Liver phenotypes in PCOS: Analysis of exogenous and inherited risk factors for liver injury in two European cohorts.

BACKGROUND & AIMS: Fatty liver disease (FLD) is common in women with polycystic ovary syndrome (PCOS). Here, we use non-invasive tests to quantify liver injury in women with PCOS and analyse whether FLD-associated genetic variants contribute to liver phenotypes in PCOS. METHODS: Prospectively, we recruited women with PCOS and controls at two university centres in Germany and Poland. Alcohol abuse was regarded as an exclusion criterion. Genotyping of variants associated with FLD was performed using TaqMan assays. Liver stiffness measurements (LSM), controlled attenuation parameters (CAP) and non-invasive HSI, FLI, FIB-4 scores were determined to assess hepatic steatosis and fibrosis. RESULTS: A total of 42 German (age range 18-53 years) and 143 Polish (age range 18-40 years) women with PCOS, as well as 245 German and 289 Polish controls were recruited. In contrast to Polish patients, Germans were older, presented with more severe metabolic profiles and had significantly higher LSM (median 5.9 kPa vs. 3.8 kPa). In the German cohort, carriers of the PNPLA3 p.I148M risk variant had an increased LSM (p = .01). In the Polish cohort, the minor MTARC1 allele was linked with significantly lower serum aminotransferases activities, whereas the HSD17B13 polymorphism was associated with lower concentrations of 17-OH progesterone, total testosterone, and androstenedione (all p < .05). CONCLUSIONS: FLD is common in women with PCOS. Its extent is modulated by both genetic and metabolic risk factors. Genotyping of variants associated with FLD might help to stratify the risk of liver disease progression in women suffering from PCOS.

Acute Sheehan's syndrome manifesting initially with diabetes insipidus postpartum: a case report and systematic literature review.

PURPOSE: Acute Sheehan's syndrome is a rare, but potentially life-threatening, obstetric event that can be complicated by diabetes insipidus. Little information on the diagnosis and treatment of Sheehan's syndrome with diabetes insipidus is available. We report on a 28-year-old patient who developed acute Sheehan's syndrome with diabetes insipidus after giving birth, and on a systematic review of similar cases. METHODS: We performed a systematic review of the literature cataloged in PubMed and Google Scholar using the keywords "Sheehan syndrome" OR "Sheehan's syndrome" AND "diabetes insipidus" to identify relevant case reports published between 1990 and 2021. Eight Reports met the inclusion criteria (English-language abstracts available, onset in the puerperium, information about the day of the onset). RESULTS: In the present case, postpartum curettage was necessary to remove the residual placenta. The total amount of blood loss was severe (2500 ml). On the second day postpartal, the patient developed polyuria. Laboratory analysis revealed hypernatremia with increased serum osmolality and decreased urinary osmolality. Hormone analysis showed partial hypopituitarism involving the thyroid, corticotropic, and gonadotropic axes. The prolactin level was elevated. Brain magnetic resonance imaging showed pituitary gland infarction. Desmopressin therapy was initiated and resolved the polyuria. Hormone replacement therapy was administered. Four months later, the patient was well, with partial diabetes insipidus. The literature review indicated that this case was typical in terms of symptoms and disease onset. Most reported cases involve hypotension and peripartum hemorrhage, but some patients without hemorrhage also develop Sheehan's syndrome. Elevated prolactin levels are uncommon and associated with poor prognosis in patients with Sheehan's syndrome. CONCLUSION: Acute Sheehan's syndrome with diabetes insipidus involves nearly all pituitary hormone axes, indicating severe disease. Prolactin elevation could suggest that a case of Sheehan's syndrome is severe.

Correlation between the Incontinence Severity Index (ISI) and the quality of life dimensions of the King's Health Questionnaire (KHQ) in German-speaking urinary incontinent women.

