Sertoli-Leydig cell tumor: a clinicopathological analysis in a comprehensive, national cohort.

INTRODUCTION: Sertoli-Leydig cell tumors are rare tumors of the ovary. Moderate and poorly differentiated tumors can metastasize and have a poor outcome. A pathogenic variant in DICER1 is associated with an increased risk of developing these tumors along with other clinical phenotypes. We aimed to describe a national cohort of all Sertoli-Leydig cell tumors with regard to clinicopathological characteristics and frequency of DICER1 pathogenic variants. METHODS: In May 2018, all patients registered from January 1997 to December 2017 with the Systematized Nomenclature of Medicine code M86310 (Sertoli-Leydig cell tumor) were obtained from the Danish National Pathology Registry. Validation of the diagnosis depended on comments in the reports that two pathologists validated the initial diagnosis or revision of the pathology at another facility. We performed descriptive statistics to describe baseline characteristics, and cancer related survival was calculated using Kaplan-Meier analysis followed by a log rank test for differences between variables RESULTS: 41 women with Sertoli-Leydig cell tumors were identified. Median age was 41 years (range 6-79). The stages according to the International Federation of Gynecology and Obstetrics (FIGO) were: stage I, 85% (n=35), stage II, 2% (n=1), stage III, 5% (n=2), and stage IV, 7% (n=3). The 5 year cancer related survival was 100% for patients with localized disease (stages I-II) and 0% in advanced tumor stages (stages III-IV). Histological differentiation grade of the tumors was well differentiated in 29% (n=12), moderately differentiated in 56% (n=23), and poorly differentiated in 15% (n=6), and the 5 year cancer related survival was 100%, 96%, and 33%, respectively, according to grade. All patients underwent surgery. Twenty-two patients had fertility sparing surgery and four of these had given birth at the time of follow-up. Analysis of DICER1 was performed in eight women. Four carried a pathogenic variant. Four patients received adjuvant chemotherapy, three because of advanced tumor stage, and one because of a poorly differentiated Sertoli-Leydig cell tumor. CONCLUSION: The prognosis for women with Sertoli-Leydig cell tumors with localized disease is excellent. Women with advanced stages (III-IV) have a poor prognosis, regardless of adjuvant chemotherapy. Fertility sparing surgery seems to be a viable option for localized Sertoli-Leydig cell tumors. DICER1 screening was rarely performed in previous cohorts and concomitant organ screening programs are topics for discussion.

Effect of 24 mg dexamethasone preoperatively on surgical stress, pain and recovery in robotic-assisted laparoscopic hysterectomy.

Background: Robotic-assisted hysterectomy is an alternative to laparoscopic surgery as part of a minimal invasive regimen. Several treatment strategies are followed to improve the overall outcome and minimize surgical stress. Glucocorticoids provide significant analgesic and antiemetic effects but their role in reducing inflammatory stress in a fast-track, multi-modal setting in patients undergoing minimally invasive surgery remains to be investigated in details. Methods: This study will evaluate in a randomized trial the effect of a single dose of 24 mg dexamethasone on 100 women undergoing robotic-assisted hysterectomy with regard to surgical stress, measured by c-reactive protein as primary outcome and, further, other stress markers like white blood cell subtypes. The postoperative recovery will be registered in validated charts and questionnaires for pain and analgesic use, quality of recovery, incontinence, sexual and work life. Furthermore, in a sub-analysis, transcriptional profiling will be performed to explore the mechanism of systemic innate and adaptive immune system perturbation induced by surgical stress. Conclusion: The study will provide solid evidence on markers of immunomodulation biomarkers and in addition the subjective effects and underlying mechanisms of perioperative glucocorticoid in women undergoing robotic hysterectomy. These include important aspects of life quality like pain, fatigue, freedom of medications, resuming work and sexual activities.

Use and development of contraceptive apps.

This state-of-the-art review evaluates whether contraceptive apps could improve knowledge resulting in greater interest and use of long-acting contraception, what type of information an app should contain, and who may benefit most from apps. The studies found a high interest in easy accessibility and respect for privacy. Science-based information and facilitation of knowledge about all contraceptives were desired. Contraceptive apps were useful in presenting women with validated information and complement professional advice.

Diabetes risk after a normal oral glucose tolerance test during pregnancy.

