Changes in Endometriosis-Associated Symptoms Following Immunization against SARS-CoV-2: A Cross-Sectional Study.

Background: There are many reports about variations in the menstrual cycle after infection with SARS-CoV-2 or vaccination against it. However, data on SARS-CoV-2 infection or vaccination-related changes in menstruation-associated endometriosis-typical symptoms such as dysmenorrhea, dyspareunia, dyschezia, dysuria, and bloating are rare or missing. Methods: This retrospective study was performed as an online survey among employees and students at the University Hospital Ulm, Germany. Changes regarding the presence of mentioned symptoms and after immunization (vaccination and/or infection) were evaluated with the McNemar Test. Additionally, the risk factors associated with these changes and associations between a subjectively perceived general change in menstruation and changes in the symptoms were evaluated. Results: A total of 1589 respondents were included in the final analysis. Less than 4% of respondents reported the occurrence of new symptoms that they had not experienced before immunization. Overall, there was a significant reduction in the presence of dysmenorrhea, back pain, dyschezia, bloating, and dyspareunia after immunization against coronavirus (p < 0.001). Only 2.3% of all participants reported to have been diagnosed with endometriosis. Factors associated with changes in endometriosis-typical symptoms following immunization were body mass index, age, endometriosis, and thyroid disease. Conclusions: Our results provide unique data about a reduction in the incidence of endometriosis-associated symptoms as dysmenorrhea, dyschezia, and dyspareunia after immunization against COVID-19.

Three-dimensional model for improvement of endometriosis care (3D-E).

OBJECTIVE: Endometriosis affects approximately 10% of women of reproductive age and leads to significant morbidity and financial burden. Consequently, countries such as France and Germany are formulating strategies to combat endometriosis. In this study, we propose the implementation of our three-dimensional model (3D-E) to raise awareness about endometriosis and enhance timely diagnosis, treatment, and long-term care for affected patients. METHODS: Based on the adapted Six Sigma Principle and the modified recommendation of Sales et al. for implementing evidence-based findings into a clinical routine, we first conducted a comprehensive investigation to identify risk factors leading to diagnostic delay of endometriosis. After identifying improvable factors, the applicable options were selected due to defined criteria such as integrability in the clinical routine, cost-effectiveness, and evidence-based-principle. Finally, solutions feasible for health care providers were integrated and the 3D-E model was established. RESULTS: Some of the main risk factors contributing to diagnostic delays are symptoms acceptance and misinterpreted symptoms, especially if presenting to nongynecologists in cases of extragenital endometriosis with atypical presentation. Therefore, we tried to sensitize colleagues (first dimension) with a review paper in Germany's largest medical journal and started an elective for medical students (second dimension) at our university. In order to involve additional health care professionals in endometriosis care (third dimension), we are preparing the concept of the EndoNurse. CONCLUSION: The 3D-E model is a relatively low-cost, comprehensive, and worldwide adaptable approach for facilitating knowledge transfer, sensitizing health care providers, and improving endometriosis diagnostics and therapy for patients with endometriosis who are in the center of the model.

Disturbances of menstrual cycle after immunization against SARS-CoV-2 and their risk factors: Cross-sectional clinical study.

OBJECTIVE: Abnormalities of the menstrual cycle were reported after infection with SARS-CoV-2 and vaccination against it, but the available data are very heterogeneous, do not reflect intermenstrual variations or regional differences, and their risk factors are missing. METHODS: We performed a survey-based study among 6383 employees and students of Ulm University Hospital in Germany between March 1 and 31, 2021. Attributes of menstrual cycles such as cycle length (CL), menses duration (MD), and bleeding volume (BV) were reported as categorical variables before and after immunization against SARS-CoV-2 (first, second, third vaccination or infection). Additionally, the potential risk factors for cycle changes were evaluated and all participants reported the subjective perception of changes, their duration, and time of occurrence. RESULTS: The final analysis included 1726 participants. CL and BV significantly changed after vaccination, but not MD. The subjective perception showed only slight levels of agreement with the objective changes, with the highest Cohen's kappa for CL. The risk factors for the variations in CL were previous cycle irregularities, and risk factors for the changes in BV were age and body mass index. The combination of vaccines (homogenous or heterogeneous) and different types of immunization (infection and vaccination) had no significant effect on cycle irregularities. CONCLUSION: In summary, immunization against SARS-CoV-2 causes changes in the characteristics of the menstrual cycle, which are mostly temporary. The individual risk factors, but not the type of immunization, can affect the mentioned changes.

