Determinants of transplantation success with cryopreserved ovarian tissue: data from 196 women of the FertiPROTEKT network.

STUDY QUESTION: What are the pregnancy and live birth rates for ovarian tissue transplantation and which factors are associated with the success rate? SUMMARY ANSWER: Pregnancy and live birth rates per transplanted woman are 32.7% and 26.5% and success rate is associated with female age and first versus repeated transplantation. WHAT IS KNOWN ALREADY: Live birth rates after ovarian tissue transplantations have been reported to be between around 24% and 41% per patient. Success rates seem to be negatively associated with increasing female age at the time of tissue cryopreservation and with pelvic radiation. Success rates are apparently not reduced after overnight transportation of ovarian tissue before freezing. STUDY DESIGN, SIZE, DURATION: Registry analysis of 244 transplantations in 196 women, performed by 26 FertiPROTEKT network centres from 2007 to 2019 with follow-up till December 2020. PARTICIPANTS/MATERIALS, SETTING, METHODS: Orthotopic ovarian tissue transplantations were performed in 196 women, 191 with previous malignant and 5 with previous non-malignant diseases. Size of transplanting centres varied between 1 and 100 transplantations per centre (median: 2). Factors possibly associated with success rate such as female age, first and repeated transplantation, experience of the transplanting centre and overnight transportation of the ovarian tissue before freezing were analysed. MAIN RESULTS AND THE ROLE OF CHANCE: Average age of all 196 transplanted women was 31.3 years (SD 5.2; range 17-44) at the time of cryopreservation of tissue and 35.9 years (SD 4.8; range 23-47) at the time of transplantation. Pregnancy rate was 30.6% (95% CI, 24.2-37.6%) per first transplantation and 32.7% (95% CI, 26.1-39.7%) per patient. Pregnancy rate was higher after first transplantation (30.6% (95% CI, 24.2-37.6%)) compared to second and subsequent transplantations (11.8% (95% CI, 3.3-27.5%)). Live birth rate per first transplantation was 25.0% (95% CI, 19.1-31.7%) and per patient 26.5% (95% CI, 20.5-33.3%). Success rate decreased with increasing age at the time of ovarian tissue freezing. Live birth rate was 28.2% (95% CI, 20.9-36.3%) in women <35 years and 16.7% (95% CI, 7.9-29.3%) in women >35 years. Pregnancy rates after first transplantation were higher in centres who had performed ≥10 transplantations (35.1%) compared to centres with <10 transplantation (25.4%) (P = 0.12). Corresponding live birth rates were 27.0% and 18.6%. Success rates were not different in women with and without overnight transportation of tissue before cryopreservation. LIMITATIONS, REASONS FOR CAUTION: The data were drawn from a registry analysis. Data such as ovarian reserve and premature ovarian insufficiency were not available for all women. Data might be influenced by different follow-up policies of the centres. WIDER IMPLICATIONS OF THE FINDINGS: The study reveals the high potential of ovarian tissue freezing and transplantation, but only if freezing is performed in younger women. The study suggests focus should be placed on the first and not on repeated transplantations. It also opens the discussion of whether transplantation should rather be performed by experienced centres. STUDY FUNDING/COMPETING INTEREST(S): No funding. No competing interests. TRIAL REGISTRATION NUMBER: N/A.

Surface Energy and Wetting Behavior of Dolomite in the Presence of Carboxylic Acid-Based Deep Eutectic Solvents.

This study endeavors to apply experimental and theoretical analyses to assess the viability of wettability alteration for two carboxylic acid-based deep eutectic solvents (DESs). To prepare these chemicals, oxalic acid and citric acid were used as hydrogen bond donors mixed with choline chloride as the hydrogen bond acceptor in an equimolar ratio. In the theoretical part, dolomite and crude oil were characterized using a three-phase setup. Then, the adhesion propensity of brines/crude oil toward dolomite was evaluated by calculating the work of adhesion. Contact angle and interfacial tension measurements were conducted in the experimental part to investigate the impact of chemicals on brine-crude oil and brine-rock interactions. Results revealed that the oxalic acid-based DES outperformed the citric acid-based DES in terms of interfacial tension reduction. In addition, choline chloride/oxalic acid (1:1) could effectively restore the wettability of the dolomite sample to its original state with a wettability alteration index of 82%. Theoretical calculations also confirmed the wettability alteration potential of DESs. Finally, a correlation was proposed to predict the contact angle of brine on the dolomite surface in the presence of crude oil using surface-energy components of brine, crude oil, and dolomite.

Changes in fatigue, barriers, and predictors towards physical activity in advanced cancer patients over a period of 12 months-a comparative study.