INTRODUCTION: Our aim was to conduct a follow-up of a cohort of women screened for GDM with a normal oral glucose tolerance test (OGTT) during pregnancy to investigate the incidence and time of diagnosis of manifest diabetes mellitus and identify risk factors for subsequent development of diabetes. METHODS: This was a follow-up study of a cohort with normal and borderline OGTT in 1991/1992. Among the original 352 women, only five were lost to follow-up. RESULTS: In total, 64 women (18%) had manifest diabetes. Their median age was 57 years after 28 years of follow-up. This amounts to three times the expected rate compared with the background population. The rate of manifest diabetes rises 10-20 years after pregnancy and after the age of 40 years. A normal fasting glucose and also a borderline fasting glucose at OGTT during pregnancy were associated with an increased risk of manifest diabetes (p less-than 0.001), also after adjustment for age, Body Mass Index, non-Danish origin and smoking during pregnancy (p less-than 0.002). CONCLUSION: The incidence of diabetes is higher in women with various risk factors for DM and a previously normal OGTT in pregnancy than in the background population. Our results are useful in identifying the time during which women may benefit from effective implementation of evidence-based treatment to postpone and avert manifest DM, even though they had a normal OGTT during pregnancy. FUNDING: none. TRIAL REGISTRATION: The trial was registered with the the Regional Ethics Committee and the Data Protection Agency, nos. 2014-41-3433, 1-16-02-824-17 (under running permission no. 621549), 1-16-02-825-17, and 1-16-02-180-17, all under the cover of data handling agreement no. 509 with the Danish Health Authority.

Gestational diabetes mellitus and autism spectrum disorder in the child.

Gestational diabetes mellitus (GDM) is associated with a number of complications, including developmental disorders in the child but the specific association is unclear. The purpose of this review is to summarize the latest knowledge about the association between GDM and one of the developmental disorders, namely autism spectrum disorder (ASF) in the child. Large cohort studies found that GDM increases the risk of ASF in the child, and that the risk increases the earlier the mother is diagnosed with GDM.

Diagnostic delay of gynaecological cancer in women with postmenopausal bleeding.

INTRODUCTION: Postmenopausal bleeding is the primary reason for referral to the gynaecological fast-track suspected cancer programme due to an elevated risk of endometrial cancer. The aim of this study was to examine the diagnostic flow among women with postmenopausal bleeding. METHODS: Data were collected and analysed from 362 women at Sygehus Sønderjylland referred with the International Classification of Diseases, tenth edition, diagnosis "DN950 postmenopausal bleeding" from 2015 to 2019. RESULTS: We found a mean 83-day period between the initial consultation and the final cancer diagnosis. Combined, the 362 women underwent 354 diagnostic procedures of which 204 were endometrial sampling with aspiration (vabrasio). In 44% of the cases, sampling by vacuum aspirator was either unsuccessful due to pain or cervical stenosis or was deemed insufficient for pathological assessment. Gynaecological cancer was diagnosed in 16 (4%) of the women, hereof 13 (3.6%) had endometrial cancer. CONCLUSIONS: We found a remarkable delay not complying with the intentions of national guidelines with respect to final diagnostics of endometrial cancer. Vacuum aspirator is a frequently used diagnostic tool, but has shortcomings in relation to the success rate of the procedure and insufficient sampling. Gynaecological cancer was found at a rate of 3-5% as reported by other Danish studies. Because of the limitations associated with a one-step diagnostic procedure with vabrasio, attention to follow-up may reduce diagnostic delay. FUNDING: none. TRIAL REGISTRATION: This study was registered with the Region of South Denmark (no. 21/18387) and Sygehus Sønderjylland (no. 1298-001) as a quality improvement project.

Which elements were significant in reducing obstetric anal sphincter injury? A prospective follow-up study.

BACKGROUND: To examine which elements of an obstetric anal sphincter injury (OASI) care bundle were protective for OASI. Several interventional trials showed that application of a care bundle involving a hands-on approach to perineal protection may reduce the risk of OASI. Previously, we found that only the element "hand on the fetal head" in itself was protective, although the risk of a type 2 error was calculated to be 50%. METHODS: A prospective follow-up study in an obstetric department in Denmark with 3200 deliveries per year. We included a cohort of 10,383 women giving birth vaginally from gestational week 22 + 0 from 2016 through 2019. We documented on a person-level the five elements of the care bundle together with maternal and obstetrical characteristics. The elements were 1) communication, 2) visible perineum, 3) hand on fetal head, 4) perineal support and 5) certification. Regression analysis was used for analysis of associations. The primary outcome measure was OASI. RESULTS: The total rate of OASI in vaginally delivering women was 1.9%. The incidence was 3.2% in nulliparous women giving birth vaginally. The rate of cesarean section was 16.5% and for episiotomy 2.4%. The reduction in the incidence of OASI was sustained since 2013. Hand on the fetal head and perineal support both were protective factors for OASI. In case of a nulliparous woman with a neonate weighing 3500 g giving birth spontaneously, the relative risk (RR) for OASI was 0.50 (95% CI 0.49- 0.51) with use of hand on the fetal head together with perineal support against no use. Similarly, with a nulliparous woman giving birth to a neonate of 3500 g by vacuum extraction, the RR for OASI was 0.65 (95% CI 0.62-0.68) against no use. CONCLUSIONS: Both hand on the fetal head and perineal support were associated with a reduced risk of OASI.

