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Objective: A planned study to test the hypothesis that dydrogesterone given during the first trimester of pregnancy can positively influence the immune system of women suffering from recurrent miscarriages and thereby lead to successful pregnancies. The primary objective is to show whether the administration of dydrogesterone during the first trimester of pregnancy increases the release of progesterone-induced blocking factor (PIBF) and causes a shift from Th-1 cytokines to Th-2 cytokines. Further objectives are an analysis of pregnancy outcome and to investigate the tolerability and safety of dydrogesterone use during pregnancy., Methods: A prospectively randomized, placebo-controlled study of 20 mg dydrogesterone per day during the first trimester of pregnancy in women aged between 18 and 38 and with a history of idiopathic recurrent miscarriage. Start of treatment will be after ovulation. The study will be conducted in a two-stage adaptive design, starting with a sample size of 20 patients per treatment group. The concentrations of Th-1 and Th-2 cytokines in the serum and PIBF in the urine will be measured. Efficacy will be measured primarily by the ratio IFNgamma/IL-10., Conclusion: The results of this study will contribute to the discussion of a current concept of immunomodulation in pregnancy and potentially provide a treatment option for patients suffering from recurrent miscarriage.

Objective: To evaluate the association between a common polymorphism of the Vitamin D receptor gene (VDR) and the timing of female reproductive functions in humans., Methods: One thousand fifty-eight consecutive women were included in this cross-sectional study. We analyzed the intron 8 Bsm I restriction fragment length polymorphism (RFLP) of VDR on chromosome 12q using a microarray-based system., Results: The presence of the VDR polymorphism did not influence the timing of menarche and natural menopause and was not associated with the number of spontaneous abortions, full term pregnancies (FTP) as well as the total number of pregnancies. Of note, women with at least one mutant allele of VDR were at a significantly decreased risk for experiencing surgical menopause (odds ratio [OR] 0.65, 95% confidence interval [CI], 0.46-0.92, P = 0.02). Smoking and a body mass index (BMI) > 25 were associated with an earlier natural menopause and an increased risk for surgical menopause, respectively., Conclusions: While no association of a common polymorphism of VDR with the timing of menarche and menopause was ascertained, we found the presence of at least one mutant allele of VDR to be associated with a decreased risk of experiencing surgical menopause, i.e., premenopausal hysterectomy, in a large series of Caucasian women.

A common -1607 GG/G polymorphism of the matrix metalloproteinase-1 (MMP1) gene promoter was investigated in a series of Caucasian women with polycystic ovary syndrome (PCOS) and controls, by direct sequencing. In this prospective case-control study, the odds for women with at least one mutant GG allele of the MMP1 promoter to be diagnosed with PCOS was 2.7.

Objective: Deficiency of the gene encoding endothelial nitric oxide synthase, i.e. Nos3, has been reported to be associated with late menarche, reduced ovulation rates, fewer deliveries, and earlier onset of menopause in a mouse model., Methods: We assessed the Glu298Asp and the T-786C polymorphisms of Nos3 in 87 consecutive healthy postmenopausal women by pyro- and capillary-sequencing, respectively. Results were correlated with age at menarche and natural menopause, number of miscarriages and live births, as well as body mass index (BMI) and smoking habits., Results: Allelic frequencies of the Glu298Asp polymorphism of Nos3 were 121 (69.5%) and 53 (30.5%) for the wild-type G allele and the mutant T allele, respectively. Forty-one women (47.1%) were homozygote wild-type (G/G), 39 (44.9%) were heterozygote (G/T), and 7 (8.0%) were homozygote mutant (T/T). Allelic frequencies of the T-786C polymorphism of Nos3 were 105 (60.6%) and 69 (39.4%) for the wild-type T allele and the mutant C allele, respectively. Thirty-three women (38.0%) were homozygote wild-type (T/T), 39 (45.1%) were heterozygote (T/C), and 15 (16.9%) were homozygote mutant (C/C). Presence of at least one mutant allele of the Glu298Asp or the T-786C polymorphisms of Nos3 were not associated with age at menarche, natural menopause, and number of miscarriages and deliveries. BMI above 27 kg/m2 and smoking were associated with earlier onset of natural menopause (47.8 years versus 50.2 years (P = 0.01) and 46.8 years versus 49.8 years (p = 0.02))., Conclusions: Our data show that smoking and increased BMI, but not Glu298Asp or the T-786C polymorphisms of Nos3, are associated with an early onset of natural menopause.

