A randomized comparison of video demonstration versus hands-on training of medical students for vacuum delivery using Objective Structured Assessment of Technical Skills (OSATS).

BACKGROUND: To compare medical students' skills for vaginal operative delivery by vacuum extraction (VE) after hands-on training versus video demonstration. METHODS: We randomized medical students to an expert demonstration (group 1) or a hands-on (group 2) training using a standardized VE algorithm on a pelvic training model. Students were tested with a 40-item Objective Structured Assessment of Technical Skills (OSATS) scoring system after training and 4 days later. OSATS scores were the primary outcome. Performance time, self-assessment, confidence, and global rating scale were secondary outcomes. We assessed the constructive validity of OSATS in this VE model comparing metric scores of experts and students. RESULTS: In all, 137 students were randomized. OSATS scores were higher in group 2 (n = 63) compared with group 1 (n = 74) (32.89 ±â€Š6.39 vs 27.51 ±â€Š10.27, respectively; P < 0.0001). Global rating scale (1.49 ±â€Š0.76 vs 2.33 ±â€Š0.94, respectively; P < 0.0001), confidence (2.22 ±â€Š0.75 vs 3.26 ±â€Š0.94, respectively; P = 0.04), self-assessment (2.03 ±â€Š0.62 vs 2.51 ±â€Š0.77, respectively; P < 0.0001), and performance time (38.81 ±â€Š11.58 seconds vs 47.23 ±â€Š17.35 seconds, respectively; P = 0.001) also favored group 2. After 4 days, this effect persisted with OSATS scores still being significantly higher in group 2 (30.00 ±â€Š6.50 vs 25.59 ±â€Š6.09, respectively; P = 0.001). The assessed OSATS scores showed constructive validity. In a multiple linear regression analysis, group assignment independently influenced OSATS scores, whereas sex, handedness, sports activities, and type of curriculum were not independently associated with OSATS scores. CONCLUSIONS: Hands-on training is superior to video demonstration for teaching VE on a pelvic model.

Objective Structured Assessment of Technical Skills (OSATS) evaluation of theoretical versus hands-on training of vaginal breech delivery management: a randomized trial.

OBJECTIVE: To compare the skills of performing a vaginal breech (VB) delivery after hands-on training versus demonstration. STUDY DESIGN: We randomized medical students to a 30-min demonstration (group 1) or a 30-min hands-on (group 2) training session using a standardized VB management algorithm on a pelvic training model. Subjects were tested with a 25 item Objective Structured Assessment of Technical Skills (OSATS) scoring system immediately after training and 72 h thereafter. OSATS scores were the primary outcome. Performance time (PT), self assessment (SA), confidence (CON), and global rating scale (GRS) were the secondary outcomes. Statistics were performed using the Mann-Whitney U-test, chi-square test, and multiple linear regression analysis. RESULTS: 172 subjects were randomized. OSATS scores (primary outcome) were significantly higher in group 2 (n=88) compared to group 1 (n=84) (21.18±2.29 vs. 20.19±2.37, respectively; p=0.006). The secondary outcomes GRS (10.31±2.28 vs. 9.17±2.21; p=0.001), PT (214.60±57.97 s vs. 246.98±59.34 s; p<0.0001), and CON (3.14±0.89 vs. 2.85±0.90; p=0.04) were also significantly different between groups, favoring group 2. After 72 h, primary and secondary outcomes were not significantly different between groups. In a multiple linear regression analysis, group assignment (odds ratio [OR] 1.60; 95% confidence interval [CI] 1.14-2.05; p<0.0001) and gender (OR 2.91; 95% CI 2.45-3.38; p<0.0001) independently influenced OSATS scores. CONCLUSION: Hands-on training leads to a significant improvement of VB management in a pelvic training model, but this effect was only seen in the short term.

Objective structured assessment of technical skills evaluation of theoretical compared with hands-on training of shoulder dystocia management: a randomized controlled trial.

