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Mayer-Rokitansky-Küster-Hauser syndrome (MRKHS) is characterized by congenital absence of the uterus, cervix, and the upper part of the vagina in females. Whole-gene deletion and loss-of-function variants in TBX6 have been identified in association with MRKHS. We aimed to expand the spectrum of TBX6 variants in MRKHS and explore the biological effect of the variant alleles.Rare variants in TBX6 were called from a combined multiethnic cohort of 622 probands with MRKHS who underwent exome sequencing or genome sequencing. Multiple in vitro functional experiments were performed, including messenger RNA analysis, western blotting, transcriptional activity assay, and immunofluorescence staining.We identified 16 rare variants in TBX6 from the combined cohort, including 1 protein-truncating variant reported in our previous study and 15 variants with unknown effects. By comparing the prevalence of TBX6 variants in the Chinese MRKHS cohort vs 1038 female controls, we observed a significant mutational burden of TBX6 in affected individuals (P = .0004, odds ratio = 5.25), suggesting a causal role of TBX6 variants in MRKHS. Of the 15 variants with uncertain effects, 7 were shown to induce a loss-of-function effect through various mechanisms. The c.423GA (p.Leu141=) and c.839+5GA variants impaired the normal splicing of TBX6 messenger RNA, c.422TC (p.Leu141Pro) and c.745GA (p.Val249Met) led to decreased protein expression, c.10CT (p.Pro4Ser) and c.400GA (p.Glu134Lys) resulted in perturbed transcriptional activity, and c.356GA (p.Arg119His) caused protein mislocalization. We observed incomplete penetrance and variable expressivity in families carrying deleterious variants, which indicates a more complex genetic mechanism than classical Mendelian inheritance.Our study expands the mutational spectrum of TBX6 in MRKHS and delineates the molecular pathogenesis of TBX6 variants, supporting the association between deleterious variants in TBX6 and MRKHS.

Purpose Assessment of HER2 overexpression using immunohistochemistry (IHC) and/or in situ hybridisation (ISH) for the detection of HER2 amplifications is standard to identify patients for established HER2-directed treatments. Patients with lower HER2 expression levels have recently also become candidates for novel therapies targeting HER2. This study aimed to assess tumour and patient characteristics and prognosis in patients with advanced breast cancer (aBC), relative to low HER2 expression levels. Methods PRAEGNANT is a prospective aBC registry (NCT02338167), focusing on molecular biomarkers. Patients in all therapy lines receiving any kind of treatment are eligible. This analysis includes patients with conventionally HER2-negative aBC. Clinical outcome was compared in the groups with no (IHC score 0) or with low HER2 expression (IHC 1+, or IHC 2+/ISH negative). Results Low HER2 expression levels in triple-negative aBC patients did not influence progression-free survival. Overall survival appeared poorer in patients with IHC 2+ compared with patients with no HER2 expression in the unadjusted analysis (hazard ratio 2.24, 95% confidence interval 0.1.12–4.47). However, this effect was not maintained in the adjusted analysis. In HER2-negative, hormone receptor–positive patients, low HER2 expression appeared to have no effect on prognosis, neither progression-free survival nor overall survival. Conclusions We could not demonstrate that HER2 expression at a low level and assessed in clinical routine can differentiate patients into prognostic groups. However, the prevalence of patients with a low expression makes this population interesting for clinical trials with potentially active treatments using HER2 as a target.

Invasive lobular carcinoma (ILC) is a distinct type of breast cancer and is accounting up to 10-15 % of all mammary carcinomas showing a pronounced increase in incidence rates over the last two decades. We generated three induced pluripotent stem cell (iPSC) lines from CD34+ progenitor cells isolated from a mammary carcinoma patient diagnosed with ILC. Here, we describe the characterization of the iPSCs by array-based comparative genomic hybridization (array CGH), immunocytochemistry, flow cytometry, reverse transcriptase polymerase chain reaction and directed in vitro differentiation. The iPSC lines will find application in the field of breast cancer research.