PURPOSE: Physical activity (PA) is recommended to improve advanced cancer patients' (ACP) physical functioning, fatigue, and quality of life. Yet, little is known about ACPs' attitude towards PA and its influence on fatigue and depressiveness over a longer period. This prospective, non-interventional cohort study examined ACPs' fatigue, depression, motivation, and barriers towards PA before and after 12 months of treatment among ACP METHODS: Outpatients with incurable cancer receiving treatment at a German Comprehensive Cancer Center reporting moderate/severe weakness/tiredness during self-assessment via MIDOS II were enrolled. Fatigue (FACT-F), depression (PHQ-8), cancer-related parameters, self-assessed PA behavior, motivation for and barriers against PA were evaluated (T0). Follow-up data was acquired after 12 months (T1) using the same questionnaire. RESULTS: At follow-up, fatigue (p=0.017) and depressiveness (p=0.015) had increased in clinical relevant extent. Physically active ACP did not show significant progress of FACT-F (p=0.836) or PHQ-8 (p=0.799). Patient-reported barriers towards PA remained stable. Logistic regression analyses identified motivation as a positive predictor for PA at both time points (T0, ß=2.152, p=0.017; T1, ß =2.264, p=0.009). Clinically relevant depression was a negative predictor for PA at T0 and T1 (T0, ß=-3.187, p=0.044; T1, ß=-3.521, p=0.041). CONCLUSION: Our findings emphasize the importance of psychological conditions in physical activity behavior of ACP. Since psychological conditions seem to worsen over time, early integration of treatment is necessary. By combining therapy approaches of cognitive behavioral therapy and exercise in interdisciplinary care programs, the two treatment options might reinforce each other and sustainably improve ACPs' fatigue, physical functioning, and QoL. TRIAL REGISTRATION: German Register of Clinical Trials, DRKS00012514, registration date: 30.05.2017.

Induction of labour using prostaglandin E2 as an inpatient versus balloon catheter as an outpatient: a multicentre randomised controlled trial.

OBJECTIVE: To compare clinical outcomes following induction of labour (IOL) using a balloon catheter and going home, versus prostaglandin (PG) as an inpatient. DESIGN: Randomised controlled trial. SETTING: Eight Australian maternity hospitals. POPULATION: Women with uncomplicated term singleton pregnancies undergoing IOL for low-risk indications including post-term, advanced maternal age and 'social' reasons. METHODS: Between September 2015 and October 2018, 347 women were randomised to a balloon outpatient group and 348 to a PG inpatient group. The PG group received Dinoprostone, either 2 mg gel or 10 mg controlled-release tape. The balloon group had a double-balloon catheter inserted and went home. MAIN OUTCOME MEASURES: The primary outcome was a composite neonatal measure comprising nursery admission, intubation/cardiac compressions, acidaemia, hypoxic ischaemic encephalopathy, seizure, infection, pulmonary hypertension, stillbirth or death. Clinical and process outcomes are reported. RESULTS: There were no statistically significant differences in the primary outcome comparing balloon with PG (18.6% versus 25.8%; relative risk = 0.77, 95% CI 0.51-1.02; P = 0.070), cord arterial pH <7.10 (3.5% versus 9.2%; P = 0.072), nursery admissions (12.6% versus 15.5%; P = 0.379), neonatal antibiotic use (12.1% versus 17.6%; P = 0.103), or mode of birth. Nulliparous women in the balloon group had lower rates of the primary outcome (20.4% versus 31.0%;P = 0.032); Parous women were less likely to have an unassisted vaginal birth (77.6% versus 92.3%; P = 0.045). CONCLUSIONS: Balloon catheters may be a superior method of cervical priming for nulliparous women, whereas this may not be the case for parous women. It is feasible that nulliparous women go home after commencing balloon catheter IOL, and the likelihood of adverse outcomes is low. TWEETABLE ABSTRACT: Multicentre trial shows outpatient induction using balloon catheter is safe and feasible for nulliparous women.

Fatigue, barriers to physical activity and predictors for motivation to exercise in advanced Cancer patients.

