Statement of the Obstetrics and Prenatal Medicine Working Group (AGG - Preterm Birth Section) on "Outpatient Management for Pregnant Women with Preterm Premature Rupture of Membranes (PPROM)".

Preterm premature rupture of membranes (PPROM) is one of the leading causes of perinatal morbidity and mortality. After a PPROM, more than 50% of pregnant women are delivered within 7 days. Fetal and maternal risks are primarily due to infection and inflammation, placental abruption, umbilical cord complications and preterm birth. Standard care usually consists of an expectant approach. Management includes the administration of antenatal steroids and antibiotic therapy. Patients with PPROM require close monitoring. The management of pregnant women with PPROM (inpatient vs. outpatient) is still the subject of controversial debate. The international guidelines also do not offer a clear stance. The statement presented here discusses the current state of knowledge.

Cervical pessary to prevent preterm birth and poor neonatal outcome: An integrity meta-analysis of randomized controlled trials focusing on adherence to the European Medical Device Regulation.

BACKGROUND: Findings from randomized trials (RCTs) on cervical pessary treatment to prevent spontaneous preterm birth are inconsistent. OBJECTIVES: Our hypothesis suggests that adhering to the European Medical Device Regulation (MDR) and following the instructions for use are essential prerequisites for successful therapy. Conversely, the non-adherence to these guidelines will probably contribute to its failure. SEARCH STRATEGY AND SELECTION CRITERIA: Based on validated criteria from integrity assessments we performed a systematic review identifying 14 RCTs evaluating the effect of cervical pessaries. DATA COLLECTION AND ANALYSIS: We analyzed the implications of 14 criteria each accounting for 0-2 points of a score reflecting the clinical evaluation plan (CEP) as proposed by the MDR to evaluate the risk-benefit ratio of medical devices. MAIN RESULTS: Seven RCTs in each singleton and twin pregnancies (5193 "cases") were included, detecting a high heterogeneity within control groups (I2 = 85% and 87%, respectively, P < 0.01). The CEP score varied from 11 to 26 points for all studies. The most common reasons for low scores and potential data compromise were poor recruitment rates, no (completed) power analysis, and no pre-registration, but mainly non-adherence to technical, biological, and clinical equivalence to the instructions for use as required by the MDR. All trials with score values greater than 20 had applied audit procedures. Within this group we found significantly reduced rates of spontaneous preterm birth at less than 34 weeks within the pessary group in singleton (odds ratio 0.28; 95% confidence interval 0.12-0.65) and twin pregnancies (odds ratio 0.30; 95% confidence interval 0.13-0.67). Similarly, there was a significant reduction in the composite poor neonatal outcome in singleton (odds ratio 0.25; 95% confidence interval 0.10-0.61) and twin pregnancies (odds ratio 0.54; 95% confidence interval 0.35-0.82) after a pessary as compared with controls. CONCLUSION: Non-audited RCTs and meta-analyses mixing studies of different clinical quality as pre-defined by a CEP and the MDR pose the risk for erroneous conclusions.

Synthetic Osmotic Dilators for Pre-Induction Cervical Ripening - an Evidence-Based Review.