OBJECTIVE: To compare the skills of performing a shoulder dystocia management algorithm after hands-on training compared with demonstration. METHODS: We randomized medical students to a 30-minute hands-on (group 1) and a 30-minute demonstration (group 2) training session teaching a standardized shoulder dystocia management scheme on a pelvic training model. Participants were tested with a 22-item Objective Structured Assessment of Technical Skills scoring system after training and 72 hours thereafter. Objective Structured Assessment of Technical Skills scores were the primary outcome. Performance time, self-assessment, confidence, and global rating scale were the secondary outcomes. Statistics were performed using Mann-Whitney U test, χ test, and multiple linear regression analysis. RESULTS: Two hundred three participants were randomized. Objective Structured Assessment of Technical Skills scores were significantly higher in group 1 (n=103) compared with group 2 (n=100) (17.95±3.14 compared with 15.67±3.18, respectively; P<.001). The secondary outcomes global rating scale (GRS; 10.94±2.71 compared with 8.57±2.61, respectively; P<.001), self-assessment (3.15±0.94 compared with 2.72±1.01; P=.002), and confidence (3.72±0.98 compared with 3.34±0.90, respectively; P=.005), but not performance time (3:19±0:48 minutes compared with 3:31±1:05 minutes; P=.1), were also significantly different, favoring group 1. After 72 hours, Objective Structured Assessment of Technical Skills scores were still significantly higher in group 1 (n=67) compared with group 2 (n=60) (18.17±2.76 compared with 14.98±3.03, respectively; P<.001) as were GRS (10.80±2.62 compared with 8.15±2.59; P<.001) and self assessment (SA; 3.44±0.87 compared with 2.95±0.94; P=.003). In a multiple linear regression analysis, group assignment (group 1 compared with 2; P<.001) and sex (P=.002) independently influenced Objective Structured Assessment of Technical Skills scores. CONCLUSION: Hands-on training helps to achieve a significant improvement of shoulder dystocia management on a pelvic training model. CLINICAL TRIAL REGISTRATION: www.ClinicalTrials.gov, NCT01618565. LEVEL OF EVIDENCE: I.

Association of untrained labor companion with operative delivery rate: retrospective study of 2247 women.

OBJECTIVE: Support of a pregnant woman during labor by her partner is widely accepted, but the effect of the presence of the partner on delivery outcome is unknown. METHODS: We conducted a retrospective cohort study to evaluate delivery outcome, defined as spontaneous delivery vs. vaginal-operative delivery or cesarean section, in patients with a singleton pregnancy between 38 weeks and 0 days of gestation (38/0) and 41 weeks and 6 days of gestation (41/6), who planned a vaginal delivery at the Department of Obstetrics, Medical University of Vienna, between January 2007 and December 2009, with respect to the presence of the father in the delivery room compared to the presence of an untrained female supportive companion or no companion. Univariate and multivariate logistic regression analyses were used to assess delivery outcome with respect to clinical variables, such as patient age, parity, body mass index (BMI), induction of labor, fetal birth weight, and years of education of the parturient. RESULTS: The study included 2247 women; 212 (9%, group I) were accompanied by a female supportive companion, 1396 (62%, group II) were accompanied by a male supportive companion, and 639 women (29%, group III) were accompanied by no supportive companion. The vaginal-operative and cesarean delivery rates were not significantly different among the three groups (19% in group I vs. 17% in group II vs. 18% in group III, p=0.5). In a multivariate analysis, operative delivery outcome was significantly associated with higher maternal age (p<0.001), lower parity (p<0.0001), and labor induction (p=0.001) but not with gender of the supportive companion (male vs. no companion: p=0.11; female vs. no companion: p=0.90; male vs. female companion: p=0.23). CONCLUSION: Parity, maternal age, and labor induction but not the presence or the gender of the supportive companion are associated with the rate of operative deliveries.

Gene expression signatures of breast tissue before and after cross-sex hormone therapy in female-to-male transsexuals.

