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To describe pregnancy outcomes in women who conceived after undergoing transcervical fibroid ablation (TFA) as treatment for symptomatic uterine fibroids.TFA was used to treat symptomatic uterine fibroids with radiofrequency energy, both under clinical trial protocol and commercial usage in hospitals in Europe, the United Kingdom, Mexico, and the United States. All women who reported pregnancies to their physicians after undergoing TFA with the SonataThere have been 36 pregnancies representing 20 deliveries among 28 women who were treated with TFA. Five women conceived more than once postablation, and four conceived as a result of assisted reproductive technology (ART). Outcomes include 8 vaginal deliveries, 12 Cesarean sections, 3 therapeutic abortions, and 8 first trimester spontaneous abortions (four occurring in a patient with a history of recurrent pregnancy loss and an immunologic disorder). Five women are currently pregnant, two of whom previously delivered after TFA. There were no 5-minute Apgar scores7, and all neonates weighed2500 g. All deliveries occurred at ≥37 weeks except for one delivery at 35 6/7 weeks. There were no uterine ruptures or abnormal placentation and no reports of postpartum hemorrhage or stillbirths. Ablated fibroids included transmural, submucous, and intramural myomata up to 7 cm in diameter.Normal pregnancy outcomes at term have occurred after TFA with the Sonata System, including in women with recurrent abortion and in those undergoing ART. There were no instances of low Apgar scores, low birthweight, stillbirth, postpartum hemorrhage, or uterine rupture (FAST-EU, NCT01226290; SONATA, NCT02228174; SAGE, NCT03 118037). (J GYNECOL SURG 38:207).

BackgroundEndometriosis is a benign, hormone-dependent, chronic inflammatory gynecological disease accompanied by cyclic and acyclic pelvic pain and other complaints. The long lists of research recommendations in the AWMF guideline [5] and ESHRE Endometriosis Guideline [6] show that there is still a great need for research in all aspects of the disease. Diagnostic delay, defined as the mean time between symptom onset and confirmed diagnosis, is a particular problem associated with endometriosis. Some quantitative and qualitative studies have investigated possible reasons for this. A range of physician-related [7, 8] and patient-related factors [9] as well as stigmatization of the topic of menstruation by society have been identified [10, 11]. The consequences of the disease being diagnosed late (or too late) on the course of disease, the quality of life and the costs of the disease have already been documented in studies [12, 13]. However, a systematically derived cut-off value that clearly distinguishes between short and long delay is still lacking. Therefore, the aim of our study was to derive a threshold value for the definition of a target corridor for endometriosis diagnosis based on descriptive and analytical methods.MethodsSince our review of the rather sparse publications on diagnostic delay did not yield satisfactory results, we used descriptive statistics and location parameters to calculate a cut-off value for German population data from the EndoCost study. Statistical methods were used for correlation analysis of shortDD versus longDD (correlation analysis and logistic regression) and group membership (discriminant analysis). ResultsFive years was identified as the cut-off value that significantly differentiated between shortDD and longDD based on various disease-related variables. This suggests that endometriosis should be definitively diagnosed within less than five years to minimize the risk of an unfavorable course of the disease. Our findings confirmed that an early onset of endometriosis-related symptoms is the most important risk factor for a long diagnostic delay. Consequently, adolescent females should receive increased attention as an especially vulnerable group. Evidently, there is an urgent need to develop adequate concepts to improve the endometriosis education and care among this target group.

Background Over the past decades the use of assisted reproduction technology (ART) increased worldwide. ARTs are associated with an elevated risk for cardiovascular complications. However, a potential relation between subfertility/ARTs and the heart disease peripartum cardiomyopathy (PPCM) has not been systematically analyzed yet. Methods A retrospective cohort study was carried out, including n = 111 PPCM patients from the German PPCM registry. Data from PPCM patients were compared to those from postpartum women in the German general population. Results The prevalence of reported subfertility was high among PPCM patients (30%; 33/111). Most of the subfertile PPCM patients (55%; 18/33) obtained vitro fertilizations (IVF) or intracytoplasmic sperm injections (ICSI). PPCM patients were older (p p p p p n = 15 subfertile PPCM patients revealed that 33% (5/15) carried pathogenic or likely pathogenic gene variants associated with cardiomyopathies and/or cancer predisposition syndrome. Conclusions Subfertility occurred frequently among PPCM patients and was associated with increased age, hormonal disorders, higher twin pregnancy rate and high prevalence of pathogenic gene variants suggesting a causal relationship between subfertility and PPCM. Although this study found no evidence that the ART treatment per se increases the risk for PPCM or the risk for an adverse outcome, women with subfertility should be closely monitored for signs of peripartum heart failure. Graphical abstract

