Diagnosis and Therapy of Female Pelvic Organ Prolapse. Guideline of the DGGG, SGGG and OEGGG (S2e-Level, AWMF Registry Number 015/006, April 2016).

Aims: The aim was to establish an official interdisciplinary guideline, published and coordinated by the German Society of Gynecology and Obstetrics (DGGG). The guideline was developed for use in German-speaking countries. In addition to the Germany Society of Gynecology and Obstetrics, the guideline has also been approved by the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). This is a guideline published and coordinated by the DGGG. The aim is to provide evidence-based recommendations obtained by evaluating the relevant literature for the diagnostic, conservative and surgical treatment of women with female pelvic organ prolapse with or without stress incontinence. Methods: We conducted a systematic review together with a synthesis of data and meta-analyses, where feasible. MEDLINE, Embase, Cinahl, Pedro and the Cochrane Register were searched for relevant articles. Reference lists were hand-searched, as were the abstracts of the Annual Meetings of the International Continence Society and the International Urogynecological Association. We included only abstracts of randomized controlled trials that were presented and discussed in podium sessions. We assessed original data on surgical procedures published since 2008 with a minimum follow-up time of at least 12 months. If the studies included descriptions of perioperative complications, this minimum follow-up period did not apply. Recommendations: The guideline encompasses recommendations for the diagnosis and treatment of female pelvic organ prolapse. Recommendations for anterior, posterior and apical pelvic organ prolapse with or without concomitant stress urinary incontinence, uterine preservation options, and the pros and cons of mesh placements during surgery for pelvic organ prolapse are presented. The recommendations are based on an extensive and systematic review and evaluation of the current literature and include the experiences and specific conditions in Germany, Austria and Switzerland.

L1 cell adhesion molecule (L1CAM) as a pathogenetic factor in endometriosis.

BACKGROUND: Endometriosis is a benign and progressive disease with a high prevalence. Women with endometriosis, especially with atypical endometriosis, have a higher probability for developing ovarian cancer compared with women without endometriosis. The L1 cell adhesion molecule (L1CAM) is over expressed in ovarian and endometrial carcinomas and is associated with a bad prognosis. Here, we have analysed L1CAM expression in endometriosis. METHODS AND RESULTS: In our study with the samples from 79 patients with, and 37 patients without, endometriosis, we found that endometriosis cell lines and short-term cultures of endometrium from women with endometriosis expressed L1CAM at the mRNA and protein level. Quantitative RT-PCR analysis showed that L1CAM was expressed at significantly higher level in the epithelial compartment from patients with endometriosis compared with healthy controls (P = 0.0126). By immunohistochemical staining, 15 of 31 ovarian endometriotic lesions (48%) were shown to have L1CAM-positive staining. Of these 15 L1CAM-positive samples, 13 were atypical endometriotic lesions. Soluble L1 present in the conditioned medium of epithelial endometrium cultures from women with endometriosis was able to stimulate neurite outgrowth as measured in a chicken ganglion assay. CONCLUSIONS: We propose that L1CAM could promote endometriosis development by increasing enervation and aggravation. L1CAM expression is higher in atypical endometriosis compared with normal endometriosis.

Endometrial stromal sarcomas--a retrospective analysis of 11 patients.

BACKGROUND: Endometrial stromal sarcoma (ESS) is a malignant tumour with its origin in the endometrial stroma. Little is known about the pathogenesis, risk factors, optimal therapy or outcome of this disease. PATIENTS AND METHODS: Eleven patients with ESS, treated between 1972 and 1996, are reported on. The hospital records of all the patients, including pathology and operative reports, were reviewed and information on treatment, recurrence and survival was obtained. RESULTS: The mean age of our patients was 56.6 years. The main symptom was abnormal vaginal bleeding. Most patients were diagnosed at FIGO stage I. Treatment modalities were surgery, radiation and, in one patient, chemotherapy. The median follow-up time was 42.1 months; 27.3% of the patients had local recurrence. The 1-year, 2-year and 5-year survival rates were 36.3%, 18.1% and 9.1%, respectively. CONCLUSION: ESS is a uterine sarcoma with a difficult differential diagnosis. Patients are frequently diagnosed in an early tumour stage but still experience local or distant recurrence. The prognosis is poor, with early recurrence and low long-time survival rates. The treatment includes surgery and adjuvant radiation, with endocrine therapy being a promising new approach. In order to obtain more information about the pathogenesis of the tumour and to find the optimal therapy, it is necessary that studies, even with small numbers of patients, are undertaken.

