Training of young medical professionals: implementation of modern training concepts, taking into account the changed framework conditions for training-a pilot project for operational subjects.

INTRODUCTION: For years, generations of medical students have complained that practice-oriented learning is neglected in medical studies. Further training assistants also complain about limited opportunities to learn subject-specific practical activities. MATERIAL AND TECHNIQUES: We are presenting a pilot project at the University Women's Hospital in Homburg, in which medical students complete an endoscopic hands-on course as part of the block internship gynaecology and obstetrics. During the course the students perform classic skills training and hand-eye coordination exercises and learn the first steps in endoscopic suturing (suture and rows of knots). The training concepts used can be implemented on simple boxing trainers and can therefore also be reproduced in clinics or in a private setting. OUTCOME: Altogether, 73 medical students did participate in the laparoscopy course. We were able to prove that the knotting time for a simple knot can be reduced from an average of 247 s to 40 s (80%) after completing our training programme. Based on the evaluation sheet that the students filled out after the course, we found a very-high acceptance for surgical simulation training within the student cohort. DISCUSSION: Practical surgical exercises can complement the curriculum well and, as we can show with our work, are rated very positively by the students. For students in higher semesters, such practical courses can also provide an insight into the respective subject area and thus counteract the lack of skilled workers in surgical subjects. The practical year should not be the first contact with these practical courses, as at this timepoint a certain favoured subject has often already being chosen by the students.

ESHRE Task Force on Ethics and Law 23: medically assisted reproduction in singles, lesbian and gay couples, and transsexual people†.

This Task Force document discusses ethical issues arising with requests for medically assisted reproduction from people in what may be called 'non-standard' situations and relationships. The document stresses that categorically denying access to any of these groups cannot be reconciled with a human rights perspective. If there are concerns about the implications of assisted reproduction on the wellbeing of any of the persons involved, including the future child, a surrogate mother or the applicants themselves, these concerns have to be considered in the light of the available scientific evidence. When doing so it is important to avoid the use of double standards. More research is needed into the psychosocial implications of raising children in non-standard situations, especially with regard to single women, male homosexual couples and transsexual people.

ESHRE Task Force on Ethics and Law 21: genetic screening of gamete donors: ethical issues.

This Task Force document explores the ethical issues involved in the debate about the scope of genetic screening of gamete donors. Calls for expanded donor screening arise against the background of both occasional findings of serious but rare genetic conditions in donors or donor offspring that were not detected through present screening procedures and the advent of new genomic technologies promising affordable testing of donors for a wide range of conditions. Ethical principles require that all stakeholders' interests are taken into account, including those of candidate donors. The message of the profession should be that avoiding all risks is impossible and that testing should remain proportional.

ESHRE task force on ethics and Law22: preimplantation genetic diagnosis.

This Task Force document discusses some relatively unexplored ethical issues involved in preimplantation genetic diagnosis (PGD). The document starts from the wide consensus that PGD is ethically acceptable if aimed at helping at-risk couples to avoid having a child with a serious disorder. However, if understood as a limit to acceptable indications for PGD, this 'medical model' may turn out too restrictive. The document discusses a range of possible requests for PGD that for different reasons fall outwith the accepted model and argues that instead of rejecting those requests out of hand, they need to be independently assessed in the light of ethical criteria. Whereas, for instance, there is no good reason for rejecting PGD in order to avoid health problems in a third generation (where the second generation would be healthy but faced with burdensome reproductive choices if wanting to have children), using PGD to make sure that one's child will have the same disorder or handicap as its parents, is ethically unacceptable.

Health outcomes of children born after IVF/ICSI: a review of current expert opinion and literature.

