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. 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. 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. Dutch Trial Register ( NTR5480 ). Registered 29 October 2015.

Objectives: A history of recurrent miscarriage is associated with future cardiovascular disease. The aim of this study was to determine novel cardiovascular biomarkers in women with a history of recurrent miscarriage as this might lead to a better understanding of the association. Study design: Women who visited the recurrent miscarriage clinic at Leiden University Medical Centre (between 2000 and 2010), and had three consecutive miscarriages <= 30 years were invited to participate in this follow-up study (between 2012 and 2014). The reference group consisted of women with at least one uncomplicated pregnancy and a history of no miscarriage, matched on zip code, age, and date of pregnancy. Main outcome measures: Cardiovascular biomarkers were determined, classified into; inflammation (HsCRP, lipoprotein-associated phospholipase A2), thrombosis (homocysteine, folate, anti-cardiolipin antibodies and anti-beta-2-glycoprotein antibodies), lipid metabolism (lipoprotein(a)), renal function (creatinine, microalbuminuria), myocardial damage (N-terminal pro-brain natriuretic peptide, high sensitive TroponineT) and multiple mechanisms (albumin, vitamin D). Results: In both groups, 36 women were included. Women with recurrent miscarriage had a significantly higher median HsCRP (1.49 mg/L) compared to women with no miscarriage (1.01 mg/L, p= 0.03) and a significantly lower mean albumin (46.0 vs 47.6g/L, p= 0.004) and vitamin D (55.6 vs 75.4nmol/L, p= 0.007), respectively. Differences remained after adjustments for classic cardiovascular risk factors (BMI, smoking, diabetes mellitus, and hypertension). Conclusions: Our findings suggest a proinflammatory state in women with a history of recurrent miscarriage, which suggests a less optimal health, compared to women with no miscarriage. More research (observational and intervention) is warranted to investigate the association with vitamin D.

Objective: Hypertensive disorders during pregnancy increase cardiovascular risk later in life by 2 to 9 -fold. Endothelial activation is one of the underlying mechanisms of cardiovascular risk. Therefore, we decided to investigate endothelial activation in primiparous women, 2.5 years after a hypertensive pregnancy disorder. Study design: Plasma samples were taken from women 2.5 years after gestational hypertension (GH) or late onset preeclampsia (cases) and from women 2.5 years after a normotensive pregnancy (controls). We studied the effects of patient plasma on the endothelial barrier function of primary human umbilical vein endothelial cells (HUVECs) using Electric Cell-Substrate Impedance Sensing (ECIS) and we measured levels of endothelial activation markers soluble intercellular adhesion molecule 1 (sICAM-1) and soluble endothelial selectin (sE-selectin) in the plasma samples of patients. Results: Plasma from primiparous women with a history of late onset preeclampsia disrupted the endothelial barrier more than plasma from women with a history of GH. Endothelial resistance was reduced by 22% in samples taken after preeclampsia, 16% after normotensive pregnancy and 3% after GH (p <= 0.0001 GH versus preeclampsia and p = 0.0003 versus normotensive pregnancy). We did not find differences in the levels of soluble endothelial activation markers (sICAM-1 p = 0.326 and sE-selectin p = 0.978). However, the BMI >= 25 showed a strong correlation with increased levels of sICAM-1 (p = 0.046) and sE-selectin (p = 0.002). Conclusion: Our results indicate that GH and late onset preeclampsia are distinct disease entities with a different pathogenic mechanism underlying their cardiovascular risk. Furthermore, this study supports the hypothesis that these two diseases are early manifestations of cardiovascular vulnerability due to an unfavorable risk profile, and that obesity plays a main role. Our results suggest that this high-risk female population would be eligible for preventive care. (C) 2018 Elsevier B.V. All rights reserved.