BACKGROUND: The Incontinence Severity Index (ISI) is a patient questionnaire to ascertain severity of urinary incontinence (UI) via two items. The aim of this study was to translate the ISI into German, to compare it with the German-language King's Health Questionnaire (KHQ), an already validated German-language questionnaire within the scope of UI to measure condition-specific quality of life (QoL), and to gain more insights into association between symptom severity and QoL in German-speaking women affected. METHODS: A total of 161 urinary incontinent women completed the ISI and the KHQ. Mean scores of the KHQ domains were computed and separated into severity-groups ascertained by the ISI (slight, moderate, severe, and very severe). Differences between severity-groups were examined using Kruskal-Wallis and Mann-Whitney U test. Correlation between ISI and KHQ were computed using Spearman's correlation coefficient to investigate construct validity of the ISI as well as association between symptom severity and QoL. RESULTS: Overall, mean scores of the KHQ domains increased with increasing severity level. A consistent significant increase was found in role, physical, and social limitations (p < 0.05). Furthermore, the ISI showed moderate to strong correlations with related domains (convergent validity) and weak correlations with non-related domains of the KHQ (discriminant validity). CONCLUSIONS: Construct validity of the German-language ISI is acceptable. Therefore this study supports its use in German-speaking women but further studies have to be done to gain more comprehensive insights into its psychometric properties. Moreover, increasing symptom severity is associated with decreasing QoL, especially concerning role, physical, and social limitations. TRIAL REGISTRATION NUMBER: DRKS00018777.

Comparison of Maternal Serum Levels and Placental mRNA Levels of Dickkopf-1 in Preeclamptic and Normal Pregnant Women at Delivery.

Background Preeclampsia remains a major cause of perinatal and maternal mortality and morbidity worldwide. Wnt/ß-catenin signaling is known to be critically involved in placenta development processes. Dickkopf-1 (DKK1) is a key regulator of this transduction pathway. The aim of this study is to compare maternal serum DKK1 levels and placental mRNA levels of DKK1 and ß-catenin in preeclamptic and normal pregnant women at delivery. Methods The present study included 30 women with preeclampsia and 30 women with normal pregnancy. Maternal serum DKK1 levels were measured by ELISA. Placental mRNA levels of DKK1 and ß-catenin were detected using RT-PCR. Results Decreased maternal serum DKK1 levels were associated with worse maternal and fetal complications including HELLP syndrome, determination of one or more pathological symptom and IUGR diagnosis. No significant difference in maternal serum DKK1 levels was reported between preeclamptic women and women with normal pregnancy. Placental mRNA DKK1 levels were lower in preeclamptic women compared with normal pregnant women. Placental mRNA ß-catenin levels showed no significant difference between two groups. Conclusions Our findings reported the aberrant placental mRNA DKK1 levels in patients with preeclampsia. In addition, worse preeclampsia features were associated with decreased maternal serum DKK1 levels. Hence, aberrant Wnt/ß-catenin signaling might present a plausible mechanism in preeclampsia pathogenicity. Dysregulated expression of DKK1 at gene level in the placenta but not at protein level in the maternal serum might confirm the notion that preeclampsia is a type of placenta-derived disease.

Evaluation of the SF-36 questionnaire for assessment of the quality of life of endometriosis patients undergoing treatment: A systematic review and meta-analysis.