The Sixth Evian Annual Reproduction (EVAR) Workshop Group Meeting was held to evaluate the impact of IVF/intracytoplasmic sperm injection on the health of assisted-conception children. Epidemiologists, reproductive endocrinologists, embryologists and geneticists presented data from published literature and ongoing research on the incidence of genetic and epigenetic abnormalities and congenital malformations in assisted-conception versus naturally conceived children to reach a consensus on the reasons for potential differences in outcomes between these two groups. IVF-conceived children have lower birthweights and higher peripheral fat, blood pressure and fasting glucose concentrations than controls. Growth, development and cognitive function in assisted-conception children are similar to controls. The absolute risk of imprinting disorders after assisted reproduction is less than 1%. A direct link between assisted reproduction and health-related outcomes in assisted-conception children could not be established. Women undergoing assisted reproduction are often older, increasing the chances of obtaining abnormal gametes that may cause deviations in outcomes between assisted-conception and naturally conceived children. However, after taking into account these factors, it is not clear to what extent poorer outcomes are due to the assisted reproduction procedures themselves. Large-scale, multicentre, prospective epidemiological studies are needed to investigate this further and to confirm long-term health consequences in assisted-conception children. Assisted reproduction treatment is a general term used to describe methods of achieving pregnancy by artificial means and includes IVF and sperm implantation. The effect of assisted reproduction treatment on the health of children born using these artificial methods is not fully understood. In April 2011, fertility research experts met to give presentations based on research in this area and to look carefully at the evidence for the effects of assisted reproduction treatment on children's health. The purpose of this review was to reach an agreement on whether there are differences in the health of assisted-conception children with naturally conceived children. The researchers discovered no increased risk in birth defects in assisted-conception children compared with naturally conceived children. They found that IVF-conceived children have lower birth weights and higher fat under the skin, higher blood pressure and higher fasting glucose concentrations than naturally conceived children; however, growth, development and cognitive function are similar between groups. A very low risk of disorders of genetic control was observed in assisted-conception children. Overall, there did not appear to be a direct link between assisted reproduction treatment and children's health. The researchers concluded that the cause of some differences in the health of children conceived using assisted reproduction treatment may be due to the age of the woman receiving treatment. Large-scale, research studies are needed to study the long-term health of children conceived using assisted reproduction treatment.

ESHRE Task Force on ethics and Law 20: sex selection for non-medical reasons.

This Task Force document revisits the debate about the ethics of sex selection for non-medical reasons in the light of relevant new technological developments. First, as a result of improvement of the Microsort® flow cytometry method, there is now a proven technique for preconception sex selection that can be combined both with IVF and IUI. Secondly, the scenario where new approaches that are currently being developed for preimplantation genetic screening (PGS) may lead to such screening becoming a routine part of all IVF treatment. In that scenario professionals will more often be confronted with parental requests for transfer of an embryo of a specific sex. Thirdly, the recent development of non-invasive prenatal testing based on cell-free fetal DNA in maternal plasma allows for easy and safe sex determination in the early stages of pregnancy. While stressing the new urgency that these developments give to the debate, the Task Force did not come to a unanimous position with regard to the acceptability of sex selection for non-medical reasons in the context of assisted reproduction. Whereas some think maintaining the current ban is the best approach, others are in favour of allowing sex selection for non-medical reasons under conditions that take account of societal concerns about the possible impact of the practice. By presenting these positions, the document reflects the different views about this issue that also exist in the field. Specific recommendations include the need for a wider delineation of accepted 'medical reasons' than in terms of avoiding a serious sex-linked disorder, and for a clarification of the legal position with regard to answering parental requests for 'additional sex selection' in the context of medically indicated preimplantation genetic diagnosis, or routine PGS.

Cold-shock domain family member YB-1 expression in endometrium and endometriosis.

