Magnetic Resonance-Guided Focused Ultrasound Surgery for Gynecologic Indications.

Magnetic resonance-guided focused ultrasound surgery (MRgFUS) appears to be an effective and safe treatment for uterine fibroids and adenomyosis, particularly in women who wish to preserve fertility. In abdominal wall endometriosis and painful recurrent gynecologic malignancies, MRgFUS can relieve pain, but more research is needed. There is no widespread reimbursement due to the lack of large prospective or randomized controlled trials comparing MRgFUS with standard therapy.

Waste analysis and energy use estimation during MR-HIFU treatment: first steps towards calculating total environmental impact.

OBJECTIVES: To assess the environmental impact of the non-invasive Magnetic Resonance image-guided High-Intensity Focused Ultrasound (MR-HIFU) treatment of uterine fibroids, we aimed to perform a full Life Cycle Assessment (LCA). However, as a full LCA was not feasible at this time, we evaluated the CO2 (carbon dioxide) emission from the MRI scanner, MR-HIFU device, and the medication used, and analyzed solid waste produced during treatment. METHODS: Our functional unit was one uterine fibroid MR-HIFU treatment. The moment the patient entered the day care-unit until she left, defined our boundaries of investigation. We retrospectively collected data from 25 treatments to assess the CO2 emission based on the energy used by the MRI scanner and MR-HIFU device and the amount and type of medication administered. Solid waste was prospectively collected from five treatments. RESULTS: During an MR-HIFU treatment, the MRI scanner and MR-HIFU device produced 33.2 ± 8.7 kg of CO2 emission and medication administered 0.13 ± 0.04 kg. A uterine fibroid MR-HIFU treatment produced 1.2 kg (range 1.1-1.4) of solid waste. CONCLUSIONS: Environmental impact should ideally be analyzed for all (new) medical treatments. By assessing part of the CO2 emission and solid waste produced, we have taken the first steps towards analyzing the total environmental impact of the MR-HIFU treatment of uterine fibroids. These data can contribute to future studies comparing the results of MR-HIFU LCAs with LCAs of other uterine fibroid therapies. CRITICAL RELEVANCE STATEMENT: In addition to (cost-) effectiveness, the environmental impact of new treatments should be assessed. We took the first steps towards analyzing the total environmental impact of uterine fibroid MR-HIFU. KEY POINTS: • Life Cycle Assessments (LCAs) should be performed for all (new) medical treatments. • We took the first steps towards analyzing the environmental impact of uterine fibroid MR-HIFU. • Energy used by the MRI scanner and MR-HIFU device corresponded to 33.2 ± 8.7 kg of CO2 emission.

Effectiveness and complication rates of high intensity focused ultrasound treatment for abdominal wall endometriosis: A systematic review.

In this review, a systematic literature search on the effectiveness and complication rates of ultrasound-guided and magnetic resonance-guided high-intensity focused ultrasound (USg-/MRgHIFU) for abdominal wall endometriosis (AWE) was conducted in six databases in May/June 2023. Original articles of (non)randomized trials, cohort studies, case-control studies and case series published in peer-reviewed journals were included. Of the included studies the level of evidence (LoE) and methodological quality using the ROBINS-I and IHE-QAT was assessed. Primary outcomes were non-perfused volume ratio (NPV%), lesion size, pain scores, side effects and complication rates according to Society of Interventional Radiology (SIR) guidelines. Secondary outcomes were recurrence and re-intervention rates. Seven cohort studies (one of good methodological quality) (LoE 3) on USgHIFU were included (n = 212, AWE lesions = 240-245). Six months after USgHIFU treatment, pain scores were reduced with 3.3-5.2 points (baseline: 5.1-6.8, n = 135). Self-limiting side effects were pain (85.7 % (114/133)) and swelling (34.6 % (46/133)) in the treatment area. Complications occurred in 17.7 % (32/181), all of which were minor. Recurrence occurred in 12.8 % (11/86). Three of these seven cohort studies compared USgHIFU (n = 61) with surgical excision (n = 74). Pooled results showed no significant differences in pain scores, complications (resp. 26.3 % (10/38) vs. 32.6 % (15/46) (p = 0.53)) and recurrences (resp. 4.9 % (3/61) vs. 5.4 % (4/74) (p = 0.90)). This systematic review suggests that HIFU is an effective and safe treatment option for AWE. USgHIFU treatment led to reduced pain scores and lesion size, was free of major complications and had a pooled recurrence rate of 12.8 %. Compared to surgical excision pooled results showed no significant differences in pain scores, complications and recurrences after USgHIFU. However, many of the included studies had limitations in their methodological quality and therefore the results should be interpreted with caution. Well-structured high-quality randomized controlled trials comparing HIFU to standard care should be conducted to provide more conclusive evidence.