Background To test the effects of guided endurance training on work ability in middle-aged female hospital workers of various occupations. Methods We randomized 265 healthy, sedentary, middle-aged women (45–65 years) to an endurance training group (EG 210 min/week) or a wait-list control group (CG). At baseline and at 6-month follow-up, we assessed work ability (Work Ability Index [WAI]), physical activity (Freiburger activity questionnaire) and peak oxygen uptake (VO2peak) by cardiopulmonary exercise testing. To examine the influence of baseline work ability, participants were divided into poor-moderate (WAI 1, 7–36 points, n = 83), good (WAI 2, 37–43 points, n = 136) and excellent (WAI 3, 44–49 points, n = 46) WAI subgroups. Results Cardiorespiratory fitness improved significantly after 6 months in the EG but not in the CG. The WAI total score increased significantly in the EG (38.3 ± 5.0 to 39.8 ± 4.9 points) but not in the CG (39.4 ± 4.7 to 39.3 ± 4.9 points), with a significant difference between groups (p p Conclusions A 6-month guided exercise training intervention significantly increases cardiorespiratory fitness with concomitant improvements in work ability in middle-aged previously sedentary hospital employees. Women with low baseline work ability seem to particularly benefit from the intervention, which implies that similar interventions may be particularly beneficial for this group of individuals. Trial registration German Clinical Trails Register Identifier: DRKS00005159. Registered 25 September 2013.

Purpose of Review Persistent genital arousal disorder (PGAD) is a rare, yet debilitating, disease, which was first described at the beginning of this century and has not yet been considered by the ICD-10 or DSM-5. Since affected subjects usually suffer tremendously, this review aims at offering an overview of pharmacological approaches to treat this disorder. Recent Findings Until now, no randomised placebo-controlled clinical trials have been conducted on PGAD, and the international registries have not recorded any ongoing trials. Current knowledge on pharmacological options for the treatment of PGAD relies mainly on case reports/case series. Most importantly, there is evidence that some drugs such as SSRIs and SNRIs might induce or worsen PGAD. Summary Knowledge on pharmacological treatment options for PGAD is not yet evidence-based, while some reports even assume an induction of PGAD by serotonergic antidepressants. Nevertheless, practitioners should be aware of PGAD and carefully discuss with the patient an individual treatment trial by considering the experience up to now.

Background: Nowadays, frozen-thawed embryo transfer (FET) cycles represent a high proportion of fertility treatments worldwide. Recent studies suggest differences in pregnancy outcomes depending on the FET treatment protocol used. The reason for this is still unclear, but the number of corpora lutea (CL) at conception is discussed as a possible factor. This study aims to investigate whether maternal and neonatal outcomes for pregnancies following FET lacking a CL differ from FET with one or more CL in order to explore a potential link between CL absence and adverse pregnancy outcomes.Methods: The study was designed as a retrospective, multi-center observational study with two cohorts after singleton live birth [0 CL cohort (FET in a programmed cycle, n = 114) and ≥ 1 CL cohort (FET in a natural or stimulated cycle, n = 68)]. Participants completed a questionnaire on the outcome of pregnancy and birth records were analyzed in a descriptive way. Multivariable logistic and linear regressions were performed in order to explore associations between CL absence and pregnancy outcomes. The strength of the agreement between the information in the survey and the diagnoses extracted from the files was assessed by Cohen's Kappa.Results: The risk of hypertensive disorders of pregnancy was higher after FET in the absence of a CL compared to FET with CL presence (aOR 5.56, 95% CI 1.12 – 27.72). Birthweights and birthweight percentiles were significantly higher in the 0 CL group. CL absence was a predictor of higher birthweight (adjusted coefficient B 179.74, 95% CI 13.03 – 346.44) and higher birthweight percentiles (adjusted coefficient B 10.23, 95%, 95% CI 2.28 – 18.40) particularly in female newborns of the 0 CL cohort. While the strength of the agreement between the reported information in the survey and the actual diagnoses extracted from the files was good for the majority of outcomes of interest it was fair in terms of hypertension (κ = 0.38).Conclusion: This study supports observations suggesting a potential link between a lack of CL at conception and adverse maternal and neonatal outcomes. Further investigations on causes and pathophysiological relationships are yet to be conducted.

Purpose This study sought the views of women with impaired fertility on the impact of the COVID-19 pandemic on their fertility treatment and psychological wellbeing. Methods A cross-sectional, anonymous, online questionnaire was completed in June–December 2020 by 249 women attending fertility clinics across Germany. All women seeking treatment in fertility clinics were eligible to participate. The online survey covered questions about the patient’s quality of life, their opinions about the professional societies’ recommendations and their effects as well as any concerns about infection with SARS-CoV-2. Results Three-quarters of participants disagreed with the pausing of fertility treatments. Women who participated from October to December 2020, when the incidence rate was high, were as likely to disagree as participants that participated from June to September 2020 (73% vs 79%, p = 0.3). Seventy-two participants (29%) had their appointments cancelled. Nearly all (97%) reported being upset by this, with 40 (56%) reporting that they were extremely or very disappointed about the cancellation. Women who had to wait 10 weeks or longer were more likely to be upset by the postponement or cancellation of their appointment than women who had to wait a shorter amount of time (p = 0.01). Many participants (41%) were worried about possible negative effects a SARS-CoV-2 infection might have related to their fertility, pregnancy or unborn child. Conclusion Postponement of treatments increased distress among patients and should be avoided when possible. Fertility clinics must provide information about the current state of knowledge of SARS-CoV-2 infections in pregnancies and options for immunization.