Endometriosis has a negative influence on the physical, psychological, and social aspects of a patient's life; therefore, it affects the health-related quality of life (HRQoL). The current review aimed to investigate the efficiency of a 36-item generic questionnaire survey (SF-36) for patients with endometriosis who were undergoing medical or surgical treatment. A search strategy including the key words 'endometriosis', 'quality of life' (QOL), and 'questionnaire SF-36' was applied using the PubMed/MEDLINE, EMBASE, and Cochrane databases in order to include articles that evaluated the QOL among women with endometriosis using the SF-36. Only articles that included interviews of patients both before and after surgical or medical endometriosis treatment or those articles that compared study groups were considered. The qualitative analysis was based on 37 articles, whereas the quantitative analysis utilized 14 articles. The research participants included 11,101 women, among whom 6,888 patients were diagnosed with endometriosis. The analysis recorded 17 studies dealing with all types of endometriosis, 9 studies dealing with deep infiltrative endometriosis (DIE), and 9 studies dealing with bowel endometriosis or DIE with bowel involvement. QOL was evaluated using only SF-36 in 12 studies that collectively included 1,912 women and using SF-36 in association with other questionnaires in 25 studies that collectively included 8,022 women. For patients with endometriosis, physical functioning [odds ratio (OR), 78.87; 95% confidence interval (CI), 68.97-88.77; I2=98.77%; P≤0.001] was the most affected life parameter. This parameter showed the highest improvement after surgical intervention (OR, 63.39; 95% CI, 48.71-78.07; I2=97.65%; P≤0.001) or hormonal treatment (OR, 38.65; 95% CI, 14.39-62.91; I2=38.65%; P≤0.001). The 36-item survey generic questionnaire seems to be an efficient tool for assessment of the QOL of life of women with endometriosis who are undergoing surgical or medical treatment. It can be applied before and after the procedure, and it can also be used for comparing study groups.

Psychometric properties of the German-language questionnaire for urinary incontinence diagnosis (QUID) in women with urinary incontinence.

PURPOSE: The aim of this study was to translate the questionnaire for urinary incontinence diagnosis (QUID) into German and to assess its psychometric properties in German-speaking women with urinary incontinence (UI). The QUID contains two subscales to measure symptom severity of stress urinary incontinence (SUI) and urge urinary incontinence (UUI) and to distinguish between both forms. METHODS: A total of 161 women with UI completed the QUID and the King's Health Questionnaire (KHQ), each in the German version. To examine construct validity Spearman's correlation coefficients between both questionnaires were computed. Furthermore, the internal consistency (Cronbach's alpha) of the QUID and its criterion validity were examined. Looking at criterion validity, sensitivity, specificity, ROC curves, and Youden-indexes were computed for both subscales. RESULTS: The QUID showed good construct validity by strong correlations with related domains of the KHQ. Cronbach's alpha values were good for both subscales of the QUID (SUI-subscale: 0.76; UUI-subscale: 0.86). Sensitivity and specificity were 83% (95% CI, 0.72-0.9) and 45% (95% CI, 0.25-0.67) for the SUI-subscale and 83% (95% CI, 0.7-0.91) and 56% (95% CI, 0.4-0.72) for the UUI-subscale. Youden-index was 0.28 for the SUI-subscale and 0.39 for the UUI-subscale at the given cut-off values. CONCLUSION: Psychometric properties of the German-language QUID are principally good and support its use in the German-speaking area. However, the modest specificity when distinguishing between SUI and UUI should be taken into account. TRIAL REGISTRATION NUMBER: DRKS00018777 (date of registration: 16-January-2020).

Urogynecology in obstetrics: impact of pregnancy and delivery on pelvic floor disorders, a prospective longitudinal observational pilot study.

PURPOSE: To assess changes in the pelvic floor anatomy that cause pelvic floor disorders (PFDs) in primigravidae during and after pregnancy and to evaluate their impact on women's quality of life (QoL). METHODS: POP-Q and translabial ultrasound examination was performed in the third trimester and 3 months after delivery in a cohort of primigravidae with singleton pregnancy delivering in a tertiary center. Results were analyzed regarding mode of delivery and other pre- and peripartal factors. Two individualized detailed questionnaires were distributed at 3 months and at 12 months after childbirth to determinate QoL. RESULTS: We recruited 45 women, of whom 17 delivered vaginally (VD), 11 received a vacuum extraction delivery (VE) and 17 a Cesarean section in labor (CS). When comparing third-trimester sonography to 3 months after delivery, bladder neck mobility increased significantly in each delivery group and hiatal area increased significantly in the VD group. A LAM avulsion was found in two women after VE. Connective tissue weakness (p = 0.0483) and fetal weight at birth (p = 0.0384) were identified as significant risk factors for the occurrence of PFDs in a multivariant regression analysis. Urinary incontinence was most common with 15% and 11% of cases at 3, respectively, 12 months after delivery. 42% of women reported discomfort during sexual intercourse, 3 months after delivery and 24% 12 months postpartum. Although 93% of women engage a midwife after delivery, only 56% participated in pelvic floor muscle training. CONCLUSION: Connective tissue weakness and high fetal weight at birth are important risk factors for the occurrence of PFDs. Nevertheless, more parturients should participate in postpartal care services to prevent future PFDs.