Success rates of assisted reproductive techniques (ART) are approximately 30%, with the most important limiting factor being embryo implantation. Mechanical endometrial injury, also called ‘scratching’, has been proposed to positively affect the chance of implantation after embryo transfer, but the currently available evidence is not yet conclusive. The primary aim of this study is to determine the effect of endometrial scratching prior to a second fresh in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycle on live birth rates in women with a failed first IVF/ICSI cycle.

INTRODUCTION:The association between hypertensive pregnancy disorders and cardiovascular disease later in life is well described. In this study we aim to develop a prognostic model from patients characteristics known before, early in, during and after pregnancy to identify women at increased risk of cardiovascular disease e.g. chronic hypertension years after pregnancy complicated by hypertension at term. METHODS:We included women with a history of singleton pregnancy complicated by hypertension at term. Women using antihypertensive medication before pregnancy were excluded. We measured hypertension in these women more than 2years postpartum. Different patients characteristics before, early in, during and after pregnancy were considered to develop a prognostic model of chronic hypertension at 2-years. These included amongst others maternal age, blood pressure at pregnancy intake and blood pressure six weeks post-partum. Univariable analyses followed by a multivariable logistic regression analysis was performed to determine which combination of predictors best predicted chronic hypertension. Model performance was assessed by calibration (graphical plot) and discrimination (area under the receiver operating characteristic (AUC)). RESULTS:Of the 305 women in who blood pressure 2.5years after pregnancy was assessed, 105 women (34%) had chronic hypertension. The following patient characteristics were significant associated with chronic hypertension: higher maternal age, lower education, negative family history on hypertensive pregnancy disorders, higher BMI at booking, higher diastolic blood pressure at pregnancy intake, higher systolic blood pressure during pregnancy and higher diastolic blood pressure at six weeks post-partum. These characteristics were included in the prognostic model for chronic hypertension. Model performance was good as indicated by good calibration and good discrimination (AUC; 0.83 (95% CI 0.75 - 0.92). CONCLUSION:Chronic hypertension can be expected from patient characteristics before, early in, during and after pregnancy. These data underline the importance and awareness of detectable risk factors both for increased risk of complicated pregnancy as well as increased risk of cardiovascular disease later in life.

The aims of this study were to analyze reproductive outcomes of women and men born very preterm (gestational age < 32 weeks) or with a very low birth weight (< 1500 g) in 1983 in the Netherlands and to compare their reproductive outcomes with the total population at a similar age of 28 years. Young adults who were born after a pregnancy complicated by very preterm (VP) delivery or with a very low birth weight (VLBW) in the Netherlands in 1983 (Project on Preterm and Small for Gestational Age Infants (POPS) cohort) were invited to complete an online questionnaire at the age of 28. In total, 293 POPS-28 participants (31.6 %) completed the questionnaire including 185 female and 108 male participants. Female and male participants who were born VP or with a VLBW had significant reduced reproductive rates compared to the total Dutch population at 28 years of age (female 23.2 vs 31.9 % and male 7.4 vs 22.2 %). Pregnancies of the female participants were in 14 % complicated by preterm delivery in at least one pregnancy.Conclusion: This study indicates that women and men born VP or with a VLBW have reduced reproductive rates at the age of 28 compared to the total Dutch population at a similar age.