Müllerian anomalies comprise the Mayer-Rokitansky-Küster-Hauser syndrome as well as fusion defects of the müllerian ducts. Recurrent micro-aberrations like deletions in 16p11.2 encompassing TBX6 were found to be causative in these patients. TBX6 encodes a transcription factor which plays a role in paraxial mesoderm differentiation/specification. In previous studies, we and other groups found possibly pathogenic variants in TBX6 in patients with müllerian anomalies. Since we suggested TBX6 as a strong candidate, we performed sequential analysis of the TBX6 gene in additional 125 patients with müllerian anomalies, and 2 possibly pathogenic missense variants and 1 nonsense substitution in TBX6 in 4/125 patients were found. The missense variant c.484G>A, which we have described in a previous study, was reidentified but with no higher frequency as in our controls. We detected 3 possibly pathogenic variants in TBX6 and could show that the variant c.484G>A is not causative for disorders of the müllerian ducts in the non-Finnish European population. In summary, we present increasing evidence for association of variants in TBX6 with malformations of the müllerian ducts.

BackgroundTo test the effects of guided endurance training on work ability in middle-aged female hospital workers of various occupations. Methods We randomized 265 healthy, sedentary, middle-aged women (45-65 years) to an endurance training group (EG 210 min/week) or a wait-list control group (CG). At baseline and at 6-month follow-up, we assessed work ability (Work Ability Index [WAI]), physical activity (Freiburger activity questionnaire) and peak oxygen uptake (VO2peak) by cardiopulmonary exercise testing. To examine the influence of baseline work ability, participants were divided into poor-moderate (WAI 1, 7-36 points, n=83), good (WAI 2, 37-43 points, n=136) and excellent (WAI 3, 44-49 points, n=46) WAI subgroups.ResultsCardiorespiratory fitness improved significantly after 6 months in the EG but not in the CG. The WAI total score increased significantly in the EG (38.3±5.0 to 39.8±4.9 points) but not in the CG (39.4±4.7 to 39.3±4.9 points), with a significant difference between groups (pConclusionsA 6-month guided exercise training intervention significantly increases cardiorespiratory fitness with concomitant improvements in work ability in middle-aged previously sedentary hospital employees. Women with low baseline work ability seem to particularly benefit from the intervention, which implies that similar interventions may be particularly beneficial for this group of individuals.

For the last two decades, obesity rates have been increasing in both developed and developing countries, with the number of obese women roughly doubling during this period (Stevens et al. in Popul Health Metr 10(1):33, 2012). Obesity represents one of the biggest epidemics of the 21st century. The aim of this retrospective study is to characterise the outcomes of gynaecologic surgeries in cases of extremely obese women with a body mass index (BMI) over 40 kg/m2. This study is a retrospective case control study in a single-centre setting. Our clinical database was searched for gynaecological operations performed on morbidly obese patients (BMI > 40 kg/m2) between 2009 and 2014 in the Department of Gynaecology and Obstetrics at Hannover Medical School. We matched these results with random patients of normal body weight who had similar surgical procedures and diseases. We included 97 obese patients in our case group and 99 patients in the control group. We found an association between a strongly elevated BMI and peri- and postoperative morbidity. Both intraoperative and postoperative complications are significantly increased in morbid obesity with a BMI over > 40 kg/m2. We observed intraoperative complications in 55.6% and postoperative complications in 50.5% of patients with extreme obesity. In contrast, the complication rate in the control group with a normal BMI was 11% intraoperatively (p = 0.0001) and 3% postoperatively (p = 0.0001). The data showed that perioperative and postoperative morbidity could be reduced by laparoscopic surgery in many cases, with a significant lower rate of difficulties with closing the wound, a significant shorter duration of surgery and a significant lower rate of infections combined with a significant lower reoperation rate and shorter hospital stay. In gynaecological–oncological diseases, we could demonstrate a reduced radicality during the operative procedure due to extreme obesity. Dealing with the growing number of obese patients is essential, because the problems emerging from obesity are manifold for the treating hospitals as well as the general health system. For this high-risk patient group, it is indispensable to obtain a thorough overview of the patient’s overall situation preoperatively to ensure good perioperative care and complications management.

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

The putative association between hormones and cognitive performance is controversial. While there is evidence that estradiol plays a neuroprotective role, hormone treatment has not been shown to improve cognitive performance. Current research is flawed by the evaluation of combined hormonal effects throughout the menstrual cycle or in the menopausal transition. The stimulation phase of a fertility treatment offers a unique model to study the effect of estradiol on cognitive function. This quasi-experimental observational study is based on data from 44 women receiving IVF in Zurich, Switzerland. We assessed visuospatial working memory, attention, cognitive bias, and hormone levels at the beginning and at the end of the stimulation phase of ovarian superstimulation as part of a fertility treatment. In addition to inter-individual differences, we examined intra-individual change over time (within-subject effects). The substantial increases in estradiol levels resulting from fertility treatment did not relate to any considerable change in cognitive functioning. As the tests applied represent a broad variety of cognitive functions on different levels of complexity and with various brain regions involved, we can conclude that estradiol does not show a significant short-term effect on cognitive function.