Mechanical methods have gained growing interest for pre-induction cervical ripening in women with an unripe cervix, since they have a better safety profile compared to prostaglandins. Balloon catheters have been the gold standard method for decades, while there was a lack of data on synthetic osmotic cervical dilators. Not until 2015, when Dilapan-S was approved by the Food and Drug Administration (FDA) for induction of labor, numerous studies have been published on the use of Dilapan-S in this field. The rate of vaginal deliveries associated with the use of Dilapan-S ranges from 61.6 to 81.7%, and no serious complications needing further interventions have been reported to this date. Dilapan-S was shown to be as effective as the Foley balloon catheter as well as the 10 mg PGE 2 vaginal insert and orally applied misoprostol (25 µg every 2 hours) in achieving vaginal delivery, but patient's satisfaction during the cervical ripening process was significantly higher compared to the other methods and the rate of uterine hyperstimulation was significantly lower compared to prostaglandins (PGs). Minor complications (e.g. vaginal bleeding) associated with the use of Dilapan-S were < 2%, and maternal infectious morbidity was not higher compared to Foley balloon and vaginal PGE 2 or misoprostol. Due to these beneficial properties Dilapan-S might be an ideal option for outpatient cervical ripening, as shown in a recent randomized clinical trial comparing inpatient to outpatient cervical ripening. Furthermore, according to the manufacturers' product information, Dilapan-S is the only cervical ripening method that is not contraindicated for induction of labor in women with a previous cesarean section. Upcoming guidelines should consider synthetic osmotic cervical dilators as an effective and safe method for cervical ripening/induction of labor acknowledging that more evidence-based data are mandatory, particularly in patients with a previous cesarean section.

[Hyperemesis Gravidarum - an Interprofessional and Interdisciplinary Challenge - Evidence-Based Review]. / Hyperemesis gravidarum ­ eine interprofessionelle und interdisziplinäre Herausforderung.

Hyperemesis gravidarum (HG) is a multifactorial disease characterized by severe and persisting nausea and vomiting, impairment of oral intake, weight loss of at least 5%, electrolyte abnormalities, and dehydration. The prevalence of HG ranges from 0.3 to 10% worldwide. The diagnosis is made by the patient's prehistory, clinical symptoms, physical examination, and the typical laboratory abnormalities. Therapeutic cornerstones are nutrition advice, consultation of life style, psychological/psychosocial support of the mother as well as the administration of antiemetics in a stepwise approach, depending on the severity of symptoms, and finally admission to hospital in severe cases. Treatment of patients requires close interprofessional and interdisciplinary cooperation.

Correction: Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/025, September 2022) - Part 1 with Recommendations on the Epidemiology, Etiology, Prediction, Primary and Secondary Prevention of Preterm Birth.

[This corrects the article DOI: 10.1055/a-2044-0203.].

Correction: Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, September 2022) - Part 2 with Recommendations on the Tertiary Prevention of Preterm Birth and on the Management of Preterm Premature Rupture of Membranes.

[This corrects the article DOI: 10.1055/a-2044-0345.].

Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/025, September 2022) - Part 1 with Recommendations on the Epidemiology, Etiology, Prediction, Primary and Secondary Prevention of Preterm Birth.

Aim This revised guideline was coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). It aims to improve the prediction, prevention, and management of preterm birth, based on evidence from the current literature, the experience of members of the guidelines commission, and the viewpoint of self-help organizations. Methods The members of the contributing professional societies and organizations developed recommendations and statements based on international literature. The recommendations and statements were presented and adopted using a formal process (structured consensus conferences with neutral moderation, written Delphi vote). Recommendations Part 1 of this short version of the guideline presents statements and recommendations on the epidemiology, etiology, prediction, and primary and secondary prevention of preterm birth.

Prevention and Therapy of Preterm Birth. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Registry Number 015/025, September 2022) - Part 2 with Recommendations on the Tertiary Prevention of Preterm Birth and on the Management of Preterm Premature Rupture of Membranes.

Aim The revision of this guideline was coordinated by the German Society for Gynecology and Obstetrics (DGGG), the Austrian Society for Gynecology and Obstetrics (OEGGG) and the Swiss Society for Gynecology and Obstetrics (SGGG). The aim of the guideline is to improve the prediction, prevention and management of preterm birth based on evidence from the current literature, the experience of members of the guidelines commission, and the viewpoint of self-help organizations. Methods The members of the contributing professional societies and organizations developed recommendations and statements based on international literature. The recommendations and statements were presented and adopted using a formal process (structured consensus conferences with neutral moderation, written Delphi vote). Recommendations Part 2 of this short version of the guideline presents statements and recommendations on the tertiary prevention of preterm birth and the management of preterm premature rupture of membranes.