BACKGROUND: In order to counteract fatigue, physical activity (PA) is recommended for all stages of cancer. However, only few advanced cancer patients (ACP) are physically active. Quantitative data with high numbers of ACP reporting barriers to PA are missing. This study aimed to identify barriers to PA in ACP with tiredness/weakness and investigate their motivation towards it. METHODS: Outpatients with metastatic cancer receiving cancer care at a German Cancer Center reporting moderate/severe tiredness/weakness during self-assessment (MIDOS II) were enrolled. We assessed Fatigue-(FACF-F) and Depression (PHQ8) Scores, demographics, cancer-specific parameters, motivation for PA, physical, psychological and social barriers. RESULTS: 141 of 440 eligible patients (32.0%) with different diagnoses agreed to participate. Patients frequently reported "I feel weakened due to my tumor therapy" (n = 108; 76.6%), physical symptoms (tiredness, weakness, dyspnea, joint-problems, pain, nausea [n = 107; 75.9%]) and fatigue (n = 99; 70.2%) as barriers to PA. However, no significant group differences regarding these barriers were found between physically active and inactive patients. Social barriers were rarely chosen. Motivated patients were 5.6 times more likely to be physically active (p < 0.001), also motivation turned out to be the strongest predictor for a physically active behavior (ß = 1.044; p = 0.005). Motivated attitude towards PA was predicted by fatigue (ß = - 2.301; p = 0.008), clinically relevant depression (ß = - 1.390, p = 0.039), knowledge about PA and quality of life (QoL) (ß = 0.929; p = 0.002), PA before diagnosis (ß = 0.688; p = 0.005 and Interest in exercise program (ß = 0.635; p = 0.008). CONCLUSION: "I feel weakened due to my tumor therapy" is the most reported barrier to PA among both, physically and inactive patients. Motivation for PA is the strongest predictor of performing PA. Interest in PA, knowledge about PA/QoL and PA before diagnosis are main predictors of a motivated attitude. Absence/presence of social barriers did not associate with motivation, fatigue and depression proved to be a negative predictor. Programs including information, motivational counseling and individualized training should be offered for ACP to overcome barriers and reduce fatigue. TRIAL REGISTRATION: German Register of Clinical Trials DRKS00012514, registration date: 30.5.2017.

Addressing the pitfalls when designing intervention studies to discover and validate biomarkers of habitual dietary intake.

INTRODUCTION: Dietary exposure monitoring within populations is reliant on self-reported measures such as Food Frequency Questionnaires and diet diaries. These methods often contain inaccurate information due to participant misreporting, non-compliance and bias. Urinary metabolites derived from individual foods could provide additional objective indicators of dietary exposure. For biomarker approaches to have utility it is essential that they cover a wide-range of commonly consumed foods and the methodology works in a real-world environment. OBJECTIVES: To test that the methodology works in a real-world environment and to consider the impact of the major sources of likely variance; particularly complex meals, different food formulations, processing and cooking methods, as well as the dynamics of biomarker duration in the body. METHODS: We designed and tested a dietary exposure biomarker discovery and validation strategy based on a food intervention study involving free-living individuals preparing meals and collecting urine samples at home. Two experimental periods were built around three consecutive day menu plans where all foods and drinks were provided (n = 15 and n = 36). RESULTS: The experimental design was validated by confirming known consumption biomarkers in urinary samples after the first menu plan. We tested biomarker performance with different food formulations and processing methods involving meat, wholegrain, fruits and vegetables. CONCLUSION: It was demonstrated that spot urine samples, together with robust dietary biomarkers, despite major sources of variance, could be used successfully for dietary exposure monitoring in large epidemiological studies.

Influence of patient and tumor characteristics on early therapy persistence with letrozole in postmenopausal women with early breast cancer: results of the prospective Evaluate-TM study with 3941 patients.

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

Best practice perioperative strategies and surgical techniques for preventing caesarean section surgical site infections: a systematic review of reviews and meta-analyses.

BACKGROUND: Surgical site infection (SSI) following caesarean section is a problem for women and health services. Caesarean section is a high volume procedure and the estimated incidence of SSI may be as high as 9%. OBJECTIVES: The objective of this study was to identify a suite of perioperative strategies and surgical techniques that reduce the risk of SSI following caesarean section. SEARCH STRATEGY: Six electronic databases were searched to systematically review literature reviews, systematic reviews and meta-analyses published from 2006 to 2016. Search terms included: endometritis, SSI, caesarean section, meta-analysis, review, systematic. SELECTION CRITERIA: Studies were sought in which competing perioperative strategies and surgical techniques relevant for caesarean section were identified and quantifiable infection outcomes were reported. General infection control strategies were excluded. DATA COLLECTION AND ANALYSIS: Data on study characteristics and clinical effectiveness were extracted. Quality, including bias within individual studies, was examined using a modified A Measurement Tool to Assess Systematic Reviews (AMSTAR) checklist. Recommendations for SSI risk-reducing strategies were developed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. MAIN RESULTS: Of 466 records retrieved, 44 studies were selected for the evidence synthesis. Recommended strategies were: administer pre-incision antibiotic prophylaxis, prepare the vagina with iodine-povidone solution and spontaneous placenta removal. CONCLUSIONS: We recommend clinicians implement pre-incision antibiotic prophylaxis, vaginal preparation and spontaneous placenta removal as an infection control bundle for caesarean section. FUNDING: Queensland University of Technology. TWEETABLE ABSTRACT: Infection control for caesarean: pre-incision AB prophylaxis, vaginal prep, spontaneous placenta removal.

