregnancy and adversely affects pregnancy outcome, thus becoming relevant in the algorithm of reproductive dysfunction. RECENT FINDINGS: Although menstrual irregularities are common, ovulation and conception can still occur in hypothyroidism, where thyroxine treatment restores a normal menstrual pattern and reverses hormonal changes. Subclinical hypothyroidism may be associated with ovulatory dysfunction and adverse pregnancy outcome. Thyroid autoimmunity increases the miscarriage rate, and thyroxine treatment does not seem to protect. Menstrual disturbances, frequent in thyrotoxicosis are restored following treatment. In males, thyrotoxicosis has a significant but reversible effect on sperm motility. Although radioactive Iodine (I) in ablation doses may transiently affect the gonads, it does not decrease fertility or increase genetic malformation rate in the offspring. SUMMARY: Awareness of the thyroid status in the infertile couple is crucial, because of its significant, frequent and often reversible or preventable effect on infertility. Many aspects of the role of thyroid disorders however in infertility need further research.     

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.     

左旋甲状腺素对甲状腺功能正常的甲状腺自身抗体阳性妇女妊娠结局影响的荟萃分析

目的:系统评价左旋甲状腺素（LT 4）治疗对甲状腺功能正常的甲状腺自身抗体阳性妇女妊娠结局的影响。 方法:检索Medline数据库、荷兰医学文摘（EMBASE）数据库、Cochrane图书馆（Cochrane Library）数据库、中国知网（CNKI）数据库、中国生物医学文献数据库（CBM）、万...     

Disfunción tiroidea en las pacientes abortadoras. ¿Existen argumentos para el cribado?

Objectives

Normal thyroid function is crucial for adequate maternal and fetal development in pregnancy. There is solid evidence of the pernicious effects of thyroid dysfunction in pregnancy for both mother and fetus. One of these effects is miscarriage and recurrent pregnancy losses. Nevertheless, there is no general agreement on the advisability of screening for thyroid dysfunction in pregnant women, even when there is a previous history of pregnancy loss. This study aimed to determine the prevalence of thyroid dysfunction (including anti-thyroid autoimmunity without abnormal T3/T4/TSH levels) in patients with spontaneous abortion.

Subjects and methods

T3-T4-TSH-antithyroid antibodies (thyroglobulin and thyroperoxidase) were determined at diagnosis in 132 consecutive women with spontaneous miscarriage.

Results

Nearly 25% of the patients had undiagnosed and untreated thyroid disturbance.

Conclusion

The results obtained suggest that the prevalence of thyroid dysfunction in patients with spontaneous miscarriage is higher than previously reported in our environment.     

The correlation of autoantibodies and uNK cells in women with reproductive failure

There is conflicting evidence on the role of autoimmune disorders in reproductive failure, including recurrent miscarriage (RM) and recurrent implantation failure (RIF), after in vitro fertilisation (IVF). Several commonly studied autoimmune markers in women with reproductive failure include antiphospholipid antibodies (APAs), thyroid peroxidase antibodies (TPA) and uterine natural killer (uNK) cells. However, there have not been any studies that have examined the correlation of these markers in women with reproductive failure. To determine if women who tested positive for autoantibodies (APA and thyroid peroxidase antibodies) have significantly higher uNK cell numbers than women who tested negative for these antibodies, the percentage of stromal cells that stained positive for CD56 was identified by immunocytochemistry in endometrial biopsies from 42 women with unexplained RM (29 women tested negative for autoantibodies and 13 women tested positive for autoantibodies) and 40 women with unexplained RIF (30 women tested negative for autoantibodies and 10 women tested positive for autoantibodies). Biopsies were obtained on days LH+7 to LH+9. There was no significant difference in uNK cell numbers between women with unexplained RM who tested negative and those who tested positive for autoantibodies. Similarly, there was no significant difference in uNK cell numbers between women with unexplained RIF who tested negative and those who tested positive for autoantibodies. In women with reproductive failure the presence of autoantibodies does not appear to affect the numbers of uNK cells in the endometrium around the time of implantation.     

Recurrent Spontaneous Miscarriage: a Comparison of International Guidelines

While roughly 30% of all women experience a spontaneous miscarriage in their lifetime, the incidence of recurrent (habitual) spontaneous miscarriage is 1 – 3% depending on the employed definition. The established risk factors include endocrine, anatomical, infection-related, genetic, haemostasis-related and immunological factors. Diagnosis is made more difficult by the sometimes diverging recommendations of the respective international specialist societies. The present study is therefore intended to provide a comparison of existing international guidelines and recommendations. The guidelines of the ESHRE, ASRM, the DGGG/OEGGG/SGGG and the recommendations of the RCOG were analysed. It was shown that investigation is indicated after 2 clinical pregnancies and the diagnosis should be made using a standardised timetable that includes the most frequent causes of spontaneous miscarriage. The guidelines concur that anatomical malformations, antiphospholipid syndrome and thyroid dysfunction should be excluded. Moreover, the guidelines recommend carrying out pre-conception chromosomal analysis of both partners (or of the aborted material). Other risk factors have not been included in the recommendations by all specialist societies, on the one hand because of a lack of diagnostic criteria (luteal phase insufficiency) and on the other hand because of the different age of the guidelines (chronic endometritis). In addition, various economic and consensus aspects in producing the guidelines influence the individual recommendations. An understanding of the underlying decision-making process should lead in practice to the best individual diagnosis and resulting treatment being offered to each couple.Key words: miscarriage, genetics, infertility     