Maintenance tocolysis, tocolysis in preterm premature rupture of membranes and in cervical cerclage - a Germany-wide survey on the current practice after dissemination of the German guideline.

OBJECTIVES: To investigate the adherence of German perinatal specialist units and those of basic obstetric care to the national guideline we compared data from a nation-wide survey on the practice of maintenance tocolysis, tocolysis in preterm premature rupture of membranes and in the perioperative setting of cervical cerclage, and bedrest during and after tocolysis with recommendations from the current German Guideline 015/025 "Prevention and Treatment of Preterm Birth". METHODS: A total of 632 obstetric clinics in Germany were approached and received a link to an online questionnaire. Data were descriptively analyzed by performing measures of frequency. To compare two or more groups Fisher's exact test was used. RESULTS: The response rate was 19%; 23 (19.2%) of respondents did not perform maintenance tocolysis, while 97 (80.8%) conducted maintenance tocolysis; 30 (25.0%) of obstetric units performed cervical cerclage without tocolysis and 90 (75.0%) combined cervical cerclage with tocolysis; 11 (9.2%) of respondents did not use tocolytics in patients with preterm premature rupture of membranes, while 109 (90.8%) conducted tocolysis in these patients; 69 (57.5%) of obstetric units did not recommend bed rest during tocolysis, whereas 51 (42.5%) favored bedrest. Perinatal care centers of basic obstetric care recommend bed arrest during tocolysis statistically significant more often to their patients than those of higher perinatal care levels (53.6 vs. 32.8%, p=0.0269). CONCLUSIONS: The results of our survey are in accordance to others from different countries and reveal considerable discrepancies between evidence-based guideline recommendations and daily clinical practice.

Strategies for the prevention of maternal death from venous thromboembolism clinical recommendations based on current literature.

Venous thromboembolism (VTE) is one of the leading causes of direct maternal deaths. It has been estimated that approximately 50% of these deaths are potentially preventable. The UK Confidential Enquiries into Maternal Deaths and the National Partnership for Maternal Safety have proposed strategies for the prevention of maternal deaths from VTE based on current guideline recommendations. The main strategies include: - Early recognition and comprehensive assessment of risk factors for VTE at different times from the beginning of pregnancy until patient's discharge from hospital. - Appropriate risk stratification using standardized VTE risk assessment tools (e.g. the Royal College Scoring System). - Risk-based antenatal and postnatal heparin thromboprophylaxis adjusting the heparin dosage and the duration of prophylaxis to the individual patient's risk. - Adequate management of heparin prophylaxis before and after delivery. - Preference of universal rather than selective post-cesarean heparin thromboprophylaxis and application of perioperative mechanical prophylaxis. - Avoidance of gaps in the postpartum prescription of heparin. - Good communication and cooperation between primary and secondary care including community midwifery staff in the postpartum period. - Immediate intravenous administration of (unfractionated) heparin, if pulmonary embolism is suspected. - Critical analysis of all thromboembolic events, particularly in association with maternal death to learn from failures and to realize, if and where improvement is needed. Adequate pharmacological thromboprophylaxis has the potential to reduce the risk of VTE by 60-70% in pregnant women at increased risk.

Life Quality in Premenopausal Women after Embolization of Uterine Myomas.

