Hysteropexy in the treatment of uterine prolapse stage 2 or higher: laparoscopic sacrohysteropexy versus sacrospinous hysteropexy-a multicentre randomised controlled trial (LAVA trial).

OBJECTIVE: To investigate whether laparoscopic sacrohysteropexy (LSH) is non-inferior to vaginal sacrospinous hysteropexy (SSHP) in the surgical treatment of uterine prolapse. DESIGN: Multicentre randomised controlled, non-blinded non-inferiority trial. SETTING: Five non-university teaching hospitals in the Netherlands, one university hospital in Belgium. POPULATION: 126 women with uterine prolapse stage 2 or higher undergoing surgery without previous pelvic floor surgery. METHODS: Randomisation in a 1:1 ratio to LSH or SSHP, stratified per centre and severity of the uterine prolapse. The predefined inferiority margin was an increase in surgical failure rate of 10%. MAIN OUTCOME MEASURES: Primary outcome was surgical failure, defined as recurrence of uterine prolapse (POP-Q ≥ 2) with bothersome bulging/protrusion symptoms and/or repeat surgery or pessary at 12 months postoperatively. Secondary outcomes were anatomical recurrence (any compartment), functional outcome and quality of life. RESULTS: Laparoscopic sacrohysteropexy was non-inferior for surgical failure (n = 1, 1.6%) compared with SSHP (n = 2, 3.3%, difference -1.7%, 95% CI: -7.1 to 3.7) 12 months postoperatively. Overall, anatomical recurrences and quality of life did not differ. More bothersome symptoms of overactive bladder (OAB) and faecal incontinence were reported after LSH. Dyspareunia was more frequently reported after SSHP. CONCLUSION: Laparoscopic sacrohysteropexy was non-inferior to SSHP for surgical failure of the apical compartment at 12 months' follow up. Following LSH, bothersome OAB and faecal incontinence were more frequent, but dyspareunia was less frequent. TWEETABLE ABSTRACT: Laparoscopic sacrohysteropexy and vaginal sacrospinous hysteropexy have equally good short-term outcomes.

Single- versus double-layer closure of the caesarean (uterine) scar in the prevention of gynaecological symptoms in relation to niche development - the 2Close study: a multicentre randomised controlled trial.

BACKGROUND: Double-layer compared to single-layer closure of the uterus after a caesarean section (CS) leads to a thicker myometrial layer at the site of the CS scar, also called residual myometrium thickness (RMT). It possibly decreases the development of a niche, which is an interruption of the myometrium at the site of the uterine scar. Thin RMT and a niche are associated with gynaecological symptoms, obstetric complications in a subsequent pregnancy and delivery and possibly with subfertility. METHODS: Women undergoing a first CS regardless of the gestational age will be asked to participate in this multicentre, double blinded randomised controlled trial (RCT). They will be randomised to single-layer closure or double-layer closure of the uterine incision. Single-layer closure (control group) is performed with a continuous running, unlocked suture, with or without endometrial saving technique. Double-layer closure (intervention group) is performed with the first layer in a continuous unlocked suture including the endometrial layer and the second layer is also continuous unlocked and imbricates the first. The primary outcome is the reported number of days with postmenstrual spotting during one menstrual cycle nine months after CS. Secondary outcomes include surgical data, ultrasound evaluation at three months, menstrual pattern, dysmenorrhea, quality of life, and sexual function at nine months. Structured transvaginal ultrasound (TVUS) evaluation is performed to assess the uterine scar and if necessary saline infusion sonohysterography (SIS) or gel instillation sonohysterography (GIS) will be added to the examination. Women and ultrasound examiners will be blinded for allocation. Reproductive outcomes at three years follow-up including fertility, mode of delivery and complications in subsequent deliveries will be studied as well. Analyses will be performed by intention to treat. 2290 women have to be randomised to show a reduction of 15% in the mean number of spotting days. Additionally, a cost-effectiveness analysis will be performed from a societal perspective. DISCUSSION: This RCT will provide insight in the outcomes of single- compared to double-layer closure technique after CS, including postmenstrual spotting and subfertility in relation to niche development measured by ultrasound. TRIAL REGISTRATION: Dutch Trial Register ( NTR5480 ). Registered 29 October 2015.