BACKGROUND: The Y-box-binding protein (YB-1) is described as a potential oncogene highly expressed in tumors and associated with increased cell survival, proliferation, migration and anti-apoptotic signaling. The aim of our study was to examine the expression and role of YB-1 in human endometriosis (Eo) and its association with cell survival, proliferation and invasion. METHODS: We analyzed the gene and protein expression levels of YB-1 by quantitative real-time RT-PCR and immunoassays, respectively, in peritoneal macrophages, ovarian endometrioma and eutopic endometrial tissues/cells derived from women with (n= 120) and without (n= 91) Eo. We also evaluated the functional consequences of YB-1 knockdown in the Z12 Eo cell line by measuring cell proliferation [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromid cell proliferation assay], invasion (Matrigel invasion assay) and spontaneous and tumour necrosis factor (TNFα)-induced RANTES (regulated upon activation, normal T-cell expressed and secreted chemokine) expression and apoptosis (ELISA-based assay). RESULTS: YB-1 gene and protein expression was statistically significantly higher in ovarian lesions, eutopic endometrium and peritoneal macrophages of patients with Eo in comparison with the control group. Interestingly, the strongest YB-1 expression was observed in the epithelial compartment of endometrial tissues. In the Z12 cell line, YB-1 knockdown resulted in significant cell growth inhibitory effects including reduced cell proliferation and increased rates of spontaneous and TNFα-induced apoptosis. Significantly, higher RANTES expression and decreased cell invasion in vitro were also associated with YB-1 inactivation. CONCLUSION: High YB-1 expression could have an impact on the development and progression of Eo. This study suggests the role of YB-1 as a potential therapeutic target for Eo patients.

Oocyte cryopreservation for age-related fertility loss.

The recent introduction of oocyte vitrification has significantly advanced the outcome of oocyte cryopreservation, leading to clinical results comparable to those achieved in IVF using fresh oocytes, as reported by experienced centres. This has lead to new debate, both in the professional community and in society at large, about the acceptability of offering this technology to reproductively healthy women who want to cryopreserve their oocytes against the threat of time. Given the many demands calling for simultaneous realization in a relatively short period of their lives, many women who want to have children feel to be under considerable pressure. The option of oocyte cryopreservation may in fact give them more breathing space. In this document, it is concluded that the arguments against allowing this application of the technology are not convincing. The recommendations include the need for adequate information of women interested in oocyte cryopreservation, also in order to avoid raising false hopes. The message must remain that women's best chances of having a healthy child are through natural reproduction at a relative early age. Centres offering this service must have the necessary expertise to employ oocyte cryopreservation efficiently with the so far non-standardized protocols. As data about long-term safety is still lacking, centres also have a responsibility to contribute to the collection of these data.

Oral contraception enhances growth hormone responsiveness to hyper- and hypoglycaemia.

AIMS: Plasma glucose levels influence growth hormone concentrations. Oral contraceptives are known to affect circulating growth hormone levels and glucose metabolism. While growth hormone plays an important role in hypoglycaemia counter-regulation, it has been shown that oral contraceptives increase growth hormone concentrations. In this context, we tested if serum growth hormone concentrations display a differential response on glycaemic variations in healthy women using oral contraceptives and those not using contraceptives. METHODS: Fifteen healthy women with oral contraceptive treatment and 10 without participated in a stepwise hyper- and hypoglycaemic glucose clamp procedure. Serum growth hormone concentrations were measured at euglycaemic baseline and subsequently at plasma glucose plateaus of 8.8, 6.8, 4.8 and 2.8 mmol/l. RESULTS: Growth hormone values were significantly higher in women using oral contraceptives throughout the experiments (P = 0.001). Hyperglycaemia decreased growth hormone concentrations in women using oral contraceptives (P = 0.009), but not in those who were not using oral contraceptives (P = 0.241). Hypoglycaemia significantly elevated growth hormone concentrations in women using oral contraceptives (P = 0.009), but not in those not using oral contraceptives (P = 0.094). Maximum growth hormone values were reached at the end of the hypoglycaemic plateau, with significantly higher concentrations in the group using oral contraceptives than in the group not using oral contraceptives (P = 0.016). CONCLUSION: Healthy women on oral contraceptive treatment display an increased responsiveness of growth hormone to hypoglycaemic, as well as hyperglycaemic conditions and generally higher serum growth hormone concentrations than women without oral contraceptives. Given the known boosting effects of growth hormone on hypoglycaemic hormonal counter-regulation, oral contraceptives may thus be a pharmacological candidate contributing to combat hypoglycaemia unawareness in women with diabetes in the future.

Diagnosis and treatment options of vulvar cancer: a review.