Impact of the Vegan Diet on Sperm Quality and Sperm Oxidative Stress Values: A Preliminary Study.

BACKGROUND: Insufficient nutrition and inappropriate diet have been related to many diseases. Although the literature confirms the hypothesis that particular nutritional factors can influence the quality of semen, until today, there are no specific dietary recommendations created for infertile males. Since the male contribution to the fertility of a couple is crucial, it is of high importance to determine the dietary factors that can affect male fertility. AIM: The aim of the present study was to evaluate differences in sperm quality parameters, sperm oxidative stress values and sperm acrosome reaction between vegan diet consumers and non-vegans. SETTING AND DESIGN: Prospective study in a University Medical School. MATERIALS AND METHODS: The present study was undertaken to evaluate the sperm quality parameters of vegan diet consumers (10 males who had a strictly vegetable diet with no animal products) and compare them with non-vegans (10 males with no diet restrictions). Semen quality was assessed following the World Health Organization (2010) criteria. Acrosome and DNA integrity has been evaluated using the immunofluorescence technique. STATISTICAL ANALYSIS: All variables were analysed by IBM SPSS version 24. Mean differences among groups were compared by Mann-Whitney U-test. RESULTS: Obtained results showed that total sperm count (224.7 [117-369] vs. 119.7 [64.8-442.8]; P = 0.011) and the percentage of rapid progressively motile sperm were significantly higher in the vegan group compared with the non-vegan group (1 [0-7] vs. 17.5 [15-30]; P < 0.0001). Furthermore, the oxidation-reduction potential (0.4 [0.3-0.9] vs. 1.5 [0.6-2.8]; P < 0.0001) and the proportion of spermatozoon with DNA damage (14.7 [7-33.5] vs. 8.2 [3-19.5]; P = 0.05) were significantly higher in the non-vegan group in comparison to the vegan group. CONCLUSIONS: Results obtained in this study provide additional evidence about the favourable effect of a plant-based diet on sperm parameters. To confirm our preliminary findings, further studies including larger cohorts are warranted.

Treatment algorithm for women with endometriosis in a certified Endometriosis Unit.

INTRODUCTION: Endometriosis is a chronic hormone-dependent disease affecting approximately 25-30% of women in the third and fourth decade. Despite its frequency, it is often detected late. The aim of this overview article was to present a standardized treatment algorithm for an interdisciplinary endometriosis consultation considering conservative and surgical approaches. EVIDENCE ACQUISITION: Despite the frequency of endometriosis and a high number of publications dealing with the disease there is a lack of evidence in literature for standardized treatment algorithms allowing a rational diagnostic and therapeutic approach. In May 2019 we did a literature search in Medline. While finding 26702 publications under the term "endometriosis" there was only one publication for the search term "endometriosis consultation treatment algorithm." After screening the abstracts 144 publications in English, French or German language had been assessed as relevant for the diagnosis and therapy of endometriosis (143 overview articles and one guideline). EVIDENCE SYNTHESIS: Based on clinical evidence, we have developed a treatment algorithm for women with suspected endometriosis. The diagnosis includes a structured medical history with the identification of endometriosis-typical symptoms and a gynecological examination, if necessary additional examinations. The treatment algorithm is essentially divided into the phase of diagnosis and the phase of therapy as well as the prevention of recurrence or long-term treatment. A multi-professional team of visceral surgery, urology, nutritional medicine, physiotherapy and psychology can be consulted for support. CONCLUSIONS: The treatment of endometriosis should be multiprofessional, standardized and reproducible during specialized consultations at certified centers. So far, there are few publications on a standardized and clinically proven treatment algorithm for women with suspected endometriosis. The presented treatment algorithm could be helpful in the diagnosis and treatment of endometriosis patients, even at other centers.