Background: This study is aimed at comparing the neonatal and maternal short-term outcomes after instrumental-assisted vaginal delivery and cesarean section (CS) in labour. Methods: This retrospective study over a period of 11 years included singleton pregnancies above 34 + 0 gestational weeks, giving birth either by instrumental-assisted delivery or CS in labour. Maternal and neonatal outcome parameters were analysed using t test or linear regression. Results: A total of 1,971/2,571 deliveries were included for analysis: 149 forceps-, 393 vacuum-assisted deliveries and 1,420 CS in labour. Regarding maternal outcome, the rate of severe anaemia and hemorrhage in women who delivered by CS in labour was lower than in instrumental-assisted delivery. Analysis of neonatal outcome parameters showed a lower cord pH Conclusion: Assuming that indication and application is correct, vaginal instrumental-assisted delivery can be considered as an alternative delivery mode to second stage CS in labour.

Introduction This study aimed to identify different subgroups (clusters) of patients (n = 182) based on the previously defined variables “age” and “diagnostic delay” in order to identify varying needs of (socio-)medical care. Methods Five clusters were identified by two-step cluster analysis (SPSS 23.0). The mean values for parameters of quality of life, time course of disease progression and health service utilization were compared by chi-square and Kruskal-Wallis H test, and tested for correlations using Spearman's correlation coefficient. Results Clusters I and II patients recognized their endometriosis symptoms at a relatively late age. The results showed a short diagnostic delay and a low subjective disease burden, although cluster I was characterized by a high level of fatigue. Cluster III results indicated that a lack of social support and comparatively long diagnostic delay were major problems in this group. The women in cluster IV had the worst quality-of-life scores and a below-average utilization of services. Statistical analysis showed a significant association between an early age of onset of endometriosis symptoms and a very long delay in diagnosis. These women perceived their menstrual symptoms as “normal” or as “hypochondria”. Cluster V patients were mainly concerned about maintaining their work ability and employment. Conclusions In gynecological practice, special attention should be given to the very young women, as the early onset of endometriosis symptoms and a long delay in diagnosis may indicate the risk of an unfavorable course of the patient's medical and socio-medical history over time.

Stress is a risk factor for impaired general, mental, and reproductive health. The role of physiological and supraphysiological estradiol concentrations in stress perception and stress processing is less well understood. We, therefore, conducted a prospective observational study to investigate the association between estradiol, stress perception, and stress-related cognitive performance within serial measurements either during the natural menstrual cycle or during fertility treatment, where estradiol levels are strongly above the physiological level of a natural cycle, and consequently, represent a good model to study dose-dependent effects of estradiol. Data from 44 women receiving in vitro fertilization (IVF) at the Department of Reproductive Endocrinology in Zurich, Switzerland was compared to data from 88 women with measurements during their natural menstrual cycle. The German version of the Perceived Stress Questionnaire (PSQ) and the Cognitive Bias Test (CBT), in which cognitive performance is tested under time stress were used to evaluate subjective and functional aspects of stress. Estradiol levels were investigated at four different time points during the menstrual cycle and at two different time points during a fertility treatment. Cycle phases were associated with PSQ worry and cognitive bias in normally cycling women, but different phases of fertility treatment were not associated with subjectively perceived stress and stress-related cognitive bias. PSQ lack of joy and PSQ demands related to CBT in women receiving fertility treatment but not in women with a normal menstrual cycle. Only strong changes of the estradiol level during fertility treatment were weakly associated with CBT, but not with subjectively experienced stress. Our research emphasizes the multidimensional character of stress and the necessity to adjust stress research to the complex nature of stress perception and processing. Infertility is associated with an increased psychological burden in patients. However, not all phases of the process to overcome infertility do significantly increase patient stress levels. Also, research on the psychological burden of infertility should consider that stress may vary during the different phases of fertility treatment. Clinical trial registration: ClinicalTrials.gov # NCT02098668.

Knowledge of risks, adequate pre- and post-partum care, and counseling is essential to reduce short- and long-term consequences for women with gestational diabetes mellitus (GDM) and their offspring. Our study explored the current GDM guideline knowledge and practiced patient counseling of private gynecologists in Germany. A survey assessing the GDM guidelines and patient counseling was mailed to 775 practicing gynecologists. We evaluated the knowledge of maternal and offspring disease risks, counseling practice, and guideline awareness. Descriptive statistics were used to analyze the responses and Chi-Square or Fisher exact test to explore differences between groups. Of the 418 private gynecologists (54.1 % response rate) who responded, the majority was aware of obesity and GDM in the previous pregnancy as risk factors for GDM. To a lesser extent, risk factors like recurrent miscarriages and stillbirth were recalled. Eighty percent stated that GDM was associated with a higher risk for the development for hypertension and 96 % with type 2 diabetes in the mother. Respondents with knowledge of the current GDM guidelines were more often aware of the development of chronic diseases, counseled patients more frequently, and performed post-partum glucose screenings more regularly compared with private gynecologists with no knowledge of the guidelines. The majority of participants incorporated recent recommendations into their practice patterns for GDM. Providing private gynecologists with additional training may further improve care for women with GDM-affected pregnancies.