Objectives: Fibroids cause significant morbidity and are the most common indication for hysterectomies worldwide, delimiting a major public health problem. Uterine artery embolization (UAE) is an alternative therapy to surgical treatment of symptomatic fibroids; it has satisfactory long-time results and is no longer considered investigational for the treatment of symptomatic fibroids. This study was undertaken to evaluate changes in fibroid specific symptom severity and health-related quality of life (HRQOL) after UAE and to optimize the assessment of safety and outcomes measures for participants who receive UAE to objective compare UAE and surgical alternatives for therapy of symptomatic fibroids. Study design: The analysis was based on questionnaires completed by 270 pre-menopausal females with a mean age of 42 years (range, 38-50 years) who underwent UAE for uterine leiomyomas and/or adenomyosis from November 2013 through December 2019. Only symptomatic women were selected whose symptoms were not improving with medication and who did not wish to have children. The primary outcome measure was a change in fibroid symptoms and HRQOL (health related quality of life) after UAE. Secondary outcomes included the decrease in uterine volume after UAE. Results: Questionnaires were completed by 270 women (100%) at a mean of 12.1 months from UAE. The median follow-up period was two years. Uterine fibroid embolization led to a shrinkage at three months for the 90% of the participants. A reduction of bleeding symptoms, pain and bulk-related symptoms was observed in 89.7%, 88.9%, and 89.5% of the patients, respectively. In the long term, there was no significant difference in parameters assessed compared with the midterm follow-up findings. A total of 6 patients (2.3%) underwent fractional curettage an average of 32.1 months after intervention due to necrotic changes in submucosal fibroids. All participants continued to be satisfied with the intervention, and 240 patients (88.9%) answered that they would recommend uterine fibroid embolization to other patients. Conclusions: Women who undergo UAE have a significant decrease in symptom severity and increase in HRQOL which is associated with high levels of satisfaction with the procedure (even when subsequent therapies are pursued).

Cervical ripening as an outpatient procedure in the pandemic - minimizing the inpatient days and lowering the socioeconomic costs.

OBJECTIVES: With an increasing incidence of labor induction the socioeconomic costs are increasing and the burden on hospital capacities is rising. In addition, the worldwide SARS-CoV-2 pandemic asks for improvements in patient care during pregnancy and delivery while decreasing the patient-staff contact. Here, we are retrospectively analyzing and comparing a mechanical ripening device that is utilized as an outpatient procedure to misoprostol and dinoprostone as inpatient induction methods in a low risk cohort. METHODS: This is a retrospective comparative analysis of obstetric data on patients who presented for cervical ripening and labor induction. Ninety-six patients received a mechanical ripening agent as an outpatient procedure. As a control group, we used 99 patients with oral misoprostol (PGE1) and 42 patients with vaginal dinoprostone (PGE2) for cervical ripening in an inpatient setting. Data from 2016 until 2020 were analysed. RESULTS: Baseline characteristics showed no significant differences. Delivery modes were similar in all groups. The time period from patient admission to onset of labor was significantly shorter in the outpatient group (p<0.001): 10.9 h/0.5 days (±13.6/0.6) for osmotic dilator vs. 17.9 h/0.7 days (±13.1/0.5) for oral misoprostol vs. 21.8 h/0.8 days (±15.9/0.7) for vaginal dinoprostone. With 20.4 h/0.8 days (±14.3/0.6) the osmotic dilator group displayed significantly the shortest inpatient stay from admission to delivery (p=0.027). The patient subgroup of misoprostol had 25.7 h/1.1 days (±14.9/0.6) of inpatient stay from admission to delivery and the patient group of dinoprostone 27.5 h/1.1 days (±16.0/0.7). There were fewer hospital days in the outpatient group: 84.9 h/3.5 days vs. 88.9 h/3.7 days vs. 93.6 h/3.9 days (outpatient osmotic dilator vs. inpatient misoprostol and dinoprostone, respectively). CONCLUSIONS: New approaches are required to decrease individual contacts between patients and staff while maintaining a high quality patient care in obstetrics. This analysis reveals that outpatient mechanical cervical ripening can be as safe and effective as inpatient cervical ripening with PGE1/PGE2, while lowering patient-staff contact and total hospital stays and therefore decreasing the socioeconomic costs.

Mechanical Methods for the Induction of Labour After Previous Caesarean Section - An Updated, Evidence-based Review.

