Characterization of patients with vulvar lichen sclerosus and association to vulvar carcinoma: a retrospective single center analysis.

PURPOSE: Lichen sclerosus (LS) is a benign, cutaneous, chronic inflammatory (autoimmunological) disease. The differentiated vulvar intraepithelial neoplasia (dVIN) accounts for a precursor lesion of vulvar squamous cell carcinoma and is often associated with lichen sclerosus. Although the association between lichen sclerosus and vulvar carcinoma has long been recognized, there is a lack of evidence in literature. METHODS: This retrospective study examined pseudonymized data of 499 women diagnosed with vulvar pathology between 2008 and 2020 at the Department of Gynaecology and Obstetrics of Hannover Medical School (MHH). Data were further stratified for the time of onset, location of disease, accompanying disease, HPV status and progression of disease into vulvar squamous cell carcinoma (VSCC). RESULTS: In total, 56 patients were diagnosed with vulvar lichen sclerosus. The mean onset of disease was at 60.3 years of age. After subdividing cases of diagnosed LS into those who did not develop vulvar carcinoma in their course and those who did, the ages at onset are 52.66 ± 17.35 and 68.41 ± 10.87, respectively. The incidence of vulvar cancer in women diagnosed with lichen sclerosus was 48.2%. Twenty-five patients reported a diagnosis of VIN in their self-reported history. CONCLUSIONS: In our retrospective study, we showed a trend between vulvar lichen sclerosus and VSCC. The difference between the two age groups of patients diagnosed with lichen sclerosus who developed vulvar carcinoma and those who did not is statistically significant. Our results highlight the importance to diagnose lichen sclerosus early to ensure adequate follow-up and prevent progression to VSCC.

Perioperative morbidity of different operative approaches in early cervical carcinoma: a systematic review and meta-analysis comparing minimally invasive versus open radical hysterectomy.

PURPOSE: Radical hysterectomy and pelvic lymphadenectomy is the standard treatment for early cervical cancer. Studies have shown superior oncological outcome for open versus minimal invasive surgery, but peri- and postoperative complication rates were shown vice versa. This meta-analysis evaluates the peri- and postoperative morbidities and complications of robotic and laparoscopic radical hysterectomy compared to open surgery. METHODS: Embase and Ovid-Medline databases were systematically searched in June 2020 for studies comparing robotic, laparoscopic and open radical hysterectomy. There was no limitation in publication year. Inclusion criteria were set analogue to the LACC trial. Subgroup analyses were performed regarding the operative technique, the study design and the date of publication for the endpoints intra- and postoperative morbidity, estimated blood loss, hospital stay and operation time. RESULTS: 27 studies fulfilled the inclusion criteria. Five prospective, randomized-control trials were included. Meta-analysis showed no significant difference between robotic radical hysterectomy (RH) and laparoscopic hysterectomy (LH) concerning intra- and perioperative complications. Operation time was longer in both RH (mean difference 44.79 min [95% CI 38.16; 51.42]), and LH (mean difference 20.96 min; [95% CI - 1.30; 43.22]) than in open hysterectomy (AH) but did not lead to a rise of intra- and postoperative complications. Intraoperative morbidity was lower in LH than in AH (RR 0.90 [0.80; 1.02]) as well as in RH compared to AH (0.54 [0.33; 0.88]). Intraoperative morbidity showed no difference between LH and RH (RR 1.29 [0.23; 7.29]). Postoperative morbidity was not different in any approach. Estimated blood loss was lower in both LH (mean difference - 114.34 [- 122.97; - 105.71]) and RH (mean difference - 287.14 [- 392.99; - 181.28]) compared to AH, respectively. Duration of hospital stay was shorter for LH (mean difference - 3.06 [- 3.28; - 2.83]) and RH (mean difference - 3.77 [- 5.10; - 2.44]) compared to AH. CONCLUSION: Minimally invasive radical hysterectomy appears to be associated with reduced intraoperative morbidity and blood loss and improved reconvalescence after surgery. Besides oncological and surgical factors these results should be considered when counseling patients for radical hysterectomy and underscore the need for new randomized trials.