The aims of our study were to analyze university student’s knowledge and attitude towards parenthood, female fertility, fertility assessment, and oocyte freezing and to explore associations between these aspects and the participant’s sex or degree program they were registered for. The study was designed as an online-based cross-sectional survey. A total of 1144 participants answered 27 questions. The data were analyzed using descriptive statistics. Linear regression models were employed to explore associations between sex or university program and attitude towards parenthood, fertility assessment, and oocyte freezing. Female students and students of non-medical degree programs were more likely to plan to have children earlier than male students or students of medical degree programs. Female sex or medical degree program was associated with an overall better knowledge about women’s fertility. The better the participant’s knowledge about fertility, the more likely the students would consider assisted reproductive technology (ART) treatments as an option to become pregnant when ovarian reserve is low. The majority of students knew the principal of oocyte freezing but would not consider using it. However, in the case of a low ovarian reserve, oocyte freezing would be accepted as an option. Students planned to have children at an age when women’s fertility is already declining. Gaps in knowledge about female fertility and the potential of ART were more pronounced in male students and students of non-medical degree programs suggesting an increase of fertility awareness is necessary in these groups to prevent them from infertility and unwanted childlessness.

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

Müllerian anomalies comprise the Mayer-Rokitansky-Küster-Hauser syndrome as well as fusion defects of the müllerian ducts. Recurrent micro-aberrations like deletions in 16p11.2 encompassing TBX6 were found to be causative in these patients. TBX6 encodes a transcription factor which plays a role in paraxial mesoderm differentiation/specification. In previous studies, we and other groups found possibly pathogenic variants in TBX6 in patients with müllerian anomalies. Since we suggested TBX6 as a strong candidate, we performed sequential analysis of the TBX6 gene in additional 125 patients with müllerian anomalies, and 2 possibly pathogenic missense variants and 1 nonsense substitution in TBX6 in 4/125 patients were found. The missense variant c.484GA, which we have described in a previous study, was reidentified but with no higher frequency as in our controls. We detected 3 possibly pathogenic variants in TBX6 and could show that the variant c.484GA is not causative for disorders of the müllerian ducts in the non-Finnish European population. In summary, we present increasing evidence for association of variants in TBX6 with malformations of the müllerian ducts.

Purpose The neuropeptide oxytocin (OXT) has a variety of physiological functions in maternal behavior and attachment including sexual behavior. Based on animal research and our previous human studies, we set out to investigate intranasal administration of OXT and hypothesized that OXT should be able to modulate sexual function in women. Methods In a double-blind, placebo-controlled, crossover laboratory setting, the acute effects of intranasal administered OXT (24 international units) on sexual drive, arousal, orgasm, and refractory aspects of sexual behavior were analyzed in 27 healthy females (mean age ± SD, 27.52 ± 8.04) together with physiological parameters using vaginal photoplethysmography. Findings Oxytocin administration showed no effect on subjective sexual parameters (eg, postorgasmic tension; P = 0.051). Physiological parameters (vaginal photoplethysmography amplitude and vaginal blood volume) showed a response pattern towards sexual arousal but were not affected by OXT. Implications Using a well-established laboratory paradigm, we did not find that intranasal OXT influences female sexual parameters. Also, sexual drive and other functions were not affected by OXT. These findings indicate that OXT is not able to significantly increase subjective and objective parameters of sexual function in a setting with high internal validity; however, this might be different in a more naturalistic setting.

For the last two decades, obesity rates have been increasing in both developed and developing countries, with the number of obese women roughly doubling during this period (Stevens et al. in Popul Health Metr 10(1):33, 2012). Obesity represents one of the biggest epidemics of the 21st century. The aim of this retrospective study is to characterise the outcomes of gynaecologic surgeries in cases of extremely obese women with a body mass index (BMI) over 40 kg/mThis study is a retrospective case control study in a single-centre setting. Our clinical database was searched for gynaecological operations performed on morbidly obese patients (BMI 40 kg/mWe included 97 obese patients in our case group and 99 patients in the control group. We found an association between a strongly elevated BMI and peri- and postoperative morbidity. Both intraoperative and postoperative complications are significantly increased in morbid obesity with a BMI over 40 kg/mDealing with the growing number of obese patients is essential, because the problems emerging from obesity are manifold for the treating hospitals as well as the general health system. For this high-risk patient group, it is indispensable to obtain a thorough overview of the patient's overall situation preoperatively to ensure good perioperative care and complications management.

Fusion anomalies of the Mullerian ducts are associated with an increased risk for miscarriage and premature labor. In most cases polygenic-multifactorial inheritance can be assumed but autosomal-dominant inheritance with reduced penetrance and variable manifestation should be considered. We performed array-comparative genomic hybridization (CGH) analysis in a cohort of 103 patients with Mullerian fusion anomalies. In 8 patients we detected microdeletions and microduplications in chromosomal regions 17q12, 22q11.21, 9q33.1, 3q26.11 and 7q31.1. The rearrangement in 17q12 including LHX1 and HNF1β as well as in 22q11.21 have already been observed in MRKHS (Mayer-Rokitansky-Kuster-Hauser syndrome). In summary, we (1) detected causative micro-rearrangements in patients with Mullerian fusion anomalies, (2) show that Mullerian fusion anomalies and MRKHS may have a common etiology, and (3) identified new candidate genes for Mullerian fusion anomalies.