There are currently no up-to-date evidence-based recommendations on the preferred method to induce labour after previous Caesarean section, especially for patients with unripe cervix, as randomised controlled studies are lacking. Intravenous oxytocin and misoprostol are contraindicated in these women because of the high risk of uterine rupture. In women with ripe cervix (Bishop Score > 6), intravenous administration of oxytocin is an effective procedure with comparable rates of uterine rupture to those with spontaneous onset of labour. Vaginal prostaglandin E 2 (PGE 2 ) and mechanical methods (balloon catheters, hygroscopic cervical dilators) are effective methods to induce labour in pregnant women with unripe cervix and previous Caesarean section. According to current guidelines, the administration of PGE 2 is associated with a higher rate of uterine rupture compared to balloon catheters. Balloon catheters are therefore a suitable alternative to PGE 2 to induce labour after previous Caesarean section, even though this is an off-label use. In addition to two meta-analyses published in 2016, 12 mostly retrospective cohort/observational studies with low to moderate levels of evidence have been published on mechanical methods of cervical ripening after previous Caesarean section. But because of the significant heterogeneity of the studies, substantial differences in study design, and insufficient numbers of pregnant women included in the studies, it is not possible to make any evidence-based recommendations based on these studies. According to a recent meta-analysis, the average rate using balloon catheters is approximately 53% and the average rate after spontaneous onset of labour is 72%. The uterine rupture rate was 0.2-0.9% for vaginal PGE 2 and 0.56-0.94% for balloon catheters and is therefore comparable to the uterine rupture rate associated with spontaneous onset of labour. According to the product informations, hygroscopic cervical dilators (Dilapan-S) are currently the only method which is not contraindicated for cervical ripening/induction of labour in women with previous Caesarean section, although data are insufficient. Well-designed, randomised, controlled studies with sufficient case numbers comparing balloon catheters and hygroscopic cervical dilators with mechanical methods and vaginal prostaglandin E 2 /oral misoprostol are therefore necessary to allow proper decision-making.

Resuscitation of Term Compromised and Asphyctic Newborns: Better with Intact Umbilical Cord?

The authors hypothesize that particularly severely compromised and asphyctic term infants in need of resuscitation may benefit from delayed umbilical cord clamping (after several minutes). Although evidence is sparse, the underlying pathophysiological mechanisms support this assumption. For this review the authors have analyzed the available research. Based on these data they conclude that it may be unfavorable to immediately clamp the cord of asphyctic newborns (e.g., after shoulder dystocia) although recommended in current guidelines to provide quick neonatological support. Compression of the umbilical cord or thorax obstructs venous flow to the fetus more than arterial flow to the placenta. The fetus is consequently cut off from a supply of oxygenated, venous blood. This may cause not only hypoxemia and consecutive hypoxia during delivery but possibly also hypovolemia. Immediate cord clamping may aggravate the situation of the already compromised newborn, particularly if the cord is cut before the lungs are ventilated. By contrast, delayed cord clamping leads to fetoplacental transfusion of oxygenated venous blood, which may buffer an existing acidosis. Furthermore, it may enhance blood volume by up to 20%, leading to higher levels of various blood components, such as red and white blood cells, thrombocytes, mesenchymal stem cells, immunoglobulins, and iron. In addition, the resulting increase in pulmonary perfusion may compensate for an existing hypoxemia or hypoxia. Early cord clamping before lung perfusion reduces the preload of the left ventricle and hinders the establishment of sufficient circulation. Animal models and clinical trials support this opinion. The authors raise the question whether it would be better to resuscitate compromised newborns with intact umbilical cords. Obstetric and neonatal teams need to work even closer together to improve neonatal outcomes.

Preterm Premature Rupture of Membranes - Inpatient Versus Outpatient Management: an Evidence-Based Review.