Recurrent Miscarriage: Diagnostic and Therapeutic Procedures. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry No. 015/050, May 2022).

Purpose The aim of this guideline is to standardize the diagnosis and therapy of recurrent miscarriage (RM) using evidence from the recent literature. This is done by using consistent definitions, objective evaluations and standardized treatment protocols. Methods When this guideline was compiled, special consideration was given to previous recommendations in prior versions of this guideline and the recommendations of the European Society of Human Reproduction and Embryology, the Royal College of Obstetricians and Gynecologists, the American College of Obstetricians and Gynecologists and the American Society for Reproductive Medicine, and a detailed individual search of the literature about the different topics was carried out. Recommendations Recommendations about the diagnostic and therapeutic procedures offered to couples with RM were developed based on the international literature. Special attention was paid to known risk factors such as chromosomal, anatomical, endocrinological, physiological coagulation, psychological, infectious and immune disorders. Recommendations were also developed for those cases where investigations are unable to find any abnormality (idiopathic RM).

[PCOS - desire for children and pregnancy]. / PCOS ­ Kinderwunsch und Schwangerschaft.

Polycystic ovary syndrome (PCOS) is diagnosed according to the Rotterdam criteria, where two of the following three criteria must be met: Anovulation, hyperandrogenism, and characteristic morphology by sonography. Women diagnosed with PCOS are at higher risk for diabetes and impaired glucose tolerance. Therefore, these women should be carefully counselled about lifestyle measures and improvements in fertility and pregnancy outcomes. Some women benefit from metformin, which needs to be clarified by off-label use. For fertility, mild stimulation is possible in women with unovulatory cycles, whereas women with PCOS need to be monitored more closely for the development of gestational diabetes, preeclampsia or hypertension during pregnancy.

Fertility preservation: improved neovascularization and follicle viability in cryopreserved bovine ovarian cortex transplants by remaining medulla tissue.

OBJECTIVE: To investigate the advantages of cryopreserved medulla-containing ovarian cortex grafts with those of commonly used sole cortex grafts for fertility preservation by analyzing tissue quality, neovascularization processes, and the number of vital follicles. DESIGN: Experimental setting of cryopreserved bovine ovarian cortex tissue grafts with or without medulla tissue. SETTING: Laboratory animal research at Ulm University, Ulm, Germany. ANIMALS: Bovine ovaries and fertilized chicken eggs. INTERVENTION(S): Experimental setting of bovine ovarian tissue samples grafted on the chicken chorioallantoic membrane (CAM) after cryopreservation and thawing to examine histologic tissue integrity, apoptosis and proliferation immunohistochemically, blood vessel counts and determine the presence of neutral red-stained vital follicles. MAIN OUTCOME MEASURE(S): We used hematoxylin and eosin staining to visualize tissue structures, immunohistochemistry with anti-caspase 3 to detect apoptosis, anti-Ki67 to examine proliferation, blood vessel count on the chicken CAM to investigate neovascularization processes, and neutral red staining to evaluate vital follicles. RESULT(S): We demonstrated that in all analyzed tissue samples, after cryopreservation, thawing, and grafting on the chicken CAM, there was excellent tissue integrity and quality, as shown by extremely rare apoptosis processes analyzed using immunohistochemical caspase 3 staining (sole cortex, 0.54%; thin medulla-containing cortex, 0.43%; thick medulla-containing cortex, 0.13%; and sole medulla, 2.82%). Moreover, we detected increased neovascularization in the vicinity of medulla and medulla-containing grafts (small blood vessels: cortex 8.7, thin medulla-containing cortex 9.9, thick medulla-containing cortex 9.7, and medulla 9.8; very small blood vessels: cortex 7.0, thin medulla-containing cortex 13.0, thick medulla-containing cortex 12.0, and medulla 15.0), with higher Ki67-detected proliferation (cortex, 17.58%; thin medulla-containing cortex, 20.28%; thick medulla-containing cortex, 20.56%; and medulla, 29.9%). Additionally, we identified an increased number of vital follicles in medulla-containing cortex grafts compared with the number of vital follicles in sole cortex tissue (cortex, 256.1; thin medulla-containing cortex, 338.2; thick medulla-containing cortex, 346.6; and medulla, 8.1). CONCLUSION(S): In this experimental setting, bovine medulla-containing cortex tissue had excellent tissue structure and quality after cryopreservation and thawing and increased neovascularization and an augmented vital follicle count after grafting than the commonly used sole cortex tissue. Therefore, we suggest reconsidering the current cryopreservation and grafting processes in humans for fertility preservation by favoring retain medulla tissue at the ovarian cortex.