Background: Interpretation of observational studies on associations between prefrontal cognitive functioning and hormone levels across the female menstrual cycle is complicated due to small sample sizes and poor replicability. Methods: This observational multisite study comprised data of n = 88 menstruating women from Hannover, Germany, and Zurich, Switzerland, assessed during a first cycle and n = 68 re-assessed during a second cycle to rule out practice effects and false-positive chance findings. We assessed visuospatial working memory, attention, cognitive bias and hormone levels at four consecutive time-points across both cycles. In addition to inter-individual differences we examined intra-individual change over time (i.e., within-subject effects). Results: Estrogen, progesterone and testosterone did not relate to inter-individual differences in cognitive functioning. There was a significant negative association between intra-individual change in progesterone and change in working memory from pre-ovulatory to mid-luteal phase during the first cycle, but that association did not replicate in the second cycle. Intra-individual change in testosterone related negatively to change in cognitive bias from menstrual to pre-ovulatory as well as from pre-ovulatory to mid-luteal phase in the first cycle, but these associations did not replicate in the second cycle. Conclusions: There is no consistent association between women's hormone levels, in particular estrogen and progesterone, and attention, working memory and cognitive bias. That is, anecdotal findings observed during the first cycle did not replicate in the second cycle, suggesting that these are false-positives attributable to random variation and systematic biases such as practice effects. Due to methodological limitations, positive findings in the published literature must be interpreted with reservation.

Introduction At term, fetal weight estimation is an important factor for decisions about the delivery mode and the timing of labor induction. This study aimed to compare the accuracy of abdominal palpation with that of ultrasound performed by different examiners to estimate fetal weight. The study investigated whether differences in the examinersʼ training affected fetal weight estimates. The accuracy of the weight estimates made for fetuses with extreme birth weights was also evaluated. Finally, the accuracy of Johnsonʼs method and of Insler and Bernsteinʼs formula for estimating fetal weight were compared with the other two methods. Methods This prospective study included singleton pregnancies between 37 weeks of gestation and 12 days post-term planned for vaginal delivery or cesarean section. Ultrasound and abdominal palpation using Leopoldʼs maneuvers were performed by examiners with different levels of professional experience. Fetal weight was additionally estimated using Insler and Bernsteinʼs formula and Johnsonʼs method. Statistical analysis calculated the accuracy of fetal weight estimates for the different examiners and the four methods. Results A total of 204 women were included in the analysis. Trained ultrasound examiners were most accurate when estimating fetal weight compared with all other examiners. The comparison of all four methods showed that fetal weight was assessed most accurately with ultrasound. No learning curve could be established. BMI and advanced gestational age affected the accuracy of the estimated weight. The analysis showed that a greater deviation between estimated weight and actual weight occurred with all four methods for fetuses at either end of the extremes of fetal weight, i.e., with very low or very high birth weights. Conclusion Fetal weight should be estimated using ultrasound. A good ultrasound training is essential.

Background Female sex hormones may play a crucial role in the occurrence of cycle-related mood disorders. However, the literature is inconsistent and methodologically stringent observational studies on the relationship between sex hormones and negative affect are lacking. Methods In this longitudinal multisite study from Hannover, Germany, and Zurich, Switzerland, we examined oestrogen, progesterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone serum levels in association with negative affect as measured with the Positive and Negative Affect Schedule (PANAS). Negative affect and hormone assays were collected at four consecutive time points comprising menstrual, pre-ovulatory, mid-luteal and premenstrual phase across two cycles (n = 87 and n = 67 for the first and second cycles). The Beck Depression Inventory (BDI) was assessed once prior to the first cycle and included as a secondary measure. Results Mean negative affect scores did not significantly fluctuate across both cycles and there was in particular no symptom increase premenstrually. No sex hormone consistently related to repeated measures of negative affect across two consecutive cycles. The BDI sum-score assessed at baseline was not related to hormone levels across the first cycle. Conclusions This is the first multisite longitudinal study on the association between negative affect and sex hormone levels encompassing two consecutive menstrual cycles. Negative affect did not fluctuate across the cycle and there was no direct and uniform association between sex hormones and self-reported negative affect. These findings suggest that moderators such as personality traits and epigenetics should be considered in future research.

BACKGROUND Despite recommendations of international societies, use of baseline staging in breast cancer varies considerably. We retrospectively analyzed the prevalence of metastases in each pTN stage to estimate the benefit of staging. PATIENTS AND METHODS The prevalence of metastases at primary diagnosis (M1) and in the first year after diagnosis (M112) was determined in 2,906 patients. RESULTS The prevalence of M1 was 0.95% [95% confidence interval (CI)=0.53-1.70%] in pT1pN0, 2.17% (95% CI=1.00-4.64) in pT1pN1 and 1.53% (95% CI=0.78-2.99%) in pT2pN0. The prevalence of M112 was 2.17% (95% CI=1.47-3.18%) in pT1pN0 and 3.25% in pathological stage IIA (upper confidence bound 5.14%). In pT2pN1 the prevalence of M1 and M112 was 3.49% (95% CI=1.96-6.14%) and 6.35% (95% CI=4.15-9.60%), respectively. Results for stage pT3pN0 and higher were inconclusive. CONCLUSION Baseline staging can be safely abandoned in pathological stage I and IIA. Individual decisions should be made for pT2pN1. Staging is recommended in stages of pT3pN0 or higher.