According to current guidelines, inpatient management until birth is considered standard in pregnant women with preterm premature rupture of membranes (PPROM). With the increasing burden on obstetric departments and the growing importance of satisfaction and right to self-determination in pregnant women, outpatient management in PPROM is a possible alternative to inpatient monitoring. The most important criterion for this approach is to ensure the safety of both the mother and the child. Due to the small number of cases (n = 116), two randomised controlled trials (RCTs) comparing inpatient and outpatient management were unable to draw any conclusions. By 2020, eight retrospective comparative studies (cohort/observational studies) yielded the following outcomes: no significant differences in the rate of maternal complications (e.g., chorioamnionitis, premature placental abruption, umbilical cord prolapse) and in neonatal morbidity, significantly prolonged latency period with higher gestational age at birth, higher birth weight of neonates, and significantly shorter length of stay of preterm infants in neonatal intensive care, shorter hospital stay of pregnant women, and lower treatment costs with outpatient management. Concerns regarding this approach are mainly related to unpredictable complications with the need for rapid obstetric interventions, which cannot be performed in time in an outpatient setting. Prerequisites for outpatient management are the compliance of the expectant mother, the adherence to strict selection criteria and the assurance of adequate monitoring at home. Future research should aim at more accurate risk assessment of obstetric complications through studies with higher case numbers and standardisation of outpatient management under evidence-based criteria.

Do obstetric units adhere to the evidence-based national guideline? A Germany-wide survey on the current practice of initial tocolysis.

OBJECTIVES: Current international guidelines recommend tocolytic treatment by at least 48 h to complete fetal lung maturation and to ensure in-utero transfer to a perinatal center before 34 weeks of gestation in patients with threatened preterm birth. According to the results of former surveys, significant differences between daily clinical practice patterns and evidence-based guideline recommendations regarding tocolytic treatment have been demonstrated. We compared data from a nation-wide survey on the practice of initial tocolysis with recommendations from the current German Guideline 015/025 "Prevention and Treatment of Preterm Birth". STUDY DESIGN: 632 obstetric units in Germany received a link to an online questionnaire between January 20th and March 31st 2020, which was developed according to national and international recommendations and guidelines. Collected data was descriptively analyzed by performing measures of frequency. RESULTS: The response rate was 19%; 51 (42.5%) of the respondents consider CTG tracing with ≥ 4 contractions within 20 min, 49 (40.8%) cervical length measurement of ≤ 25 mm and 13 (10.9%) subjective contractions as the most significant decision-making criteria for tocolysis; 47 (39.2%) of obstetric units initiate tocolysis earliest at 23 + 0, 34 (28.3%) at 22 + 0, 26 (21.7%) at 23 + 5 and 13 (10.8%) at 24 + 0 weeks of gestation; 104 (86.7%) stop tocolysis latest at the 34 + 0 weeks of gestation, 42 (35.0%) obstetric units administer antenatal corticosteroids at 23 + 5, 16 (13.3%) at 22 + 0, and 13 (10.8%) at 24 + 0 weeks of gestation. Calcium channel blockers are the first-line tocolytic drug used by 59 (49.1%) of the obstetric units, followed by intravenous betamimetics as bolus (n = 26, 21.7%) and atosiban (n = 20, 16.7%). Severe side-effects were observed by 105 (70%) of the respondents in association with the use of betamimetics, 14 (9.3%) with the use of nifedipine and 30 (20.0%) with nitroglycerine patches. The German guideline was considered the most important decision-making support by 78 (65%) of the obstetric units, followed by hospital specific SOPs/algorithms (n = 31, 25.8%). CONCLUSION: Our survey highlights a considerable discrepancy between evidence-based guideline recommendations and daily clinical practice.

The rate of estrogen receptor-conversion associated with tumor progression in estrogen receptor-positive breast cancer patients following adjuvant Tamoxifen administration.