OBJECTIVE: To evaluate gene expression signatures of breast tissue in female-to-male (FtM) transsexuals under cross-sex hormone therapy (HT). DESIGN: Prospective cohort study. SETTING: Academic research institution. PATIENT(S): Five hormone-naïve FtM transsexuals before and after HT. INTERVENTION(S): Breast tissue biopsy before and after 2 years of intramuscular testosterone undecanoate (1,000 mg every 12 wk) and oral lynestrenole (5 mg daily), and gene signature analysis by global gene expression array covering 28,869 genes. MAIN OUTCOME MEASURE(S): Differential regulation of specific genes and gene expression signatures. RESULT(S): We identified 2,250 differentially expressed probe sets. One hundred twenty probe sets showed >2-fold change, of which 77 (64.2%) were up-regulated and 43 (35.8%) down-regulated. Genes involved in transcription were most overrepresented, with 43 out of 97 (44.3%) annotated probes, e.g., the transcription factor complex activator protein 1, including all three Jun genes (c-Jun, JunB, and JunD), two Fos genes (c-Fos and FosB), and activating transcription factor 3. In a Database for Annotation, Visualization, and Integrated Discovery analysis of the 2,007 down-regulated probe sets, proteins of the ribosome pathway and of two pathways involved in protein degradation, i.e., proteasome- and ubiquitin-mediated proteolysis, were significantly down-regulated. We identified eight breast cancer-associated gene expression signatures significantly overlapping with differentially regulated probe sets after cross-sex HT. CONCLUSION(S): Cross-sex HT in FtM transsexuals leads to the up-regulation and down-regulation of 243 and 2,007 distinct genes, respectively, and is associated with breast cancer-related gene expression signatures.

OCT-4 expression in follicular and luteal phase endometrium: a pilot study.

BACKGROUND: The stem cell marker Octamer-4 (OCT-4) is expressed in human endometrium. Menstrual cycle-dependency of OCT-4 expression has not been investigated to date. METHODS: In a prospective, single center cohort study of 98 women undergoing hysteroscopy during the follicular (n = 49) and the luteal (n = 40) phases of the menstrual cycle, we obtained endometrial samples. Specimens were investigated for OCT-4 expression on the mRNA and protein levels using reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Expression of OCT-4 was correlated to menstrual cycle phase. RESULTS: Of 89 women sampled, 49 were in the follicular phase and 40 were in the luteal phase. OCT-4 mRNA was detected in all samples. Increased OCT-4 mRNA levels in the follicular and luteal phases was found in 35/49 (71%) and 27/40 (68%) of women, respectively (p = 0.9). Increased expression of OCT-4 protein was identified in 56/89 (63%) samples. Increased expression of OCT-4 protein in the follicular and luteal phases was found in 33/49 (67%) and 23/40 (58%) of women, respectively (p = 0.5). CONCLUSIONS: On the mRNA and protein levels, OCT-4 is not differentially expressed during the menstrual cycle. Endometrial OCT-4 is not involved in or modulated by hormone-induced cyclical changes of the endometrium.

Incidence of thrombophilia and venous thrombosis in transsexuals under cross-sex hormone therapy.

OBJECTIVE: To evaluate the incidence of venous thromboembolism (VTE) in transsexual patients and the value of screening for thrombophilia in this population. DESIGN: Retrospective cohort study. SETTING: Academic research institution. PATIENT(S): Two hundred fifty-one transsexuals (162 male-to-female [MtF] and 89 female-to-male [FtM] transsexuals). INTERVENTION(S): Screening for activated protein C (aPC) resistance, antithrombin III, free protein S antigen, and protein C deficiency. MAIN OUTCOME MEASURE(S): Incidence of thrombophilic defects and VTE during cross-sex hormone therapy. RESULT(S): Activated protein C resistance was detected in 18/251 patients (7.2%), and protein C deficiency was detected in one patient (0.4%). None of the patients developed VTE under cross-sex hormone therapy during a mean of 64.2 +/- 38.0 months. There was no difference in the incidence of thrombophilia comparing MtF and FtM transsexuals (8.0% [13/162] vs. 5.6% [5/89], respectively). CONCLUSION(S): VTE during cross-sex hormone therapy is rare. General screening for thrombophilic defects in transsexual patients is not recommended. Cross-sex hormone therapy is feasible in MtF as well as in FtM patients with aPC resistance.

Side effects of phytoestrogens: a meta-analysis of randomized trials.