[TILGen study-immunological targets in patients with breast cancer : Influence of tumor-infiltrating lymphocytes]. / TILGen-Studie ­ Immunologische Angriffspunkte bei Patientinnen mit Brustkrebs : Einfluss der tumorinfiltrierenden Lymphozyten.

BACKGROUND: The interaction of our immune system with breast cancer (BC) cells prompted the investigation of tumor-infiltrating lymphocytes (TILs) and targeted, tumor antigen-specific immunotherapy. OBJECTIVES: Correlation between TILs and pathological complete response (pCR) after neoadjuvant systemic therapy (NACT). Tumor-specific antigens (TSAs) in HER2+ and triple negative BC and establishment of TSA-specific therapies within the interdisciplinary TILGen study. METHODS: Illustration of the TILGen study design. Assessment of TILs and correlation with pCR within this BC study. RESULTS: pCR was achieved in 38.4% (56/146) and associated with estrogen receptor/progesterone receptor negative (ER-/PR-) and HER2+ tumors. Lymphocytic predominant BC (LPBC) was found in 16.4% (24/146), particularly in ER-/PR- (ER-: 27.3% vs. ER+: 9.9%, PR-: 22.3% vs. PR+: 8.2%), large, and poorly differentiated BC. TILs were significantly correlated with pCR in multivariate analysis. In LPBC, pCR was achieved in 66.7%, whereas it was 32.8% in non-LPBC. CONCLUSIONS: First results confirm the influence of the human immune system on the response to NACT in HER2+ and triple negative BC. TSA-specific immunotherapy might improve the outcome in BC patients but there is an urgent need for comprehensive studies to further investigate this issue.

Prenatal and adult androgen activities in alcohol dependence.

OBJECTIVE: Alcohol dependence is more prevalent in men than in women. The evidence for how prenatal and adult androgens influence alcohol dependence is limited. We investigated the effects of prenatal and adult androgen activity on alcohol dependence. Moreover, we studied how the behaviours of pregnant women affect their children's prenatal androgen load. METHOD: We quantified prenatal androgen markers (e.g., second-to-fourth finger length ratio [2D : 4D]) and blood androgens in 200 early-abstinent alcohol-dependent in-patients and 240 controls (2013-2015, including a 12-month follow-up). We also surveyed 134 women during pregnancy (2005-2007) and measured the 2D : 4D of their children (2013-2016). RESULTS: The prenatal androgen loads were higher in the male alcohol-dependent patients compared to the controls (lower 2D : 4D, P = 0.004) and correlated positively with the patients' liver transaminase activities (P < 0.001) and alcohol withdrawal severity (P = 0.019). Higher prenatal androgen loads and increasing androgen levels during withdrawal predicted earlier and more frequent 12-month hospital readmission in alcohol-dependent patients (P < 0.005). Moreover, stress levels (P = 0.002), alcohol (P = 0.010) and tobacco consumption (P = 0.017), and lifetime stressors (P = 0.019) of women during pregnancy related positively to their children's prenatal androgen loads (lower 2D : 4D). CONCLUSION: Androgen activities in alcohol-dependent patients and behaviours of pregnant women represent novel preventive and therapeutic targets of alcohol dependence.

Ninety-five orthotopic transplantations in 74 women of ovarian tissue after cytotoxic treatment in a fertility preservation network: tissue activity, pregnancy and delivery rates.