Word catheter and marsupialisation in women with a cyst or abscess of the Bartholin gland (WoMan-trial): a randomised clinical trial.

OBJECTIVE: To compare recurrence of a cyst or abscess of the Bartholin gland after surgical treatment using a Word catheter or marsupialisation. DESIGN: Multicentre, open-label, randomised controlled trial. SETTING: Eighteen hospitals in the Netherlands and one hospital in England. POPULATION: Women with a symptomatic cyst or abscess of the Bartholin gland. METHODS: Women were randomised to treatment with Word catheter or marsupialisation. MAIN OUTCOME MEASURES: The primary outcome was recurrence of the cyst or abscess within 1 year of treatment. The secondary outcomes included pain during and after treatment (measured on a 10-point scale), use of analgesics, and time from diagnosis to treatment. Analysis was by intention-to-treat. To assess whether marsupialisation would reduce the recurrence rate by 5% (from 20 to 15%) we needed to include 160 women (alpha error 0.05, beta error 0.2). RESULTS: One hundred and sixty-one women were randomly allocated to treatment by Word catheter (n = 82) or marsupialisation (n = 79) between August 2010 and May 2014. Baseline characteristics were comparable. Recurrence occurred in 10 women (12%) allocated to Word catheter versus eight women (10%) allocated to marsupialisation: relative risk (RR) 1.1, 95% confidence interval (CI) 0.64-1.91; P = 0.70. Pain scores after treatment were also comparable. In the first 24 hours after treatment, 33% used analgesics in the Word catheter group versus 74% in the marsupialisation group (P < 0.001). Time from diagnosis to treatment was 1 hour for placement of Word catheter versus 4 hours for marsupialisation (P = 0.001). CONCLUSIONS: In women with an abscess or cyst of the Bartholin gland, treatment with Word catheter and marsupialisation results in comparable recurrence rates. TWEETABLE ABSTRACT: Comparable recurrence rates for treatment of Bartholinic abscess/cyst with Word catheter and marsupialisation.

MisoREST: surgical versus expectant management in women with an incomplete evacuation of the uterus after misoprostol treatment for miscarriage: a randomized controlled trial.

STUDY QUESTION: Is curettage more effective than expectant management in case of an incomplete evacuation after misoprostol treatment for first trimester miscarriage? SUMMARY ANSWER: Curettage leads to a higher chance of complete evacuation but expectant management is successful in at least 76% of women with an incomplete evacuation of the uterus after misoprostol treatment for first trimester miscarriage. WHAT IS KNOWN ALREADY: In 5-50% of the women treated with misoprostol, there is a suspicion of incomplete evacuation of the uterus on sonography. Although these women generally have minor symptoms, such a finding often leads to additional curettage. STUDY DESIGN, SIZE, DURATION: From June 2012 until July 2014, we conducted a nationwide multicenter randomized controlled trial (RCT). Women who had had primary misoprostol treatment for miscarriage with sonographic evidence of incomplete evacuation of the uterus were randomly allocated to either curettage or expectant management (1:1), using a web-based application. PARTICIPANTS/MATERIALS, SETTING, METHODS: We included 59 women in 27 hospitals; 30 were allocated to curettage and 29 were allocated to expectant management. A successful outcome was defined as sonographic finding of an empty uterus 6 weeks after randomization. MAIN RESULTS AND THE ROLE OF CHANCE: Baseline characteristics of both groups were comparable. Empty uterus on sonography or uneventful clinical follow-up was seen in 29/30 women (97%) allocated to curettage compared with 22/29 women (76%) allocated to expectant management (RR 1.3, 95% CI 1.03-1.6) with complication rates of 10% versus 10%, respectively (RR 0.97, 95% CI 0.21-4.4). In the group allocated to curettage, no woman required re-curettage, while two women (6.7%) underwent hysteroscopy (for other or unknown reasons). In the women allocated to expectant management, curettage was performed in four women (13.8%) and three women (10.3%) underwent hysteroscopy. LIMITATIONS, REASONS FOR CAUTION: Due to a strong patient preference, mainly for expectant management, the targeted sample size could not be included and the trial was stopped prematurely. WIDER IMPLICATIONS OF THE FINDINGS: In women suspected of incomplete evacuation of the uterus after misoprostol, curettage is more effective than expectant management. However, expectant management is equally safe and prevents curettage for most of the women. This finding could further restrain the use of curettage in the treatment of first trimester miscarriage. STUDY FUNDING/COMPETING INTERESTS: This study was funded by ZonMw, a Dutch organization for Health Research and Development, project number 80-82310-97-12066. There were no conflicts of interests. TRIAL REGISTRATION NUMBER: Dutch Trial Register NTR3310, http://www.trialregister.nl TRIAL REGISTRATION DATE: 27 February 2012. DATE OF FIRST PATIENT'S ENROLMENT: 12 June 2012.

