Live birth rate after intrauterine insemination is not different between women with lower quartile versus higher quartile normal range thyroid stimulating hormone levels.

STUDY QUESTION: Does lower quartile normal range thyroid stimulating hormone (TSH) compared to higher quartile normal range in women without thyroid hormone substitution affect live birth rate after a complete IUI treatment series? SUMMARY ANSWER: Lower quartile normal range TSH, in women without thyroid hormone substitution, does not affect live birth rate after a complete intrauterine insemination treatment series compared to higher quartile normal range TSH. WHAT IS KNOWN ALREADY: TSH is historically seen as the most sensitive test for thyroid function. Its distribution is right-skewed. Whether the preconceptional upper reference TSH values in subfertile women should be 2.5 or 4.5 mIU/L is under debate. Studies have shown that IUI patients treated with levothyroxine for TSH levels above 2.5 mIU/L show higher pregnancy rates. However, no adverse outcome is associated with untreated high normal TSH levels studied in first IUI cycles. Thyroid peroxidase antibodies have also impaired outcomes in some studies whereas others have shown an effect only in combination with high normal TSH levels. As a subgroup, patients with unexplained infertility showed increased levels of TSH. This article adds to the value of TSH evaluation and fertility outcome in four quartiles and in the context of a completed IUI treatment modus of a maximum of six inseminations. STUDY DESIGN SIZE DURATION: This is a retrospective cohort study in 909 women undergoing 3588 IUI cycles starting treatment between the first of January 2008 and the first of March 2012. PARTICIPANTS/MATERIALS SETTING METHODS: Women aged 22-45 years with TSH 0.3-4.5 mIU/L without thyroid hormone substitution were included at Amsterdam UMC, Vrije Universiteit, Amsterdam, the Netherlands, an Iodine-sufficient area. The primary endpoint was live birth. Clinical pregnancy, pregnancy loss and ongoing pregnancy were secondary endpoints. Logistic regression was used with the natural logarithm of TSH as a continuous predictor. Chi-square tests and logistic regression were used to compare groups of patients based on TSH values in four quartile TSH groups (0.3-1.21 mIU/L; 1.22-1.75 mIU/L; 1.76-2.34 mIU/L; 2.35-4.5 mIU/L) on basic characteristics and on the endpoints while adjusting for confounders. MAIN RESULTS AND THE ROLE OF CHANCE: Analysis with the natural logarithm of TSH as a continuous variable showed no association with live birth, pregnancy chance or pregnancy loss. There were no differences in any of the outcomes across the quartile TSH level ranges after regression analysis before and after adjusting for age, BMI, use of alcohol, tobacco, use or gonadotrophins, sperm count, diminished ovarian reserve, unexplained infertility and primary or secondary subfertility.The distribution of primary and secondary subfertility and smoking characteristics were remarkably different across the four groups, with proportionally the lowest prevalence of primary subfertility and the highest rate of smoking in the lowest TSH group (0.3-1.20 mIU/L). LIMITATIONS REASONS FOR CAUTION: Unknown values of free thyroxine and thyroid peroxidase antibodies, as well as the retrospective character of the study, limit the clinical interpretability. WIDER IMPLICATIONS OF THE FINDINGS: TSH in the highest quartile range (2.35-4.5 mIU/L) in subfertile women preceding IUI is not associated with a lower live birth rate or rate of clinical and ongoing pregnancy, or with loss of pregnancies, compared to subfertile women with TSH in the lower three quartile groups after complete intrauterine insemination treatment. STUDY FUNDING/COMPETING INTERESTS: The department of Obstetrics and Gynaecology, division of Reproductive Medicine, and of Internal Medicine, division of Endocrinology provided support. There are no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Dilemmas in treatment of women with familial hypercholesterolaemia during pregnancy.

Familial hypercholesterolaemia (FH) is a co-dominant monogenic disorder of lipoprotein metabolism, characterised by severely elevated levels of low-density lipoprotein cholesterol (LDL-C) from birth onwards. Treatment of FH patients with cholesterol-lowering medication is mandatory to prevent premature cardiovascular disease (CVD). As a result of a nationwide screening in the Netherlands, a large group of women with FH in the child-bearing age range has been identified. Physicians are faced with a treatment dilemma if these females present either with a wish for pregnancy or an established pregnancy, since all systemically absorbed lipid-lowering medication is contraindicated during pregnancy. Currently, no evidence-based guidelines exist on the optimal clinical approach in these patients. Animal studies have shown conflicting data on potential teratogenicity of statins. In humans, there is no strong adverse safety signal, but prospective studies are lacking. The consequences of maternal hypercholesterolaemia during pregnancy for both mother and child are not well determined, although it has been suggested that it may increase the risk of CVD in the offspring. This review describes two representative cases from clinical practice, and discusses clinical considerations for treating pregnant FH patients supplemented with what is known from the literature.

[Genetic screening of patients with familial hypercholesterolemia and insurability for life insurance policies and disability cover policies]. / Actieve opsporing van patiënten met familiaire hypercholesterolemie en verzekerbaarheid voor levens- en arbeidsongeschiktheidsverzekeringen.

In the Netherlands, people with familial hypercholesterolaemia (FH) have been actively screened since 1994 by means of DNA analysis. Recently, the Stichting Opsporing Erfelijke Hypercholesterolemie (Foundation for the Detection of Familial Hypercholesterolaemia) initiated a large scale-screening programme aimed at finding all 40,000 people. The Dutch ministry of Health, Welfare and Sport is providing the financial support. Genetic screening has social implications and raises questions on insurability. The Dutch Medical Examination Act prohibits insurers from posing questions about untreatable, serious inheritable conditions for insured sums under a certain value: for life-insurance policies < [symbol: see text] 150,000 and for disability-cover policies < [symbol: see text] 30,000 in the 1st year and < [symbol: see text] 20,000 in the 2nd year and following years. The Health Council of the Netherlands has defined FH as a serious disease, but one which responds well to treatment. Therefore insurers can request information for the purpose of an accurate risk classification. Insurance contracts can be accepted at normal rates if the target value of LDL-cholesterol < 4 mmol/l and additional risk factors such as smoking and an abnormal BMI are absent; the risk is determined by the phenotype and clinical factors and not by the genotype.

Klinefelter's syndrome and acute non-lymphocytic leukemia.

In five out of 51 adult, male patients with acute non-lymphocytic leukemia, Klinefelter's syndrome was demonstrated karyotypically. The incidence of this syndrome in our material is very much increased in comparison with the frequency at birth. In this article the medical histories of the patients are given and the possible connection between the constitutional chromosome abnormality and acute non-lymphocytic leukemia is discussed. Immunological or hormonal abnormalities or an increased virus susceptibility might be predisposing factors.