BACKGROUND: Phytoestrogens are widely used by postmenopausal women for the treatment of the climacteric syndrome. The risk of adverse effects of this treatment, however, is unknown. METHODS: Using a fixed-effects model, we performed a meta-analysis of side effects comparing phytoestrogen treatment with placebo or no treatment in randomized controlled trials. RESULTS: We identified 174 randomized controlled trials. Side effects were reported in 92/174 randomized controlled trials with 9629 participants. The overall incidence of side effects in the phytoestrogen and control groups was 2019/5502 (36.7%) and 1824/4806 (38.0%), respectively (P=.2; incidence rate ratio [IRR] 1.01; 95% confidence interval [CI], 0.95-1.08). Comparing various side effect categories, we found significantly higher rates of gastrointestinal side effects among phytoestrogen users (P=.003; IRR 1.28; 95% CI, 1.08-1.50). Gynecological (IRR 0.94; 95% CI, 0.74-1.20), musculoskeletal (IRR 1.20; 95% CI, 0.94-1.53), neurological (IRR 0.91; 95% CI, 0.70-1.19), and unspecific side effects (IRR 0.95; 95% CI, 0.88-1.03) were not significantly different between groups. Within side effect categories, we found no significantly higher rates of side effects in women using phytoestrogens. Specifically, the rates of hormone-related side effects such as endometrial hyperplasia, endometrial cancer, and breast cancer were not significantly different between groups. CONCLUSIONS: Based on the available evidence, phytoestrogen supplements have a safe side-effect profile with moderately elevated rates of gastrointestinal side effects. Rates of vaginal bleeding, endometrial hyperplasia, endometrial cancer, and breast cancer were not significantly increased among phytoestrogen users in the investigated studies.

Intrauterine fetal death and delivery complications associated with coagulopathy: a retrospective analysis of 104 cases.

OBJECTIVE: To assess the prevalence of delivery complications associated with coagulopathy in women with intrauterine fetal death (IUFD). METHODS: This is a retrospective cohort study of women with IUFD at >24 weeks gestation or a birth weight of >500 g between 1994 and 2007. Clinical data were assessed by chart review. RESULTS: One hundred four women were diagnosed with IUFD. The mean time between diagnosis of IUFD and delivery was 28.8 (+/-17.4) hours. Twelve of 104 (11.5%) women had a delivery complication associated with coagulopathy, defined as need for blood transfusion. In 8 of these 12 women, coagulopathy was associated with a preexisting preeclampsia/hemolysis, elevated liver enzymes, low platelet (HELLP) syndrome, uterine rupture after induction, or an acute clinical problem at presentation to the clinic. In 4 of 104 (4%) women, there was no attributable cause of coagulopathy other than IUFD. In these women, there was a statistically significant difference of laboratory parameters of coagulation at the time of diagnosis of IUFD compared with women who did not subsequently develop coagulopathy; platelet count 93.3 +/- 96.4 vs. 229.3 +/- 68.1 G/L, p < 0.001; prothrombin time (PT) 97.0 +/- 43.9 vs. 123.3 +/- 21.1 %, p = 0.02; activated partial thromboplastin time (aPTT) 42.9 +/- 34.0 vs. 31.5 +/- 4.3 sec, p = 0.01; thrombin time (TT) 22.8 +/- 16.5 vs. 14.1 +/- 13.3 sec, p = 0.02), plasma fibrinogen 219.0 +/- 117.5 vs. 472.9 +/- 122.8 mg/dL, p < 0.001), and antithrombin III 70.5 +/- 21.9 vs. 101.5 +/- 17.0 %, p = 0.01. CONCLUSIONS: Delivery complications associated with coagulopathy occur in 11% of women with IUFD and are associated with preexisting preeclampsia/HELLP, uterine rupture, or an acute clinical problem in most cases. In 4% of women with IUFD, coagulopathy develops without an apparent cause.

Prognostic value of human epidermal growth factor receptor 2 (Her-2)/neu in patients with advanced ovarian cancer treated with platinum/paclitaxel as first-line chemotherapy: a retrospective evaluation of the AGO-OVAR 3 Trial by the AGO OVAR Germany.

OBJECTIVES: Results on the prognostic value of human epidermal growth factor receptor 2 (HER-2)/neu in ovarian cancer are inconsistent. This exploratory analysis evaluates Her-2/neu as a prognostic factor in a large cohort of patients with advanced-stage ovarian cancer treated with platinum/paclitaxel as first-line chemotherapy within a prospective randomized trial. METHODS: Her-2/neu expression was assessed by immunohistochemistry in 359 patients (46%) treated within the AGO-OVAR 3 trial (n = 783). Patients received either cisplatin/paclitaxel or carboplatin/paclitaxel according to the study protocol. Immunohistochemistry results were scored according to the Dako score. RESULTS: Her-2/neu Dako scores of 0 or 1+ was found in 337 patients (94%) and a score of 2+ or 3+ in 22 patients (6%). Her-2/neu overexpression (2+/3+) was associated with a higher International Federation of Gynecology and Obstetrics stage and larger postoperative residual disease. There were no significant differences in response to chemotherapy between the Her-2/neu score subgroups and in progression-free survival time. In a multivariate analysis, the Her-2/neu score had no significant impact on overall survival time. CONCLUSIONS: In the present study, Her-2/neu overexpression in patients with advanced-stage ovarian cancer was rare and provided no evidence for a prognostic value of Her-2/neu in patients with advanced ovarian cancer treated with platinum/paclitaxel.