[Control of the level of human chorionic gonadotropin in urine compared to the level of serum after medically provoked abortion is a safe alternative].

Medical abortion with combined mifepristone and misoprostol is a highly effective, safe, and widely used method for medical termination of pregnancy. In this review, it is shown that self-testing with a urine human chorionic gonadotropin stix (detection limit greater than 25 IU/l) four weeks after administration of medication is a safe, practical, and cheap method to determine successful termination.

Metabolic syndrome in women with previous gestational diabetes.

To evaluate the incidence and timing of the diagnosis of metabolic syndrome in a cohort of Danish women after a pregnancy with gestational diabetes (GDM) to estimate the optimum time for preventative actions in relation to metabolic syndrome (MetS). In this follow-up study, 435 women were included from a consecutive cohort with prior history of GDM. Data on dyslipidemia, hypertension and other cardiovascular disorders (CVD) were extracted from the electronic patient journal. Any antidiabetic, cardiovascular and cholesterol-lowering medicine was ascertained in the national prescription database. Similarly, any blood test taken was evaluated. We defined a patient having MetS if the criteria of the WHO based definition of diabetes or impaired glucose regulation were met. Further, we added as alternative for glucose intolerance, a glycosylated hemoglobin (HbA1c) > 44 mmol/mol or the former level ≥ 6.5%. Further, dyslipidemia, lipid lowering medications, BMI > 30 kg/m2 or antihypertensive treatment were used. For MetS outcome, diagnosis or medication for CVD was registered. All women were followed for median 5.7 years (range 0; 9). The incidence of MetS was 28%. Thirteen percent of these qualified already within one year after pregnancy for the diagnosis of MetS. Postpartum MetS was detected after a median of 3 years (range 0; 7 years); further, 36 (8%) had been diagnosed with manifest diabetes after pregnancy. The diagnosis of postpartum MetS was strongly associated with the prevalence of manifest diabetes. Six years after pregnancy the rate of metabolic syndrome was more than tripled (25 vs. 89%, no DM vs manifest DM, RR: 6.7; 95% CI 2.7-17, p < 0.001). At 40 years the MetS rate nearly tripled if manifest DM was diagnosed (26 vs. 78%, no DM vs. manifest DM, RR: 3.3, 95% CI 1.8-6, p < 0.001). We found that GDM and later on manifest DM in women increase the risk of metabolic syndrome. There seems to be a window of opportunity before the early thirties where it would be especially beneficial to begin preventive efforts in women with GDM.

Does giving birth in a "birth environment room" versus a standard birth room lower augmentation of labor? - Results from a randomized controlled trial.

OBJECTIVE: In the last decade, there has been an increased interest in exploring the impact of the physical birth environment on midwifery practice and women's birth experiences. This study is based on the hypothesis that the environment for birth needs greater attention to improve some of the existing challenges in modern obstetric practice, for example the increasing use of augmentation and number of interventions during delivery. STUDY DESIGN: A randomized controlled trial was carried out to study the effect of giving birth in a specially designed "birth environment room" on the use of augmentation during labor. The study took place at the Department of Obstetrics and Gynecology, Herning Hospital, Denmark and included 680 nulliparous women in spontaneous labor at term with a fetus in cephalic presentation. Women were randomly allocated to either the "birth environment room" or a standard birth room. The primary outcome was augmentation of labor by use of oxytocin. Secondary outcomes were duration of labor, use of pharmacological pain relief, and mode of birth. Differences were estimated as relative risks (RR) and presented with 95% confidence intervals. RESULTS: No difference was found on the primary outcome, augmentation of labor (29.1% in the "birth environment room" versus 30.6% in the standard room, RR 0.97; 0.89-1.08). More women in the "birth environment room" used the bathtub (60.6% versus 52.4%, RR 1.18; 1.02-1.37), whereas a tendency to lower use of epidural analgesia (22.6% versus 28.2%) did not reach statistical significance (RR 0.87; 0.74-1.02). The chance of an uncomplicated birth was almost similar in the two groups (70.6% in the "birth environment room" versus 72.6% in the standard room, RR 0.97; 0.88-1.07) as were duration of labor (mean 7.9 hours in both groups). CONCLUSIONS: Birthing in a specially designed physical birth environment did not lower use of oxytocin for augmentation of labor. Neither did it have any effect on duration of labor, use of pharmacological pain relief, and chance of birthing without complications. We recommend that future trials are conducted in birth units with greater improvement potentials.

