Pre-pregnancy obesity compromises obstetric and neonatal outcomes.

OBJECTIVE: Obesity is an important issue among fertile women as it may affect obstetric and neonatal outcomes. METHODS: Obstetric and neonatal outcomes of primiparous women were retrospectively analyzed in non-obese (n=11387) and obese (n=943) women. A subgroup analysis was performed in obese women divided into three groups: Grade I obesity (Group A, n=654), Grade II obesity (Group B, n=192), and Grade III obesity (Group C, n=97). Odds ratios (OR) were expressed with the corresponding 95% confidence intervals (CI). RESULTS: The incidence of gestational diabetes (non-obese, 1.9%; obese, 7.6%; Group C, 19.6%) and preeclampsia (non-obese, 3.3%; obese, 13.5%; Group C, 17.5%) increased with rising weight. The risk of non-elective cesarean section was significantly higher in obese women than in non-obese women (21.7% vs. 13.2%). The risk of extreme preterm birth (before 28 weeks of gestation) doubled in the Grade I obesity group (OR, 2.1; 95% CI, 1.4-3.2) and nearly tripled in women with body mass index ≥35 kg/m2 (OR, 2.9; 95% CI, 1.7-4.9). CONCLUSION: Pre-pregnancy obesity is associated with higher incidences of gestational diabetes and preeclampsia. Our study shows that obese women have a higher risk of non-elective cesarean section and preterm birth.

Patients undergoing frozen-thawed embryo transfer have similar live birth rates in spontaneous and artificial cycles.

PURPOSE: To evaluate the outcome of frozen-thawed embryo transfer (FET) when freezing takes place at the pronuclear stage, a retrospective analysis was performed comparing spontaneous and artificial cycles. METHODS: 148 women received FET in a spontaneous cycle (Group A) and 55 women received FET in an artificial cycle (Group B) induced by administering estrogen (E2) and progesterone (P). Pregnancy rates, endometrial thickness and serum levels of E2, P and luteinizing hormone (LH) were measured. Statistical analysis included the mean, the standard deviation, the Chi-squared test and the T-test. RESULTS: The clinical pregnancy rate was 34.5% for Group A and 21.8% for Group B (p = 0.084), with a live birth rate of 20.9% and 12.7% respectively (p = 0.15). There was no difference in endometrial thickness or the P levels, while LH and E2 levels were significantly higher in group B (p < 0.0001). CONCLUSION: Our retrospective study shows a trend towards higher pregnancy rates and live birth rates with the administration of FET during a spontaneous cycle compared to FET during an artificial cycle. Large randomized controlled trials are needed to confirm this trend.

Prevention of ovarian damage and infertility in young female cancer patients awaiting chemotherapy--clinical approach and unsolved issues.

Great advances in the oncological therapy of childhood and adolescent cancer patients lead to an increase of young cancer survivors with a normal expectancy of life. The aggressive chemotherapy and/or radiation often compromises endocrine function with consecutive menopausal symptoms and sterility. Recently, new approaches were developed to preserve fertility with different methods to restore the ovarian function. The present review gives an overview of the current possibilities, which may be offered to these young cancer patients, as well as the chances of success and risks and the unsolved issues in special situations.

Estradiol differentially modulates the exocytotic proteins SNAP-25 and munc-18 in pituitary gonadotrophs.

Long-term treatment with estradiol increases LH secretion from female gonadotrophs. The mechanisms are not fully clarified yet. Our previous data indicated that sexual steroids might affect late steps in GnRH signal transduction such as exocytosis. The secretion of hormones from neuroendocrine cells requires the merger of secretory vesicles with the plasma membrane. This regulated exocytosis is mediated by specific proteins, which are present in the pituitary gland. Here, we examined whether two of these crucial exocytotic proteins, SNAP-25 and munc-18, are affected by estradiol in female gonadotrophs. Female rat anterior pituitary cells and alphaT3-1 cells, derived from a murine immortalized gonadotroph cell line, were treated with 100 pM estradiol for 48 h. LH secretion of anterior pituitary cells, additionally stimulated with eight consecutive pulses of 1 nM GnRH for 15 min at an interval of 1 h, was determined by RIA. Gene expression was measured by quantitative RT-PCR and protein expression by immunoblotting. Additionally, quantitative RT-PCR was performed in single rat gonadotrophs to ascribe effects exclusively to intact gonadotrophs. Pulsatile GnRH enhanced the mRNA expression of SNAP-25 and munc-18 in accordance with the LH secretory response with the greatest increase at the third pulse of GnRH. Estradiol treatment further increased GnRH-induced LH secretion at all GnRH pulses. SNAP-25 gene expression was significantly decreased at the fifth GnRH pulse and unaffected at basal after 48 h of estradiol treatment. In contrast, munc-18 mRNA levels were not significantly affected by estradiol at different GnRH-pulses in mixed anterior pituitary cells, whereas munc-18 gene expression was significantly increased at basal. In alphaT3-1 cells and single gonadotrophs, long-term estradiol treatment significantly reduced SNAP-25 protein and gene expression. In contrast, the protein and gene expression of munc-18 was significantly enhanced in both alphaT3-1 cells and single gonadotrophs. In conclusion, munc-18 and SNAP-25 were oppositionally influenced by estradiol. The results suggest that estradiol modulates the expression of exocytotic proteins in gonadotrophs and thus affects LH secretion.