Approximately 15% of endometrial carcinomas (ECs) arise in young women who may wish to avoid surgical menopause and/or preserve fertility. Our aim was to evaluate the prognostic significance of Proactive Molecular risk classifier for Endometrial Carcinoma (ProMisE) in young (50 yo) women with EC.ProMisE was applied to a retrospective cohort of women with ECs50 yo at diagnosis, and associations between the four ProMisE molecular subtypes (MMR deficient (MMRd), POLE mutated (POLE), p53 wild type (p53wt), and p53 abnormal (p53abn)) and clinicopathological parameters, including outcomes, were assessed.Of 257 ECs, there were 48 (19%) MMRd, 34 (13%) POLE, 164 (64%) p53wt and 11 (4%) p53abn. ProMisE subtypes were associated with differences in all measured clinicopathological parameters except for presence of synchronous ovarian tumours and fertility. Age at diagnosis was youngest and BMI highest in women with p53wt ECs. MMRd and p53abn tumours were more likely to be advanced stage (III/IV), high-risk (ESMO), and receive chemotherapy. ProMisE subtypes were strongly associated with outcomes (overall, disease-specific, and progression-free survival (p 0.0001 for all)). Advanced stage, grade, LVSI, myometrial invasion and ESMO risk groups showed associations with some but not all survival parameters. ProMisE maintained a strong association with OS and DSS on multivariable analysis.ProMisE molecular classification is prognostic in young women with EC, enabling early stratification and risk assignment to direct care. Further studies can assess response to therapy, fertility, and cancer-related outcomes within the framework of molecular subtype.

Background Endocrine treatment (ET) with an aromatase inhibitor (AI) is the treatment of choice in post-menopausal patients with hormone receptor–positive early breast cancer (EBC). However, adverse events (AEs) often lead to treatment discontinuation. This analysis aimed to identify side-effects that lead to patients failing to persist with letrozole treatment. Patients and methods Post-menopausal hormone receptor–positive EBC patients starting ET with letrozole were enroled in EvAluate-TM, a non-interventional study. Information regarding treatment compliance and persistence was gathered in months 6 and 12. Persistence was defined as the time from 30 d after the start to the end of treatment. The influence on persistence of musculoskeletal syndrome, menopausal disorder, sleep disorder and other AEs within the first 30 d was analysed using Cox regression analyses. Results Among 3887 patients analysed, the persistence rate after 12 months was >85%. In all, 568 patients (14.6%) discontinued the treatment, 358 of whom (63.0%) did so only because of side-effects. The main AEs influencing persistence were musculoskeletal symptoms (hazard ratio [HR] 2.55; 95% confidence interval [CI], 1.90–3.42), sleep disorders (HR 1.95; 95% CI, 1.41–2.70) and other AEs (HR 2.03; 95% CI, 1.51–2.73). Menopausal disorder was not associated with non-persistence (HR 1.17; 95% CI, 0.74–1.84). Conclusions These results suggest that side-effects of AIs such as musculoskeletal syndrome and sleep disorder lead to ET discontinuation within the first treatment year in significant numbers of EBC patients. Compliance programmes adapted for subgroups that are at risk for early non-persistence might help to ensure the recommended therapy duration. Clinical Trials Number CFEM345DDE19.

Objective: To evaluate myeloid differentiation primary response gene 88 (MyD88) and Toll-like receptor 4 (TLR4) expression in relation to clinical features of epithelial ovarian cancer, histologic subtypes, and overall survival. Patients and Methods: We conducted centralized immunohistochemical staining, semi-quantitative scoring, and survival analysis in 5263 patients participating in the Ovarian Tumor Tissue Analysis consortium. Patients were diagnosed between January 1, 1978, and December 31, 2014, including 2865 high-grade serous ovarian carcinomas (HGSOCs), with more than 12,000 person-years of follow-up time. Tissue microarrays were stained for MyD88 and TLR4, and staining intensity was classified using a 2-tiered system for each marker (weak vs strong). Results: Expression of MyD88 and TLR4 was similar in all histotypes except clear cell ovarian cancer, which showed reduced expression compared with other histotypes (P

Purpose This study describes comprehensive data from a breast cancer registry concerning the use of endocrine treatment (ET) and chemotherapy in the first, second and higher therapy lines in hormone receptor (HR) positive, HER2 negative metastatic breast cancer (MBC). Methods The PRAEGNANT study is a real-time registry for patients with MBC. Therapies were categorized into the following categories: chemotherapy, aromatase inhibitor (AI), tamoxifen, fulvestrant, or everolimus plus ET and reported for first, second and third line or higher therapy use. Also treatment sequences for the first, second and third therapy line were analyzed. Results This analysis includes 958 patients with HR positive, HER2 negative MBC. 42.7% were treated with a chemotherapy in the first therapy line compared to 45.9% receiving an ET. A total of 25.9% were treated with everolimus plus anti-hormone therapy in any therapy line. 34.1% were treated with fulvestrant as single agent therapy. Analyzing therapy sequences, the administration of three different chemotherapies in a row was the most frequently used pattern. Conclusions This analysis shows that across all three first therapy lines chemotherapy is a dominant therapy for HR positive, HER2 negative MBC patients. Education about the efficacy of ET might help to increase its use and decrease the possible burden of chemotherapy related toxicities.