STUDY QUESTION: What is the success rate in terms of ovarian activity (menstrual cycles) as well as pregnancy and delivery rates 1 year after orthotopic ovarian transplantations conducted in a three-country network? SUMMARY ANSWER: In 49 women with a follow-up >1 year after transplantation, the ovaries were active in 67% of cases and the pregnancy and delivery rates were 33 and 25%, respectively. WHAT IS KNOWN ALREADY: Cryopreservation of ovarian tissue in advance of cytotoxic therapies and later transplantation of the tissue is being performed increasingly often, and the total success rates in terms of pregnancy and delivery have been described in case series. However, published case series have not allowed either a more detailed analysis of patients with premature ovarian insufficiency (POI) or calculation of success rates based on the parameter 'tissue activity'. STUDY DESIGN, SIZE, DURATION: Retrospective analysis of 95 orthotopic transplantations in 74 patients who had been treated for cancer, performed in the FertiPROTEKT network from 2008 to June 2015. Of those 95 transplantations, a first subgroup (Subgroup 1) was defined for further analysis, including 49 women with a follow-up period >1 year after transplantation. Of those 49 women, a second subgroup (Subgroup 5) was further analysed, including 40 women who were transplanted for the first time and who were diagnosed with POI before transplantation. PARTICIPANTS/MATERIALS, SETTING, METHODS: Transplantation was performed in 16 centres and data were transferred to the FertiPROTEKT registry. The transplantations were carried out after oncological treatment had been completed and after a remission period of at least 2 years. Tissue was transplanted orthotopically, either into or onto the residual ovaries or into a pelvic peritoneal pocket. The success rates were defined as tissue activity (menstrual cycles) after 1 year (primary outcome) and as pregnancies and deliveries achieved. MAIN RESULTS AND THE ROLE OF CHANCE: The average age of all transplanted 74 women was 31 ± 5.9 years at the time of cryopreservation and 35 ± 5.2 at the time of transplantation. Twenty-one pregnancies and 17 deliveries were recorded. In Subgroup 1, tissue was cryopreserved at the age of 30 ± 5.6 and transplanted at 34 ± 4.9 years. Ovaries remained active 1 year after transplantation in 67% of cases (n = 33/49), the pregnancy rate was 33% (n = 16/49) and the delivery rate was 25% (n = 12/49). In Subgroup 5, tissue was cryopreserved at the age 30 ± 5.9 years and transplanted at 34 ± 5.2 years. Ovaries remained active 1 year after transplantation in 63% of cases (n = 25/40), the pregnancy rate was 28% (n = 11/40) and the delivery rate was 23% (n = 9/40). The success rates were age dependant with higher success in women who cryopreserved at a younger age. In Subgroup 5, tissue was exclusively transplanted into the ovary in 10% (n = 4/40) of women and into a peritoneal pocket in 75% (n = 30/40), resulting in spontaneous conceptions in 91% of patients (n = 10/11). LIMITATIONS, REASONS FOR CAUTION: The data were drawn from a retrospective analysis. The cryopreservation and transplantation techniques used have changed during the study period. The tissue was stored in many tissue banks and many surgeons were involved, leading to heterogeneity of the procedures. However, this does reflect the realistic situation in many countries. Although patients with POI were evaluated before transplantation to allow specific analysis of the transplanted tissue itself, the possibility cannot be excluded that residual ovarian tissue was also reactivated. WIDER IMPLICATIONS OF THE FINDINGS: This is the largest case series worldwide to date and it confirms that cryopreservation and transplantation of ovarian tissue can be a successful option for preserving fertility. Persistent tissue activity 12 months after transplantation suggests that the pregnancy and delivery rates may increase further in the future. As transplantation into the peritoneum results in a high success rate, this approach may be an alternative to transplantation into the ovary. However, in order to establish the best transplantation site, a randomized study is required. STUDY FUNDING/COMPETING INTEREST: This study was in part funded from the Deutsche Forschungsgemeinschaft (# DI 1525) and the Wilhelm Sander Foundation (2012.127.1) and did not receive any funding from a commercial company. No competing interests. TRIAL REGISTRATION NUMBER: None.

Re-irradiation of the chest wall for local breast cancer recurrence : Results of salvage brachytherapy with hyperthermia.

AIM: Following mastectomy and adjuvant external beam radiation therapy in patients with breast cancer, the incidence of local or locoregional recurrence is approximately 9 % (2-20 %). Alongside the often limited possibilities of surgical treatment, radiation therapy combined with superficial hyperthermia is the most effective local therapy. In the present work, a retrospective analysis of salvage brachytherapy combined with superficial hyperthermia for chest wall recurrences is presented. PATIENTS AND METHODS: Between 2004 and 2011, 18 patients with a total of 23 target volumes resulting from chest wall recurrences after previously mastectomy and external beam radiation therapy (median 56 Gy, range 50-68 Gy) were treated with superficial brachytherapy as salvage treatment: 8 patients (44 %) had macroscopic tumor, 3 (17 %) had microscopic tumor (R1), and 7 (39 %) had undergone R0 resection and were treated due to risk factors. A dose of 50 Gy was given (high-dose rate [HDR] and pulsed-dose rate [PDR] procedures). In all, 5 of 23 patients (22 %) received additional concurrent chemotherapy, and in 20 of 23 (87 %) target volumes additional superficial hyperthermia was carried out twice weekly. RESULTS: The 5­year local recurrence-free survival was 56 %, the disease-free survival was 28 %, and a 5-year overall survival was 22 %. Late side effects Common Toxicity Criteria (CTC) grade 3 were reported in 17 % of the patients: 2 of 18 (11 %) had CTC grade 3 fibrosis, and 1 of 18 (6 %) had a chronic wound healing disorder. CONCLUSION: Re-irradiation as salvage brachytherapy with superficial hyperthermia for chest wall recurrences is a feasible and safe treatment with good local control results and acceptable late side effects.