INTRODUCTION: Vulvar cancer is a rare malignancy in women. However, within the past decade, a distinct increase in the incidence of vulvar intraepithelial neoplasia (VIN) as a precursor lesion, and an increase of vulvar cancer have been reported within Europe and the USA. Surgery is the first choice in treating patients with vulvar cancer, especially in its early stages. In an attempt to decrease the incidence of complications, research was made into modifications of the surgical procedure without compromising the prognosis. The replacement of radical vulvectomy by less wide local excision is one of these modifications. As vulvar cancer is relatively rare, it is possible to give evidence-based treatment recommendations, but usually on a low evidence level. Aim of this paper is to elucidate diagnostics and surgical treatment options in the management of vulvar cancer. MATERIALS AND METHODS: We searched major databases (i.e. pubmed) with the following selection criteria: vulvar cancer, en bloc resection, triple incision, and sentinel node biopsy. CONCLUSIONS: Today, the operative therapy is much less radical and more emphasized on individualized therapeutic concepts. The tendency is to leave the ultraradical surgical options which suffer from high morbidity towards less radical, minimal invasive techniques. Due to the rarity of the disease further studies will have to be performed by international collaborative groups.

Retromesenteric para-aortic lymphadenectomy in gynecologic malignancy.

UNLABELLED: In gynecologic oncology lymphadenectomy is of prognostic and therapeutic importance because recurrence-free time and survival depend on the metastatic involvement of lymph nodes. Lymphadenectomies are not performed to such an extent as they are indicated. This might be due to a laborious or problematic preparation. The authors therefore report their experience in a seldom taught preparation of the left para-aortic compartment in the form of a learning curve. MATERIALS AND METHODS: To access the left para-aortic area, the descending colon is lifted to open the retroperitoneum along the line of Toldt. The mesentery of the descending colon was separated from the kidney along the fascia of Gerota by blunt preparation. Time was measured from the incision of the peritoneum until the renal vein was clearly visible. RESULTS: The authors collected the data from the first 25 preparations. Mean duration for the left para-aortic preparation was 7.8 minutes compared to 5.9 minutes for the right side. Duration of preparation of the left area dropped from 11.0 minutes within the first patients (#1 to #5) to 3.8 minutes in the last patients (#20 to #25). No complications were observed in the study group linked to the retromesenteric approach described. CONCLUSION: Retromesenteric para-aortic lymphadenectomy is quick to learn. The authors needed 20 preparations to observe a significant drop in the time needed for preparation. Retromesenteric para-aortic lymphadenectomy offers an excellent overview that lightens lymphadenectomy and therefore reduces the risks for patients.

Leiomyosarcoma of the vulva.

Malignant tumors of the vulva soft tissue are uncommon. About 1-3% are sarcomas. They can be mistaken as benign lesions, leading to misdiagnosis and mistreatment. A case of a 71-year-old woman with a leiomyosarcoma of the vulva is presented. The surgical excision of the lesion is described and there were no additional malignancies or lesions found. There was no need for adjuvant therapy.

[Atypical myometric fluid accumulation in graviditate--intramural pregnancy or degenerated fibroid?]. / Atypischer myometraner Flüssigkeitsverhalt in graviditate--intramurale Schwangerschaft oder degeneriertes Myom?

We wish to discuss a case of suspected fluid accumulation within the anterior uterine wall in graviditate. The initial diagnosis of a rare intramural pregnancy could not be confirmed by 4+5 gestational weeks. Following removal of the fluid and establishing the diagnosis of degenerated fibroid(s), the advancing pregnancy was somewhat uneventful, whereas the uterine wall lesion showed continuing growth. Both during delivery (via Caesarean section) and on repeated sonographic scans post partum the clinical diagnosis of uterine wall fibroids could be confirmed. The present case illustrates the feasibility of expectant monitoring of atypical fybroids in pregnancy. Nevertheless, a thorough sonographic monitoring as well as comprehensive counselling of the gravida is mandatory. Potentially more serious differential diagnoses (intramural pregnancy, uterine sarcoma) should be born in mind.

Intrafamilial medically assisted reproduction.