BACKGROUND: Hormone Receptor (HR)-discordance between primary breast cancer and metastasis is a known biological phenomenon. Discordance studies usually comprise a heterogeneous group of HR-positive and negative patients and allow for the comparison of changes in HR-status from the primary to the recurrent disease. However, in a clinical setting, the rate of estrogen receptor-conversion following endocrine therapy with agents such as Tamoxifen (TAM) in estrogen receptor-positive cancers is of primary interest as opposed to total receptor discordance. AIM: To investigate the rate of estrogen receptor-conversion associated with tumor progression in estrogen receptor-positive breast cancer patients following adjuvant TAM administration and to compare the results with the meta-analysis data of HR-discordance studies. METHODS AND RESULTS: A retrospective double-center review of biomarkers in 67 estrogen receptor-positive breast cancer patients who underwent TAM treatment in the adjuvant setting. The estrogen and progesterone receptor-status were compared at the time of diagnosis and following relapse and the Disease-free Survival, mean duration of TAM treatment as well as the operative, radiation, and cytotoxic therapies registered before TAM treatment, were recorded. Initially, all patients were estrogen receptor-positive. The average age at the time of diagnosis was 52.8 ± 12.4 years. After recurrence, only 47 patients (70.1%) were still estrogen receptor-positive with a highly significant loss of estrogen receptor-expression in 29.9% of cases. The mean duration of TAM treatment was 40.7 ± 19.9 months. 45 patients (i.e., 67.2%) progressed during the TAM treatment and the remaining 22 patients (32.8%) developed relapse after the TAM treatment had finished. Initially, there were 82.1% progesterone receptor-positive and 17.9% progesterone receptor-negative, but after relapse the progesterone receptor-positive cases diminished significantly to 53.7%, showing a progesterone receptor-loss of 28.4%. CONCLUSION: The rate of estrogen receptor-loss associated with tumor progression following TAM treatment is approximately 30%, which is of clinical relevance in order to evaluate further endocrine efficacy in these patients. This rate of receptor conversion is roughly 6-13% higher compared to the recently published meta-analysis data of discordance studies. This discrepancy could possibly be due to anti-hormonal therapy with TAM accentuating receptor conversion.

Labour Induction with Misoprostol in German Obstetric Clinics: What Are the Facts on Such Use?

Subject While the synthetic prostaglandin E1 analogue misoprostol is the most effect labour induction agent, its use is off-label for the most part. For this reason, and in view of its potential adverse effects and varying approaches to its administration, the drug has recently once again become a focus of critical attention. The objective of this survey was thus to establish a record of labour induction with misoprostol in German clinics and determine the impact of the negative reporting on everyday obstetric practice. Material and Methods In this cross-sectional study, 635 obstetrics and gynaecology departments in Germany were requested by email to participate in our survey in February/March 2020. Online responses to 19 questions were requested regarding the clinic, use of misoprostol before and after the critical reporting, use of misoprostol (sourcing, method of administration, dosage, monitoring) and other labour induction methods. Results A total of 262 (41.3%) of the clinics solicited for the survey completed the questionnaire. There were no differences regarding the care level (Perinatal Centre Level I, Perinatal Centre Level II, Clinic with Perinatal Focus or Obstetric/Private Clinic; p = 0.2104) or birth counts (p = 0.1845). In most cases, misoprostol was prepared in the clinic's own pharmacy (54%) or imported from another country (46%) and administered orally in tablet form (95%). Misoprostol dosage levels varied (25 µg [48%], 50 µg [83%], 75 µg [6%], 100 µg [47%] and > 100 µg [5%]). Most of the clinics used premanufactured tablets/capsules (59%), although Cytotec tablets were also divided (35%) or dissolved in water (5%). Misoprostol administration intervals were mainly every 4 hours (64%) or every 6 hours (30%). CTG checks were run in most cases before and after administration of a dose of misoprostol (78% and 76%) and before and after administration of a dose of prostaglandin E2 (both 88%). Presence of contractions led to no misoprostol (59%) or no prostaglandin E2 (64%) being administered in most cases. The critical reporting resulted in discontinuation of use of misoprostol in 17% of the clinics - mainly smaller obstetric/private clinics with fewer than 1000 births. Labour cocktails were used mainly in obstetric and private clinics (61%). Conclusion Misoprostol is an established agent for labour induction in German clinics. The dosing schemes used vary. Improvements of currently common management practices are required, especially in the area of labour induction (CTG checks before and after administration of labour-inducing medication, no administration of prostaglandin if contractions are ongoing). The discussion of use of misoprostol in the media resulted in stoppage of its use mainly in smaller clinics.