Objective: To investigate the association of a common polymorphism of the interleukin-6 gene (IL6) promoter with the occurence and the clinical characteristics of polycystic ovary syndrome (PCOS)., Design: Prospective, case-control study., Setting: Academic research institution., Patient(s): Sixty-two patients with PCOS and 94 healthy controls., Intervention(s): Peripheral venous puncture, ultrasonography, oral glucose tolerance test (OGTT), questionnaire., Main Outcome Measure(s): Genotype analysis with respect to the common -174 G/C polymorphism of the IL6 gene promoter, analysis of testosterone (T), androstendione, and sex hormone binding globulin serum levels, and evaluation of the OGTT., Result(s): Allele frequencies among women with PCOS and controls were 62.9% and 64.4%, respectively, for the wild-type G allele, and 37.1% and 35.6%, respectively, for the mutant C allele. We ascertained a significant association between presence of at least one mutant C allele and the clinical characteristics of affected women: these women were more likely to present with a body mass index >27 kg/m(2), elevated total T serum levels, and a pathological OGTT result., Conclusion(s): A common polymorphism of the IL6 promoter, although not associated with the presence of PCOS, is associated with the clinical characteristics of women affected by this condition.

Purpose: The azoospermia-factor region of the Y-chromosome is essential for spermatogenesis in humans. In the literature, a wide range is given for the frequency of microdeletions in this region. The purpose of this study was to evaluate our own population of patients., Methods: During a two-year period at Vienna Medical School, all male patients (n = 383) seeking assisted reproduction were screened for microdeletions. Thirty-three men had azoospermia and 154 severe oligozoospermia. Genomic DNA was prepared from peripheral lymphocytes and polymerase chain reaction analysis of the azoospermia-factor region was performed using the Promega kit., Results: No case tested positive for azoospermia-factor microdeletions. In all cases amplification of 18 non-polymorphic sequence tagged sites was obtained., Conclusions: Y-chromosome microdeletions do not seem to be an important factor for male infertility in our patients. This suggests that screening should be restricted to men with azoospermia or severe oligozoospermia only.

Purpose: To report the effect of a single dose of oxytocin on ejaculation time and seminal parameters., Methods: The prospective randomized clinical study was performed at a private assisted reproduction technology center and included 103 consecutive healthy men (semen donors or husbands of IVF patients). Oxytocin (16 IU) were administered intranasally to 49 subjects, randomly assigned to the study group just before masturbation to ejaculation. The time needed for ejaculation as well as the semen parameters was recorded according to the WHO standards, and compared to the control group of 54 subjects with no prior oxytocin treatment., Results: No significant difference was noted between the two groups concerning ejaculation time and semen parameters., Conclusions: Although the administration of oxytocin stimulates sexual behavior and performance in mammalian species, our data indicate that oxytocin has no detectable effect on ejaculation time and seminal parameters after intranasal application in normal, healthy men.

Cells of leaf explants of a monohaploid potato (Solanum tuberosum) were stimulated to mitosis on a medium with 5-bromodeoxycytidine during a period of 7 days. The cells cycled with mono- or diplochromosomes which showed differential staining of the sister chromatids and sister chromatid exchanges by the fluorescent plus Giemsa technique after two rounds of BrdC incorporation. Through the staining pattern the course of the first three cell cycles could be traced and the duration of the cycles estimated. Polyploidisation was enhanced by selective stimulation of polyploid cells and by endoreduplication of G2-phase cells. The percentage of polyploid mitoses increased from 10 to 70.