Objectives Improved progression-free survival is considered as treatment goal for patients with metastatic breast cancer (MBC) since it is assumed to delay or prevent deterioration of quality of life. Aim of our analysis was to examine the influence of disease progression on health-related quality of life (HRQoL). Materials and methods The PRAEGNANT study comprises a real-life registry for patients with MBC. HRQoL was assessed with the EORTC-QLQ-C30 Version 3.0 questionnaire at study entry and every 3 months thereafter. The primary endpoint was minimally important deterioration (MID) in global HRQoL score by ≥ five points between baseline and any follow-up assessment. A logistic regression model was built with MID (yes/no) at a follow-up timepoint as outcome variable and several covariates as predictors. Results In total, 329 patients were included in this analysis, with disease progression in 63 patients. Concerning the primary study aim, progression status predicted MID of global HRQoL status in addition to the other covariates. The adjusted odds ratio for the effect of progression status on MID was 2.22 (95% CI: 1.04 - 4.73). Comparisons of mean differences of QoL domains/scales yielded no differences. Conclusions We provide evidence that disease progression in patients with metastatic breast cancer in a real-world registry has a significant negative impact on HRQoL as measured by MID of HRQoL. This study emphasizes the relevance of avoiding progression and prolonging PFS to maintain QoL.

Background Patients’ compliance and persistence with endocrine treatment has a significant effect on the prognosis in early breast cancer (EBC). The purpose of this analysis was to identify possible reasons for non-persistence, defined as premature cessation of therapy, on the basis of patient and tumor characteristics in individuals receiving adjuvant treatment with letrozole. Patients and methods The EvAluate-TM study is a prospective, multicenter, noninterventional study in which treatment with the aromatase inhibitor letrozole was evaluated in postmenopausal women with hormone receptor-positive EBC in the early therapy phase. Treatment persistence was evaluated at two pre-specified study visits after 6 and 12 months. As a measure of early therapy persistence the time from the start to the end of treatment (TTEOT) was analyzed. Cox regression analyses were carried out to identify patient characteristics and tumor characteristics predicting TTEOT. Results Out of the total population of 3941 patients with EBC, 540 (13.7%) events involving treatment cessation unrelated to disease progression were observed. This was due to drug-related toxicity in the majority of cases (73.5%). Persistence rates were 92.2%, 86.9%, and 86.3% after 6, 12, and 15 months, respectively. The main factors influencing premature treatment discontinuation were older age [hazard ratio (HR) 1.02/year], comorbidities (HR 1.06 per comorbidity), low body mass index, and lower tumor grade (HR 0.85 per grade unit). Conclusion These results support the view that older, multimorbid patients with low tumor grade and low body mass index are at the greatest risk for treatment discontinuation and might benefit from compliance and support programs.

Study Objective The aim of our study is to test a combination of biological markers differentially expressed in samples from women with or without endometriosis. Methods Design ENDOSEARCH is a prospective multicentric international clinical trial registered with Clinical Trial.gov. Setting 20 renowned specialized centers in Europe, USA, Canada, and the Indian Ocean, granted by the European Union aiming to validate a cluster of biomarkers. Patients or Participants 1000 patients. The Patient Group includes women between 18 and 45 with suspected endometriosis undergoing laparoscopy. Patients with predominant adenomyosis and/or fibroids diagnosed by imaging, chronic, malignant, infectious, metabolic or endocrine diseases are excluded. The Control Group includes patients of same age group without any endometriosis-related clinical sign, with planned laparoscopic surgery for other indications. Samples of endometriosis lesions and endometrial biopsies for both groups are sent to a unique center (Endodiag, Paris, France) to be tested with the cluster of biomarkers. Interventions Laparoscopy for endometriosis or benign conditions (Control group). Measurements and Main Results 40% of the patients recruited in the Endometriosis group have already had at least one and up to 4 previous laparoscopies for endometriosis. Almost 50% of the patients had an AFS score of III or IV. 14% of the patients suspected of endometriosis had negative pathology while 2% of the patients in the control group had severe endometriosis at laparoscopy and were excluded. Conclusion We present the first large prospective multicentric international clinical trial aiming to test a cluster of biomarkers to diagnose endometriosis by recruiting over 1000 patients all around Europe, the US and Canada. Even in major referral centers almost 14% of the pre-op diagnosis were negative at pathology while 2% of the control group had severe endometriosis. Those preliminary results with others show the necessity of development of accurate biological tests to diagnose endometriosis and avoid unnecessary laparoscopies.