Dydrogesterone use in early pregnancy

Successful oocyte implantation and a favorable pregnancy outcome rely on optimal progesterone levels. Therefore, progesterone deficiencies associated with infertility and miscarriage have commonly been treated with progestogens that mimic the activity of progesterone. Among those is dydrogesterone, an oral retrosteroid with a structure closely related to that of progesterone yet with a greater bioavailability and higher selectivity for the progesterone receptor. This review describes the efficacy of dydrogesterone for the treatment of threatened and recurrent miscarriage, and infertility due to luteal phase insufficiency. Data from clinical trials evaluating dydrogesterone in assisted reproductive technology are also discussed. Prospective clinical trials, systematic reviews and meta-analyses have demonstrated that dydrogesterone significantly improves pregnancy outcomes in women with threatened miscarriage or with a history of miscarriage. Although this is not yet a registered indication, dydrogesterone was as effective as vaginal micronized progesterone for luteal phase support in the setting of assisted reproductive technology. The safety and tolerability of dydrogesterone treatment in pregnant women are also briefly addressed and the data support a well-established and favorable benefit–risk profile.     

子宫畸形的诊治

先天性子宫畸形可导致不孕和复发性流产,子宫畸形传统的治疗方法为开腹手术。现今宫腔镜子宫成形术（hysteroscopic metroplasty）已经替代了传统的开腹手术,成为子宫畸形最有效的治疗方法。子宫畸形成形术后的生殖预后明显改善。术后应关注妊娠子宫破裂及宫颈机能不全等问题。     

Young women's experience of termination and miscarriage: a qualitative study

In Britain, teenage pregnancy is seen as both a cause and a consequence of social exclusion. The emphasis on 'prevention' of teenage pregnancy and a limited conception of 'support' within the Teenage Pregnancy Strategy (Social Exclusion Unit, 1999) positions parenthood for young people as a negative choice; this dominant discourse is likely to influence young people's reproductive decisions and experiences. With this in mind, this article focuses on a key finding from a multidisciplinary empirical research study, conducted in a city in the West Midlands of England, which considered and explored young people's experience of support before and following termination and miscarriage. Data were collected via in-depth interviews with professionals and practitioners (n = 15), young mothers (n = 4) and one young father. Although termination and miscarriage are generally perceived as distinct and different issues, the data suggest that the issues become more blurred where younger women are concerned. The experiences of young, 'inappropriately pregnant teenagers' often remain unacknowledged and devalued. This analysis highlights the social and political context in which young women experience termination and miscarriage, and suggests that termination and miscarriage should be acknowledged as significant medical, social and emotional events in the lives of young people.     

Short-term reproductive prognosis when no cause can be found for recurrent miscarriage

The short-term reproductive prognosis of recurrent miscarriage for which no cause was found has been evaluated in 95 couples investigated between 1980 and 1986 at the First Obstetric and Gynaecological Clinic of the University of Milan. The actuarial overall 3-year livebirth delivery rate was 64%, increasing constantly with time. The reproductive success rate decreased with the number of previous miscarriages from 80% in women with two, to 60% with three and 46% with four or more miscarriages. No effect of age and socio-economic status emerged. There was a positive association between the number of previous miscarriages and the risk of miscarriage in the next pregnancy. Compared with women with two miscarriages the relative risk of another miscarriage was 2.3 for those with three previous miscarriages and 5.0 for those with four or more (chi 2 1 for trend adjusted for age = 5.2, P = 0.02).     