Clinical outcome monitoring in a reproductive surgery unit: a prospective cohort study in 796 patients.

OBJECTIVE: To systematically monitor the frequency and risk factors of adverse events (AEs) in a reproductive surgery endoscopy unit. DESIGN: Prospective cohort study. SETTING: Academic research institution. PATIENT(S): All consecutive surgical patients of a reproductive surgery unit from December 2005 to March 2007. INTERVENTION(S): Monitoring for predefined AEs by trained observers. MAIN OUTCOME MEASURE(S): Number of preventable and not preventable AEs, medical errors, and system problems. Univariate analysis and multivariate logistic regression were used to identify risk factors of AEs. RESULT(S): Seven hundred ninety-six women were included. We identified 60 AEs in 45 patients (risk 6%; 95% confidence interval [CI] 1%-11%). Adverse events were postoperative fever (n = 1), wound breakdown (n = 1), intraoperative or postoperative administration of packed erythrocytes (n = 6), surgical revision (n = 7), unplanned readmission (n = 5), transfer to intensive care unit (n = 1), conversion (n = 8), intraoperative organ injury (n = 9), blood loss >500 mL (n = 3), surgery canceled (n = 15), and other AEs (n = 4). Six patients (risk 0.8%; 95% CI 0-2%) had multiple AEs. One (0.01%) and 11 (1.4%) AEs were deemed due to medical errors and system problems, respectively. Twelve and 48 AEs were deemed preventable and not preventable, respectively. In a univariate and multivariate analysis, only duration of surgery (odds ratio 3.78; 95% CI 1.95-7.33) was significantly associated with having an AE. CONCLUSION(S): Clinical outcome monitoring is a useful tool for assessing the outcome quality of reproductive surgery by identifying potentially preventable AEs and associated risk factors.

Endocervical cytobrush for the detection of cervical dysplasia before large loop excision of the transformation zone (LLETZ).

BACKGROUND: We aimed to identify the number of histologically verified cervical intraepithelial neoplasia (CIN)/cervical cancer lesions detected by endocervical cytobrush (EC) which have been missed by repeat PAP smear and colposcopy before large loop excision of the transformation zone (LLETZ). PATIENTS AND METHODS: A retrospective cohort study of 1,676 consecutive patients in a colposcopy clinic undergoing repeat PAP smear, colposcopy, biopsy, and subsequent LLETZ. RESULTS: Data were available for 1,421 patients. EC identified 31/1,367 (2.2%) cases of CIN and/or cervical cancer missed by repeat PAP smear and colposcopy. Compared to repeat PAP smear and colposcopy, the combination of repeat PAP smear, colposcopy and EC increased the positive predictive value (PPV) (89.6% vs. 98.9%, p=0.07), but this difference was not statistically significant. Sensitivity (93.1% vs. 93.9%; p=0.8), specificity (27.7% vs. 27.7%; p=1.0), and negative predictive value (NPV) (11.9% vs. 13.1%, p=0.9) were also not significantly different. The number needed to screen (NNS) for identifying one additional case of CIN and/or invasive cancer by EC was 45. In a multivariate analysis, presence of CIN/cervical cancer in the LLETZ specimen and human papilloma virus infection, but not age, visibility of the transformation zone or presence of an endovcervical lesion were independently associated with the likelihood of CIN and/or invasive cancer detected by EC. CONCLUSION: Adding EC to repeat PAP smear and colposcopy identifies 2.2% more cases of CIN and/or cervical cancer, but does not significantly increase the sensitivity, specificity, PPV or NPV of repeat PAP smear and colposcopy.

Non-contraceptive benefits of oral contraceptives.