The HysNiche trial: hysteroscopic resection of uterine caesarean scar defect (niche) in patients with abnormal bleeding, a randomised controlled trial.

BACKGROUND: A caesarean section (CS) can cause a defect or disruption of the myometrium at the site of the uterine scar, called a niche. In recent years, an association between a niche and postmenstrual spotting after a CS has been demonstrated. Hysteroscopic resection of these niches is thought to reduce spotting and menstrual pain. However, there are no randomised trials assessing the effectiveness of a hysteroscopic niche resection. METHODS/DESIGN: We planned a multicentre randomised trial comparing hysteroscopic niche resection to no intervention. We study women with postmenstrual spotting after a CS and a niche with a residual myometrium of at least 3 mm during sonohysterography. After informed consent is obtained, eligible women will be randomly allocated to hysteroscopic resection of the niche or expectant management for 6 months. The primary outcome is the number of days with postmenstrual spotting during one menstrual cycle 6 months after randomisation. Secondary outcomes are menstrual characteristics, menstruation related pain and experienced discomfort due to spotting or menstrual pain, quality of life, patient satisfaction, sexual function, urological symptoms, medical consultations, medication use, complications, lost productivity and medical costs. Measurements will be performed at baseline and at 3 and 6 months after randomisation. A cost-effectiveness analysis will be performed from a societal perspective at 6 months after randomisation. DISCUSSION: This trial will provide insight in the (cost)effectiveness of hysteroscopic resection of a niche versus expectant management in women who have postmenstrual spotting and a niche with sufficient residual myometrium to perform a hysteroscopic niche resection. TRIAL REGISTRATION: Dutch Trial Register NTR3269 . Registered 1 February 2012. ZonMw Grant number 80-82305-97-12030.

Metastasis from breast cancer to an endometrial polyp; treatment options and follow-up. Report of a case and review of the literature.

INTRODUCTION: The female genital tract is rarely involved by metastatic tumors. The most common anatomic locations are the ovaries and the vagina. A case is presented of metastatic breast carcinoma to the vulva and endometrial polyp, both exceptional. CASE REPORT: We report the case of an 83-year-old female who presented with vaginal bleeding. Lobular breast carcinoma was diagnosed earlier and during follow-up vulvar metastasis was detected. Hysteroscopic examination because of postmenopausal bleeding revealed an endometrial polyp which was resected. The morphology and immunohistochemistry of the polyp were consistent with lobular breast cancer: metastatic breast cancer to an endometrial polyp. After reviewing the literature 15 cases of metastatic breast carcinoma to endometrial polyps have been reported. The clinical presentation and course, risk factors, treatment and follow-up are discussed. CONCLUSION: Metastasis of a breast carcinoma to the vulva and an endometrial polyp are extremely rare, but clinicians should be aware of both phenomena.

Effect of maternal anti-HPA-1a antibodies and polyclonal IVIG on the activation status of vascular endothelial cells.

Maternal anti-HPA-1a antibodies can cause severe fetal and neonatal alloimmune thrombocytopenia (FNAIT), complicated by intracranial haemorrhage (ICH). Antenatal treatment with maternal intravenous immunoglobulin (IVIG) seems to protect against ICH even when thrombocytopenia persists. The aim of this study was to investigate if anti-HPA-1a antibodies and IVIG potentially affect vascular endothelial cells (ECs) in order to identify susceptibility for ICH. Human umbilical cord endothelial cells (HUVEC) were incubated with anti-HPA-1a antibodies with or without polyclonal IVIG and evaluated for EC activation. Maternal sera with anti-HPA-1a antibodies affected neither the EC expression of intracellular adhesion molecule-1 (ICAM-1), vascular adhesion molecule-1 (VCAM-1) and tissue factor (TF) nor the release of van Willebrand factor (vWF) or interleukin (IL)-8 nor the integrity of ECs. Maternal sera obtained after IVIG treatment and polyclonal IVIG decrease constitutive and cytokine-induced ICAM-1 and VCAM-1 expression on ECs. The results show that maternal anti-HPA-1a antibodies cause no activation or damage of ECs in this model. The clinical relevance of the de-activating properties of IVIG on EC activation with respect to ICH deserves further investigation.