Several studies evaluating the clinical effectiveness of endocrine therapy alone in breast cancer patients aged 70 years or older reported comparable survival rates to conventional surgical therapy, although the incidence of local recurrences was higher. Primary endocrine therapy is therefore only recommended as an alternative approach in elderly woman with estrogen receptor positive tumors who are deemed inoperable or who refuse surgery. We report our experience with aromatase inhibitors as primary endocrine therapy for estrogen receptor positive breast cancer in postmenopausal woman who are impaired by other diseases, refuse surgery or are of old age. Fifty-six patients with fifty-seven ER+ operable breast cancers who refused surgery, were judged ineligible for surgery because of comorbidity, or were of old age were treated with endocrine therapy using aromatase inhibitors only. Digital mammography and high-end breast ultrasound were used to assess tumor sizes. The mean age of the patients was 74 years (range 52-102 years). All patients suffered from breast cancer. The mean follow-up interval was 40 months (range 5-92 months). Seven patients (12%) achieved complete clinical remission, 31 (57%) partial response giving an overall objective response rate of 69%. In addition, seven (12%) patients showed stable disease, giving a clinical benefit rate (complete remission + partial response + stable disease rate) of 81%. Eleven patients (19%) progressed after an initial partial response or stable disease. Only one patient (2%) progressed on endocrine therapy within the first months. Eventually, 22 (39%) patients underwent surgery after informed consent to achieve better local tumor control. Primary endocrine therapy with aromatase inhibitors may offer an effective and safe alternative to surgery giving a high local control rate in postmenopausal women who refuse surgery, who are judged ineligible for surgery, or are of old age.

The incidence of ectopic pregnancy (EP) in the general population is 2%, whereas the EP rate following assisted reproductive technologies (ART) is between 2.1 and 11%. EP is also an adverse effect of tubal surgery with incidences up to 40% depending on the type, location, and severity of tubal disease and the surgical procedure. This paper looks at the incidence of EP following tubal reconstructive microsurgery, analyzes risk factors for EP following own 1,295 ART cycles and looks on the incidence of EP in 128,314 pregnancies following ART according to the presence or absence of tubal infertility using data from the German IVF Registry (DIR). In our clinic, the EP rate following resterilization was 6.7%. In the presence of acquired tubal disease, the EP rate following adhesiolysis, salpingostomy, salpingoneostomy, fimbrioplasty, and anastomosis was 7.9%. The EP rate following ART in our clinic was 5.6%. Previous abdominal surgeries, microsurgical procedures, hydro-/sactosalpinges, salpingitis, salpingitis isthmica nodosa, and periadnexal adhesions showed a significant positive correlation with EP as outcome. Data of DIR demonstrate a significantly increased incidence of EP in the presence of tubal pathology. The highest EP rate related to all clinical pregnancies was 4.5% (95% CI 3.0–6.0) in smoking women

Background and Objectives Standard treatments of high-grade Cervical intraepithelial neoplasia (CIN) are conisation procedures. Theses methods have proven effectiveness but are associated with an increased risk of subsequent pregnancy complications. Recently, photodynamic therapy (PDT) of CIN using hexylaminolevulinate (HAL) may represent an alternative treatment without the risk of cervical insufficiency or scaring. This study aims to evaluate the economical aspect of CIN treatment including associated pregnancy complications by comparing both methods. Materials and Methods We developed model treatment pathways for both conisation procedures and PDT using HAL. Thereafter, we calculated total costs for both treatment pathways including necessary re-treatments or alternative treatments. The estimated impact of conisation-related cervical insufficiency, prematurity, perinatal morbidity and life-long disability were determined. The total additional costs per conisation due to perinatal morbidity were calculated. Results The total cost of treatment for CIN with a conisation procedure alone was 1,473€, whereas the PDT procedure alone accounted for 1,386€, based of assumptions of a 50% re-PDT rate, a 70% response rate and costs of 500€ for the PDT intervention itself. We computed 71, 144 and 545 newborns born prematurely due to conisation procedures

PURPOSE OF REVIEW To review the current role of tubal reconstructive surgery in the era of assisted reproductive techniques (ARTs). RECENT FINDINGS After tubal reconstructive surgery, couples may have unlimited attempts to conceive naturally. Operative risks are low; the risk for ectopic pregnancy after surgery is 4-10%. ART is associated with a number of potential complications: severe ovarian hyperstimulation syndrome (0.25-2%), multiple pregnancies (up to 25%), a higher rate of major malformations and stillbirths, and ectopic pregnancy (1-13%). Birth rates following ART differ between 19 and 35%, depending on different laws governing the fertilization of a limited number of oocytes and the number of embryos transferred. Resterilization is a main indication for microsurgery with resulting pregnancy rates up to 84%. Salpingostomy and dense adhesiolysis have the lowest success rates (term pregnancy rates: 3-65%). Proximal tubal obstructions can be successfully treated by tubocornual anastomosis. Hydrosalpinges should be removed prior to in-vitro fertilization if they cannot be reconstructed. ART is recommended for patients older than 37-38 years, for women with severe tubal pathology, after repeated ectopic pregnancies, and in case of male infertility. SUMMARY Tubal reconstructive surgery still plays a role in infertility treatment. ART has not replaced microsurgery routinely as first-line treatment for tubal infertility.