Trend natural family planning - an online survey to assess attitudes towards NFP among German-speaking women.

PURPOSE: To study trends regarding the use of contraceptive methods and digital health modalities and to identify target groups of natural family planning (NFP). MATERIAL AND METHODS: Using an online questionnaire specifically developed for this study in German (utilizing the online tool at 'www.surveymonkey.com'), we analysed the attitude towards NFP -methods and -apps, the need for contraceptive effectiveness in general, the perceived contraceptive effectiveness of NFP methods, and differences between NFP users and non-NFP users among 779 sexually active German-speaking women of fertile age (18-50 years) from November 2019 to October 2020. RESULTS AND CONCLUSIONS: Participants used NFP more frequently than they did five years ago. Women aged 30 years and older, with higher levels of education, who are living with a partner and have children, seem to be the target group for NFP methods. Concerning the wish for contraceptive effectiveness we found significant (p < .001) differences between NFP and non-NFP users. Furthermore, an increasing number of women wants to use NFP-methods and -apps for contraception; thus, non-hormonal contraceptive options should be offered. The majority of current NFP users stated that the handling and effectiveness of NFP have been improved by digitalisation.

Diagnosis and Treatment of Endometriosis. Guideline of the DGGG, SGGG and OEGGG (S2k Level, AWMF Registry Number 015/045, August 2020).

Aims The aim of this official guideline published and coordinated by the German Society of Gynaecology and Obstetrics (DGGG) in cooperation with the Austrian Society for Gynaecology and Obstetrics (OEGGG) and the Swiss Society for Gynaecology and Obstetrics (SGGG) was to provide consensus-based recommendations for the diagnosis and treatment of endometriosis based on an evaluation of the relevant literature. Methods This S2k guideline represents the structured consensus of a representative panel of experts with different professional backgrounds commissioned by the Guideline Committee of the DGGG, OEGGG and SGGG. Recommendations Recommendations on the epidemiology, aetiology, classification, symptomatology, diagnosis and treatment of endometriosis are given and special situations are discussed.

Case Report and Review of the Literature of a Rare Entity of a Uterine Fibroid: A Genital Rhabdomyoma.

Extracardiac rhabdomyomas are rare benign tumors. According to histopathologic and clinical characteristics, they are divided into 3 subgroups: adult, fetal, and genital rhabdomyomas. Various adult extracardiac rhabdomyomas have been reported in the head and neck region, whereas genital rhabdomyomas are uncommon. Here, we report on a uterine genital rhabdomyoma in a 32-yr-old woman with secondary sterility. After myomectomy, the histopathologic analysis showed a slow cycling tumor with striated muscle differentiation and without any evidence of malignancy. Immunohistochemical staining proved coexpression of actin, caldesmon, and desmin. To the best of our knowledge, this is the first case of a uterine-based genital rhabdomyoma.

Fishing for (in)continence: long-term follow-up of women with OASIS-still a taboo.