Manifest diabetes after gestational diabetes: a double-cohort, long-term follow-up in a Danish population.

PURPOSE: The aim was to follow-up two cohorts of women with GDM to investigate the incidence and time of diagnosis of manifest diabetes mellitus (DM) postpartum and identify the risk factors for diabetes in our population. METHODS: A follow-up study on two independent cohorts having oral glucose tolerance test (OGTT) in 1991/1992 and 2011-2016: Cohort 1 consisted of 406 women including 54 with GDM and 352 with a non-GDM OGTT-test and cohort 2 had 433 women diagnosed with GDM. The first cohort had nearly 25 years of follow-up and gave information on magnitude, conversion rate and type of diabetes manifestation. The second cohort was started recently to evaluate whether newer diagnostic criteria and baseline information on the old cohort are still valid for prediction of diabetes risk. RESULTS: The risk of manifest diabetes in cohort 1 at the end of follow-up was six times higher in women with previous GDM compared with non-GDM (RR = 6; 95% CI 4-11). We observed a 70% diabetes rate 25 years after pregnancy. Only family history of diabetes in cohort 2 was associated with conversion to manifest diabetes (p = 0.002), also after adjustment for age, BMI, non-Danish origin and smoking during pregnancy (p < 0.001) CONCLUSION: The incidence of diabetes after GDM is higher than that previously reported in Scandinavian populations and the rate of manifest diabetes rises steeply 15 years after pregnancy and after 40 years of age. The women of cohort 2 with recent GDM are at risk of DM at a higher rate. On this background our results are useful in identifying the time where GDM women may benefit from the effective implementation of evidence-based treatment to postpone and advert manifest DM.

Study protocol for a randomised trial evaluating the effect of a "birth environment room" versus a standard labour room on birth outcomes and the birth experience.

INTRODUCTION: In the last decade, there has been an increased interest in exploring the impact of the physical birth environment on birth outcomes. The birth environment might have an important role in facilitating the production of the hormone oxytocin that causes contractions during labour. Oxytocin is released in a safe, secure and confidence-inducing environment, and environments focused on technology and medical interventions to achieve birth may disrupt the production of oxytocin and slow down the progress of labour. An experimental "birth environment room" was designed, inspired by knowledge from evidence-based healthcare design, which advocates bringing nature into the room to reduce stress. The purpose is to examine whether the 'birth environment room', with its design and decor to minimise stress, has an impact on birth outcomes and the birth experience of the woman and her partner. MATERIALS AND METHODS: A randomised controlled trial will recruit 680 nulliparous women at term who will be randomly allocated to either the "birth environment room" or a standard room. The study will take place at the Department of Obstetrics and Gynecology at Herning Hospital, with recruitment from May 2015. Randomisation to either the "birth environment room" or standard room takes place just before admission to a birth room during labour. The primary outcome is augmentation of labour, and the study has 80% power to detect a 10% difference between the two groups (two-sided α = 0.05). Secondary outcomes are duration of labour, use of pharmacological pain relief, mode of birth, and rating of the birth experience by women and their partners. TRIAL REGISTRATION: NCT02478385(10/08/2016).

No effect of human papillomavirus vaccination on sexual debut of school children.