Objective To identify genetic causes of Mayer-Rokitansky-Kuster-Hauser (MRKH) syndrome. Design Prospective laboratory study. Setting University hospital. Patient(s) Fifty-six patients with MRKH syndrome. Intervention(s) Identification of microdeletions and –duplications in a group of 48 MRKH patients by array-CGH. Results obtained by array-CGH were confirmed by RT-qPCR. Sequential analysis of two candidate genes LHX1 and HNF1B in a group of 56 MRKH patients. Main Outcome Measure(s) Identification of chromosomal regions and genes (recurrent and private) associated with MRKH syndrome. Result(s) We could delineate three definitively relevant regions (1q21.1, 17q12, and 22q11.21) and suggest that LHX1 und HNF1B are candidate genes for MRKH syndrome, because we identified recurrent deletions affecting these genes and a possible causative missense mutation in LHX1 . Conclusion(s) Our findings suggest that different chromosomal regions are associated with MRKH syndrome.

INTRODUCTION: Conisation, the standard therapy for high-grade cervical dysplasia, is highly effective and one of the most common procedures performed in women of fertile age in Germany. However, the risk of complications such as cervical insuffiency with premature rupture of the membranes, premature delivery and low birth weight is elevated in subsequent pregnancies, and this may lead to life-long fetal disability. These costs have to be duly considered when assessing conisation procedures. METHOD: We analysed the costs of the whole treatment pathway after diagnosis of a cervical dysplasia requiring surgery. Using data from former studies and from quality assurance programs, the total costs were analysed, with particular attention paid to the costs of maternofetal morbidity. RESULTS: Total costs per conisation were 2178 €. The main cost factor turned out to be costs associated with the inability to work (1011 €). Maternofetal morbidity accounted for 705 €. The smallest cost factor was the conisation procedure which amounted to 462 € including follow-up costs. A total of 71, 144 and 545 children were born prematurely at 28, 32, and 37 weeks of gestation in Germany due to previous conisation. Of these, 18, 24, and 65 children will statistically suffer from severe, moderate or mild disability, respectively. CONCLUSION: The costs of the therapy of maternofetal morbidity represent 1/3 of the total costs of conisation. To prospectively reduce the number of conisations, the HPV vaccination rate and indications for surgery should be improved. Furthermore, conisations should be done by laser or electric loop under colposcopy.

Objective (1) To validate the mixture model in a single operator dataset and (2) to compare the detection rates for fetal chromosomal defects obtained from the mixture model with those obtained from either the delta nuchal translucency (NT) or log multiple of the median (MoM) approach. Methods Database query, viable singletons [crown-rump length (CRL) 45–84 mm corresponding to 11–13+6 weeks], December 1997 to November 2006, examined by Adam Gasiorek-Wiens, the statistical mixture model was applied. Results Seventy-four of 4171 were lost to follow-up (1.8%), 4097 singleton pregnancies included trisomy 21 (n = 34, 0.8%), trisomy 18 (n = 20, 0.5%), trisomy 13 (n = 8, 0.2%), Turner syndrome (n = 9, 0.2%) and other chromosomal abnormalities (n = 14, 0.3%). The main findings are that (1) the log-transformed NT measurements follow a mixture of two Gaussian distributions and (2) the criteria to apply either the delta-NT or log MoM models are not met. In the normal group, the majority of NT measurements were dependent on the CRL, a small group showed a median independent of the CRL. In the abnormal group it was the opposite. For a 5% false-positive rate (FPR), the trisomy 21 detection rate was 83%. Conclusions The use of the mixture model in a single operator dataset produces results compatible with the original study. The mixture model has thus been validated. Copyright © 2010 John Wiley & Sons, Ltd.

It has become evident that laparoscopic myomectomy is limited by size, number and location of fibroids. Myomectomy performed by laparotomy can be technically challenging and the surgical benefits have to be weighed against associated risks and impairing fertile potential, especially in multiple and large fibroids that may be positioned close to the cavity. Our aim was to evaluate the effect of microsurgical myomectomy technique on perioperative morbidity in premenopausal women.This retrospective study included 228 patients with symptomatic uterine fibroids and/or infertility undergoing myomectomy by laparotomy. As much as 156 patients were treated by standardized microsurgical technique and 72 patients by conventional myomectomy. The following data were recorded and analysed: postoperative haemoglobin, haemoglobin decrease, rate of blood transfusion, and number, size and location of myomas.In 228 patients, seven complications occurred (abdominal wall haematoma, bowel and colon injury, transient ileus). The transfusion rate was 1.3%. Microsurgical technique was associated with a smaller haemoglobin decrease compared to conventional myomectomy (1.77 vs. 2.38 g/dl; P = 0.007). Microsurgical technique correlated inversely with haemoglobin decrease (P0.001). Haemoglobin decrease correlated positively with myoma number (P0.001), size of myoma (P0.001) and the opening of the cavum uteri (P = 0.014).In this large series of abdominal myomectomies, procedure-related morbidity, mainly perioperative blood loss, was amongst the lowest reported when microsurgical techniques were used. In patients with multiple, large or deep intramural fibroids who desire future pregnancies, the use of microsurgical techniques may decrease intraoperative blood loss and perioperative morbidity.