Quality of life in elderly men with androgen deficiency.

The partial androgen deficiency in aging male (PADAM) has been of great interest to investigators and the public in the last few years. For males, androgens are said to be essential for the maintenance of quality of life (QoL) but there are no data available with respect to QoL and PADAM yet. In order to evaluate changes of individual well-being of males older than 50 years and with subnormal levels of free testosterone (FT) (<200 pmol l(-1)), these men were asked to fill in a questionnaire regarding QoL. The objective of this study was to compare age-matched males with androgen deficiency (group 1; n = 24) and normoandrogenic elderly men (group 2; n = 24) with respect to QoL and somatic indicators of the endocrine status. Participants suffered from benign prostatic hyperplasia (BPH) and were hospitalized for prostate surgery. Health-related QoL was assessed by the SF-12 Health Survey, including the physical health index and the mental health index. The SF-12 was enlarged by the scales 'vitality' and 'psychological well-being' of the SF-36. Additionally, patients were asked about social and clinical items. There were no statistically significant differences between the two groups regarding social and clinical parameters. The physical health index was reduced in group 1 (P < 0.05; effect size was medium (d = 0.57)) whereas the mental health index was similar in both groups. The correlation between the two health indices was very low and not statistically significant (r = 0.05, P = 0.72). Patients of group 1 described a lower vitality compared to group 2 (P < 0.05), but no differences could be observed regarding psychological well-being. Therefore, androgen-deficient patients seem to have the impression of a reduced physical ability. Our data emphasize that the subjective description of health-related aspects of QoL is a very sensitive methodological approach to discover psychological differences between patients. For the differentiation between androgen-deficient patients and those with normal testosterone levels the physical health index seems to be more sensitive than the mental health index. A question of interest is whether this difference remains detectable if testosterone is supplemented to androgen-deficient men. Whether testosterone supplementation is beneficial to these patients has to be carefully considered.

FSH time-concentration profiles before and after administration of 0.25 mg cetrorelix in the gnRH-antagonist multiple-dose protocol for ovarian hyperstimulation.

PURPOSE: To determine FSH concentration behavior before and after cetrorelix 0.25 mg administration in the GnRH-antagonist multiple-dose protocol on day 6 of ovarian stimulation with 150-300 IU daily recombinant FSH. METHODS: Blood samples for FSH measurements were drawn from seven women every 15 min from 8 h prior to the first cetrorelix administration in the GnRH-antagonist multiple-dose protocol until 15-32 h thereafter. RESULTS: No significant change of FSH concentration was observed. CONCLUSIONS: This observation indicates that no rationale exists of increasing the daily FSH dosage concomitantly to the GnRH-antagonist administration to compensate for a drop of endogenous FSH.

Polymorphisms of genes involved in innate immunity: association with preterm delivery.

An altered inflammatory activity due to functionally relevant polymorphisms of the innate immune system may influence pathways leading to labour and, therefore, impact on the frequency of preterm birth. We examined five polymorphisms of the innate immune system in a large cohort of preterm very-low-birth-weight (VLBW, n = 909) and term-born infants (n = 491) and their mothers (n = 747). The primary outcome was preterm versus term birth. Frequencies of polymorphisms in mothers of term-born infants versus mothers of VLBW infants and term infants versus preterm VLBW infants (singletons) are given. Homozygous CD14-159T: 18.5 versus 21.8% (mothers) and 19.6 versus 21.2% (infants). Homozygous interleukin IL-6-174G: 28.8 versus 38% (P = 0.018, mothers) and 30 versus 32.7% (infants). Homozygous or heterozygous nuclear oligomerization domain NOD2-3020insC: 6.9 versus 6.1% (mothers) and 5.7 versus 5.1% (infants). Heterozygous or homozygous toll-like-receptor TLR2-Arg753Gln: 6.9 versus 6.1% (mothers) and 5.7 versus 5.1% (infants). Homozygous or heterozygous TLR4-896G: 8.1 versus 11.5% (mothers) and 11.6 versus 10.5% (infants). Although the homozygous maternal IL-6-174G genotype was found to be independently associated with preterm delivery in multivariate regression analysis, the incidence of intrauterine infection was not significantly increased in mothers of preterm VLBW-infants, carrying this or other polymorphisms of the innate immune system. The overall influence of the investigated polymorphisms on the development of preterm delivery seems moderate, since only the maternal IL6-174G genotype was associated with preterm birth and none of the polymorphisms were associated with intrauterine infection as the cause of preterm birth.