For different motives, couples in need of third party assisted reproduction sometimes prefer the help of a family member over an unrelated collaborator. Quantitative (frequency) and qualitative (experience) data about this practice are lacking or scarce. Forms of intrafamilial medically assisted reproduction (IMAR) are different with respect to (i) familial closeness between the collaborator and the person whose reproductive contribution he or she replaces and whether assistance would be intra- or intergenerational, (ii) the relationship between the collaborator and the fertile partner (this relationship may or may not be consanguineous) and (iii) with regard to the material (sperm and oocytes) that is donated and the services (surrogacy) that are offered. This document aims at providing guidance to the professional handling of requests for IMAR. It briefly sketches the background of this practice and discusses a variety of relevant normative aspects.

Cancer and fertility: strategies to preserve fertility.

Fertility preservation is a key component of cancer management in young people. The Fourth Evian Annual Reproduction Workshop Meeting was held in April 2009 to discuss cancer and fertility in young adults. Specialists in oncology, assisted reproduction, embryology and clinical genetics presented published data and ongoing research on cancer and fertility, with particular focus on strategies to preserve fertility. This report is based on the expert presentations and group discussions, supplemented with publications from literature searches and the authors' knowledge. Fertility preservation should be considered for all young people undergoing potentially gonadotoxic cancer treatment. A variety of options are required to facilitate safe and effective fertility preservation for individual patients. Sperm banking is a simple and low-cost intervention. Embryo cryopreservation is the only established method of female fertility preservation. Oocyte cryopreservation offers a useful option for women without a male partner. Emergency ovarian stimulation and cryopreservation of ovarian tissue (followed by tissue transplantation or in-vitro maturation of oocytes) are experimental techniques for women who require urgent cancer treatment. Further prospective studies are required to validate cryopreservation of oocytes and ovarian tissue, in-vitro maturation of oocytes and new vitrification techniques and to identify any long-term sequelae of slow freezing of embryos.

Seasonality of spina bifida in Northern Germany.

PURPOSE: To verify a seasonal variation in the incidence of spina bifida and thus to identify possible environmental triggers leading to its developement. METHODS: An interdisciplinary approach has been taken to develop a better understanding of spina bifida through collaborative efforts from investigators specializing in genetics, fetal pathology, paediatrics, neuro-surgery and prenatal ultrasonographic diagnosis. All pregnancies with fetal spina bifida were retrospectively analyzed from May 1 1993 through May 1 2010 at Luebeck University Fetal Health Center. Results were used to construct a model to predict the occurrence of fetal spina bifida based on seasonal variation and environmental influence reflected by climatic changes and environmental pollution. Furthermore, data were categorized in respect to the date of conception and subdivided into date of conception during summer (April-September) and winter months (October-March). RESULTS: Neither a seasonal distribution of conception for fetuses with spina bifida in the defined time frame could be verified nor a relevant influence of the analyzed environmental factors on the prevalence of spina bifida could be proved. The incidence of spina bifida has remained relatively stable within the last 17 years at 2.5 per 1,000 screened pregnancies. CONCLUSION: Since we were unable to demonstrate a relationship between seasonal variation and certain environmental factors on the incidence of fetal spina bifida, other factors should be investigated for a possible association with the onset of fetal spina bifida.

Teenage deliveries in Northern Germany: always a risk factor for higher surgical delivery rates?

PURPOSE: To evaluate the impact of young maternal age on labour, intrapartum assessment and delivery mode. METHODS: A retrospective cohort analysis was conducted of 13,941 deliveries at a tertiary delivery unit between 2000 and 2009. Patients aged less than 18 years were compared with patients aged 18 years or older. The main outcome was defined as mode of delivery. Frequencies and odds ratios for adverse maternal-foetal outcomes were calculated for primiparous women. RESULTS: Of the deliveries occurring during the study period, 6,863 (49.2%) met the inclusion criteria. A total of 156 deliveries (2.3%) occurred among teenagers less than 18 years and 6,707 among patients 18 years and older. Compared with patients 18 years of age and older, younger maternal age was associated with a higher chance of spontaneous delivery [adjusted odds ratio (OR) 2.07, 95% confidence interval (CI) 1.45-2.93] than via operation (vaginal operative delivery: OR 0.98, 95% CI 0.48-2.03; secondary caesarean delivery: adjusted OR 0.51, 95% CI 0.32-0.82). CONCLUSION: Young maternal age at delivery does not represent a risk factor for high surgical delivery rates.