Conisation course for medical students-experience from a German University Hospital

Objective: Conisation of the cervix is one of the most common surgical procedures in gynaecology. Nevertheless, surgical expertise is required because if the cone is too small, the oncological risk increases and if the cone is too large, the obstetric risk increases. The aim of this prospective study was to investigate the suitability of an in-house conisation simulator for teaching medical students the practical performance of conisation. Material and Methods: Following a demonstration, students performed a loop conisation with a target depth of 8-10 mm using the simulator. Cone biopsy dimensions were analysed and a loop electrosurgical excision procedure (LEEP) score was calculated. The students were surveyed using a questionnaire of 12 items with five possible responses for each in order to investigate the suitability and realism of the teaching experience. Results: Eighty-nine students participated in the course. The median (range) cone depth was 8 (3-25) mm with a standard deviation of 3.3 mm. The observed LEEP score amounted to 1.5. The questionnaire was answered by 88 students and completed by 86. Survey results showed the course was consistently rated as positive, especially towards the increase in practical skills. The questionnaire item producing the highest score was "I enjoyed the course" while the statement "I have gained enough self-confidence for the application of high-frequency surgery" received the lowest approval score. Students considered the course to be realistic and a helpful teaching exercise. Conclusion: Practical surgery exercises on the surgical simulator were received positively. Simulation training could be extended to other gynaecological operations and to other medical subjects.

Patient satisfaction with personal patient care (PPC) in the inpatient treatment of endometriosis.

PURPOSE: The aim of this retrospective cohort study was to validate patient's satisfaction and surgical complication rate in patients treated at a certified endometriosis centre with personal patient care (PPC). METHODS: The implementation of PPC at a gynaecologic treatment centre was retrospectively evaluated by analysing perioperative complications using the Clavien Dindo (CD) classification and patient satisfaction utilizing the Picker Patient Experience Questionnaire (PPE-15) for a total of 219 symptomatic endometriosis patients treated surgically at a certified endometriosis centre (Agaplesion Diakonie Hospital, Kassel, Germany) between November 2018 and April 2019. Data from our sample on complication rates and satisfaction were compared with those from reference samples published by Radosa et al. and Jenkinson et al. RESULTS: An overall complication rate of 10.96% (24 out of 219 patients) was observed. Four endometriosis patients (1.83%) had major complications with complications grade III according to the CD classification system. 155 patients out of 219 chose to answer the PPE-15 (return rate 70.78%). 92 patients (59.35%) reported about problems during their treatment in our hospital in their PPE-15. "Doctors sometimes talked as if I was not here" was the best rated item (1.2%) in our cohort. "Staff gave conflicting information" was the most mentioned item (33.55%) by patients during their hospital stay in relation to patient dissatisfaction. CONCLUSION: Incorporation of PPC in the surgical inpatient treatment of endometriosis patients resulted in a low postoperative complication rate and a high patient satisfaction in our study cohort. Furthermore, nursing staff of endometriosis patients also needs particular attention.

Fertility preservation in female cancer patients: current knowledge and future perspectives.