[Cumulus cell apoptosis as a predictor for oocyte quality in artificial reproduction technique]. / Die Apoptoseaktivität in Cumuluszellen als ein Indikator der Eizellqualität in der Assistierten Reproduktion.

OBJECTIVE: To be able to predict the success of ART reliable tests for determining the quality of the oocytes are necessary. Apart from a vague morphologic assessment via microscopy a direct analysis of the oocyte quality is not possible. Because of the very close relation between the oocyte and the cumulus cells the analysis of the cumulus cells might give sufficient information on the oocyte quality. In this study we correlate the apoptotic activity of cumulus cells to the outcome of fertilized oocytes after Intracytoplasmic Sperm Injection (ICSI). MATERIAL AND METHODS: 246 cumulus-oocyte-complexes from patients undergoing infertility treatment with the ICSI procedure were individually collected. The comet assay was used to determine the proportion of apoptotic cells within the cumulus population of each oocyte and correlated with oocyte fertilization and oocyte quality as well as with pregnancy outcome in 86 patients. RESULTS: We were able to show that high quality embryos correlate to a low rate of apoptotic cells in their corresponding cumuli. Differences regarding the pregnancy outcome were statistically not significant. CONCLUSIONS: Our results on cumulus cell apoptosis and embryo quality confirm other publications. To arrive at statistically proven criteria for the further development of single oocytes an increase in the number of analyzed patients is necessary.

[Enhanced liposomal transfection through the application of sex steroids in gynecological cancer cells]. / Die Sexualsteroid-vermittelte Verstärkung liposomaler Transfektion gynäkologischer Krebszellen--Ein neuer Ansatz für ein selektives Targeting in der Gentherapie?

OBJECTIVE: Liposomal transfection in gene therapeutic application against gynecological malignoma does not reach satisfying efficacy. A desirable goal would be the specific intensification of transfection in these kind of cells. Steroids have successfully been used in other systems to increase liposomal transfection and hopefully there might be a specific impact of sexual steroids in cells from high sex steroid receptor expressing malignoma, like some mamma- and endometrium cancer. MATERIAL AND METHODS: The mamma carcinoma cell line T-47D was transfected with the transfection agent DOTAP and cyclodextrin solubilized steroids and cholesterol were co-applied. The efficiency of transfection was followed by luciferase activity resulting from the transfected reporter gene. RESULTS: Like cholesterol, which is already established as transfection co-agent, also the steroids progesterone, estrogen, testosterone and hydrocortisone provoked a clear increase in transfection efficiency shown in a dose dependent manner. CONCLUSIONS: These results indicate the usefulness of steroids as additives for liposomal transfection procedures in gene therapeutic application. As sexual steroid receptors migrate into the nucleus of a cell after binding its specific ligand a targeted enhancement of transfection is supposable in malignoma overexpressing steroid receptors. There is evidence that plasmid DNA can be co-transported with nuclear proteins into the nucleus.

Oocyte quality and treatment outcome in intracytoplasmic sperm injection cycles of polycystic ovarian syndrome patients.

Patients with polycystic ovarian syndrome (PCOS) have higher miscarriage rates. It is postulated that this is caused by a lower rate of mature oocytes, and a lower quality of embryos. Retrospectively we analysed 51 intracytoplasmic sperm injection (ICSI) cycles of 31 PCOS patients. These data were compared to age-matched controls (105 cycles) during the same period. All patients of both groups received gonadotrophin-releasing hormone (GnRH) agonists prior to gonadotrophin treatment. The rate of metaphase II oocytes (MII) was not different. However, the mean absolute number of normally fertilized oocytes was significantly higher in PCOS patients (5.00 versus 3.56, P < 0.01), due to a higher number of oocytes retrieved. More embryos were transferred by cycle in the PCOS group (2.69 versus 2.17, P < 0.05), with a higher cumulative embryo score. The overall and multiple pregnancy rate showed no differences and the clinical abortion rate was lower (21 versus 41.67%, P < 0.05) in the controls. Our findings demonstrate that negative factors unconnected to oocyte morphology must be present in PCOS patients. It is possible that only cytoplasmic, not nuclear, maturity is influenced in these patients.