Vivek Nama

Tubal ectopic pregnancy: diagnosis and management

Ectopic pregnancy is the gynaecological emergency par excellence and remains the leading cause of pregnancy-related first trimester deaths in the UK. Its prevalence continues to rise because of increases in the incidence of the risk factors predisposing to ectopic pregnancy. Classically, the diagnosis is based on a history of pelvic pain associated with amenorrhoea, a positive pregnancy test with or without slight vaginal bleeding. While the immediate differential diagnosis includes threatened or inevitable miscarriage, the likelihood of ectopic pregnancy is increased if transvaginal sonography (TVS) reveals an empty uterine cavity, and is confirmed if an adnexal mass with or without an embryo is seen. However, the diagnosis is often not that simple, especially when the patient presents early, has minimal pain, is haemodynamically stable, and TVS shows an empty uterus but no obvious adnexal mass. This could then be an early intrauterine pregnancy, or could indeed be an ectopic—a diagnosis of pregnancy of unknown location is made while additional investigations are made. The latter usually include serial measurements of serum beta human chorionic gonadotrophin (beta-hCG) and repeat TVS. Changes in beta-hCG levels in normal, failing and ectopic pregnancy are now reasonably well characterised, and at early stages of presentation where the risk of rupture of an ectopic are minimal, the patient can often be managed as an outpatient while the diagnosis is pursued. In the patient who presents with pain and haemodynamic instability, the diagnosis is often obvious, and the management is immediate laparotomy. However, in modern gynaecological practice in the developed world the vast majority of ectopic pregnancies present early, and the general consensus is that laparoscopic management offers both economic and aesthetic advantages, and should be used whenever possible. Salpingectomy (excision of the fallopian tube containing the ectopic) is performed if the contra-lateral tube is healthy, while salpingotomy (linear incision made in the fallopian tube with removal of ectopic pregnancy and conservation of tube) is performed if the contra-lateral tube is unhealthy. Medical therapy using methotrexate given systemically or injected directly into the ectopic pregnancy is an option occasionally used with good results. There appear to be no major differences in subsequent fertility outcomes, or risk of recurrence of ectopic pregnancy, between the surgical or medical treatments. Although the rates of ectopic pregnancy are not falling in the developed world, mortality and morbidity are falling mainly due to early and improving diagnostic and treatment modalities. Mass screening and treatment of Chlamydia in the young, sexually active populations, and education regarding risk factors, may in future result in a reduction in the rates. Lack of resource mean that the picture may remain dismal for some time to come in the developing world, but the development of basic protocols, improved training and the infusion of basic resources may go a long way to improving the situation.

Microvascular Remodelling in Preeclampsia: Quantifying Capillary Rarefaction Accurately and Independently Predicts Preeclampsia

BACKGROUND Preeclampsia is a major cause of maternal and neonatal mortality and morbidity. The incidence of preeclampsia seems to be rising because of increased prevalence of predisposing disorders, such as essential hypertension, diabetes, and obesity, and there is increasing evidence to suggest widespread microcirculatory abnormalities before the onset of preeclampsia. We hypothesized that quantifying capillary rarefaction could be helpful in the clinical prediction of preeclampsia. METHODS We measured skin capillary density according to a well-validated protocol at 5 consecutive predetermined visits in 322 consecutive white women, of whom 16 subjects developed preeclampsia. RESULTS We found that structural capillary rarefaction at 20-24 weeks of gestation yielded a sensitivity of 0.87 with a specificity of 0.50 at the cutoff of 2 capillaries/field with the area under the curve of the receiver operating characteristic value of 0.70, whereas capillary rarefaction at 27-32 weeks of gestation yielded a sensitivity of 0.75 and a higher specificity of 0.77 at the cutoff of 8 capillaries/field with area under the curve of the receiver operating characteristic value of 0.82. Combining capillary rarefaction with uterine artery Doppler pulsatility index increased the sensitivity and specificity of the prediction. Multivariable analysis shows that the odds of preeclampsia are increased in women with previous history of preeclampsia or chronic hypertension and in those with increased uterine artery Doppler pulsatility index, but the most powerful and independent predictor of preeclampsia was capillary rarefaction at 27-32 weeks. CONCLUSIONS Quantifying structural rarefaction of skin capillaries in pregnancy is a potentially useful clinical marker for the prediction of preeclampsia.

Capillary remodelling in normal pregnancy: Can it mediate the progressive but reversible rise in blood pressure? Novel insights into cardiovascular adaptation in pregnancy.