BACKGROUND: There is increasing awareness of the opportunity that many contraceptive interventions may provide for additional health benefits. However, treatment of medical problems with oral contraceptives (OCs) is often an 'off-label' practice. OBJECTIVE: The aim of this review is to summarize available data on non-contraceptive benefits of OCs. METHODS: Review of the literature. RESULTS: OCs have been shown to reduce the risk of ovarian, endometrial, and colorectal cancer. It has been suggested that OCs may be used in treatment of endometriosis, menorrhagia, and uterine leiomyomas. Pelvic inflammatory disease, dysmenorrhea, premenstrual syndrome, and acne have been shown to improve under OCs. CONCLUSION: OCs are important for global and female health. Besides contraception, non-contraceptive effects of OCs are evidence based, well established, and commonly used in clinical practice.

TNFalpha -308 C-->t and -863 C-->a polymorphisms and spermiogram characteristics.

BACKGROUND: Genetic factors may play a role in male infertility. METHODS: In a prospective case-control study, we assessed the allele and genotype frequencies of the TNFalpha -308 C-->T and -863 C-->A polymorphisms, detected by PCR of sperm DNA, of 577 Caucasian men recruited in an infertility clinic. Semen sampling was performed and spermiogram results were correlated to genetic data. RESULTS: The allele frequencies of the TNFalpha -308 C-->T and -863 C-->A polymorphisms were not significantly different between non-normozoospermic (n = 447) and normozoospermic (n = 130) men [758/894 (85%) and 134/894 (15%) vs. 213/269 (82%) and 43/260 (18%), p = 0.5, odds ratio (OR) 1.1, 95% confidence interval (CI) 0.74-1.76, and 749/894 (84%) and 145/894 (16%) vs. 212/260 (82%) and 48/260 (18%), p = 0.4, OR 1.2, 95% CI 0.78-1.76, respectively]. The genotype frequencies of the TNFalpha -308 C-->T and -863 C-->A polymorphisms were also not significantly different between non-normozoospermic and normozoospermic men. In addition, mutant alleles were not overrepresented in subgroups of men with the oligoasthenoteratozoospermia syndrome and asthenozoospermia. CONCLUSION: The TNFalpha -308 C-->T and -863 C-->A polymorphisms are not associated with spermiogram characteristics and do not represent molecular markers for genetic susceptibility to male infertility.

A polymorphism of the CYP17 gene related to sex steroid metabolism is associated with female-to-male but not male-to-female transsexualism.

OBJECTIVE: To assess the association between transsexualism and allele and genotype frequencies of the common cytochrome P450 (CYP) 17 -34 T>C single nucleotide polymorphism (SNP). DESIGN: Case-control study. SETTING: Academic research institution. PATIENT(S): 102 male-to-female (MtF) and 49 female-to-male (FtM) transsexuals, 756 male controls, and 915 female controls. INTERVENTION(S): Buccal swabs and multiplex polymerase chain reaction on a microarray system. MAIN OUTCOME MEASURE(S): Analysis of the CYP17 -34 T>C SNP. RESULT(S): CYP17 -34 T>C SNP allele frequencies were statistically significantly different between FtM transsexuals and female controls (CYP17 T: 55/98 [56%] and CYP17 C: 43/98 [44%] versus CYP17 T: 1253/1826 [69%] and CYP17 C: 573/1826 [31%], respectively). In accordance, genotype distributions were also different between FtM transsexuals and female controls using a recessive genotype model (CYP17 T/T+T/C: 39/49 [80%] and C/C 10/49 [20%] vs. CYP17 T/T+T/C: 821/913 [90%] and C/C 92/913 [10%], respectively). The CYP17 -34 T>C allele and genotype distributions were not statistically significantly different between MtF transsexuals and male controls. Of note, the CYP17 -34 T>C allele distribution was gender-specific among controls (CYP17 C: males; 604 of 1512 [40%] vs. females; 573 of 1826 [31%]). The MtF transsexuals had an allele distribution equivalent to male controls, whereas FtM transsexuals did not follow the gender-specific allele distribution of female controls but rather had an allele distribution equivalent to MtF transsexuals and male controls. CONCLUSION(S): These data support CYP17 as a candidate gene of FtM transsexualism and indicate that loss of a female-specific CYP17 T -34C allele distribution pattern is associated with FtM transsexualism.

A common polymorphism of the SRD5A2 gene and transsexualism.