Study Objective The Mayer-Rokitansky-Kuester-Hauser (MRKH) syndrome is characterized by vaginal and uterine aplasia in a 46,XX individual. Multiple abnormalities may be associated with MRKH syndrome, and it appears to overlap other syndromes. The aim of this study was to describe the spectrum of associated malformations and syndromes as well as abnormal karyotypic findings in a large cohort of 346 patients. Design, Setting, and Participants The study is a retrospective analysis of 346 MRKH patients treated in the University Hospital in Tuebingen between 1998 and 2013. Main Outcome Measures The dataset was screened for typical associated malformations as well as atypical malformations and abnormal karyotypes. A complete review of the literature was included. Results Among our cohort of 346 patients, we found that 53.2% had MRKH type 1, 41.3% had MRKH type 2, and 5.5% had MURCS syndrome. The group with associated malformations included 57.6% renal, 44.4% skeletal, and 30.8% other malformations. Additionally, we found 2 cases of absent radius syndrome, 3 cases of anal atresia, and 1 patient with oculodentodigital dysplasia, and other atypical malformations. Abnormal karyotypes were found in 5 cases, and 39 siblings and 11 parents had known malformations. Conclusions This study supports the hypothesis that the syndrome has a multifactorial pathogenesis. With the high numbers of associated malformations reported in this study, patients with MRKH syndrome should be regarded as having a complex syndrome. Molecular–genetic analyses in larger numbers of children after surrogacy, twin pregnancies, and familial cases may make it possible to obtain further information about the etiology of the syndrome.

Purpose To apply our previously published residual ex vivo γH2AX foci method to patient-derived tumour specimens covering a spectrum of tumour-types with known differences in radiation response. In addition, the data were used to simulate different experimental scenarios to simplify the method. Materials and methods Evaluation of residual γH2AX foci in well-oxygenated tumour areas of ex vivo irradiated patient-derived tumour specimens with graded single doses was performed. Immediately after surgical resection, the samples were cultivated for 24h in culture medium prior to irradiation and fixed 24h post-irradiation for γH2AX foci evaluation. Specimens from a total of 25 patients (including 7 previously published) with 10 different tumour types were included. Results Linear dose response of residual γH2AX foci was observed in all specimens with highly variable slopes among different tumour types ranging from 0.69 (95% CI: 1.14–0.24) to 3.26 (95% CI: 4.13–2.62) for chondrosarcomas (radioresistant) and classical seminomas (radiosensitive) respectively. Simulations suggest that omitting dose levels might simplify the assay without compromising robustness. Conclusion Here we confirm clinical feasibility of the assay. The slopes of the residual foci number are well in line with the expected differences in radio-responsiveness of different tumour types implying that intrinsic radiation sensitivity contributes to tumour radiation response. Thus, this assay has a promising potential for individualized radiation therapy and prospective validation is warranted.

Study Objective To assess the long-term outcome of an optimized minimally invasive neovaginoplasty technique in vaginal agenesis. Design Combined retrospective and prospective study. Setting University hospital. Participants 240 patients with congenital vaginal agenesis. Interventions Patients with an indication for neovagina creation underwent laparoscopically assisted neovaginoplasty involving vaginoabdominal blunt perforation and intracorporeal traction using tension threads and an abdominally positioned extracorporeal traction device. Main Outcome Measures Long-term anatomic success, functional success compared with similar-aged controls, long-term complications, and incidence of human papilloma virus (HPV) infections. Results During median follow-up for 16 (range 11-141) months, mean functional neovaginal length remained stable at 9.5 cm in all patients, including those who had no sexual intercourse and had stopped wearing the vaginal dummy. Median dummy wearing time was 8.6 months. Time to epithelialization depended on the time of onset and frequency of sexual intercourse. At long-term follow-up, median total Female Sexual Function Index score was 30.0, comparable with similar-aged controls. No common long-term complications occurred. Four patients required cauterization of granulation tissue. 7/240 (2.9%) patients were HPV-positive with low- to high-grade squamous intraepithelial lesions, 3 patients reverting to HPV-negative status at long-term follow-up. Conclusions Our technique creates a neovagina of adequate size and secretory capacity for normal coitus, requiring no prolonged dilation postoperatively, even in the absence of sexual intercourse. The procedure is fast, effective and minimally traumatic, has a very low long-term complication rate and provides very satisfactory long-term functional results.