OBJECTIVE To conduct a longitudinal study of skin capillary density changes throughout normal pregnancy and correlate them to changes in blood pressure. DESIGN Prospective, longitudinal cohort study. SETTING London teaching hospital. STUDY DESIGN Two hundred and twenty-five Caucasian, Primigravid women with singleton pregnancy, normotensive throughout pregnancy, and with normal pregnancy outcomes. We used intra-vital video microscopy to measure basal (i.e. functional) and maximal (i.e. structural) skin capillary density (CD) according to a well-validated protocol. The subjects were studied at baseline (11-16weeks gestation) and at four consecutive visits (20-24weeks, 27-32weeks, 34-38weeks, and 5-15weeks postpartum). Blood pressure measurements were taken during the same visits. RESULTS We found that normal pregnancy was associated with progressive capillary rarefaction, with the overall trend in the fall in both functional and structural CD being statistically significant (p<0.001). The fall in CD was a remarkable mirror image to a progressive rise in systolic and diastolic blood pressures, there being a significant correlation between systolic blood pressure and structural CD. Postpartum measurements of both CD and blood pressure were similar to base line levels. CONCLUSIONS Progressive capillary rarefaction is a normal accompaniment of human pregnancy that may mediate the progressive rise in systolic and diastolic pressures. Both the CD and blood pressure changes are reversible, returning to baseline in the puerperium.

138 MICROVASCULAR REMODELLING IN PREECLAMPSIA; QUANTIFYING CAPILLARY RAREFACTION ACCURATELY AND INDEPENDENTLY PREDICTS PREECLAMPSIA

Background Preeclampsia is a major cause of maternal and neonatal mortality and morbidity. There is increasing evidence to suggest widespread microcirculatory abnormalities before the onset of preeclampsia. We have recently reported that women who later on in pregnancy developed preeclampsia had significant reduction in their skin capillary density (ie, rarefaction) before the onset of preeclampsia. We hypothesised that quantifying capillary rarefaction could be helpful in the clinical prediction of preeclampsia. Methods We measured skin capillary density according to a well-validated protocol at 5 consecutive predetermined visits in 322 consecutive Caucasian women, of which 305 subjects completed the study. Results We found that structural capillary rarefaction at 20–24 weeks gestation yielded a sensitivity of 0.87 with a specificity of 0.50 at the cut-off of 2 capillaries/mm2 with the Area Under the Curve of the Receiver Operating Characteristic value of 0.70 whilst capillary rarefaction at 27–32 weeks gestation yielded a sensitivity of 0.75 and a higher specificity of 0.77 at the cut-off of 8 capillaries/mm2 with ROC AUC value of 0.82. Combining capillary rarefaction with uterine artery Doppler pulsatility index increased the sensitivity and specificity of the prediction. Multivariate analysis shows that the odds of preeclampsia are increased in women with previous history of preeclampsia or chronic hypertension, in those with increased uterine artery Doppler pulsatility index, but the most powerful and independent predictor of preeclampsia was capillary rarefaction at 27–32 weeks. Conclusions Quantifying structural rarefaction of skin capillaries in pregnancy is a potentially useful and accurate clinical marker for the prediction of preeclampsia.

142 Onset of preeclampsia is preceded by structural capillary rarefaction

Introduction Microvascular rarefaction, defined as reduced vascular density, is a consistent finding in hypertension. Functional and structural capillary rarefaction occurs in individuals with sustained and borderline essential hypertension, and in their normotensive offspring. Women who develop preeclampsia are at increased risk of hypertension in later life. We hypothesised that capillary rarefaction precedes the onset of preeclampsia and could play a role in its pathogenesis. Methods In this longitudinal cohort study we recruited 322 Caucasian women, of which 305 subjects completed the study. We used intravital video-microscopy to measure basal (ie, functional) and maximal (ie, structural) skin capillary densities according to a well-validated protocol and measured plasma angiogenic and anti-angiogenic factors. Subjects were studied at five consecutive visits. Results Preeclampsia occurred in 16 women (mean onset at 35.6±4.8 weeks) and 272 women had normal pregnancy. In women with normal pregnancy significant structural reduction in capillary density occurred at 27–32 weeks, which had resolved by the puerperium (mean change: −2.2 capillaries/field, 95% CI −3.6 to −0.7). In contrast, in women who developed preeclampsia, more significant structural rarefaction was observed earlier at 20–24 weeks (mean change: −6.1 capillaries/field, 95% CI −9.2 to −2.9), which persisted into the puerperium. We also found that the change in soluble Endoglin from 11–16 weeks to 27–32 weeks was significantly correlated with the change in structural capillary density. Conclusions This is the first study to show that significant structural capillary rarefaction precedes the onset of preeclampsia. Capillary rarefaction could play a role in the pathogenesis of this disease.