PURPOSE: Obstetric anal sphincter injuries (OASIS) increase the risk for pelvic floor dysfunctions. The goal of this study was to examine the long-term outcomes after OASIS on pelvic floor functions and quality of life. MATERIAL AND METHODS: Between 2005 and 2013, 424 women had an OASIS at the Women University Hospital Ulm. Out of these 71 women completed the German pelvic floor questionnaire, which includes questions regarding prolapse symptoms as well as bladder, bowel and sexual function. In addition, 64 women were physically examined, including a speculum examination to evaluate the degree of prolapse, a cough test to evaluate urinary stress incontinence (SI) and an evaluation of both pelvic floor sphincter (modified Oxford score) and anal sphincter contraction. RESULTS: A high rate of pelvic floor disorders after OASIS was found, as 74.6% of women reported SI, 64.8% flatus incontinence and 18.3% stool incontinence, respectively. However, only few women stated a substantial negative impact on quality of life. The clinical examination showed that a positive cough test, a weak anal sphincter tone and a diagnosed prolapse correlated with the results of the self-reported questionnaire. CONCLUSION: On one hand, OASIS has an influence on pelvic floor function going along with lots of complaints, while on the other hand, it still seems to be a taboo topic, as none of the participants spoke about the complaints after OASIS with a doctor. Therefore, the gynecologist should actively address these issues and offer therapy options for the women with persisting problems.

Pregnancy induced Cushing's syndrome and primary aldosteronism: a case report.

BACKGROUND: First manifestation of Cushing's syndrome during pregnancy is rare. The diagnosis of both Cushing's and primary aldosteronism within a pregnancy has not been previously documented. Diagnosis is especially challenging due to the normal physiological changes that occur during pregnancy. Consequently, many tests that are normally used for diagnosis are not reliable. Tumor based etiologies can be surgically removed. Etiologies that are not tumor based are challenging to treat during pregnancy. CASE PRESENTATION: A 25 year old G1P0 was admitted in the 22 5/7 week of pregnancy with elevated blood pressure (200/100 mm Hg), acne, moon facies, abdominal striae and hirsutism. With five antihypertensive medications her blood pressure remained 190/100 mm Hg. The patient was admitted to the ICU for intravenous medications and monitoring. She was diagnosed with Cushing's syndrome and primary aldosteronism. In spite of therapy with spironolactone and metyrapone she developed preeclampsia and was delivered in the 26 0/7 week of pregnancy. At her follow up visit eight weeks postpartum she had blood pressure within normal limits, no clinical signs or symptoms, and all medications had been discontinued. CONCLUSIONS: Early diagnosis of pregnancy induced Cushing's syndrome and primary aldosteronism requires an interdisciplinary approach. Late detection has been associated with increased perinatal morbidity and mortality including but not limited to placental abruption and intrauterine demise. Collaboration is essential in the optimization of maternal and fetal outcomes.

Diagnosis and Therapy Before Assisted Reproductive Treatments. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Register Number 015-085, February 2019) - Part 1, Basic Assessment of the Woman.

Introduction Supporting and counselling couples with fertility issues prior to starting ART is a multidisciplinary diagnostic and therapeutic challenge. The first German/Austrian/Swiss interdisciplinary S2k guideline on "Diagnosis and Therapy Before Assisted Reproductive Treatments (ART)" was published in February 2019. This guideline was developed in the context of the guidelines program of the German Society of Gynecology and Obstetrics (DGGG) in cooperation with the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). Aims One third of the causes of involuntary childlessness are still unclear, even if the woman or man have numerous possible risk factors. Because the topic is still very much taboo, couples may be socially isolated and often only present quite late to a fertility center. At present, there is no standard treatment concept, as currently no standard multidisciplinary procedures exist for the diagnostic workup and treatment of infertility. The aim of this guideline is to provide physicians with evidence-based recommendations for counselling, diagnostic workup and treatment. Methods This S2k guideline was developed on behalf of the Guidelines Commission of the DGGG by representative members from different professional medical organizations and societies using a structured consensus process. Recommendations The first part of this guideline focuses on the basic assessment of affected women, including standard anatomical and endocrinological diagnostic procedures and examinations into any potential infections. Other areas addressed in this guideline are the immunological workup with an evaluation of the patient's vaccination status, an evaluation of psychological factors, and the collection of data relating to other relevant factors affecting infertility. The second part will focus on explanations of diagnostic procedures compiled in collaboration with specialists from other medical specialties such as andrologists, human geneticists and oncologists.