Protective operative techniques in radical hysterectomy in early cervical carcinoma and their influence on disease-free and overall survival: a systematic review and meta-analysis of risk groups.

PURPOSE: Radical hysterectomy with pelvic lymphadenectomy presents the standard treatment for early cervical cancer. Recently, studies have shown a superior oncological outcome for open versus minimal invasive surgery, however, the reasons remain to be speculated. This meta-analysis evaluates the outcomes of robotic and laparoscopic hysterectomy compared to open hysterectomy. Risk groups including the use of uterine manipulators or colpotomy were created. METHODS: Ovid-Medline and Embase databases were systematically searched in June 2020. No limitation in date of publication or country was made. Subgroup analyses were performed regarding the surgical approach and the endpoints OS and DFS. RESULTS: 30 studies fulfilled the inclusion criteria. Five prospective, randomized-control trials were included. Patients were analyzed concerning the surgical approach [open surgery (AH), laparoscopic surgery (LH), robotic surgery (RH)]. Additionally, three subgroups were created from the LH group: the LH high-risk group (manipulator), intermediate-risk group (no manipulator, intracorporal colpotomy) and LH low-risk group (no manipulator, vaginal colpotomy). Regarding OS, the meta-analysis showed inferiority of LH in total over AH (0.97 [0.96; 0.98]). The OS was significantly higher in LH low risk (0.96 [0.94; 0.98) compared to LH intermediate risk (0.93 [0.91; 0.94]). OS rates were comparable in AH and LH Low-risk group. DFS was higher in the AH group compared to the LH group in general (0.92 [95%-CI 0.88; 0.95] vs. 0.87 [0.82; 0.91]), whereas the application of protective measures (no uterine manipulator in combination with vaginal colpotomy) was associated with increased DFS in laparoscopy (0.91 [0.91; 0.95]). CONCLUSION: DFS and OS in laparoscopy appear to be depending on surgical technique. Protective operating techniques in laparoscopy result in improved minimal invasive survival.

Protective measures for patients with advanced cancer during the Sars-CoV-2 pandemic: Quo vadis?

Cancer patients represent a vulnerable cohort during the Sars-CoV-2 pandemic. Oncological societies have generated a plethora of recommendations, but precise instructions about routine oncological procedures remain scarce. Here, we report on local COVID-19 protection measures established in an interdisciplinary approach at a tertiary care center during the first wave of the pandemia in Germany. Following these measures, no additional morbidity or mortality during oncological procedures was observed, and no nosocomial infections were registered. However, Validation of our measures is outstanding and regional SARS-CoV-2 prevalence was low. However, specific oncological measures might be important to ensure optimal oncological results, especially for advanced cancer stages during this and future pandemia. In the future, communication about these measures might be crucial to a cancer patient´s assigned network to reduce the danger of excess mortality within the second wave of the COVID-19 pandemic.

Completion of radical hysterectomy does not improve survival of patients with cervical cancer and intraoperatively detected lymph node involvement: ABRAX international retrospective cohort study.