Objective To investigate peritoneal adhesion formation of monopolar contact coagulation (MCC) versus noncontact argon plasma coagulation (APC) in a rat model. Design Randomized, controlled, single-blinded animal study. Setting University laboratory. Animal(s) Sixteen female Wistar rats. Intervention(s) Bilateral lesions were created on the abdominal wall with MCC and APC in a standard fashion. After 10 days, the rats were euthanized to evaluate the peritoneal trauma sites. Main Outcome Measure(s) Adhesion incidence, quantity, and quality were scored 10 days postoperatively and studied histopathologically. Result(s) Average energy intake was 99.5 ± 7.39 J for APC and 95.7 ± 9.62 J for monopolar contact coagulation. Incidence of adhesion formation was 50.0% for noncontact APC and 85.4% for MCC. MCC induced significantly more vascular adhesions. Histological evaluation revealed no significant differences regarding average depth of lesions induced by APC and MCC. Both groups showed almost identical morphology of necrosis and granulation tissue formation. Conclusion(s) This study compares for the first time adhesion formation of MCC versus noncontact APC in a rat model. With a similar energy intake, contact coagulation induced a significantly higher rate of adhesion formation. APC-induced adhesions were significantly less vascularized compared with MCC adhesions. Besides the thermal effects of both coagulation methods, the direct mechanical contact of the MCC electrode with the highly sensitive peritoneum is thus determined to be a pivotal additional stimulus for adhesion formation.

Background Neovaginal prolapse occurs rarely, and a standard treatment has not yet been defined. Case We report 2 cases of patients with vaginal agenesis with a symptomatic neovaginal prolapse; one occurring 25 years after self-dilation and another occurring 24 years after sigmoid vaginoplasty. At 48 and 18 months after surgical treatment with laparoscopic nerve-preserving colposacropexy using 2 types of mesh and 2 kinds of sutures to anchor the mesh at the neovaginal wall, both women are asymptomatic and highly satisfied with the result, without prolapse recurrence or mesh/suture erosion. Summary and Conclusion For the surgical management of neovaginal prolapse after sigmoid vaginoplasty and vagina creation after self-dilation, we recommend the nerve-preserving sacrocolpopexy as a safe method to achieve durable functional outcomes and good anatomic vaginal level I and II support.

To compare the EnSeal device with standard bipolar coagulation forceps in laparoscopic supracervical hysterectomy (LASH).Prospective, randomized, controlled trial (Canadian Task Force classification I).University hospital.One hundred sixty patients who underwent LASH.Eighty patients underwent LASH using the EnSeal device (experimental group), and 80 patients underwent LASH using standard bipolar coagulation forceps (control group) (www.clinicaltrials.gov; study identifier NCT01806012).Mean (SD) total operative time was 78.18 (33.96) minutes in the experimental group and 86.30 (35.34) minutes in the control group (p = .03). Documented blood loss was50 mL in 72 patients in the experimental group and 62 patients in the control group (p = .03), and was 50 to 100 mL in 8 patients in the experimental group and 18 patients in the control group (p.001). Postoperative hospital stay was significantly shorter for patients in the experimental group compared with the control group: 2.01 (0.44) days vs 2.17 (0.47) days, respectively (p = .03). There was no difference in postoperative pain scores and complications between the two treatment groups.Total resection time was shorter in the experimental group, and the other investigated clinical parameters were not inferior in the experimental group compared with the control group. The results of the present study indicate that use of the EnSeal device is at least as reliable as the conventional electrocoagulation technique in LASH.