INTRODUCTION: Protecting fertility in the presence of cancer has become highly significant, as the desire to give birth to a child is increasingly postponed to later in life, and long-term survival with cancer has increased. A variety of fertility-preserving methods have been developed. EVIDENCE ACQUISITION: To find them, we performed a literature search in Medline using the key words "female fertility preservation in cancer" in December 2017. A total of 2381 different publications were found. EVIDENCE SYNTHESIS: After screening the abstracts 78 publications in English, French, or German language had been assessed as relevant (17 dealing with medical approaches, six with surgical approaches, 15 with oocyte cryopreservation, 11 with ovarian tissue cryopreservation and 29 were review articles). In general, there are medical (non-surgical) and surgical approaches. Medical approaches comprise administration of GnRH-analogues during gonad toxic oncologic treatment, and cryopreservation of oocytes after ovarian stimulation. Surgical approaches comprise traditional methods of organ-saving surgery and ovarian transposition outside of the radiation portal as well as ovary cryopreservation as standard. CONCLUSIONS: It is important to inquire about a prospective desire to have children with premenopausal women with cancer and comprehensively explain the fertility conserving methods available. Every premenopausal woman with cancer should be counseled about the methods of fertility protection currently available at a multiprofessional center.

Influence of androgen levels on conception probability in patients undergoing fertility treatment: a retrospective cohort study.

PURPOSE: Primary and secondary sterility have become an issue of increasing importance due to demographic and social changes in society. Data regarding the association between female androgen levels and the probability of successful conception after fertility treatment are sparse and contradictive. This study was designed to assess this clinical question. METHODS: In this retrospective single-center cohort study concentrations of androgens androstenedione, dehydroepiandrosteronsulfat (DHEAS) and testosterone (ng/ml) were investigated in the serum of patients presenting for sterility at the department of reproductive medicine of Saarland University hospital Homburg between January 2015 and December 2017. Androgen levels were correlated with reproductive outcomes. Statistical analysis was performed with the aid of SPSS version 24. Significance for conception rates in dependence of androgen concentration was assessed using Kruskal-Wallis test (significance was estimated with p < 0.05). RESULTS: The laboratory values of a total of 301 patients were examined (64% primary, 36% secondary sterility). Median age at first visit at the fertility department was 32.7 years (range 20-47 years). 64 pregnancies were observed during the study period (conception rate 21.3%). 23 out of 301 patients (7.6%) suffered from hypoandrogenaemia, 248 (82.4%) had normal androgen levels and 30 (10%) showed hyperandrogenaemia (p = 0.25). Regarding patients in whom fertility treatment was successful 3 (4.7%) showed hypoandrogenaemia, 54 (84.4%) were normoandrogenaemic and 7 (10.9%) had hyperandrogenaemia (p = 0.40 Kruskal-Wallis test). CONCLUSIONS: We found no association between female androgen levels and sterility and reproductive outcomes.

Oral etoposide for metastatic choriocarcinoma: a case report and review of guidelines.

BACKGROUND AND PURPOSE: Choriocarcinoma (CCA) is a rare form of malignant trophoblastic disease. Systemic polychemotherapy with etoposide, methotrexate, actinomycin D, cyclophosphamide, and vincristine (EMA/CO) is the mainstay of treatment for metastatic disease. Due to the rarity of the condition, however, the evidence basis for this management is small and other chemotherapy regimens may also be effective. The reported case presents anecdotal evidence of an effective etoposide monotherapy treatment. METHOD: CASE PRESENTATION: We report the case of a patient with gestational choriocarcinoma and pulmonary metastases initially treated with methotrexate. Due to local disease progression, she underwent hysterectomy and continued treatment with methotrexate. After pulmonary progression, she was switched to oral etoposide. RESULTS: After four cycles of etoposide monotherapy at a oral dosage of 100 mg d1-7, q28, the patient had no evidence of disease according to human chorionic gonadotropin serum levels and imaging studies. The treatment was well tolerated with World Health Organization (WHO) grade 2 alopecia and hot flushes as the most prominent side effects. The patient has achieved a sustained complete remission with a follow-up of 6 years. CONCLUSION: Oral etoposide may be an effective treatment alternative to EMA/CO in selected patients with oligometastatic CCA.