Thyroid antibody titer and avidity in patients with recurrent miscarriage

OBJECTIVE: To determine whether the titer and avidity of the thyroid peroxidase antibody differs between pregnant women in their first trimester who have a history of recurrent miscarriage and whose pregnancies continue to term and those whose pregnancies fail again later in the first trimester. DESIGN: Controlled clinical study. SETTING: Healthy volunteers in an academic research environment. PATIENT(S): Pregnant women in their first trimester who had a history of recurrent miscarriage (> or = 3 miscarriages) and who were known to be positive for the thyroid peroxidase antibody. INTERVENTION(S): None of the patients received any medication. MAIN OUTCOME MEASURE(S): Thyroid peroxidase antibody titer and avidity (i.e., the net binding strength between antibody and antigen). RESULT(S): At the time of presentation, thyroid peroxidase antibody titer and avidity was significantly higher in those women who later miscarried compared with those whose pregnancies continued. In those whose pregnancies continued to term, titer and avidity declined as the pregnancy progressed. CONCLUSION(S): Autoimmunity plays a role in recurrent miscarriage. Among a group of patients who had had recurrent miscarriages, there appeared to be differences in the humoral response to the pregnancy between those whose pregnancies continued to term and those whose pregnancies failed again.     

Do uterine natural killer (uNK) cells contribute to female reproductive disorders?

The most abundant immune cells in the uterine decidua around the time of implantation and early placental development are the uterine natural killer (uNK) cells. Altered numbers of uNK cells have been associated with several human reproductive disorders, including recurrent miscarriage, recurrent implantation failure, uterine fibroids, sporadic miscarriage, fetal growth restriction and preeclampsia. Understanding of the function of uNK cells in non-pregnant and pregnant endometrium is now increasing; the potential contribution of altered numbers and function of uNK cells to reproductive disorders is the focus of this review.     

Genetics of recurrent pregnancy loss

Recurrent pregnancy loss (RPL) is a devastating reproductive problem affecting approximately 5% of couples trying to conceive. Genetic factors appear to be highly associated with reproductive loss. In this article, genetic factors are reviewed in terms of random numerical chromosome errors in miscarriage specimens and carriers of structural chromosome rearrangements that may result in unbalanced chromosome errors in pregnancies. Recently, research has generated interest in genetic markers for recurrent loss such as skewed X-chromosome inactivation and human leukocyte antigen-G polymorphisms. Assisted reproductive technologies (specifically, preimplantation genetic diagnosis) have been offered to couples with recurrent pregnancy loss; however, more data need to be evaluated before routine use can be advocated. Management of genetic factors in RPL should include therapy based on the highest level of evidence, genetic counseling, and close monitoring of subsequent pregnancies.     

Thyroid autoantibodies and pregnancy outcomes

Autoimmune thyroid disease has been associated with several adverse pregnancy outcomes. Increased risk of spontaneous miscarriage and placental abruption in women with thyroid antibodies has been confirmed in multiple studies. However, benefit of intervention and treatment of autoimmune thyroid disease in otherwise euthyroid pregnant women has not been sufficiently studied. The data on the association of thyroid antibodies and recurrent pregnancy loss or preterm birth are conflicting and a statistically significant association has not been shown in large studies. At present time, routine screening and treatment of autoimmune thyroid disease in euthyroid pregnant women is not warranted.     

Sterilität und Schilddrüse

Overt hyperthyroidism is rare in women wishing to conceive. Due to the severe manifestations conception is usually not possible and swift diagnosis and definite treatment, preferably surgical, are recommended. Subclinical hyperthyroidism does not have a significant impact on female fertility per se. In contrast both overt and subclinical hypothyroidisms impede female fertility, the most common cause being autoimmune thyroid disease. Overt hypothyroidism always requires thyroxine treatment and for subclinical hypothyroidism treatment with thyroxine may facilitate conception. An important aspect of thyroxine treatment of women with latent hypothyroidism is to avoid overt hypothyroidism in pregnancy and its deleterious maternal and fetal consequences. For the same reason iodine supplementation should be performed regularly except in cases with active hyperthyroidism or high TSH receptor antibodies. Elevated thyroid peroxidase antibody levels correlate with an increased rate of miscarriage and preterm delivery, however, a causal relationship is unclear and no intervention is possible. In subfertile men screening can only be recommended when thyroid dysfunction is clinically apparent.     

Cytokine expression in the endometrium of women with implantation failure and recurrent miscarriage

One potential cause of reproductive failure such as infertility and recurrent miscarriage may be an endometrial defect. Numerous studies in mice have suggested the importance of various different cytokines in successful pregnancy outcome. This article reviews the literature available on the role of T helper cytokines and IL-1, IL-11, LIF, IL-12 and IL-18 in infertility and recurrent miscarriage, with particular emphasis on the role that endometrial cytokines may play. Although there are numerous studies on cytokines in recurrent miscarriage, much less has been reported on their role in infertility with or without failure after IVF. There is also considerable variation in the results obtained from various different studies, which may be due to different populations studied, the different timing of the sample collection, and whether the cytokines were measured in whole tissue or a specific cell population. The presence of complicated networks of cytokines and their overlapping biological activities means that alteration of one cytokine is likely to affect others and this also makes the study of their role in implantation failure very difficult. There is an urgent need to re-examine the role played by various cytokines in reproductive failure through carefully planned and vigorously designed studies and to compare the different types of reproductive failure.