Distribution of persistent organochlorine contaminants in infertile patients from Tanzania and Germany.

PURPOSE: To test whether environmental pollutants could affect fertility in humans. METHODS: 31 women and 16 men from Tanzania and 21 couples from Germany were included (n = 89). Pesticides and polychlorinated biphenyls were measured in serum, follicular fluid or seminal plasma by gaschromatography and related to sperm quality and pregnancy rates. RESULTS: Higher concentrations of DDT+DDE and dieldrin in Tanzania and higher concentrations of PCBs in Germany and in men were detected. All compounds showed higher concentrations in serum and lowest concentrations in seminal plasma. A lower pregnancy rate in German women with high serum concentrations of DDT+DDE was observed. The toxins had no impact on sperm quality. CONCLUSIONS: The distribution of toxins between agricultural and industrial countries is different. Seminal plasma seems to be inert against chemicals. In patients with high serum concentrations of DDT and DDE pregnancy rates were impaired.

Insulin resistance in patients with polycystic ovary syndrome.

With a prevalence of 5%-10% the polycystic ovary syndrome (PCOS) is an exceptionally common disorder of premenopausal women. According to prospective studies, women with PCOS present abnormal glucose tolerance and diabetes mellitus in 31%-35% and 7.5%-10%, respectively. PCOS patients have a higher prevalence of cardiovascular risk factors such as hypertension, type 2 diabetes and dyslipidaemia. The rate of spontaneous abortions as well as the risk to develop gestational or type 2 diabetes is increased in PCOS. Therefore, PCOS is not only a reproductive problem but a complex endocrine disease with important health implications. The role of the glucose metabolism in PCOS, the health consequences and possible interventions are reviewed in this article.

Granulomatous mastitis.

INTRODUCTION: Granulomatous mastitis (GM) is a rare disease which predominantly occurs in premenopausal women shortly after their last childbirth. ETIOLOGY: Its etiology is unclear, however, the disease has been shown to be correlated with breast-feeding and the use of oral contraceptives. An autoimmune component has also been discussed. PRESENTATION: It presents with the clinical symptoms of galactorrhea, inflammation, breast mass, tumorous indurations and ulcerations of the skin. In mammography and sonography nodular opacities and hypoechoic nodules are found. Very often clinical and radiological findings mimic breast cancer. HISTOLOGICAL DIAGNOSIS: The diagnosis is made by histopathology. Histological features in GM include signs of a chronic granulomatous inflammation with giant cells, leucocytes, epitheloid cells and macrophages as well as abscesses. TREATMENT: Therapy of GM consists of complete surgical excision combined with oral steroid therapy, eventually in combination with anti-inflammatory drugs or colchicine. Use of methotrexate has also been successful. In case of formation of abscesses antibiotic therapy should be applied before steroid therapy. Immune-suppressive therapy should be performed until complete remission as rates of recurrence can be up to 50%.

GnRH antagonists in the treatment of infertility.

GnRH analogues were introduced into clinical practice more than 20 years ago. The recent development of new GnRH antagonists (GnRHant) has revolutionized the treatment protocols of infertility. Ovarian stimulation has become easier, safer and more convenient for patients. This review presents data on the physiological background of GnRH and its analogues--agonists as well as antagonists--and highlights the different aspects of the clinical use of these substances. Two protocols, the single dose and multiple dose protocol are available and lead to comparable results. Data from prospective, randomized trials as well as meta-analyses suggest, that a more tailored, individualized approach concerning the day of administration of GnRHant may lead to more favorable results with regard to ovarian response, implantation and pregnancy rates. Possible negative effects of GnRHant, mainly based on in vitro models are discussed. The outcome of children born after GnRHant use has shown, that this medication is safe. On the whole, the use of GnRHant is advantageous as compared to the traditional way of ovarian stimulation, i.e., the GnRH agonist long protocol. However, especially the effectiveness of these compounds will have to be clarified in the near future by carefully designed prospective, randomized studies.

[Insulin resistance in polycystic ovary syndrome]. / Die Insulinresistenz beim polyzystischen Ovar-Syndrom.

With a prevalence of 5-10% the polycystic ovary syndrome (PCOS) is a common disorder of premenopausal women. According to prospective studies abnormal glucose tolerance and diabetes mellitus present in about 10.0% and 35.0% of adult women with PCOS, respectively. PCOS patients have a higher prevalence of cardiovascular risk factors such as hypertension and dyslipidaemia. The rate of spontaneous abortions as well as the risk of developing gestational diabetes is increased in PCOS. Therefore, PCOS is not only a reproductive problem, but a complex endocrine disease with important health implications. The role of glucose metabolism in PCOS, the health consequences and possible interventions are reviewed in this article.