OBJECTIVES:Hypertension in pregnancy is associated with cardiovascular disease (CVD) later in life. Blood pressure monitoring in women who experienced hypertension in pregnancy after puerperium has been suggested to be important for early detection and prevention of CVD. The aim of this study is to evaluate if hypertension six weeks postpartum is associated with chronic hypertension in women with a history of term hypertensive pregnancy disorders. STUDY DESIGN:Women with a history of term gestational hypertension or preeclampsia were included in a follow up study of the HYPITAT trial. Blood pressures were measured six weeks and 2.5years postpartum according to the study protocol. MAIN OUTCOME MEASURES:Hypertension was defined as a diastolic blood pressure ⩾90mmHg and/or a systolic blood pressure ⩾140mmHg or use of antihypertensive medication. Differences in categorical variables between groups were analyzed by Chi-Square tests. Blood pressure was analyzed using unpaired t-tests and Wilcox ranked tests. RESULTS:Among 187 women who had term hypertensive pregnancy disorders, 75 (40%) had hypertension at six weeks postpartum. Of these 46 (61%) had hypertension 2.5years postpartum. In contrast, of 112 women without hypertension at six weeks postpartum, 36 (32%) had hypertension 2.5years (OR 3.3, 95% CI 1.8-6.2). CONCLUSION:Among 61% of women who had hypertensive pregnancy disorders at term, high blood pressure at six weeks postpartum indicated chronic hypertension. This warrants the importance of identification of hypertension 6weeks postpartum for women's future health.

INTRODUCTION:Cardiovascular disease (CVD) is the leading cause of mortality and morbidity in women. Epidemiological studies have shown an increased risk of a CVD event in women who have had a hypertensive disorder in one of their previous pregnancies. These data also suggest that these increased risks are associated with severity and time of onset of pre-eclampsia. Risk factors for CVD have not yet been compared between women who experienced early versus late and mild versus severe hypertensive disorders of pregnancy. OBJECTIVES:In this study we compared classic CVD risk factors of postpartum women with previous early-onset preeclampsia (EOPE), late onset pre-eclampsia (LOPE) and pregnancy induced hypertension (PIH). METHODS:A total of 81 women with previous EOPE (delivery required ⩽34weeks), 76 with LOPE (delivery ⩾36weeks) and 229 with PIH were included along with 79 healthy controls. Statistical analyses were performed using generalized linear models in PASW statistics 17.0, SPSS Inc. RESULTS:Adjusted means of blood pressure, fasting plasma glucose levels and LDL levels were significantly increased after all hypertensive disorders of pregnancy compared to controls. This increase of CVD risk factors was significantly correlated with severity and time of onset of the disease (Table 1). The prevalence of metabolic syndrome (BMI>30kg/m(2) and ⩾2 of the following; triglycerides ⩾150mg/dl, HDL cholesterol ⩾50mg/dl, systolic blood pressure ⩾130 or diastolic blood pressure ⩾85 and fasting plasma glucose levels ⩾100mg/dl) did not differ between the study groups; women who had PIH had the highest number of components of the metabolic syndrome (). CONCLUSION:These results further establish the predisposition to CVD in women with previous pre-eclampsia or PIH. EOPE is associated with a more pronounced CVD risk factor profile than LOPE or PIH, which may explain the previously described higher CVD event risk.

The association between preeclampsia and cardiovascular disease has been an increasing area of interest over the last years. Cardiovascular disease is the number one cause of death in women in the western world and more women than men die of heart disease each year. The most common pregnancy disorder is preeclampsia. Preeclampsia is defined by hypertension and de novo proteinuria and remains responsible for high maternal and fetal morbidity and mortality worldwide. Pregnancy has been described as a "stress test" for future cardiovascular disease, to identify women young enough to benefit from screening. Women with a history of early onset (severe) preeclampsia have the highest risk of cardiovascular disease later. However, the exact underlying link between the two disorders is still unknown. In this review we describe different facets of the association between preeclampsia and cardiovascular disease and we give an overview of the recent literature.