Increased MR-guided high intensity focused ultrasound (MR-HIFU) sonication efficiency of uterine fibroids after carbetocin administration.

Purpose: We investigated whether administration of the long-acting uterus stimulant carbetocin increased intra-subject sonication efficiency during Magnetic Resonance image guided High Intensity Focused Ultrasound (MR-HIFU) treatment of uterine fibroids. Method: In this prospective cohort study, thirty women with symptomatic uterine fibroids undergoing MR-HIFU treatment were included between January 2018 and January 2019. Treatment started with three sonications on one side of the uterine fibroid. Subsequently, one ampoule of 1 mL carbetocin (100 µg/mL) was administered intravenously and treatment continued with three sonications on the other side of the uterine fibroid. We compared the intra-subject sonication efficiency, in terms of Energy Efficiency Factor (EEF), thermal dose volume and sonication time to ablate one cm3 of fibroid tissue, before and after carbetocin administration. Adverse events that occurred within 30 min after carbetocin administration were recorded. Results: Sonication efficiency improved after carbetocin administration as indicated by a significant decrease in EEF and sonication time (p = 0.006 and p = 0.001 respectively), and a significant increase in thermal dose volume reached (p = <0.001). Five women (16.7%) experienced temporary tachycardia, one women in combination with headache, within 30 min after carbetocin administration. Conclusion: Administration of the long-acting uterus stimulant carbetocin improved the MR-HIFU treatment intra-subject sonication efficiency in women with symptomatic uterine fibroids.

Confidential enquiry into maternal deaths in the Netherlands, 2006-2018.

INTRODUCTION: To calculate the maternal mortality ratio (MMR) for 2006-2018 in the Netherlands and compare this with 1993-2005, and to describe women's characteristics, causes of death and improvable factors. MATERIAL AND METHODS: We performed a nationwide, cohort study of all maternal deaths between January 1, 2006 and December 31, 2018 reported to the Audit Committee Maternal Mortality and Morbidity. Main outcome measures were the national MMR and causes of death. RESULTS: Overall MMR was 6.2 per 100 000 live births, a decrease from 12.1 in 1993-2005 (risk ratio [RR] 0.5). Women with a non-western ethnic background had an increased MMR compared with Dutch women (MMR 6.5 vs. 5.0, RR 1.3). The MMR was increased among women with a background from Surinam/Dutch Antilles (MMR 14.7, RR 2.9). Half of all women had an uncomplicated medical history (79/161, 49.1%). Of 171 pregnancy-related deaths within 1 year postpartum, 102 (60%) had a direct and 69 (40%) an indirect cause of death. Leading causes within 42 days postpartum were cardiac disease (n = 21, 14.9%), hypertensive disorders (n = 20, 14.2%) and thrombosis (n = 19, 13.5%). Up to 1 year postpartum, the most common cause of death was cardiac disease (n = 32, 18.7%). Improvable care factors were identified in 76 (47.5%) of all deaths. CONCLUSIONS: Maternal mortality halved in 2006-2018 compared with 1993-2005. Cardiac disease became the main cause. In almost half of all deaths, improvable factors were identified and women with a background from Surinam/Dutch Antilles had a threefold increased risk of death compared with Dutch women without a background of migration.

Nationwide confidential enquiries into maternal deaths because of obstetric hemorrhage in the Netherlands between 2006 and 2019.