BACKGROUND: The management of cervical cancer patients with intraoperative detection of lymph node involvement remains controversial. Since all these patients are referred for (chemo)radiation after the surgery, the key decision is whether radical hysterectomy should be completed as originally planned, taking into account an additional morbidity associated with extensive surgical dissection prior to adjuvant treatment. The ABRAX study investigated whether completing a radical uterine procedure is associated with an improved oncological outcome of such patients. PATIENTS AND METHODS: We performed retrospective analyses of 515 cervical cancer patients (51 institutions, 19 countries) who were referred for primary curative surgery between 2005 and 2015 (stage IA-IIB, common tumour types) in whom lymph node involvement was detected intraoperatively. Patients were stratified according to whether the planned uterine surgery was completed (COMPL group, N = 361) or abandoned (ABAND group, N = 154) to compare progression-free survival. Definitive chemoradiation was given to 92.9% patients in the ABAND group and adjuvant (chemo)radiation or chemotherapy to 91.4% of patients in the COMPL group. RESULTS: The risks of recurrence (hazard ratio [HR] 1.154, 95% confidence intervals [CI] 0.799-1.666, P = 0.45), pelvic recurrence (HR 0.836, 95% CI 0.458-1.523, P = 0.56), or death (HR 1.064, 95% CI 0.690-1.641, P = 0.78) were not significantly different between the two groups. No subgroup showed a survival benefit from completing radical hysterectomy. Disease-free survival reached 74% (381/515), with a median follow-up of 58 months. Prognostic factors were balanced between the two groups. FIGO stage and number of pelvic lymph nodes involved were significant prognostic factors in the whole study cohort. CONCLUSION: We showed that the completion of radical hysterectomy does not improve survival in patients with intraoperatively detected lymph node involvement, regardless of tumour size or histological type. If lymph node involvement is confirmed intraoperatively, abandoning uterine radical procedure should be considered, and the patient should be referred for definitive chemoradiation. CLINICAL TRIALS IDENTIFIER: NCT04037124.

Prophylactic HPV vaccination after conization: A systematic review and meta-analysis.

INTRODUCTION: Human papillomavirus (HPV) vaccination is essential for cervical cancer prevention. However, the value of HPV vaccination in the context excisional treatment of high-grade cervical intraepithelial neoplasia (CIN 3) remains unclear. METHODS: In this meta-analysis, three retrospective and three prospective studies, three post-hoc analyses of RCTs and one cancer registry study analysing the effect of pre- or post-conization vaccination (bi- or quadrivalent vaccine) against HPV were included after a systematic review of literature. Random-effect models were prepared to evaluate the influence of vaccination on recurrent CIN 2+. RESULTS: Primary end point was CIN2+ in every study. The overall study population included 21,059 patients (3,939 vaccinations vs. 17,150 controls). The results showed a significant risk reduction for the development of new high-grade intraepithelial lesions after HPV vaccination (relative risk (RR) 0.41; 95% CI [0.27; 0.64]), independent from HPV type. Due to the heterogeneous study population multiple sub analyses regarding HPV type, age of patients, time of vaccination and follow-up were performed. Age-dependent analysis showed no differences between women under 25 years (RR 0.47 (95%-CI [0.28; 0.80]) and women of higher age (RR 0.52 (95%-CI [0.41; 0.65]). Results for HPV 16/18 positive CIN2+ showed a RR of 0.37 (95% CI [0.17; 0.80]). Overall, the number of women that would have to be vaccinated before or after conization to prevent one case of recurrent CIN 2+ (NNV) is 45.5. CONCLUSION: Meta-analysis showed a significant risk reduction of developing recurrent cervical intraepithelial neoplasia after surgical excision and HPV vaccination compared to surgical excision only.

Psychological distress in cervical cancer screening: results from a German online survey.

PURPOSE: The PODCAD study aimed at assessing the degree of psychological stress that women experience due to notification of an abnormal Papanicolaou (Pap) smear finding or a positive human papillomavirus (HPV) test result. METHODS: We designed a survey to address the question of psychological burden due to abnormal Pap smear results and/or positive HPV tests. In this online campaign approach, we aimed to reach > 2000 women all over Germany irrespective of kind and number of abnormal screening findings. We asked for different kinds of anxiety, distress and uncertainty regarding both, Pap and HPV status. RESULTS: A total of 3753 women completed the survey at least partially, and almost 2300 fully completed the survey. Of these, more than 50% were affected already since more than 1 year, and almost half of them had experienced at least three Pap smears in follow-up examinations. Almost 70% of the women were afraid of developing cancer. Intriguingly, almost half of the women with abnormal findings were not aware of their stage of the Pap smear. Furthermore, almost 30% of the women displayed signs of a post-traumatic stress disorder. CONCLUSION: Abnormal results in cervical cancer screening have an impact on patients' psychology, irrespective of the knowledge and severity of the findings. Better information concerning risks and benefits of cervical cancer screening and about the meaning of the outcome of its procedures are required to decrease this anxiety.

