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Endothelial damage, impaired microvascularization and immune maladaptation have been described as aetiological factors in recurrent miscarriages. We investigated the relationship between idiopathic recurrent miscarriage (IRM) and a (GT)(n) repeat microsatellite polymorphism of the gene encoding haem oxygenase 1 (HO-1), known to modulate immune functions such as T-helper (TH) cell function and to be associated with cardiovascular disease. We investigated 162 women with IRM and 129 healthy, post-menopausal controls. The length of the HO-1 (GT)(n) microsatellite was assessed by PCR and direct sequencing in all women. Results were correlated with clinical data. The distribution of genotypes was in Hardy-Weinberg equilibrium. The HO-1 (GT)(n) microsatellite repeat numbers ranged from 13 to 37, with (GT)(23) and (GT)(30) being the most common alleles in both groups. We compared alleles consisting of < or =27 GT repeats, termed class S (short) alleles and alleles consisting of >28 GT repeats, termed class L (long) alleles. Seventy per cent of women with IRM had an S allele either in heterozygous (L/S) or homozygous (S/S) form, compared to 56% of controls (P = 0.02; OR 0.54; 95% CI 0.32-0.90). With respect to S allele frequencies, we found no significant difference among women with IRM and controls [P = 0.3; odds ratio (OR) 1.23, 95% confidence interval (CI) 0.86-1.76]. Comparing women with primary and secondary IRM, no difference with respect to the length of the HO-1 (GT)(n) microsatellite was ascertained. In summary, this is the first report on a HO-1 (GT)(n) microsatellite polymorphism among women with IRM, demonstrating that the investigated polymorphism is associated with IRM in a relatively large Caucasian population.

Ovarian hyperstimulation syndrome (OHSS) is a severe complication arising from controlled ovarian stimulation treatment. This iatrogenic condition is potentially lethal and occurs in 0.3-5% of stimulated ovarian cycles. hCG exacerbates OHSS. The pathophysiology of OHSS is still unknown; therefore, treatment regimens are aimed at ameliorating symptoms. Prominent features of OHSS are an elevated risk of thromboembolism due to enhanced production of von Willebrand factor by endothelial cells and ascites, or pulmonary edema due to increased vascular permeability followed by third space fluid accumulation. Both of these sequelae can be evoked by vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF). High concentrations of VEGF/VPF have been demonstrated in ascitic fluid from patients with OHSS, but the source of VEGF/VPF in these patients remained unidentified. Here we report that the messenger ribonucleic acid expression of VEGF/VPF in human luteinized granulosa cells (GCs) is dose and time dependently enhanced by hCG in vitro. Furthermore, VEGF/VPF proteins are produced by GCs. Our results suggest that the effects of hCG on the development and course of OHSS may be mediated by the production of VEGF/VPF by GCs.

Our results indicate an over-representation of the Pro allele of the p53 gene in women with IRM, giving support to the theory that p53 has a potential role during pregnancy.

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Background Subacute thyroiditis (SAT) is a rare inflammatory disease that presents diagnostic challenges. The underlying pathophysiology and prediction of outcomes are elusive. We investigated the long-term follow-up of SAT for up to 30 years and determined predictors for later hypothyroidism. Methods SAT outcome data from 127 patients (age: 47.6 ± 11.0 yrs., BMI: 24.7±4.8 kg/m²) were analyzed retrospectively. Patients with pre-existing and known causes of hypothyroidism unrelated to SAT were excluded. We also excluded patients without an accelerated erythrocyte sedimentation rate. SAT outcome parameters included anterior neck pain or tenderness of the thyroid, inflammation markers, hypoechoic areas in thyroid ultrasound, hyperthyroidism, fine-needle aspiration, and thyroid scan. Pre-treatment TSH-levels, gender, age, ultrasound findings, anti-thyroid antibodies and markers of inflammation were considered as possible predictors of SAT outcome. Results More than 26.8% of SAT patients developed permanent hypothyroidism within 3 years of treatment. The patient groups later developing hypothyroidism did not differ in age, BMI, pre-treatment TSH levels or initial dosage of prednisolone treatment. However, high cumulative doses of prednisolone were associated with a higher prevalence of hypothyroidism. Also, women were more likely to develop hypothyroidism (OR: 3.18 (95% CI: 1.14–8.65); p=0.0176). Conclusions Our study suggests that one-quarter of patients with SAT develop hypothyroidism in the long-term. Hypothyroidism was predicted by high cumulative doses of prednisolone treatment and female gender. The reported lower prevalence of hypothyroidism in other countries may represent the faster establishment of diagnosis, different treatment protocols, or lower susceptibility to loss of thyroid function. Swift establishment of the diagnosis and rapid tapering of steroids may result in a higher proportion of patients with euthyroidism.

Suppression of serum LH and FSH, by testosterone (T) alone or in combination with other agents, has proved to be the most promising approach to male contraception. T enanthate, the only androgen preparation tested in male contraceptive efficacy trials so far, must be injected every week due to its short terminal elimination half-life of 4.5 days and leads to supraphysiological T serum levels. A new T ester synthesized under WHO and NIH auspices, testosterone buciclate (TB), showed a favorable pharmacokinetic profile, with a terminal half-life of 29.5 days when tested in hypogonadal men. Here we describe the results of the first clinical trial with TB for male contraception. After two control examinations, normal healthy male volunteers were given a single im injection of 600 mg TB (group I; n = 4) and 1200 mg TB (group II; n = 8) on day 0. Follow-up examinations were performed every 2 weeks up to week 32. In both groups mean serum T levels remained in the normal physiological range throughout the study course. Serum levels of dihydrotestosterone (DHT) showed a dose- and time-dependent increase, with serum levels slightly above the normal range in group II for several weeks and a maximal concentration of 3.8 +/- 0.5 nmol/L (mean +/- SE) in week 6. No suppression of spermatogenesis to oligozoospermia was observed in group I. However, in group II, spermatogenesis was suppressed to azoospermia in three of eight volunteers in week 10 that persisted up to weeks 14, 20, and 22, respectively. In these three men, LH and FSH were suppressed by TB injections to the respective assay detection limits, whereas in the other five subjects, mean serum levels were only decreased to values near the lower normal limit for LH and FSH, respectively. In addition, throughout the study course, a significant difference in serum sex hormone-binding globulin was detected between the responders (mean values, 21.2-26.4 nmol/L) and nonresponders (mean values, 36.2-46.3 nmol/L). Serum levels of LH as well as total and free T at baseline and after TB injection were lower in the responders than in the nonresponders. Both subgroups showed similar increases in serum LH and FSH after GnRH stimulation. In a newly introduced GnRH antagonist suppression test, serum LH and T were decreased to significantly lower levels in the responders. These results indicate a different hormonal equilibrium and probably different susceptibility to feedback regulation of the responders compared to the nonresponders.(ABSTRACT TRUNCATED AT 400 WORDS)

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