Congenital genital malformations occurring in the female population are estimated to be 5 per 1000 and associate with infertility, abortion, stillbirth, preterm delivery and other organ abnormalities. Complete aplasia of the uterus, cervix and upper vagina (Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome) has an incidence of 1 per 4000 female live births. The molecular etiology of congenital genital malformations including MRKH is unknown up to date. The homeobox (HOX) genes HOXA10 and HOXA13 are involved in the development of human genitalia. In this investigation, HOXA10 and HOXA13 genes of 20 patients with the MRKH syndrome, 7 non-MRKH patients with genital malformations and 53 control women were sequenced to assess for DNA variations. A total of 14 DNA sequence variations (10 novel and 4 known) within exonic and untranslated regions were detected in HOXA10 and HOXA13 among our cohorts. Four HOXA10 and two HOXA13 DNA sequence variations were found solely in patients with genital malformations. In addition to mutations resulting in synonymous amino acid substitutions, in the HOXA10 gene a missense mutation was identified and predicted by computer analysis as probably damaging to protein function in two non-MRKH patients, one with a bicornate and the other patient with a septated uterus. A novel exonic HOXA10 cytosine deletion was also identified in a non-MRKH patient with a septate uterus and renal malformations resulting in a premature stop codon and loss of the homeodomain helix 3/4. This cytosine deletion and the missense mutation in HOXA10 were analysed by real time PCR and sequencing, respectively, in two additional larger cohorts of 103 patients with MRKH and 109 non-MRKH patients with genital malformations. No other patients were found with the cytosine deletion however one additional patient was identified regarding the missense mutation. Rare DNA sequence variations in the HOXA10 gene could contribute to the misdevelopment of female internal genitalia.

Objective To develop a human in vivo in situ model for analyzing the extent and the basic mechanisms of thermal spread and thermal tissue damage. Design Prospective, open, uncontrolled, nonrandomized, single-center exploratory study. Setting University hospital. Patients Eighteen adult patients undergoing open abdominal hysterectomy for benign disease. Interventions Unilateral fallopian tube tissue desiccation (10 seconds) with a laparoscopic bipolar clamp at routine settings. Main Outcome Measures Deep tissue temperature (thermal probe), tissue surface temperature (thermal camera), and gross and histologic assessments of lesions with a newly developed composite scoring system. Results Fifteen specimens from 18 patients were evaluated. Lateral thermal damage (LTD; determined by lactate dehydrogenase staining), was strongly correlated with maximum desiccation temperature. Deep tissue LTD and surface LTD were linearly related. Histologic and macroscopic criteria for thermal effects and damage and the corresponding scores proved functional and strongly correlated with LTD. Measurement of deep tissue and tissue surface temperatures consistently yielded complete temporal and spatial temperature distributions that were describable by the heat equation. Conclusions Our novel in vivo in situ model allows standardized, reproducible, quantitative assessment of electrosurgery-induced thermal effects and damage in human tissue. It will likely provide further insight into the underlying biothermomechanics and may prove useful in the development of safety guidelines for laparoscopic electrosurgery.

Objective To improve the laparoscopic Vecchietti procedure and optimize instrumentation for treatment of congenital vaginal agenesis with a minimum of complications and optimal functional outcome, in comparison with the conventional laparoscopic Vecchietti procedure. Design Prospective comparative interventional study. Setting University hospital. Patient(s) One hundred one patients with congenital vaginal agenesis. Intervention(s) The interventions compared were [1] a new laparoscopic, Vecchietti-based method using vaginoabdominal blunt perforation without vesicorectal tunneling and [2] the laparoscopic Vecchietti procedure. Main Outcome Measure(s) Duration of surgery and traction, functional results, surgical and technical complications. Result(s) Without tunneling and with new instruments, mean operative time was more than halved, from 113.0 to 47.5 minutes, with a significantly reduced complication rate for bladder lesions and no bowel lesions. Mean traction time was similarly reduced, from 11.7 to 4.8 days. No instrument-related complications were seen with our new instrument set. After 6 months, the longer neovagina of 10.6 cm that was achieved with the new method was still 2.5 cm longer than the conventional result. No patients needed lubricants or had sustained pain during intercourse. Conclusion(s) Our new method for neovagina creation resulted in shorter operation and traction times, better functional results, and fewer surgical complications and no technical ones. It is therefore a safer, shorter, more effective, and less traumatic procedure.

