Ulla Breth Knudsen

Management of ovarian cysts

Background.u2002 The treatment of an ovarian cyst relies on its nature, and accurate preoperative discrimination of benign and malignant cysts is therefore of crucial importance. This study was undertaken to review the literature concerning the preoperative diagnosis and treatment of ovarian cysts.

One or two day mifepristone–misoprostol interval for second trimester abortion

Methods. A retrospective 2‐year cohort study of 127 women, with gestation between 13 and 24 weeks and a live fetus, seeking induced abortion. The aim was to compare the effect of a 1‐day and a 2‐day interval between oral mifepristone (200 mg) and vaginal misoprostol (400 μg) every 3 h. Results. The time to fetal expulsion was longer (9.8 versus 7.5 h; p<0.01) in the 1‐day than in the 2‐day group, but the median number of applications were identical and abortion occurred in 98% within 24 h in both groups The time to abortion was longer in women with a gestation of 17–22 weeks compared to women with lower gestation (10.2 versus 6.8 h; p<0.001), and longer in nulliparae than in parous women (10.0 versus 6.7 h; p<0.001). Conclusion. The combined regimen of mifepristone and misoprostol is effective in the second trimester, and the interval between the drugs can be reduced allowing individualised patient care.

Oncogenic events associated with endometrial and ovarian cancers are rare in endometriosis

Endometriosis displays some features that resemble malignant processes, including invasive growth, resistance to apoptosis and distant implantation. The objective of this study was to investigate whether gene alterations that are frequent in endometrial and/or ovarian cancers contribute to the pathogenesis of endometriosis. Biopsies were obtained from ectopic endometriosis lesions from 23 patients with revised American Fertility Score stage 1 (n= 1), 2 (n= 10), 3 (n= 11) or 4 (n= 1) endometriosis. Six genes (APC, CDKN2A, PYCARD, RARB, RASSF1 and ESR1) were analyzed for promoter hypermethylation using methylation-specific melting curve analysis, and 9 genes (BRAF, HRAS, NRAS, CTNNB1, CDK4, FGFR3, PIK3CA, TP53 and PTEN) were analyzed for mutations using denaturing gradient gel electrophoresis and direct sequencing. An oncogenic mutation in KRAS (c.34G > T; p.G12C) was detected in a single lesion. No gene alterations were found in the remaining samples. Our data suggest that genetic and epigenetic events contributing to endometrial and ovarian cancers are rare in endometriosis. However, other proto-oncogenes and tumor suppressor genes should be tested for alterations in order to identify the molecular basis of the susceptibility of endometriosis to malignant transformation.

A simple one-stop menstrual problem clinic with use of hysterosonography for the diagnosis of abnormal uterine bleeding.

BACKGROUNDnThe purpose of the present study was to evaluate a one-stop outpatient bleeding disorder clinic in a Scandinavian population.nnnMETHODSnOne hundred and fourteen women under the age of 60 years referred to the clinic for bleeding disorders. The consultation included pelvic ultrasound, hysterosonography and, when indicated, endometrial sampling.nnnRESULTSnIn 93% of the patients a sufficient diagnosis of the uterine cavity was attained at a one-stop visit. Eighty-six percent of the patients were investigated according to the one-stop program, and in 73% of the patients a treatment plan could be formulated during the consultation. Twenty-one percent had selective resection of intracavitary abnormalities. In 3% no intracavitary abnormality was found at hysteroscopy, even though hysterosonography had indicated this.nnnCONCLUSIONSnMost patients under the age of 60 with bleeding disorders can be investigated by a one-stop out-patient procedure with the use of hysterosonography and endometrial sampling. Diagnostic or operative hysteroscopy was needed in cases of insufficient hysterosonography and suspicion of intracavitary abnormalities. This procedure can assist in determining the therapeutic approach and can often lessen the extent of surgical intervention or obviate it altogether.

Low prevalence of DNA viruses in the human endometrium and endometriosis

The chronic female disease endometriosis causes debilitating pain and lowered fertility. The aetiology is unknown, but indications of an infectious agent are present. This study investigates the possible involvement of a pathogenic virus in endometriosis patients and controls. DNA was purified from biopsies and subjected to highly sensitive PCR tests detecting human papillomavirus (HPV) types, the herpes family viruses HSV-1 and -2, CMV, and EBV, and the polyomaviruses SV40, JCV, BKV, KIV, WUV, and MCV. The prevalence of pathogenic DNA viruses in the human endometrium was generally low (0–10%). The virus prevalence was found to vary slightly when comparing the endometrium of healthy women and women with endometriosis. However, these were not significant differences, and no viruses were identified in endometriotic lesions. These results do not point towards any evidence that endometriosis is caused by these viruses.