Morbidity, fertility and pregnancy outcomes after myoma enucleation by laparoscopy versus laparotomy.

OBJECTIVES: Myomas are defined as benign tumours that arise from smooth muscle cells of the uterus. Clinically, they are found in 5-77% of women of reproductive age. The prevalence rate varies considerably in the literature and a large number of fibroids do not cause symptoms. The lifetime risk of acquiring myomas is 70% for Caucasian women and ≥ 80% for African American women. MATERIALS/METHODS: The data of 265 patients undergoing surgery for symptomatic myomas by laparoscopy or laparotomy, performed in the gynaecological department of Hannover Medical School, Hannover, Germany, between 2009 and 2013, were retrospectively analysed in this retrospective design study. RESULTS: High pregnancy rates (up to 70%) and birth rates (up to 86%) after myomectomy, regardless of the surgical approach adopted, were found in the current study. The trend was that ≥ 3 myomas and those that were ≥ 6 cm in size were almost always removed by laparotomy in our clinic. It was possible to remove up to 42 myomas without having to perform a hysterectomy. A statistically significant negative correlation was observed in relation to the association between the size of the largest myoma extracted and the pregnancy rate (p = 0.02). A statistically significant correlation between the number of removed myomas and the pregnancy rate was observed for patients who wished to bear children (p = 0.010). Elevated complication rates (of up to 50%) were reported for more than three extracted myomas with a statistically significance (p = 0.0471). CONCLUSIONS: It is necessary to ensure sound preoperative selection of the surgical approach in order to achieve the most optimal results, especially for those patients who wished to bear children.

Array-comparative genomic hybridization analysis in patients with Müllerian fusion anomalies.

Fusion anomalies of the Müllerian ducts are associated with an increased risk for miscarriage and premature labor. In most cases polygenic-multifactorial inheritance can be assumed but autosomal-dominant inheritance with reduced penetrance and variable manifestation should be considered. We performed array-comparative genomic hybridization (CGH) analysis in a cohort of 103 patients with Müllerian fusion anomalies. In 8 patients we detected microdeletions and microduplications in chromosomal regions 17q12, 22q11.21, 9q33.1, 3q26.11 and 7q31.1. The rearrangement in 17q12 including LHX1 and HNF1ß as well as in 22q11.21 have already been observed in MRKHS (Mayer-Rokitansky-Küster-Hauser syndrome). In summary, we (1) detected causative micro-rearrangements in patients with Müllerian fusion anomalies, (2) show that Müllerian fusion anomalies and MRKHS may have a common etiology, and (3) identified new candidate genes for Müllerian fusion anomalies.

Estimation of neonatal outcome artery pH value according to CTG interpretation of the last 60 min before delivery: a retrospective study. Can the outcome pH value be predicted?

PURPOSE: The aim of this study was to analyze whether the umbilical artery pH value can be estimated throughout CTG assessment 60 min prior to delivery and if the estimated umbilical artery pH value correlates with the actual one. This includes analysis of correlation between CTG trace classification and actual umbilical artery pH value. Intra-and interobserver agreement and the impact of professional experience on visual analysis of fetal heart rate tracing were evaluated. METHODS: This was a retrospective study. 300 CTG records of the last 60 min before delivery were picked randomly from the computer database with the following inclusion criteria; singleton pregnancy >37 weeks, no fetal anomalies, vaginal delivery either spontaneous or instrumental-assisted. Five obstetricians and two midwives of different professional experience classified 300 CTG traces according to the FIGO criteria and estimated the postnatal umbilical artery pH. RESULTS: The results showed a significant difference (p < 0.05) in estimated and actual pH value, independent of professional experience. Analysis and correlation of CTG assessment and actual umbilical artery pH value showed significantly (p < 0.05) diverging results. Intra- and interobserver variability was high. Intraobserver variability was significantly higher for the resident (p = 0.001). No significant differences were detected regarding interobserver variability. CONCLUSION: An estimation of the pH value and consequently of neonatal outcome on the basis of a present CTG seems to be difficult. Therefore, not only CTG training but also clinical experience and the collaboration and consultation within the whole team is important.