The relation between genetic variation of the androgen metabolism and transsexualism is unknown. In a case-control study of 100 male-to-female (MtF) transsexuals, 47 female-to-male (FtM) transsexuals, and 1670 controls, the authors assess allele and genotype frequencies of the steroid 5-alpha reductase (SRD5A2) Val89Leu polymorphism using polymerase chain reaction. Allele and genotype frequencies are not significantly different between MtF transsexuals and male controls (SRD5A2 V: 137/200 [69%] and SRD5A2 L: 63/200 [31%] vs 1065/1510 [71%] and 445/1510 [29%], respectively; P = .6; odds ratio [OR], 1.10; 95% confidence interval [CI], 0.76-1.58; SRD5A2 V/V+V/L: 92/100 [92%] and L/L 8/100 [8%] vs SRD5A2 683/755 [91%] and 72/755 [9%], respectively, P = .7; OR, 0.82; 95% CI, 0.24-2.84). Allele and genotype frequencies are also not significantly different between FtM transsexuals and female controls (SRD5A2 V: 70/94 [74%] and SRD5A2 L: 24/94 [26%] vs 1253/1830 [69%] and 573/1830 [31%], respectively; P = .3; OR, 0.75; 95% CI, 0.45-1.26; SRD5A2 V/V+V/L: 44/47 [93%] and L/L 3/47 [7%] vs 823/915 [90%] and 92/915 [10%], respectively, P = .6; OR, 0.61; 95% CI, 0.11-3.32). Of note, there is no gender-specific genotype distribution among controls. The SRD5A2 Val89Leu SNP is not associated with transsexualism, refuting SRD5A2 as a candidate gene of transsexualism.

A tumor necrosis factor-alpha promoter polymorphism and pregnancy complications: results of a prospective cohort study in 1652 pregnant women.

The purpose of this article is to investigate the frequency of the tumor necrosis factor-alpha (TNF-alpha) -308 G/A single nucleotide polymorphism in women with intrauterine fetal death, preeclampsia, preterm delivery, and small-for-gestational-age (SGA) infants. In a prospective cohort study, DNA from 1652 consecutive pregnant women was analyzed for TNF-alpha -308 G/A by polymerase chain reaction. Women who developed at least 1 of the predefined pregnancy complications were used as cases and compared to women without pregnancy complications. Of 1652 women, 268 (16.2%) developed at least 1 pregnancy complication. TNF-alpha -308 G/A allele frequencies (G: 463/536 [86%] and A: 73/536 [14%] vs G: 2366/2768 [85%] and A: 402/2768 [15%], respectively; P = .6; odds ratio [OR], 0.93; 95% confidence interval [CI], 0.69-1.25) and genotype distributions (G/G+G/A: 259/268 [97%] and A/A 9/268 [3%] vs G/G+G/A: 1352/1384 [98%] and A/A 32/1384 [2%], respectively; P = .4; OR, 0.20; 95% CI, 0.002-14.81) were not significantly different between cases and controls. The authors observed no statistically significant difference in TNF-a -308 G/A genotype distributions comparing controls and women with intrauterine fetal death, preeclampsia, preterm delivery <34 weeks' gestation, preterm delivery >34 weeks' gestation, SGA infants <3rd percentile, and SGA infants of the 4th to 10th percentile. TNF-alpha -308 G/A is not a genetic marker for identifying women at increased risk of common pregnancy complications.

Methylenetetrahydrofolate reductase C677T polymorphism and pregnancy complications.

OBJECTIVE: To investigate the frequency of the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in women with intrauterine fetal death, preeclampsia, preterm delivery, and small for gestational age (SGA) infants. METHODS: In a prospective cohort study, DNA from 2,000 pregnant women were analyzed for MTHFR C677T by DNA microarray (wild-type allele, C; mutant allele, T). RESULTS: One thousand six hundred seventy-five women completed the study. Of these, 16.6% (278 women with 556 genetic alleles) developed at least one pregnancy complication and were designated study cases. There were 1,397 women (with 2,794 genetic alleles) who served as controls. MTHFR C677T allele frequencies were significantly different between cases and controls (C [wild-type]: 346 of 556 [62%]; T [mutant]: 210 of 556 [38%] compared with C: 1,911 of 2,794 [68%]; T: 883 of 2,794 [32%]; P=.005; odds ratio [OR] 1.23, 95% confidence interval [CI] 1.06-1.42). Genotype distributions were also different between cases and controls (C/T+T/T [abnormal]: 174 of 278 [63%]; C/C [normal]: 104 of 278 [37%] compared with C/T+T/T: 728 of 1,397 [52%]; C/C 669 of 1,397 [48%]; P=.002; OR 1.54, 95% CI 1.18-2.02). The clinical effect of the MTHFR C677T polymorphism was restricted to women with SGA infants (P=.05; OR 1.33, 95% CI 1.00-1.77). No significant differences in genotype distributions were observed among women with intrauterine fetal death, preeclampsia, and preterm delivery. CONCLUSION: MTHFR C677T is a genetic marker for identifying women at increased risk of SGA infants. LEVEL OF EVIDENCE: II.