INTRODUCTION: Obstetric hemorrhage-related deaths are rare in high income countries. Yet, with increasing incidences of obstetric hemorrhage in these countries, it is of utmost importance to learn lessons from each obstetric hemorrhage-related death to improve maternity care. Our objective was to calculate the obstetric hemorrhage-related maternal mortality ratio (MMR), assess causes of obstetric hemorrhage-related deaths, and identify lessons learned. MATERIAL AND METHODS: Nationwide mixed-methods prospective case-series with confidential enquiries into maternal deaths due to obstetric hemorrhage in the Netherlands from January 1, 2006 to December 31, 2019. RESULTS: The obstetric hemorrhage-related MMR in the Netherlands in 2006-2019 was 0.7 per 100 000 livebirths and was not statistically significantly different compared with the previous MMR of 1.0 per 100 000 livebirths in 1993-2005 (odds ratio 0.70, 95% confidence interval 0.38-1.30). Leading underlying cause of hemorrhage was retained placenta. Early recognition of persistent bleeding, prompt involvement of a senior clinician and timely management tailored to the cause of hemorrhage with attention to coagulopathy were prominent lessons learned. Also, timely recourse to surgical interventions, including hysterectomy, in case other management options fail to stop bleeding came up as an important lesson in several obstetric hemorrhage-related deaths. CONCLUSIONS: The obstetric hemorrhage-related MMR in the Netherlands in 2006-2019 has not substantially changed compared to the MMR of the previous enquiry in 1993-2005. Although obstetric hemorrhage is commonly encountered by maternity care professionals, it is important to remain vigilant for possible adverse maternal outcomes and act upon an ongoing bleeding following birth in a more timely and adequate manner. Our confidential enquiries still led to important lessons learned with clinical advice to professionals as how to improve maternity care and avoid maternal deaths. Drawing lessons from maternal deaths should remain a qualitative and moral imperative.

Comparison of (Cost-)Effectiveness of Magnetic Resonance Image-Guided High-Intensity-Focused Ultrasound With Standard (Minimally) Invasive Fibroid Treatments: Protocol for a Multicenter Randomized Controlled Trial (MYCHOICE).

BACKGROUND: Magnetic resonance image-guided high-intensity-focused ultrasound (MR-HIFU) is a rather new, noninvasive option for the treatment of uterine fibroids. It is safe, effective, and has a very short recovery time. However, a lack of prospectively collected data on long-term (cost-)effectiveness of the MR-HIFU treatment compared with standard uterine fibroid care prevents the MR-HIFU treatment from being reimbursed for this indication. Therefore, at this point, when conservative treatment for uterine fibroid symptoms has failed or is not accepted by patients, standard care includes the more invasive treatments hysterectomy, myomectomy, and uterine artery embolization (UAE). Primary outcomes of currently available data on MR-HIFU treatment often consist of technical outcomes, instead of patient-centered outcomes such as quality of life (QoL), and do not include the use of the latest equipment or most up-to-date treatment strategies. Moreover, data on cost-effectiveness are rare and seldom include data on a societal level such as productivity loss or use of painkillers. Because of the lack of reimbursement, broad clinical implementation has not taken place, nor is the proper role of MR-HIFU in uterine fibroid care sufficiently clear. OBJECTIVE: The objective of our study is to determine the long-term (cost-)effectiveness of MR-HIFU compared with standard (minimally) invasive fibroid treatments. METHODS: The MYCHOICE study is a national, multicenter, open randomized controlled trial with randomization in a 2:1 ratio to MR-HIFU or standard care including hysterectomy, myomectomy, and UAE. The sample size is 240 patients in total. Women are included when they are 18 years or older, in premenopausal stage, diagnosed with symptomatic uterine fibroids, conservative treatment has failed or is not accepted, and eligible for MR-HIFU. Primary outcomes of the study are QoL 24 months after treatment and costs of treatment including direct health care costs, loss of productivity, and patient costs. RESULTS: Inclusion for the MYCHOICE study started in November 2020 and enrollment will continue until 2024. Data collection is expected to be completed in 2026. CONCLUSIONS: By collecting data on the long-term (cost-)effectiveness of the MR-HIFU treatment in comparison to current standard fibroid care, we provide currently unavailable evidence about the proper place of MR-HIFU in the fibroid treatment spectrum. This will also facilitate reimbursement and inclusion of MR-HIFU in (inter)national uterine fibroid care guidelines. TRIAL REGISTRATION: Netherlands Trial Register NL8863; https://www.trialregister.nl/trial/8863. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/29467.