Will it ever be possible to balance the risk of intracranial haemorrhage in fetal or neonatal alloimmune thrombocytopenia against the risk of treatment strategies to prevent it?

BACKGROUND AND OBJECTIVES: Intracranial haemorrhage (ICH) of the fetus or newborn is a severe complication of fetal or neonatal alloimmune thrombocytopenia (FNAIT). In order to attain management decisions to prevent ICH, the risk of ICH in successive pregnancies with thrombocytopenia, with or without a history of ICH, must be established. MATERIALS AND METHODS: We performed a search of medline for ICH cases in untreated FNAIT pregnancies. After exclusion of cases with confounding factors, 24 reports, describing 62 pregnancies of 27 mothers, were eligible. In addition, two mothers with five pregnancies were included from our own case records. Observational studies were examined to estimate the risk of ICH in subsequent FNAIT pregnancies without a history of ICH. Finally, medline was searched for complication rates in the treatment of FNAIT pregnancies. RESULTS: In 52% of the ICH cases, a previous sibling suffered from ICH. The recurrence rate of ICH in the subsequent offspring of women with a history of FNAIT with ICH was 72%[confidence interval (CI): 46-98%] without inclusion of fetal deaths and 79% (CI: 61-97%) with inclusion of fetal deaths. In 48% of the ICH cases, the previous sibling had thrombocytopenia but not ICH. Population studies revealed an overall ICH risk in thrombocytopenic infants of 11% (CI: 0.8-23%) without inclusion of fetal deaths and 15% (CI: 1.5-19%) with inclusion of fetal deaths. Assuming occurrence in 48%, the risk of ICH in a subsequent pregnancy following a history of FNAIT without ICH, was estimated to be 7% (CI: 0.5-13%). Invasive treatment strategies carry a risk of 2.8% (CI: 1.2-4.4%) on complications. CONCLUSIONS: The number of eligible publications on ICH in untreated FNAIT pregnancies is strikingly limited. The recurrence rate is high. As sufficient data on successive FNAIT cases without ICH are lacking, the occurrence of ICH in pregnancies with thrombocytopenia, but without ICH in a previous sibling, cannot be predicted. We estimate this risk to be 7%. This risk must be balanced against the risk of interventions in treatment strategies.

A less invasive treatment strategy to prevent intracranial hemorrhage in fetal and neonatal alloimmune thrombocytopenia.

OBJECTIVE: The purpose of this study was to evaluate whether a less invasive treatment strategy results in a higher platelet count of the neonate and prevents intracranial hemorrhage in pregnant women who are at risk for fetal or neonatal alloimmune thrombocytopenia. STUDY DESIGN: Between March 1989 and August 2000, 48 women with 56 pregnancies were treated. The population was divided into groups. A diagnostic fetal blood sample was taken in 7 cases that had a history of a sibling with an intracranial hemorrhage (group I; n = 8); treatment was provided, when necessary, with platelet transfusions and maternal administration of immunoglobulin. The other 48 cases, with a history of a sibling with severe thrombocytopenia but without intracranial hemorrhage, were retrospectively divided into group IIa (n = 16) and IIb (n = 32). In group IIa, at least 2 diagnostic fetal blood samples were taken, and when necessary, intrauterine platelet transfusion and immunoglobulin were administered (invasive treatment). In group IIb, no initial diagnostic fetal blood sampling was performed (noninvasive treatment). In 23 cases, immunoglobulin was administered, which was followed by predelivery fetal blood sampling in 8 cases. In 9 cases, only predelivery fetal blood sampling was performed, when necessary, followed by intrauterine platelet transfusion. RESULTS: Results of our noninvasive treatment strategy were comparable to results of the invasive method in the prevention of intracranial hemorrhage (intracranial hemorrhage was not observed). In addition, there was an increasing trend in median platelet count and a lower number of cases with severe thrombocytopenia (<50 x 10(9)/L) in the noninvasive compared with the invasive treatment group (median platelet count, 92 and 31 x 10(9)/L, respectively). CONCLUSION: Our results indicate that a less invasive treatment strategy in patients who are at risk for fetal or neonatal alloimmune thrombocytopenia and who have no history of a previous child who was affected with intracranial hemorrhage seems justified.