Serum markers of macrophage activation in pre-eclampsia: no predictive value of soluble CD163 and neopterin

Background. Alternatively activated macrophages expressing the CD163 and CD206 surface receptors are the dominant immune‐cell type found in the placenta. The placental number and distribution of macrophages is altered in pre‐eclampsia, and the generalised inflammatory reaction associated with pre‐eclampsia might lead to shedding of soluble CD163 into the circulation. Methods. Serum samples from 18 women with pre‐eclampsia and 90 normal pregnancies were obtained from a longitudinal study of 955 pregnant women at Randers County Hospital, Denmark. sCD163 and Neopterin were measured by ELISA on samples collected in weeks 18, 28, 32, and 38 of pregnancy. Results. sCD163 levels in pregnancy (2–3 mg/l) were similar to previously measured levels in non‐pregnant women, and did not increase from week 18 to 38. There was a tendency towards higher sCD163 in week 38 in pre‐eclamptic women compared to healthy women. Neopterin increased throughout pregnancy in both healthy (from median 5.4 to 6.7 nmol/l, p<0.0001) and pre‐eclamptic women (from 5.0 to 8.0 nmol/l, p<0.0001), but there were no differences between groups at any time‐point. sCD163 correlated to neopterin in both the control (r = 0.25, p<0.0001) and in the pre‐eclampsia group (r = 0.32, p = 0.011). C‐reactive protein was higher in pre‐eclampsia than in healthy pregnancies by week 38 (159 versus 91 nmol/l, p = 0.0189). Conclusions. The macrophage serum‐markers sCD163 and neopterin are not pre‐symptomatic nor prognostic markers for pre‐eclampsia.

Pre‐symptomatic increase in urine‐orosomucoid excretion in pre‐eclamptic women

Background. Although the pre‐eclamptic pathogenesis begins at least around the 18th week of pregnancy, clinically evident disease often does not appear until the third trimester. This long pre‐symptomatic latency period has led to intensive research for early markers of evolving disease. We evaluated urine excretion and plasma levels of orosomucoid and albumin longitudinally in healthy and pre‐eclamptic pregnancies. Orosomucoid is an acute phase protein involved in inflammation and protection of the endothelium. Methods. From a prospective, longitudinal cohort study consisting of 1,631 women, 32 women developed pre‐eclampsia, and 5 controls for every case of pre‐eclampsia were found. Blood samples were collected 4 times and urine samples 6 times from the 18/19th week and throughout pregnancy. Orosomucoid and albumin in plasma were analysed by standard methods, and in urine by sandwich ELISA. Results. Orosomucoid/creatinin excretion ratio was significantly higher early in pre‐eclamptic pregnancies (from the 20th week of pregnancy, p = 0.0053) compared with healthy pregnancies, the difference increased throughout pregnancy. Albumin/creatinin ratio increased subsequent to the increase in orosomucoid. In the plasma samples, orosomucoid was significantly higher late in pre‐eclamptic pregnancies (≥36th week, p = 0.0275). Conclusions. Pre‐eclampsia is associated with a pre‐symptomatic increase in the urine excretion of orosomucoid, and orosomucoid excretion precedes that of albumin. Orosomucoid excretion can probably be used as a prognostic tool in combination with other screening methods, and seems to be a more sensitive marker for evolving pre‐eclampsia than albumin. Plasma orosomucoid is significantly increased late in pre‐eclampsia. Thus, the increased excretion of orosomucoid must primarily originate from altered renal processing of orosomucoid.

An outpatient regimen of combined oral mifepristone 400 mg and misoprostol 400 µg for first-trimester legal medical abortion

Aim.u2002 To evaluate the success rate of medical abortion using an outpatient regimen of oral mifepristone 400u2003mg and oral misoprostol 400u2003µg for legal abortion in womenu2003<u200356 days pregnant.

Virus Infection and Type I Interferon in Endometriosis

Endometriosis is a chronic disease in which endometrium-like lesions are located ectopically, frequently in the pelvic cavity but also in more distant regions. It has been estimated that 5 to 10% of fertile women are suffering from the disease, and in a population of women with dysmenorrhoea (painful periods), around 50% have endometriosis (Faquhar, 2007). The symptoms include chronic pelvic pain, dysmenorrhoea, dyspareunia (pain during intercourse), and subfertility. The pathogenesis of endometriosis is unclear. Endometriosis is hormonal-dependent and therefore mainly found in women in the fertile age, although rare cases have been found in men and postmenopausal women. The risk is increased sevento nine-fold for women who have a close relative (mother and/or sister) with endometriosis, indicating some genetic involvement (Simpson et al., 1980). Endometriosis displays malignant-like features, such as invasiveness and metastasis, and DNA viruses might play a role in endometriosis, like human papillomavirus (HPV) is part of the pathogenesis of cervix cancer (zur Hausen, 2009). Signs of inflammation are the key findings in endometriosis. From the above, some evidence points towards a possible involvement of the type I interferons (IFNs). This chapter will discuss whether DNA-viruses and the innate immune system might be involved in the pathogenesis of endometriosis.