Systematic review of reproductive outcomes after High Intensity Focused Ultrasound treatment of uterine fibroids.

PURPOSE: Myomectomy is currently the gold standard for the treatment of uterine fibroids in women who desire pregnancy. However, this surgical fibroid removal has a long convalescence. Promising alternatives may be non-invasive High Intensity Focused Ultrasound (HIFU) under either MRI (MR-HIFU) or ultrasound guidance (USgHIFU). In this systematic review, an overview is provided of reproductive outcomes after these two relatively new ablation techniques. METHOD: A systematic literature search was performed to identify studies reporting reproductive outcomes after HIFU treatment of fibroids. Only peer reviewed, full papers were included. Outcomes included pregnancy-, live-birth- miscarriage and caesarian section rate, time to conceive, reported complications, and possible prognostic factors. RESULTS: In total 21 studies were included. Fourteen studies reported 124 pregnancies after MR-HIFU. Two placenta previas and no uterus ruptures were reported. Pregnancy rates were only retrospectively collected and ranged between 7% and 36%. Miscarriage rate in the oldest and largest prospective registry was 39%. After USgHIFU 366 pregnancies were reported with one fetal intrauterine death, six placenta previas and no uterus ruptures. The only prospective study reported a pregnancy rate of 47% and a miscarriage rate of 11%. Possible prognostic factors like age were not available in most studies. CONCLUSIONS: Based on the heterogeneous data currently available, reproductive outcomes after HIFU appear non-inferior to outcomes after the current standard of care. However, a (randomized) controlled trial comparing reproductive outcomes after HIFU and standard care is necessary to provide sufficient evidence on the preferred fibroid treatment for women with a pregnancy wish.

Levonorgestrel-releasing intrauterine system versus endometrial ablation for heavy menstrual bleeding.

BACKGROUND: Heavy menstrual bleeding affects the physical functioning and social well-being of many women. The levonorgestrel-releasing intrauterine system and endometrial ablation are 2 frequently applied treatments in women with heavy menstrual bleeding. OBJECTIVE: This study aimed to compare the effectiveness of the levonorgestrel-releasing intrauterine system with endometrial ablation in women with heavy menstrual bleeding. STUDY DESIGN: This multicenter, randomized controlled, noninferiority trial was performed in 26 hospitals and in a network of general practices in the Netherlands. Women with heavy menstrual bleeding, aged 34 years and older, without a pregnancy wish or intracavitary pathology were randomly allocated to treatment with either the levonorgestrel-releasing intrauterine system (Mirena) or endometrial ablation, performed with a bipolar radiofrequency device (NovaSure). The primary outcome was blood loss at 24 months, measured with a Pictorial Blood Loss Assessment Chart score. Secondary outcomes included reintervention rates, patient satisfaction, quality of life, and sexual function. RESULTS: We registered 645 women as eligible, of whom 270 women provided informed consent. Of these, 132 women were allocated to the levonorgestrel-releasing intrauterine system (baseline Pictorial Blood Loss Assessment Chart score, 616) and 138 women to endometrial ablation (baseline Pictorial Blood Loss Assessment Chart score, 630). At 24 months, mean Pictorial Blood Loss Assessment Chart scores were 64.8 in the levonorgestrel-releasing intrauterine system group and 14.2 in the endometrial ablation group (difference, 50.5 points; 95% confidence interval, 4.3-96.7; noninferiority, P=.87 [25 Pictorial Blood Loss Assessment Chart point margin]). Compared with 14 women (10%) in the endometrial ablation group, 34 women (27%) underwent a surgical reintervention in the levonorgestrel-releasing intrauterine system group (relative risk, 2.64; 95% confidence interval, 1.49-4.68). There was no significant difference in patient satisfaction and quality of life between the groups. CONCLUSION: Both the levonorgestrel-releasing intrauterine system and endometrial ablation strategies lead to a large decrease in menstrual blood loss in women with heavy menstrual bleeding, with comparable quality of life scores after treatment. Nevertheless, there was a significant difference in menstrual blood loss in favor of endometrial ablation, and we could not demonstrate noninferiority of starting with the levonorgestrel-releasing intrauterine system. Women who start with the levonorgestrel-releasing intrauterine system, a reversible and less invasive treatment, are at an increased risk of needing additional treatment compared with women who start with endometrial ablation. The results of this study will enable physicians to provide women with heavy menstrual bleeding with the evidence to make a well-informed decision between the 2 treatments.