[Evaluation of gradual conversion to a less invasive therapeutic strategy for pregnant women with alloimmune thrombocytopenia in the fetus for prevention of intracranial hemorrhage]. / Evaluatie van de geleidelijke overgang naar een minder invasieve strategie voor de behandeling van zwangeren met allo-immuuntrombocytopenie bij de foetus, ter preventie van hersenbloeding.

OBJECTIVE: To evaluate a less invasive management strategy for pregnant women with neonatal alloimmune thrombocytopenia without a history of intracranial haemorrhage. DESIGN: Retrospective and descriptive. METHOD: In Leiden University Medical Centre, the Netherlands, in the period 1994-August 1999, 31 women with 32 pregnancies were treated. Six women had a history of a sibling with thrombocytopenia and intracranial haemorrhage and 26 a history of a sibling with (severe) thrombocytopenia without haemorrhage. Treatment options consisted of weekly administered intravenous immunoglobulin (ivIG) to the mother without diagnostic cordocentesis, cordocentesis with foetal blood sampling and intrauterine platelet transfusions to the fetus. In the group without history of intracranial haemorrhage fetal blood sampling and platelet transfusion were gradually abandoned as much as possible. RESULTS: In the children of the treated pregnant women there were no instances of intracranial haemorrhage. In addition, the platelet count in cord blood was higher, compared with patients treated before 1994 and with literature data. CONCLUSION: A less invasive management strategy in case of a history without intracranial haemorrhage seems justified based on results in our population. Administration of ivIG without diagnostic cordocentesis, however, results in a lost opportunity to verify the indication and the effectiveness of treatment.

[Sickle cell anemia during pregnancy]. / Sikkelcelanemie tijdens de zwangerschap.

A 31-year-old pregnant Creole woman with sickle-cell anaemia went through a crisis of acute cholecystitis at 29 weeks' amenorrhoea. The crisis subsided after cholecystectomy, at which relative reduction of the number of sickle-cells by blood transfusions, adequate oxygenation, fluid, and antibiotic prophylaxis were provided. After 35 weeks' amenorrhoea, a healthy son was delivered by caesarean section. After the delivery, she developed fever and abdominal aches with a wound infection, and 10 days later a generalized epileptic attack. She recovered without sequelae. Pregnancy in a woman with sickle-cell anaemia may induce a sickle-cell crisis. The maternal morbidity and mortality and perinatal mortality are high, in spite of a pronounced decrease due to improved care.

Hereditary cerebral hemorrhage with amyloidosis (Dutch): a model for congophilic plaque formation without neurofibrillary pathology.

Plaque-like lesions and amyloid angiopathy were investigated in the frontal cerebral cortex of four patients with hereditary cerebral hemorrhage with amyloidosis (Dutch) (HCHWA-D), using immunohistochemical [antibodies to beta amyloid protein (A beta), beta protein precursor (beta PP), synaptophysin, ubiquitin (UBQ), cathepsin D, paired helical filaments (PHF) and glial fibrillary acidic protein (GFAP)], enzymehistochemical (acid phosphatase) and silver [methenamine silver (MS) and Palmgren] staining methods. Whereas A beta- and MS-positive diffuse plaques were found in all patients, only the three older patients showed neuritic or congophilic plaques, which were acid phosphatase and cathepsin D positive and contained beta PP-, synaptophysin- and UBQ-positive, but PHF-negative neurites. These plaques were surrounded by reactive astrocytes. Similar immuno- and enzymereactivity was found around congophilic blood vessels. Thus, apart from neuronal degeneration in a subset of plaque-like lesions and around blood vessels, this study shows an age-related morphology of the plaques in HCHWA-D, corresponding to that in Down's syndrome (DS), with the difference that neurofibrillary (NF) pathology is absent in HCHWA-D in contrast to DS. HCHWA-D may be considered as a model for congophilic plaque formation not associated with NF pathology.