Cardiovascular disease (CVD) is the leading cause of death in women in the western world. Several studies have described the association between hypertensive pregnancy disorders and CVD in later life. Our aim was to compare postpartum cardiovascular risk factors in women who had a shorter and women who had a longer exposure to endothelial activation during their term hypertensive pregnancy.We studied a subsample of women with pregnancy-induced hypertension or mild preeclampsia at term, who had participated in the randomized HYPITAT trial comparing induction of labour (IOL cohort) (n = 110) or expectant monitoring (EM cohort) (n = 91). We assessed, 2.5 years postpartum, cardiovascular risk factors, i.e. blood pressure, anthropometrics, glucose, HbA1C, insulin, HOMA score, total cholesterol, HDL cholesterol, triglycerides, high sensitive CRP, micro-albumin and metabolic syndrome, and compared these risk factors between the induction and expectant groups.The mean time from randomization to delivery was 3.3 days in the induction group and 10.3 days in the expectant group (p < .001), generating a difference in exposure of 7 days. After a mean follow-up period of 2.5 years, the prevalence of hypertension (IOL 34%; EM 37%, p = .66) and metabolic syndrome (IOL 26%; EM 27%, p = 1.0) was similar in both groups. Furthermore, systolic and diastolic blood pressure, BMI, waist circumference, glucose, HbA1C, insulin, HOMA score, lipids, HsCRP-levels and micro-albumin were all comparable between women who had induction of labour and those who had expectant monitoring.In women with hypertensive disorders in pregnancy at term, induction of labour does not affect the clinical and biochemical cardiovascular profile at 2.5 years postpartum.

A 25-year-old woman presented in the third trimester of pregnancy with severe abdominal pain in the lower right abdominal quadrant. Differential diagnosis included urolithiasis, adnexal torsion and appendicitis. A definitive diagnosis could not be made based on clinical and laboratory examination. Ultrasonography revealed a 3-cm cyst in the lower right abdomen, which was considered unlikely to cause abdominal pain. During laparotomy, adnexal torsion was found, which was deemed to be the cause of the abdominal pain. The twisted portion was uncoiled and the dark-coloured cyst was extirpated. The cyst was determined to be a cystic adenoma. Adnexal torsion is rarely caused by cysts smaller than 5 cm, especially in the third trimester. Emergency laparoscopy/laparotomy should be performed if adnexal torsion is suspected to confirm the diagnosis and uncoil the twist to prevent ovarian damage. Adnexal torsion should be considered in the differential diagnosis of acute abdominal pain in the third trimester of pregnancy.

A 25-year-old woman presented in the third trimester of pregnancy with severe abdominal pain in the lower right abdominal quadrant. Differential diagnosis included urolithiasis, adnexal torsion and appendicitis. A definitive diagnosis could not be made based on clinical and laboratory examination. Ultrasonography revealed a 3-cm cyst in the lower right abdomen, which was considered unlikely to cause abdominal pain. During laparotomy, adnexal torsion was found, which was deemed to be the cause of the abdominal pain. The twisted portion was uncoiled and the dark-coloured cyst was extirpated. The cyst was determined to be a cystic adenoma. Adnexal torsion is rarely caused by cysts smaller than 5 cm, especially in the third trimester. Emergency laparoscopy/laparotomy should be performed if adnexal torsion is suspected to confirm the diagnosis and uncoil the twist to prevent ovarian damage. Adnexal torsion should be considered in the differential diagnosis of acute abdominal pain in the third trimester of pregnancy.

A 25-year-old woman presented in the third trimester of pregnancy with severe abdominal pain in the lower right abdominal quadrant. Differential diagnosis included urolithiasis, adnexal torsion and appendicitis. A definitive diagnosis could not be made based on clinical and laboratory examination. Ultrasonography revealed a 3-cm cyst in the lower right abdomen, which was considered unlikely to cause abdominal pain. During laparotomy, adnexal torsion was found, which was deemed to be the cause of the abdominal pain. The twisted portion was uncoiled and the dark-coloured cyst was extirpated. The cyst was determined to be a cystic adenoma. Adnexal torsion is rarely caused by cysts smaller than 5 cm, especially in the third trimester. Emergency laparoscopyllaparotomy should be performed if adnexal torsion is suspected to confirm the diagnosis and uncoil the twist to prevent ovarian damage. Adnexal torsion should be considered in the differential diagnosis of acute abdominal pain in the third trimester of pregnancy.