Development and clinical evaluation of a 3-step modified manipulation protocol for MRI-guided high-intensity focused ultrasound of uterine fibroids.

OBJECTIVES: The clinical applicability of magnetic resonance image-guided high-intensity focused ultrasound (MR-HIFU) treatment of uterine fibroids is often limited due to inaccessible fibroids or bowel interference. The aim of this study was to implement a newly developed 3-step modified manipulation protocol and to evaluate its influence on the number of eligible women and treatment failure rate. METHODS: From June 2016 to June 2018, 165 women underwent a screening MRI examination, 67 women of whom were consecutively treated with MR-HIFU at our institution. Group 1 (n = 20) was treated with the BRB manipulation protocol which consisted of sequential applications of urinary bladder filling, rectal filling, and urinary bladder emptying. Group 2 (n = 47) was treated using the 3-step modified manipulation protocol which included (1) the BRB maneuver with adjusted rectal filling by adding psyllium fibers to the solution; (2) Trendelenburg position combined with bowel massage; (3) the manual uterine manipulation (MUM) method for uterine repositioning. A comparison was made between the two manipulation protocols to evaluate differences in safety, the eligibility percentage, and treatment failure rate due to unsuccessful manipulation. RESULTS: After implementing the 3-step modified manipulation protocol, our ineligibility rate due to bowel interference or inaccessible fibroids decreased from 18% (16/88) to 0% (0/77). Our treatment failure rate due to unsuccessful manipulation decreased from 20% (4/20) to 2% (1/47). There were no thermal complications to the bowel or uterus. CONCLUSIONS: Implementation of the 3-step modified manipulation protocol during MR-HIFU therapy of uterine fibroids improved the eligibility percentage and reduced the treatment failure rate. TRIAL REGISTRATION: Registry number NL56182.075.16 KEY POINTS: • A newly developed 3-step modified manipulation protocol was successfully implemented without the occurrence of thermal complication to the bowel or uterus. • The 3-step modified manipulation protocol increased our eligibility percentage for MR-HIFU treatment of uterine fibroids. • The 3-step modified manipulation protocol reduced our treatment failure rate for MR-HIFU treatment of uterine fibroids.

Use of multiparametric MRI to characterize uterine fibroid tissue types.

BACKGROUND: Although the biological characteristics of uterine fibroids (UF) have implications for therapy choice and effectiveness, there is limited MRI data about these characteristics. Currently, the Funaki classification and Scaled Signal Intensity (SSI) are used to predict treatment outcome but both screening-tools appear to be suboptimal. Therefore, multiparametric and quantitative MRI was studied to evaluate various biological characteristics of UF. METHODS: 87 patients with UF underwent an MRI-examination. Differences between UF tissues and myometrium were investigated using T2-mapping, Apparent Diffusion Coefficient (ADC) maps with different b-value combinations, contrast-enhanced T1-weighted and T2-weighted imaging. Additionally, the Funaki classification and SSI were calculated. RESULTS: Significant differences between myometrium and UF tissue in T2-mapping (p = 0.001), long-TE ADC low b-values (p = 0.002), ADC all b-values (p < 0.001) and high b-values (p < 0.001) were found. Significant differences between Funaki type 3 versus type 1 and 2 were observed in SSI (p < 0.001) and T2-values (p < 0.001). Significant correlations were found between SSI and T2-mapping (p < 0.001; ρs = 0.82), ADC all b-values (p = 0.004; ρs = 0.31), ADC high b-values (p < 0.001; ρs = 0.44) and long-TE ADC low b-values (p = 0.004; ρs = 0.31). CONCLUSIONS: Quantitative MR-data allowed us to distinguish UF tissue from myometrium and to discriminate different UF tissue types and may, therefore, be a useful tool to predict treatment outcome/determine optimal treatment modality.

Magnetic resonance-high intensity focused ultrasound (MR-HIFU) therapy of symptomatic uterine fibroids with unrestrictive treatment protocols: A systematic review and meta-analysis.