We compared the efficiency and safety of a newly developed morcellator with a conventional device for minimally invasive supracervical hysterectomy. The prospective, randomized parallel-group study was set in a department of obstetrics and gynecology within an Academic Teaching Hospital. Patients included 48 women; 20 treated with an existing laparoscopic morcellator (Group 1); 28 treated with newly developed laparoscopic morcellator (Group 2). The weight-adjusted dissection time was reduced significantly by more than half with the new morcellator (p

Objective With an incidence of up to 5% in the general population, genital malformations are a frequent clinical occurrence. The aim of this study was to assess whether a connection could be demonstrated between various degrees of severity of genital malformations and associated abnormalities. Design All patients were classified using the Vagina, Cervix, Uterus, Adnex, and Associated Malformation (VCUAM) classification. Setting University hospital. Patient(s) Two hundred eleven premenopausal patients with female genital malformations. Intervention(s) The patients underwent diagnostic workup for genital malformations using laparoscopy as well as hysteroscopy. Associated malformations were detected by either magnetic resonance imaging (MRI) or ultrasound. Main Outcome Measure(s) Demonstration of a connection between various degrees of severity of genital malformations and associated abnormalities. Result(s) In 72 cases (36%) out of 202 patients with uterine malformations (VCUAM U1–4) we found associated abnormalities. The predominant findings were alterations in the renal system. When vaginal abnormality (VCUAM V1–5) alone was taken into consideration, an associated developmental disturbance in the renal tract was found in 30% of cases (n = 32 from 107). Conclusion(s) A close connection was demonstrated between genital malformations and associated abnormalities. For this reason, the diagnostic workup in patients with malformations should always include the renal system. Depending on the severity of the clinical picture, examinations may need to be extended further.

Objective With an incidence of up to 5% in the general population, genital malformations are a frequent clinical occurrence. However, using the existing published classifications of malformations, difficulties arise in classifying genital malformations appropriately. The aim of the present study was to produce a simple, systematic, and reproducible classification system. Design A systematic arrangement of genital and associated malformaltions, using a structure similar to that in the TNM classification of oncological tumors, was developed and validated. Setting Patients with genital malformations in a university hospital. Patient(s) Ninty-nine premenopausal patients with genital malformations. Intervention(s) Patients were diagnosed for genital malformation using laparoscopy or magnetic resonance imaging. Main Outcome Measure(s) A new classification (VCUAM) is presented to evaluate patients with different genital malformations. Result(s) The external and internal female genital organs were divided into the following subgroups in accordance with the anatomy: vagina (V), cervix (C), uterus (U), and adnexa (A). Associated malformations were assigned to a subgroup (M) relative to each specific organ. The classification was validated in a group of 99 patients with genital malformations. Conclusion(s) The VCUAM classification for the first time makes it possible to reflect even complex malformations in a precise and individual fashion, taking associated malformations into account. The classification makes it easier to provide appropriate clinical care for the affected patients.

Objective To find a potential underlying cause for Mayer-Rokitansky-Kuster-Hauser syndrome (MRKHS) discordance in monozygotic twins. Design Prospective comparative study. Setting University hospital. Patient(s) Our study genetically analyzed 5 MRKHS-discordant monozygotic twin pairs with the unique opportunity to include saliva and rudimentary uterine tissue. Intervention(s) Blood, saliva, or rudimentary uterine tissue from five MRKHS-discordant twins was analyzed and compared between twin pairs as well as within the same individual where applicable. We used copy number variations (CNVs) to identify differences. Main Outcome Measure(s) CNVs in blood, rudimentary uterine tissue, and saliva, network analysis, and review of the literature. Result(s) One duplication found in the affected twin included two genes, matrix metalloproteinase 14 ( MMP14 ) and low-density lipoprotein receptor–related protein 10 ( LRP10 ), which have known functions in the embryonic development of the uterus and endometrium. The duplicated region was detected in rudimentary uterine tissue from the same individual but not in saliva, making a tissue-specific mosaicism a possible explanation for twin discordance. Additional network analysis revealed important connections to differentially expressed genes from previous studies. These genes encode several molecules involved in extracellular matrix (ECM) remodeling and neoangiogenesis. Conclusion(s) MMP-14, LRP-10, ECM, and neoangiogenesis genes are identified as candidate genes in a tissue-specific mosaicism. The detected clusters provide evidence of deficient vascularization during uterine development and/or disturbed reorganization of ECM components, potentially during mullerian duct elongation signaled by the embryologically relevant phosphatidylinositol 3-kinase/protein kinase B pathway. Therefore, we consider these genes to be new candidates in the manifestation of MRKHS.