Diagnosis and Treatment Before Assisted Reproductive Treatments. Guideline of the DGGG, OEGGG and SGGG (S2k Level, AWMF Register Number 015-085, February 2019) - Part 2, Hemostaseology, Andrology, Genetics and History of Malignant Disease.

Introduction Supporting and counselling couples with fertility issues prior to starting ART is a multidisciplinary diagnostic and therapeutic challenge. The first German-language interdisciplinary S2k guideline on "Diagnosis and Therapy Before Assisted Reproductive Treatments (ART)" was published in February 2019. The guideline was developed in the context of the guidelines program of the German Society of Gynecology and Obstetrics (DGGG) in cooperation with the Swiss Society of Gynecology and Obstetrics (SGGG) and the Austrian Society of Gynecology and Obstetrics (OEGGG). Aim In one third of cases, the cause of involuntary childlessness remains unclear, even if the woman or man have numerous possible risk factors. Because the topic is still very much taboo, couples may be socially isolated and often only present quite late to a fertility center. There is no standard treatment concept for these patients at present, as there are currently no standard multidisciplinary procedures for the diagnostic workup and treatment of infertility. The aim of this guideline is to provide physicians with evidence-based recommendations for counselling, diagnosis and treatment. Methods This S2k guideline was developed on behalf of the Guidelines Commission of the DGGG by representative members from different professional medical organizations and societies using a structured consensus process. Recommendations This second part of the guideline describes the hematological workup for women as well as additional diagnostic procedures which can be used to investigate couples and which are carried out in cooperation with physicians working in other medical fields such as andrologists, geneticists and oncologists.

Recurrent Miscarriage: Diagnostic and Therapeutic Procedures. Guideline of the DGGG, OEGGG and SGGG (S2k-Level, AWMF Registry Number 015/050).

PURPOSE: Official guideline of the German Society of Gynecology and Obstetrics (DGGG), the Austrian Society of Gynecology and Obstetrics (ÖGGG) and the Swiss Society of Gynecology and Obstetrics (SGGG). The aim of this guideline was to standardize the diagnosis and treatment of couples with recurrent miscarriage (RM). Recommendations were based on the current literature and the views of the involved committee members. METHODS: Based on the current literature, the committee members developed the statements and recommendations of this guideline in a formalized process which included DELPHI rounds and a formal consensus meeting. RECOMMENDATIONS: Recommendations for the diagnosis and treatment of patients with RM were compiled based on the international literature. Specific established risk factors such as chromosomal, anatomical, endocrine, hemostatic, psychological, infectious and immunological disorders were taken into consideration.

[Metformin for the treatment of polycystic ovary syndrome]. / Metformin bei polyzystischem Ovarsyndrom.

For several years there is an evidence for a relationship between the polycystic ovary syndrome (PCOS) and of insulin resistance; therefore metformin, an insulin sensitizer, is used for the treatment for more than 10 years. However, the evidence for metformin is assessed controversially. This review will give an overview about the data published on this topic.

Aggressive Intrinsic Subtypes in Breast Cancer: A Predictor of Guideline Adherence in Older Patients With Breast Cancer?