Systematic Comparison of Different Meta-analyses, Systematic Reviews and HTA Reports on Cervical Cancer Screening based on Cytology or HPV Test.

Introduction: Cervical cancer screening programs all over the world are being radically revised; preventive screening is increasingly based on detecting infection with human papillomavirus (HPV). This change was driven by large international studies (comparing cytological and HPV-based screening), which were then summarized in systematic reviews or HTA reports. We carried out a systematic comparison of these meta-analyses, comparing their contents, quality, results and recommendations. Material and Methods: A systematic search in MEDLINE identified eight meta-analyses. Seven more papers were also included in our analysis. The quality of these publications was reviewed using the AMSTAR criteria and presented in tabular form. Results: There were significant differences with regard to the primary studies included in the meta-analyses, the quality of the meta-analyses, the endpoints, and the outcomes and recommendations based on these endpoints. Conclusion: Different meta-analyses on the same or similar issues sometimes came to quite different conclusions because they used different approaches. This is quite significant because the underlying primary data did not change. The data indicated that HPV-based screening was superior. The heterogeneity of the meta-analyses affects the decisions taken by policymakers in the healthcare system.

Knowledge and Implementation of the S3 Guideline on Gestational Diabetes among Gynecologists and Diabetologists Four Years after Publication: Results of a Survey of 773 Gynecologists and 76 Diabetologists on their Knowledge of the Guideline on Gestational Diabetes (AWMF 057-008, 2011).

BACKGROUND: An S3 guideline on the diagnosis and differentiated management of gestational diabetes (GDM) was published in Germany in 2011. This guideline replaced the previously applicable recommendations for the diagnosis and treatment of GDM and, for the first time, compiled evidence-based recommendations for the care of patients with GDM. The new guideline has focused particularly on the counselling offered to all patients with GDM about the associated long-term health risks. In this study we investigated the state of knowledge about the guideline among gynecologists and diabetologists in Thuringia and Lower Saxony. METHOD: A questionnaire with 23 questions was sent out to 773 gynecologists and 76 diabetologists providing outpatient care in Lower Saxony and Thuringia. The statistical analysis was descriptive and inferential for comparisons between groups. RESULTS: The response rate was 54 %; an average of 47.6 % of the individual questions were answered correctly in the completed questionnaires. The questions were answered correctly significantly more frequently by persons in the group with a good knowledge of the guidelines (75 vs. 61 %, p < 0.001). There were no significant differences between groups when differences between federal states or medical specialties were compared. CONCLUSIONS: The results of our study show a good general state of knowledge of the guideline and point to a high level of willingness to implement the recommendations of the S3 guideline on GDM. With regard to the follow-up care provided to patients with GDM and depression, this study found a significant need for further training.

[Indications, technique and results of the STARR procedure]. / Indikation, Technik und Ergebnisse der STARR-Operation.

Rectal intussusception and ventral rectocele are frequent morphological findings in patients suffering from obstructed defecation syndrome (ODS). After failed conservative treatment a surgical option can be discussed. Surgical approaches include the stapled transanal rectal resection (STARR) procedure, which is performed as a transanal approach by using two circular (PPH01) staplers for ventral and dorsal full-thickness resection of the distal rectum. Both retrospective and prospective studies as well as data from the German STARR registry demonstrated that the STARR procedure is safe and effective for symptom improvement and resolution in ODS associated with rectal intussusception in the short-term; however, disappointing functional results, particularly related to fecal incontinence and urgency, severe complications and high rates of revision surgery have also been documented. In general, based on the diagnostic and therapeutic challenges in ODS related to rectal intussusception, patient selection for STARR seems to be the key for success; therefore, this review summarizes and evaluates the indications, surgical technique, results, controversies and current trends of the "conventional" STARR procedure using two circular (PPH01) staplers.