PURPOSE: Reevaluation of the effectiveness of Magnetic Resonance-High Intensity Focused Ultrasound (MR-HIFU) therapy for uterine fibroids by excluding studies with restrictive treatment protocols that are no longer used. METHODS: The National Guideline Clearinghouse, Cochrane Library, TRIP, MEDLINE, EMBASE and WHO International Clinical Trials Registry Platform (ICTRP) databases were searched from inception until the 22nd of June 2018. Keywords included "MR-HIFU", "MRgFUS", and "Leiomyoma". Only studies about MR-HIFU treatment of uterine fibroids with at least three months of clinical follow-up were evaluated for inclusion. Treatments with ultrasound-guided HIFU devices or protocols not aiming for complete ablation were eliminated. The primary outcome was the improvement in fibroid-related symptoms. Technical outcomes included screening and treatment failures, treatment time, application of bowel-interference mitigation strategies and the Non-Perfused Volume (NPV) percentage. Other secondary outcomes were the quality of life, fibroid shrinkage, safety, re-interventions, reproductive outcomes, and costs. Meta-analysis was performed using a random-effects model (DerSimonian and Laird). RESULTS: A total of 18 articles (1323 treated patients) met the inclusion criteria. All selected studies were case series except for one cross-over trial. Overall, the quality of the evidence was poor to moderate. The mean NPV% directly post-treatment was 68.1%. The use of bowel-interference mitigation strategies may lead to increased NPV%. The mean symptom reduction at 12-months was 59.9% and fibroid shrinkage was 37.7%. The number of adverse events was low (8.7%), stratification showed a difference between HIFU systems. The re-intervention percentage at 3-33.6 months follow-up ranged from 0 to 21%. Longer follow-up was associated with a higher risk at re-interventions. Reproductive outcomes and costs couldn't be analyzed. CONCLUSIONS: Treatment guidelines aiming for complete ablation enhanced the effectiveness of MR-HIFU therapy. However, controlled trials should define the role of MR-HIFU in the management of uterine fibroids.

Maternal mortality after cesarean section in the Netherlands.

OBJECTIVES: Maternal mortality is rare in high-resource settings. This hampers studies of the association between maternal mortality and mode of birth, although this topic remains of importance, given the changing patterns in mode of birth with increasing cesarean section rates in most countries. Purpose of this study was to examine incidence of cesarean section-related maternal mortality in the Netherlands and association of surgery with the chain of morbid events leading to death. STUDY DESIGN: We performed a retrospective cohort study using the Confidential Enquiry into Maternal Deaths, including all 2,684,946 maternities in the Netherlands between January 1st, 1999, and December 31st, 2013, registered in the Dutch Perinatal Registry. All available medical records of cases reported to the Dutch Maternal Mortality and Severe Morbidity Audit Committee were assessed by two researchers, and one or two additional experts in case of contradicting opinions, based on a set of pre-identified clinical criteria. Main outcome measures were (1) incidence and relative risk of maternal death following cesarean section and vaginal birth and (2) incidence of death directly related to cesarean section and death in which cesarean section was one of the contributing factors. RESULTS: Risk of death after cesarean section was 21.9 per 100.000 cesarean sections (86/393,443) versus 3.8 deaths per 100.000 vaginal births (88/2,291,503): Relative Risk (RR) 5.7 (95% Confidence Interval [CI] 4.2-7.7). Death directly related to complications of cesarean section occurred in 8/86 women: 2 per 100,000 cesarean sections. With addition of 43 women in which cesarean section did not initiate, but contributed to the chain of events leading to mortality, risk of death increased to 13 per 100,000 cesarean sections (51/393,443; RR 3.4; 95%CI 2.4-4.8). At the start of cesarean section, pre-existing morbidity was present in 70/86 women (81.4%). CONCLUSIONS: Compared to vaginal birth, maternal mortality after cesarean section was three times higher following exclusion of deaths that had no association with surgery. In approximately one in ten deaths after cesarean section, surgery did in fact initiate the chain of morbid events.

[Isolated fallopian tubal torsion; rare or overlooked?] / Geïsoleerde tubatorsie: zeldzaam of miskend?