INTRODUCTION: We aimed to describe sexual behaviour and knowledge about sexually transmitted infections (STI) among Danish adolescents stratified by gender and human papillomavirus (HPV) vaccination status. METHODS: We conducted a questionnaire study in Viborg Municipality, Denmark. A validated questionnaire was sent to all ninth-grade pupils without prior notice to either teachers or pupils. RESULTS: In 2014, 776 pupils attended the ninth grade, 685 (88%) of whom participated in the study. A total of 376 (55%) reported having received the HPV vaccine. HPV-vaccinated girls (p = 0.03) and boys (p = 0.04) had more knowledge about STI than those who were unvaccinated. A total of 157 (23%) pupils reported having had intercourse, with a mean age at debut of 14.4 (standard deviation ± 1) years and no significant difference by gender or vaccination status. From first to latest intercourse, we found a significant decline in total condom use among all pupils (p < 0.001), with the most significant decline being observed among HPV-vaccinated pupils (p < 0.001), in particular among HPV-vaccinated girls (p < 0.001). In addition, a non-significant increase was observed in the lack of use of contraception (16% versus 27%) from first to latest intercourse, with no difference being observed by gender or vaccination status. CONCLUSIONS: Overall, no difference in the proportion of pupils with sexual debut or mean age at sexual debut was observed between HPV-vaccinated and unvaccinated adolescents in Denmark. However, HPV-vaccinated adolescents were more likely to stop using a condom despite their higher STI awareness. FUNDING: Author Anne Hammer received funding from the Danish Cancer Society. TRIAL REGISTRATION: not relevant.

[Androgen-secreting tumours of the ovaries].

The diagnosis of an androgen-secreting tumour of the ovaries should be considered in women with hyperandrogenism. Clinical manifestations of hyperandrogenism include virilisation with hirsutism, vocal change, increased muscle mass, hypertrophy of clitoris and alopecia. Definitive diagnosis is made by histopathologic examination, and the most common diagnoses are granulosa cell tumour, ovarian stromal hyperplasia and Sertoli-Leydig cell tumour. The differential diagnoses include polycystic ovary syndrome, benign or malignant adrenal tumour and adrenal hyperplasia.

[Congenital uterine anomalies and their association with fertility and pregnancy outcomes].

Congenital uterine anomalies (CUAs) are present in up to 10% of all women. Data suggest that women with CUAs are at higher risk of recurrent spontaneous abortions and adverse pregnancy outcomes. It is still debated whether these women have impaired fertility. The complication rate is likely to be overrepresented and assumedly many women with CUAs have normal reproduction and uneventful pregnancies. In women with CUAs and infertility or numerous spontaneous abortions surgical treatment should be considered.

[Post-partum ovarian vein thrombosis].

In this case report a 38-year-old woman presented with lower abdominal pain three weeks postpartum. She had been delivered by caesarean section after twin pregnancy and was given low-molecular heparin prophylaxis to be taken six weeks post caesarean. The initial clinical examination was normal. A CT scan revealed thrombosis in the right ovarian vein. Therapeutic dosage of low-molecular heparin was initiated, and the patient was further referred for thrombophilia workup. Post-partum ovarian vein thrombosis is a very rare condition but a diagnosis to keep in mind, when women present with lower abdominal pain even weeks after labour.

[Caesarean delivery in a woman with a unicorn uterus and foetal breech presentation].

In this case report a unicorn uterus was diagnosed at a caesarean delivery in a 23-year-old woman with known foetal breech presentation and suspected low foetal weight. She had had a failed attempt of cephalic version two weeks before delivery, and her baby's weight was checked regularly in third term. Unicorn uterus is associated with a higher risk of spontaneous abortions, infertility, preterm labour, foetal malpresentation, low birth weight, caesarean delivery and renal malformations. Although pregnancies in these women can be uneventful, it is advised, that women with unicorn uteri are followed closely during their pregnancies.

Microvascular disease during pregnancy in type 1 diabetes is associated with ambulatory arterial stiffness.

OBJECTIVES: The objective of this study was to evaluate the association between the ambulatory arterial stiffness index (AASI) and markers of microvascular disease during pregnancy in women with type 1 diabetes. STUDY DESIGN: A total of 151 women with type 1 diabetes mellitus were recruited for repeat 24-h BP recordings thrice during pregnancy and once three months post partum. Fifty women without diabetes served as controls. The AASI and pulse pressure (PP) were computed from blood pressure recordings. Repeated measures analysis of variance was used for comparison between groups during and after pregnancy. Linear regression analysis was performed with AASI and PP as dependent variables and albuminuria and retinopathy as independent variables. MAIN OUTCOME MEASURES: AASI during diabetic pregnancy and association with microvascular disease. RESULTS: Micro- or macroalbuminuria was present in 23% of the women and 58% had either simplex or proliferative retinopathy. The AASI was inversely associated with the coefficient of determination, which means that the stiffer vascular wall the more random variability in BP. CONCLUSION: AASI showed a strong association with microvascular disease during pregnancy in women with type 1 diabetes. Together with the flattened circadian rhythm this indicates a pregnancy-related functional change in the vascular bed.