Single deepest vertical pocket or amniotic fluid index as evaluation test for predicting adverse pregnancy outcome (SAFE trial): a multicenter, open-label, randomized controlled trial.

OBJECTIVE: To determine whether the amniotic fluid index (AFI) or the single deepest vertical pocket (SDP) technique for estimating amniotic fluid volume is superior for predicting adverse pregnancy outcome. METHODS: This was a multicenter randomized controlled trial including 1052 pregnant women with a term singleton pregnancy across four hospitals in Germany. Women were assigned randomly, according to a computer-generated allocation sequence, to AFI or SDP measurement for estimation of amniotic fluid volume. Oligohydramnios was defined as AFI ≤ 5 cm or the absence of a pocket measuring at least 2 × 1 cm. The diagnosis of oligohydramnios was followed by labor induction. The primary outcome measure was postpartum admission to a neonatal intensive care unit. Further outcome parameters were the rates of diagnosis of oligohydramnios and induction of labor (for oligohydramnios or without specific indication), and mode of delivery. RESULTS: Postpartum admission to a neonatal intensive care unit was similar between groups (4.2% (n = 21) vs 5.0% (n = 25); relative risk (RR), 0.85 (95% CI, 0.48-1.50); P = 0.57). In the AFI group, there were more cases of oligohydramnios (9.8% (n = 49) vs 2.2% (n = 11); RR, 4.51 (95% CI, 2.2-8.57); P < 0.01) and more cases of labor induction for oligohydramnios (12.7% (n = 33) vs 3.6% (n = 10); RR, 3.50 (95% CI, 1.76-6.96); P < 0.01) than in the SDP group. Moreover, an abnormal cardiotocography was seen more often in the AFI group than in the SDP group (32.3% (n = 161) vs 26.2% (n = 132); RR, 1.23 (95% CI, 1.02-1.50); P = 0.03). The other outcome measures were not significantly different between the two groups. CONCLUSIONS: Use of the AFI method increased the rate of diagnosis of oligohydramnios and labor induction for oligohydramnios without improving perinatal outcome. The SDP method is therefore the favorable method to estimate amniotic fluid volume, especially in a population with many low-risk pregnancies. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Accuracy of sonographic fetal weight estimation: influence of the scan-to-delivery interval in combination with the applied weight estimation formula.

INTRODUCTION: To evaluate the influence of the time interval between examination and delivery on the accuracy of sonographic fetal weight estimation (WE). MATERIALS AND METHODS: 8723 singleton pregnancies were included in this retrospective cohort study. Fetuses were divided into eight groups with regard to the time interval between estimation and delivery (group 1: 0 days; group 2: 1-3 days; group 3: 4-7 days; group 4: 8-14 days; group 5: 15-21 days; group 6: 22-28 days; group 7: 29-35 days; group 8: 36-42 days). The accuracy of WE was compared between the different time interval groups and five commonly used formulas using means of percentage errors (MPE), medians of absolute percentage errors, and proportions of estimates within 10 % of actual birth weight. RESULTS: In group one, the Hadlock I and Warsof formula showed a systematic underestimation of fetal weight (negative MPEs). No systematic error was found with the Hadlock II formula and the equations of Merz and Shepard showed a systematic overestimation (positive MPEs). MPE values of the Hadlock I, II and Warsof formulas were closest to zero in WEs of group two. From group three to six, MPE values decreased continuously. With the Merz and Shepard equations MPEs were closest to zero in group four. DISCUSSION: The best accuracy of sonographic WE with most of the commonly used equations is achieved within a scan-to-delivery interval of 1 week.

[Documentation Time and Effort and Associated Resources for Patients with Primary Breast Cancer from Diagnosis to End of Follow-Up - Results of a Multicentre Validation]. / Dokumentationsaufwand und verbundene Ressourcen bei Patientinnen mit einem primären Mammakarzinom - von der Primärdiagnose bis zur Abschluss der Nachsorge - Ergebnisse der multizentrischen Erhebung.