Isolated fallopian tubal torsion (IFTT) is a rare cause of lower abdominal pain. It's difficult to diagnose preoperatively due to non-specific clinical symptoms. Furthermore, IFTT is often not considered in the differential diagnosis. Prompt diagnosis is critical, to prevent progression of symptoms and to maintain fertility; therefore, this article discusses diagnostic pitfalls and reports on key imaging features of IFTT that may facilitate preoperative diagnosis. IFTT should be suspected in a female patient with acute lower abdominal pain and a unilateral pelvic mass close to a normal ipsilateral ovary; there may be a history of prior tubal ligation. Specific imaging findings include the sonographic 'whirlpool sign' and absent flow during colour Doppler ultrasound. CT is often performed when the diagnosis remains unclear, but has no clinical consequences. IFTT requires emergency surgical treatment; detorsion without resection can be considered in women who would like to retain potential future fertility, but salpingectomy is often inevitable due to necrosis.

Regional differences in severe postpartum hemorrhage: a nationwide comparative study of 1.6 million deliveries.

BACKGROUND: The incidence of severe postpartum hemorrhage (PPH) is increasing. Regional variation may be attributed to variation in provision of care, and as such contribute to this increasing incidence. We assessed reasons for regional variation in severe PPH in the Netherlands. METHODS: We used the Netherlands Perinatal Registry and the Dutch Maternal Mortality Committee to study severe PPH incidences (defined as blood loss ≥ 1000 mL) across both regions and neighborhoods of cities among all deliveries between 2000 and 2008. We first calculated crude incidences. We then used logistic multilevel regression analyses, with hospital or midwife practice as second level to explore further reasons for the regional variation. RESULTS: We analyzed 1599867 deliveries in which the incidence of severe PPH was 4.5%. Crude incidences of severe PPH varied with factor three between regions while between neighborhoods variation was even larger. We could not explain regional variation by maternal characteristics (age, parity, ethnicity, socioeconomic status), pregnancy characteristics (singleton, gestational age, birth weight, pre-eclampsia, perinatal death), medical interventions (induction of labor, mode of delivery, perineal laceration, placental removal) and health care setting. CONCLUSIONS: In a nationwide study in The Netherlands, we observed wide practice variation in PPH. This variation could not be explained by maternal characteristics, pregnancy characteristics, medical interventions or health care setting. Regional variation is either unavoidable or subsequent to regional variation of a yet unregistered variable.

Association of preeclampsia with podocyte turnover.

BACKGROUND AND OBJECTIVES: Preeclampsia is characterized by hypertension and proteinuria, and increased shedding of podocytes into the urine is a common finding. This finding raises the question of whether preeclamptic nephropathy involves podocyte damage. This study examined podocyte-related changes in a unique sample of renal tissues obtained from women who died of preeclampsia. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All patients with preeclampsia who died in The Netherlands since 1990 and had available autopsy tissue were identified using a nationwide database of the Dutch Pathology Registry (PALGA). This resulted in a cohort of 11 women who died from preeclampsia. Three control groups were also identified during the same time period, and consisted of normotensive women who died during pregnancy (n=25), and nonpregnant controls either with (n=14) or without (n=13) chronic hypertension. Glomerular lesions, including podocyte numbers, podocyte proliferation, and parietal cell activation, were measured. RESULTS: Patients with preeclampsia had prominent characteristic glomerular lesions. The results showed that the number of podocytes per glomerulus did not differ significantly between the patients with preeclampsia and the control groups. However, preeclampsia was associated with a significant increase in intraglomerular cell proliferation (7.3% [SD 9.4] of the glomeruli of patients with preeclampsia had Ki-67-positive cells versus 1.6% [SD 3.3] of the glomeruli of hypertensive controls and 1.1% [SD 1.3] of nonpregnant controls; P=0.004) and activated parietal epithelial cells on a podocyte location (34% [SD 13.1] of the glomeruli of patients with preeclampsia versus 18.0% [SD 15.3] of pregnant controls, 11.9% [SD 13.2] of hypertensive controls, and 10.8% [SD 13.4] of nonpregnant controls; P=0.01). CONCLUSIONS: These findings suggest that the recently described mechanisms of podocyte replacement play a role in preeclampsia. These results provide key new insights into the pathogenesis of preeclamptic nephropathy, and they open new possibilities for developing therapeutic modalities.