BACKGROUND: Treatment side effects, comorbidities, and guideline-adherent treatment (GL+) influence the oncologic outcome of older breast cancer patients (oBCP) (age ≥ 70 years). The focus of this analysis was to investigate the associations among tumor characteristics, guideline adherence, and outcome and to compare these associations between younger breast cancer patients (yBCP) (age 50-69 years) and oBCP. METHODS: This is a retrospective multicenter cohort study with 17 participating certified breast cancer centers. The analysis of 10,897 patient records collected from 1992 to 2008 for GL+ and clinical outcome was performed. Tumor and patient characteristics and their associations with GL+ were compared between oBCP and yBCP. RESULTS: Nonguideline-adherent treatment (GL-) was associated with higher tumor stages and comorbidities. This effect was stronger in the oBCP group (P < .001). GL+ was significantly more common in yBCP than in oBCP (P < .001). The oBCP had significantly higher tumor stages, including tumor size (P < .001), nodal status (P < .001), and positive hormone receptors (P = .001). Tumor grading was lower (P = .001), and HER2neu overexpression was less frequent (P = .003) in oBCP. Overall survival and disease-free survival are significantly impaired if GL- occurred in patients with breast cancer independently of age. CONCLUSIONS: GL- is associated with decreased disease-free survival and overall survival in both age groups. GL+ decreases advanced tumor characteristics in all age groups but significantly more in oBCP. If patients received GL+, we were unable to detect a statistical significant difference in the survival parameters.

Tumor biology in older breast cancer patients--what is the impact on survival stratified for guideline adherence? A retrospective multi-centre cohort study of 5378 patients.

PURPOSE: The tumor biology of older breast cancer patients (oBCP) is usually less aggressive, however applied adjuvant treatment is often less potent resulting in an impaired disease free survival and overall survival in this group. This study tries to answer the following questions for the biological subtypes of oBCP (70+ y): METHODS: Between 1992 and 2008 the BRENDA ('BRENDA' = quality of BREast caNcer care unDer evidence-bAsed guidelines) study group recorded medical data of 17 participating certified breast cancer centers in Germany. We performed a retrospective multi-center database analysis of 5632 patient records. Guideline-adherent-treatment (GL+) of oBCP(n = 1918) was compared to GL+ of yBCP(n = 3714). RESULTS: OBCP were more likely to have hormone receptor positive (HR+) and HER2neu negative (HER2-) breast cancer (77.5% vs 74.5%). The rate of GL- was significantly different (p < 0.001) between the age groups and the biological subgroups (yBCP vs oBCP: 21.8%vs38.8% (HR+/HER2-); 30.6%vs49.7% (HR+/HER2+); 23.6%vs69.5% (HR-/HER2+); 31.4%vs67.8% (TNBC)). The survival parameters for HR+/HER2- and TNBC were significantly worse in case of GL- regarding chemotherapy, and if applicable endocrine therapy. A similar association only existed in HR-/HER2+ tumors for GL- for radiotherapy and in HR+/HER2+ tumors for chemotherapy. CONCLUSIONS: Beside the significantly different distribution of biological subtypes in the age groups there is an association between biological subtype, and GL+ influencing survival parameters in oBCP.

Predicting fatigue in older breast cancer patients receiving radiotherapy. A head-to-head comparison of established assessments.

OBJECTIVES: Because of substantial toxicities in older adults, chemotherapy is often omitted while the frequency of radiotherapy changes only minimally. In this study, we addressed the value of different assessments for predicting fatigue after radiotherapy in older breast cancer patients. PATIENTS AND METHODS: We included 74 women with primary breast cancer over the age of 65 years treated with radiotherapy (26 % with additional chemotherapy). Assessments were conducted before adjuvant treatment and after radiotherapy. The assessments included the Vulnerable Elders Survey (VES-13), the Karnofsky Performance Status (KPS), the EORTC Quality of Life assessment (EORTC-QLQ-C30), a cancer-specific comprehensive geriatric assessment (cancer-specific CGA), and the Fried frailty score. Multiple linear regression analyses were used to assess correlations with the FACIT-fatigue scale. RESULTS: Patients were on average 71 years old (range, 65-86 years). Most tumors (n=62) were classified as intermediate risk according to the St. Gallen consensus. The cancer-specific CGA was best associated with fatigue (p < 0.001, ß estimate = 1.75), followed by the Fried frailty score (for the score of 1 versus reference of 2 and higher: p = 0.035, ß estimate = - 5.74). There were no significant ceiling effects but there were substantial floor effects for the VES-13, KPS, and frailty score. CONCLUSION: The cancer-specific CGA and the Fried frailty score (driven mainly by the item "exhaustion") outperformed the other indices in predicting fatigue in a group of rather well-functioning older women with primary breast cancer.