INTRODUCTION: Tumour documentation is essential for quality assurance of oncological therapies and as a source of reliable information about the in- and outpatient care. The documentation effort and the associated resource consumption were analysed for the example of breast cancer. MATERIAL AND METHODS: The different steps in the care of patients with primary breast cancer in a standardised disease situation were defined from initial diagnosis to the end of the follow-up. After the pilot phase, a multicentre validation (n=7 centres) was performed with the support of the Federal Ministry of Health. The documentation time points were horizontally collected and analysed with regard to amount, duration and personnel expenses. RESULTS: 57% of the documentation costs are caused by the physicians. Regarding the different centres, documentation costs were calculated between € 352.82 and € 1 084.08 per patient from diagnosis to completion of aftercare. Non-certified centres had a reduced documentation effort and thus lower costs. CONCLUSIONS: The results demonstrate the need for a reduction of the documentation effort - particularly for physicians - the most expensive profession in the health system. A quality improvement is expected from the certification with its special requirements. In this context, there is a justified demand for an adequate remuneration of the documentation effort for certified centres. Furthermore, it is necessary to reduce the number of variables for quality assurance and to define them centrally. A comprehensive multi-disciplinary documentation should be achieved. Investments in a single data set and interface enhancements of existing documentation systems should be realised.

Obesity and survival among women with ovarian cancer: results from the Ovarian Cancer Association Consortium.

BACKGROUND: Observational studies have reported a modest association between obesity and risk of ovarian cancer; however, whether it is also associated with survival and whether this association varies for the different histologic subtypes are not clear. We undertook an international collaborative analysis to assess the association between body mass index (BMI), assessed shortly before diagnosis, progression-free survival (PFS), ovarian cancer-specific survival and overall survival (OS) among women with invasive ovarian cancer. METHODS: We used original data from 21 studies, which included 12 390 women with ovarian carcinoma. We combined study-specific adjusted hazard ratios (HRs) using random-effects models to estimate pooled HRs (pHR). We further explored associations by histologic subtype. RESULTS: Overall, 6715 (54%) deaths occurred during follow-up. A significant OS disadvantage was observed for women who were obese (BMI: 30-34.9, pHR: 1.10 (95% confidence intervals (CIs): 0.99-1.23); BMI: ⩾35, pHR: 1.12 (95% CI: 1.01-1.25)). Results were similar for PFS and ovarian cancer-specific survival. In analyses stratified by histologic subtype, associations were strongest for women with low-grade serous (pHR: 1.12 per 5 kg m(-2)) and endometrioid subtypes (pHR: 1.08 per 5 kg m(-2)), and more modest for the high-grade serous (pHR: 1.04 per 5 kg m(-2)) subtype, but only the association with high-grade serous cancers was significant. CONCLUSIONS: Higher BMI is associated with adverse survival among the majority of women with ovarian cancer.

Sonographic weight estimation in fetal macrosomia: influence of the time interval between estimation and delivery.

PURPOSE: To evaluate the influence of the time interval between examination and delivery on the accuracy of sonographic weight estimation (WE) in fetal macrosomia. MATERIALS AND METHODS: 896 singleton pregnancies (birth weight > 4,000 g) with a total of 1,281 sonographic weight estimations were included in this retrospective cohort study. Fetuses were divided into six groups with regard to the time interval between estimation and delivery: group 1: scan-to-delivery interval: 0 days; group 2: scan-to-delivery interval: 1-3 days; group 3: scan-to-delivery interval: 4-7 days; group 4: scan-to-delivery interval: 8-14 days; group 5: scan-to-delivery interval: 15-21 days; group 6: scan-to-delivery interval: 22-42 days. The accuracy of WE was compared between five commonly used formulas using means of percentage errors (MPE), random error, medians of absolute percentage errors (MAPE), and proportions of estimates within 10 % of actual birth weight. RESULTS: Significant differences were found between the time interval groups with regard to MAPE and MPE values (p < 0.001). All formulas showed a systematic underestimation of fetal weight (negative MPEs) (p < 0.05). MPE values were closest to zero in time interval group 1 and 2. From group 3 to 6, a continuous decrease was observed. The lowest MAPE was found with the Merz formula in group 1 and 2. Values increased continuously from group 3 to 6. Differences between time interval group one and three did not reach statistical significance. CONCLUSIONS: WE in fetal macrosomia shows the best results when examinations are performed within 7 days before delivery, using the formula of Merz et al. Accuracy significantly decreases after this time period.

Intrapartum sonographic weight estimation.