Cervical ripening after cesarean section: a prospective dual center study comparing a mechanical osmotic dilator vs. prostaglandin E2.

OBJECTIVES: Worldwide, the overall cesarean section is rising. Trial of labor after cesarean (TOLAC) is an overall safe option with an immediate impact on neonatal and maternal short- and long-term health. Since the use of prostaglandins in cervical ripening is associated with an increased risk of uterine rupture, mechanical methods as balloon catheters or osmotic dilators have been suggested for cervical ripening prior to induction of labour. Here we are analyzing and comparing the VBAC rate, as well as maternal and fetal outcome in cervical ripening prior to TOLAC. METHODS: This prospective dual center study analyses maternal and neonatal outcomes of TOLAC in women with an unfavorable cervix requiring cervical ripening agent. The prospective application of an osmotic dilator (Dilapan-S, n=104) was analysed in comparison to the retrospective application of off-label dinoprostone (n=102). RESULTS: The overall fetal and neonatal outcome revealed no significant differences in both groups. Patients receiving cervical ripening with the osmotic dilator delivered vaginally/by ventouse in 52% of cases, compared to 53% when using dinoprostone (p=0.603). The interval between application to onset of labor was significantly higher in the osmotic dilator group (37.9 vs.20.7 h, p=<0.001). However, time from onset of labor to delivery was similar in both groups (7.93 vs. 7.44 h, p=0.758). There was one case of uterine rupture in the dinoprostone group. CONCLUSIONS: Our data shows that the application of the osmotic dilator leads to similar outcomes in VBAC rate and time from onset of labor to delivery as well as safety in both groups compared to off-label use dinoprostone. Cervical ripening using the mechanical dilator is a viable and effective option, without the risk of uterine hyperstimulation.

Profiling of intact blood proteins by matrix-assisted laser desorption/ionization mass spectrometry without the need for freezing - Dried serum spots as future clinical tools for patient screening.

RATIONALE: To open up new ways for matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS)-based patient screening, blood serum is the most preferred specimen because of its richness in patho-physiological information and due to ease of collection. To overcome deleterious freeze/thaw cycles and to reduce high costs for shipping and storage, we sought to develop a procedure which enables MALDI-MS protein profiling of blood serum proteins without the need for serum freezing. METHODS: Blood sera from patients/donors were divided into portions which after pre-incubation were fast frozen. Thawed aliquots were deposited on filter paper discs and air-dried at room temperature. Intact serum proteins were eluted with acid-labile detergent-containing solutions and were desalted by employing a reversed-phase bead system. Purified protein solutions were screened by MALDI-MS using standardized instrument settings. RESULTS: MALDI mass spectra from protein solutions which were eluted from filter paper discs and desalted showed on average 25 strong ion signals (mass range m/z 6000 to 10,000) from intact serum proteins (apolipoproteins, complement proteins, transthyretin and hemoglobin) and from proteolytic processing products. Semi-quantitative analysis of three ion pairs: m/z 6433 and 6631, m/z 8205 and 8916, as well as m/z 9275 and 9422, indicated that the mass spectra from either pre-incubated fast-frozen serum or pre-incubated dried serum spot eluted serum contained the same information on protein composition. CONCLUSIONS: A workflow that avoids the conventional cold-chain and yet enables the investigation of intact serum proteins and/or serum proteolysis products by MALDI-MS profiling was developed. The presented protocol tremendously broadens the clinical application of MALDI-MS and simultaneously allows a reduction in the costs for storage and shipping of serum samples. This will pave the way for clinical screening of patients also in areas with limited access to health care systems, and/or specialized laboratories.