Direct comparison of two vaginal self-sampling devices for the detection of human papillomavirus infections.

BACKGROUND AND OBJECTIVES: Two devices for vaginal self-sampling of dry cell material (Evalyn Brush, Rovers Medical Devices; Qvintip, Aprovix) were compared using the Abbott RealTime High Risk HPV test. STUDY DESIGN: Both self-sampling devices (change of order with every patient) including instructions for use and a questionnaire were handed to 146 patients in a colposcopy clinic prior to scheduled colposcopies with collection of cervical reference specimens by gynaecologists using a broom-like device. Matched self-collected and physician collected specimens were transferred to ThinPrep medium and tested for the presence of hr-HPV. Biopsies were taken if indicated by colposcopy. RESULTS: Evaluation of 136 patients with complete data (136/146; 93.2%) showed high agreement of overall hr-HPV detection rates between self-collected and clinician-collected specimens (Evalyn: 91.2% [kappa 0.822]; Qvintip: 89.0% [kappa 0.779]). Colposcopy and histological evaluation revealed 55 women without cervical intraepithelial neoplasia (CIN), 32 CIN1, 34 CIN2, 14 CIN3 and one adenocarcinoma in situ. Hr-HPV testing detected all CIN3+ cases on the clinician-taken or Evalyn self-samples (14/14) and 93% of them on the Qvintip samples (13/14). There was no significant difference regarding the sensitivity for CIN2+ or CIN3+ and specificity of hr-HPV testing on self- vs. clinician samples and on Evalyn vs. Qvintip. Based on signal intensities of ß-globin, the observed DNA concentration with Evalyn samples (mean CN: 22.0; 95%-CI: 21.5-22.6) was found to be significantly higher compared to that of Qvintip samples (mean CN: 23.8; 95%-CI 23.2-24.4), regardless of the order of self-sampling (p<0.0001). Most women considered self-sampling easy and comfortable. Qvintip was considered easier than the Evalyn Brush to understand (p<0.001) and to use (p=0.002). DISCUSSION: This study confirms that hr-HPV testing with a clinically validated PCR-based HPV assay is as accurate on self-samples as on clinician-samples without significant difference between both self-sampling devices.

Correlation of fetal scalp blood sampling pH with neonatal outcome umbilical artery pH value.

PURPOSE: Fetal scalp blood sampling is considered as a complimentary tool in addition to cardiotocography to assess fetal well-being. This blood sampling is important as the obstetrician has to judge and make decisions regarding the further management of the delivery based on this pH result. The aim of this study was to analyze the correlation between fetal scalp blood pH and the umbilical artery pH after birth. Furthermore, it was investigated whether tocolysis, a performed episiotomy or cord encirclement have an influence on the umbilical artery pH. METHODS: This retrospective study over a period of 11 years included all singleton pregnancies without fetal anomalies, which were monitored by fetal scalp blood sampling during labor. RESULTS: 844 out of 1502 deliveries were included for analysis. The analysis demonstrates a good correlation between fetal scalp pH value and outcome pH value. Subgroup analysis with fetal scalp blood pH <7.20 showed a difference in 40 of 82 cases, with an outcome pH value ≥7.20, but this difference was statistically insignificant. Neither did tocolysis, episiotomy or the presence of cord encirclement show an overall effect, nor did they have an impact on the subgroup. CONCLUSION: Obstetricians must consider that the values of fetal scalp blood are not always reliable and can be false. However, on the basis of CTG and fetal scalp blood pH, decisions are made regarding delivery interventions. Therefore, we would encourage the consideration of taking two samples routinely at every attempt of fetal blood sampling.

New Screening Proposals: the Federal Joint Commission Defines the Parameters for Cervical Cancer Screening from 2018: Statement of the Gynecology Oncology Working Group (AGO).

The Gynecology Oncology Working Group (AGO e. V.) unequivocally welcomes the decision taken by the German Federal Joint Commission (Gemeinsamer Bundesausschuss, G-BA) on March 19, 2015 regarding screening for cervical cancer. AGO is convinced that, in view of recent medical advances, this evidence-based decision will improve screening for cervical cancer.