Preeclampsia is associated with the presence of transcriptionally active placental fragments in the maternal lung.

Preeclampsia is associated with increased levels of the circulating antiangiogenic factor sFlt-1 and with an excessive shedding of placenta-derived multinucleated syncytial aggregates into the maternal circulation. However, it remains unclear whether these aggregates are transcriptionally active in the maternal organs and can, therefore, contribute to the systemic manifestations of preeclampsia. In this study, we measured placental soluble fms-like tyrosine kinase-1 (sFlt-1) mRNA levels in preeclamptic- and control placentas and performed RNA in situ hybridization to localize the main placental expression site of sFlt-1 mRNA. Because the maternal lung is the first capillary bed that circulating syncytial aggregates traverse, we studied the presence and persistence of placental material in lungs of preeclamptic and control subjects. To confirm the placental origin of these aggregates in maternal lungs, immunohistochemistry for the placenta-specific marker hCG (human chorionic ghonadotropin) and Y chromosome in situ hybridization were performed. Using human placental tissue, we found that syncytial knots are the principal site of expression of the antiangiogenic factor sFlt-1. In addition, autopsy material obtained from women with preeclampsia (n=9) showed significantly more placenta-derived syncytial aggregates in the lungs than in control subjects (n=26). Importantly, these aggregates still contained the antiangiogenic factor sFlt-1 after their entrapment in the maternal lungs. The current study confirms the important role of syncytial knots in placental sFlt-1 mRNA production. In addition, it shows a significant association between preeclampsia and larger quantities of sFlt-1 containing syncytial aggregates in maternal lungs, suggesting that the transfer of syncytial aggregates to the maternal compartment may contribute to the systemic endothelial dysfunction that characterizes preeclampsia.

Maternal mortality and severe maternal morbidity from acute fatty liver of pregnancy in the Netherlands.

OBJECTIVE: To assess maternal death and severe maternal morbidity from acute fatty liver of pregnancy (AFLP) in the Netherlands. STUDY DESIGN: A retrospective study of all cases of maternal mortality in the Netherlands between 1983 and 2006 and all cases of severe maternal morbidity in the Netherlands between 2004 and 2006, in which all 98 maternity units in the Netherlands participated. Maternal mortality ratio (MMR) and incidence of severe maternal morbidity were the main outcome measures. RESULTS: The MMR from direct maternal mortality from AFLP was 0.13 per 100,000 live births (95% CI 0.05-0.29). The incidence of severe maternal morbidity from AFLP was 3.2 per 100,000 deliveries (95% CI 1.8-5.7). CONCLUSIONS: AFLP is a rare condition which still causes severe maternal morbidity and in some cases mortality. Referral to a tertiary care hospital for treatment of this uncommon disease should be considered.

Indirect maternal mortality increases in the Netherlands.

OBJECTIVE: To assess causes, trends, and substandard care in indirect maternal mortality in the Netherlands. DESIGN: Confidential enquiry into causes of maternal death. SETTING: Nationwide in the Netherlands. POPULATION: A total of 2,557,208 live births. METHODS: Data analysis of indirect maternal deaths in the period 1993-2005. MAIN OUTCOME MEASURES: Indirect maternal mortality. RESULTS: Of the study subjects, 97 were classified as indirect deaths, representing a maternal mortality ratio of 3.3/100,000 live births, a significant increase compared to the preceding enquiry in the period 1983-1992 (MMR 2.4, OR 1.5, 95%CI 1.0-2.1). The percentage of cases not directly reported to the Maternal Mortality Committee decreased from 15 to 5%. Cardiovascular disorders were the leading cause of indirect maternal mortality, followed by cerebrovascular disorders. Vascular dissection (n = 19) was the most frequent specified cause of death. Risk factors were advanced maternal age, non-indigenous origin (Surinam and Dutch Antilles), and medical health risks before pregnancy. Substandard care was present in 35%, mainly being misjudgment of the severity of the condition and delay in initiating therapy. CONCLUSION: The rise of mortality due to indirect causes is considered a reflection of the change in risk profile of women of childbearing age and the result of demographic alterations concerning ethnicity and maternal age. The identification of high risk groups, preferably by programs of preconception care, should lead to improved care for these women, with a multidisciplinary approach when needed.