PURPOSE: To evaluate the accuracy of intrapartum sonographic weight estimation (WE). MATERIALS AND METHODS: This retrospective, cross-sectional study included 1958 singleton pregnancies. Inclusion criteria were singleton pregnancy with cephalic presentation, vaginal delivery and ultrasound examination with complete biometric parameters performed on the day of delivery during the latent or active phase of labor, and absence of chromosomal or structural anomalies. The accuracy of intrapartum WE was compared to a control group of fetuses delivered by primary cesarean section at our perinatal center and an ultrasound examination with complete biometric parameters performed within 3 days before delivery (n = 392). Otherwise, the same inclusion criteria as in the study group were applied. The accuracy of WE was compared between five commonly applied formulas using means of percentage errors (MPE), medians of absolute percentage errors (MAPE), and proportions of estimates within 10 % of actual birth weight. RESULTS: In the whole study group, all equations showed a systematic underestimation of fetal weight (negative MPEs). Overall, best MAPE and MPE values were found with the Hadlock II formula, using BPD, AC and FL as biometric parameters (Hadlock II, MPE: -1.28; MAPE: 6.52). MPEs differed significantly between WE in the study and control group for all evaluated formulas: in the control group, either no systematic error (Hadlock III, IV and V) or a significant overestimation (Hadlock I, II) was found. Regarding MAPEs, application of the Hadlock III (HC, AC, FL) and V (AC) formula resulted in significant lower values in the control group (Hadlock III, MAPE: 7.48 vs. 5.95, p = 0.0008 and Hadlock V, MAPE: 8.79 vs. 7.52, p = 0.0085). No significant differences were found for the other equations. CONCLUSIONS: A systematic underestimation of fetal weight has to be taken into account in sonographic WE performed intrapartum. Overall, the best results can be achieved with WE formulas using the BPD as the only head measurement.

Comparison of Whole Ovary Cryotreatments for Fertility Preservation.

The goal of this study was to compare a traditional slow-freeze method (TF) with an open unidirectional slow freeze cooling system (UF) for whole ovary cryopreservation. Therefore, whole pig ovaries were randomly assigned to (A) fresh control, (B) traditional slow freeze (TF) or (C) unidirectional slow freeze (UF). Ovaries were perfused with 10% DMSO in Krebs-Ringer. For TF, whole ovaries were placed in specimen jars containing 10% DMSO and placed into a specialized container for freezing filled with propan-2-ol. For UF, whole ovaries were placed within a specially designed container containing 10% DMSO and transferred to a specialized freezing machine (CTE 920). Histological evaluation demonstrated intact morphology of follicles in all groups; however, an overall decrease of follicle numbers in TF (46%) and UF (50%) compared to fresh control. Live/dead assay indicated significantly lower populations of live cells in both TF (60%) and UF (58%) compared to fresh tissue (74%). TUNEL assay confirmed a difference in percentage of apoptotic follicles between fresh and TF, but there was no significant difference between fresh and UF. To improve the structural and functional integrity of whole ovaries, further investigation, especially into directional freezing, is needed. Whole ovary cryopreservation could provide opportunities for women facing fertility loss due to chemo- or radiotherapy treatment.

Sonographic Weight Estimation in Small-for-Gestational-Age Fetuses.

PURPOSE: To determine the accuracy of sonographic weight estimation (WE) for small-for-gestational-age (SGA) fetuses, and to further differentiate the evaluation between symmetric and asymmetric SGA fetuses. MATERIALS AND METHODS: The accuracy of WE in SGA fetuses (n = 898) was evaluated using 14 sonographic models and was further differentiated between symmetric (n = 750) and asymmetric (n = 148) SGA fetuses. SGA fetuses were considered to be asymmetric with a head circumference to abdominal circumference ratio above the 95th percentile. The accuracy of the different formulas was compared using means of percentage errors (MPE), medians of absolute percentage errors (MAPE), and proportions of estimates within 10 % of actual birth weight. RESULTS: RESULTS for the subgroup of asymmetric SGA fetuses differed significantly from the subgroup of symmetric SGA fetuses. MPE values were closer to zero with most of the formulas in the asymmetric SGA group. Apart from the Siemer, Shepard, Merz and Warsof equations, all formulas showed an underestimation of fetal weight in asymmetric SGA fetuses. In contrast, in the symmetric SGA group, all of the formulas commonly used for fetuses in a normal weight range showed a systematic overestimation of fetal weight. Overall the best accuracy was achieved by using the Sabbagha equation (MPE 1.7 %; SD 9.0 %; MAPE: 6.0). CONCLUSION: An accurate WE in SGA fetuses is feasible using the Sabbagha formula. However, one has to be aware of the significant differences in WE between symmetric and asymmetric SGA fetuses.