Total laparoscopic hysterectomy without uterine manipulator: description of a new technique and its outcome.

INTRODUCTION: Hysterectomy remains the most common major gynecological operation. This is the first study that describes a new technique of TLH without using any kind of uterine manipulator or vaginal tube (TLHwM) and analyzes the intra- and postoperative surgical outcome of the first 67 cases. PATIENTS AND METHODS: Between October 2008 and December 2009, 67 patients underwent TLH without uterine manipulator or vaginal tube. We analyzed the differences in the outcome by using three different kinds of surgical instruments: in 21 cases the TLHwM was performed using conventional 5 mm bipolar and scissors, in 22 cases using Sonosurgical, and in 24 cases using PKS cutting forceps. RESULTS: There was no intra- or postoperative complications. The overall mean operating time was by TLHwM with salpingo-oophorectomy 98 min and without salpingo-oophorectomy, 80 min. The mean operating time using cutting forceps was significantly lower. The mean uterine weight was 263 g. DISCUSSION: Uterine manipulator seems to be a safe and practical surgical method, especially for patients with vaginal stenosis and in cases of enlarged uterus. With its short operation time and no complication rate, we believe that this method is an enrichment of the laparoscopic hysterectomy techniques.

94 months follow-up after laparoscopic assisted vaginal resection of septum rectovaginale and rectosigmoid in women with deep infiltrating endometriosis.

BACKGROUND: Endometriosis with bowel involvement is the most invasive form and can cause infertility, chronic pelvic pain and bowel symptoms. Effective surgical treatment of endometriosis requires complete excision of endometriosis and in same case may require segmental rectosigmoid resection. METHODS: Between December 1997 and October 2003, 55 patients with rectovaginal endometriosis underwent a combined laparoscopic vaginal technique. 30 patients were found at a follow-up and underwent a telephone interview. The questionnaire covered questions about symptoms related to recurrences of intestinal endometriosis, dyspareunia, dysmenorrhea and pregnancy. RESULTS: Twenty-seven of 30 (90%) women have no clinical symptoms of reported recurrence of endometriosis. Two patients (6.6%) had evidence of recurrence of bowel endometriosis. Dysmenorrhoea disappeared in 28 (93.3%), dyspareunia in 26 (86.7%) and pelvic pain in 27 (90%) patients. 17 patients (31%) tried to become pregnant and 11 of these patients (65%) became pregnant: 9 patients delivered healthy newborns, 18 pregnancies occurred and 19 healthy children were born. CONCLUSIONS: Despite the small number of follow-up patients, our 94-month follow-up data demonstrated that endometriosis with bowel involvement and radical resection was associated with significant reductions in painful and dysfunctional symptoms, a low recurrence rate (6.6%) and high pregnancy rate (36.6%).

Laparoscopic nerve-sparing surgery of deep infiltrating endometriosis: description of the technique and patients' outcome.

INTRODUCTION: The radical surgery of the deep infiltrating endometriosis of the rectovaginal septum and the uterosacral ligaments with or without bowel resection can cause a serious damage of the pelvic autonomic nerves with urinary retention and the need of self-catheterization. PATIENTS AND METHODS: We introduce a case series report of 16 patients with laparoscopic nerve-sparing surgery of deep infiltrating endometriosis. We describe the technique step by step and compare the patients' outcome with patients who had undergone a non-nerve-sparing surgical technique. In 12 patients, a double-sided and in four patients, a single-sided identification of the inferior hypogastric nerve and plexus were performed. RESULTS: In all patients at least single-sided resection of the uterosacral ligaments were performed. Postoperatively dysmenorrhoea, pelvic pain, and dyspareunia disappeared in all patients. The average operating time was 82 min (range 45-185). Postoperatively, the overall time to resume voiding function was 2 days. The residual urine volume was in all patients <50 ml at two ultrasound measurements. DISCUSSION: Identification of the inferior hypogastric nerve and plexus was feasible. In comparison with non-nerve-sparing surgical technique, no cases of bladder self-catheterization for a long or even life time was observed, confirming the importance of the nerve-sparing surgical procedure.