Accuracy of intraoperative frozen section analysis in borderline tumors of the ovary: a retrospective analysis of 96 cases and review of the literature.

OBJECTIVE: To assess the sensitivity and positive predictive value (PPV) of intraoperative frozen section diagnosis of borderline tumors of the ovary (BTO). METHODS: Retrospective analysis at the Department of Obstetrics and Gynecology, University of Vienna, between 1995 and 2007 and review of the literature. Frozen section analysis and definitive histology reports were compared. Univariate and multivariate regression models were used to assess the influence of patient and tumor characteristics on the likelihood of underdiagnosis and overdiagnosis. RESULTS: Agreement between frozen section diagnosis and definitive histology was observed in 69/96 (71.9%) patients, yielding an overall sensitivity and a positive predictive value of 75.0% and 94.5%, respectively. Underdiagnosis and overdiagnosis occurred in 27/96 (28%) and 0/96 (0%) patients, respectively. In a univariate and multivariate analysis, tumor diameter, but not patient age, tumor histology, tumor stage, presence of a bilateral tumor, serum CA-125 and concurrent presence of endometriosis was a predictor of underdiagnosis of frozen section analysis. We identified 29 studies investigating the accuracy of frozen section analysis of BTO. Three studies exclusively examined BTO in 140, 48 and 33 cases, respectively. Data of these three studies and the present study were pooled, yielding an overall sensitivity and PPV of 71.1% and 84.3%, respectively. Overdiagnosis and underdiagnosis were identified in 21/317 (6.6%) and in 97/317 (30.6%) cases, respectively. CONCLUSION: Intraoperative frozen section diagnosis of BTO has a low sensitivity and PPV and overdiagnosis and underdiagnosis are frequent. Surgical management based on intraoperative frozen section diagnosis should be used with caution.

Phytoestrogens in clinical practice: a review of the literature.

OBJECTIVE: To review clinical studies assessing the effect of phytoestrogen supplementation on the signs and symptoms of the climacteric syndrome and on the incidence of breast cancer, cardiovascular disease, and skeletal fractures. DESIGN: Literature research using PubMed and the Cochrane controlled trials register. SETTING: None. PATIENT(S): None. INTERVENTION(S): None. MAIN OUTCOME MEASURE(S): None. RESULT(S): Six systematic reviews and meta-analyses of 25 randomized, controlled trials (RCTs) assessing the use of phytoestrogens for the treatment of the climacteric syndrome were identified. Systematic reviews of RCTs show contradictory results, and meta-analyses demonstrate no statistically significant reduction of vasomotor symptoms for phytoestrogens. Individual RCTs report significant reductions in vasomotor symptoms for red clover and soy phytoestrogens. In selected patient populations, such as in women with early natural postmenopause and mild to moderate vasomotor symptoms, a systematic review of five RCTs found a significant reduction of hot flashes in five out of five RCTs. Twenty-two case-control and cohort studies examined the incidence of breast cancer among women with and without a diet high in phytoestrogens. A meta-analysis of 21 studies found a significantly reduced incidence of breast cancer among past phytoestrogen users. RCTs document beneficial effects of phytoestrogens on surrogate parameters such as bone mineral density, vasodilation, platelet aggregation, insulin resistance, and serum concentrations of triglycerides, high-density lipoprotein, and low-density lipoprotein. None of the available RCTs documents a protective effect of phytoestrogens for the clinical end points of breast cancer, bone fracture, or cardiovascular events. CONCLUSION(S): Based on the available evidence, phytoestrogens should only be used in selected women, i.e., those presenting with mild to moderate vasomotor symptoms in early natural postmenopause. None of the compounds investigated so far have been proven to protect against breast cancer, bone fracture, or cardiovascular disease.