Accuracy of Colposcopically Guided Diagnostic Methods for the Detection of Cervical Intraepithelial Neoplasia.

Introduction: Many factors can affect the accuracy of colposcopically guided biopsy, endocervical curettage (ECC) and differential cytology, all of which are standard, minimally invasive procedures used to detect cervical intraepithelial neoplasia. Method: All conizations carried out between 2007 and 2013 in the gynecological department of Hannover Medical School were retrospectively reviewed. The agreement between colposcopic diagnosis and histology was evaluated retrospectively. The analysis included 593 complete datasets out of a total of 717 cases treated. Results: The overall agreement was 85.5 %; the accuracy was significantly higher (p = 0.029) when three biopsy specimens were taken rather than just one. The agreement between diagnosis and histological findings from conization was highest for women < 30 years (90.7 %) and lowest for women > 50 years (72.1 %; p = 0.008). The agreement between preoperative differential cytology and histology results after conization was 86.7 % and improved as patient age increased (p = 0.035). The agreement between ECC findings and the results of conization was only 49.1 % irrespective of patient age, transformation zone or the patient's menopausal status. Conclusion: The accuracy of colposcopically guided biopsy appears to increase when three biopsy specimens are taken and is particularly high for younger patients. Differential cytology was also found to be highly accurate and is particularly useful for patients aged more than 50 years. The accuracy of ECC was significantly lower; however ECC can provide important additional information in selected cases.

Mutations in WNT9B are associated with Mayer-Rokitansky-Küster-Hauser syndrome.

Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is a well-known malformation pattern of the Müllerian ducts (MDs) characterized by congenital absence of the uterus and vagina. To date, most cases remain unexplained at molecular level. As female Wnt9b-/- mice show a MRKHS-like phenotype, WNT9B has emerged as a promising candidate gene for this disease. We performed retrospective sequence analyses of WNT9B in 226 female patients with disorders of the MDs, including 109 patients with MRKHS, as well as in 135 controls. One nonsense mutation and five likely pathogenic missense mutations were detected in WNT9B. Five of these mutations were found in cases with MRKHS accounting for 4.6% of the patients with this phenotype. No pathogenic mutations were detected in the control group (p = 0.017). Interestingly, all of the MRKHS patients with a WNT9B mutation were classified as MRKHS type 1, representing 8.5% of the cases from this subgroup. In previous studies, two of the patients with a WNT9B mutation were found to carry either an additional deletion of LHX1 or a missense mutation in TBX6. We conclude that mutations in WNT9B were frequently associated with MRKHS in our cohort and some cases may be explained by a digenic disease model.

Background Knowledge and Attitude of Pregnant Women towards Ultrasound Screening at 20-23 Weeks Gestation.

BACKGROUND: Prenatal ultrasound screening in the second trimester is widely used in maternal health care. Prenatal diagnosis and prenatal screening is often exposed to several accusation, such as inducing unnecessary anxiety, carrying out a selection and forcing pregnant women into attending ultrasound screening. The aim of this study was to investigate the knowledge and the intention of pregnant women attending the second trimester ultrasound screening. PATIENTS AND METHODS: This was a prospective study. Women attending the 20 weeks anomaly scan were given an anonymous questionnaire to evaluate the background knowledge about the anomaly scan and their opinion about prenatal screening. RESULTS: 600 (96.7%) of 620 recruited women filled in the questionnaire completely. To the majority (>80%) of women it is important to exclude severe fetal anomalies and to secure normal fetal growth. The background knowledge of the women was good, but a clear supply of information and a detail counselling would improve the understanding, especially in the group of lower education. The majority of the women stated that the 20 weeks anomaly scan should be offered to every woman. CONCLUSION: Prenatal ultrasound examination is not only essential from a medical point of view for example for important information regarding the status of the fetus, but also has a major impact as a positive psychological factor for pregnant women.