Histological study of uterine cervix during termination of early pregnancy by mifepristone and prostaglandins

OBJECTIVE: To study the histological changes of uterine cervix during termination of early pregnancy by mifepristone and prostaglandins (PG). METHODS: A total of 24 women who requested medical abortion was recruited. For each woman, 3 cervical biopsies were taken: before mifepristone treatment; 48 hours after mifepristone 150 mg single dose treatment (i.e. immediately before PG administration); and 1 hour after gestational sac expulsion. Specimens were studied by optical and electron microscopy. RESULTS: Significant collagenolysis as demonstrated by marked reduction and irregularity of collagen fibers, abundant accumulation of an amorphorous material of ground substance, and infiltration of neutrophilic polymorphonuclear leukocytes were shown in stroma as well as in the deep portion of cervix after mifepristone as compared to the samples of early pregnant cervix before treatment. These changes presented to a further extent after the expulsion of gestational sac. CONCLUSION: The changes observed were similar to previous reports during cervical dilatation in term delivery. The present study confirmed the histological cervical ripening effect by mifepristone and suggested it may be used as cervical ripening agent before induction of labor as well.     

Ultrasonographic and Biochemical Markers of Preterm Labor

> At present preterm delivery is the leading cause of perinatal morbidity and mortality and its incidence is remained stable during the past 10 years. Conventional methods of identifying patients at risk of preterm delivery such as obstetrics history, demographic factors or evaluation of uterine contractions and cervix by digital examination show disappointintly low sensitivity and positive predictive value. In this review we describe new ultrasonographic and biochemical approaches that have been recently proposed to screen for preterm labor both in patients with intact and with premature rupture of the membranes. The ultrasonographic detection of a short uterine cervix and/or of a dilation of the internal os, expression of weakening of the lower uterine segment or cervical ripening, seems to efficiently predict patients at risk of preterm delivery. The efficiency of this marker may be improved by the association with the assay of fetal fibronectin or pro inflammatory cytokines (interleukin-6 and interleukin-8) in cervical secretions. Further by the concentrations of interleukin-6 and interleukin-8 in cervical secretions seems to be possible to predict among patients in preterm labor those secondary to subclinical endoamniotic infection or chorioamnionitis. The use of these new markers in the future may allow a better identification of patients at risk of preterm labor and a proper selection of the treatment (medical or surgical) required for such patients.     

Nitric oxide donors induce ripening of the human uterine cervix: a randomised controlled trial

OBJECTIVE: To determine whether nitric oxide donors can induce cervical ripening before surgical termination of pregnancy in the first trimester. DESIGN: Prospective, randomised controlled trial. SETTING: Department of Obstetrics and Gynaecology, Royal Infirmary, Glasgow. PARTICIPANTS: Forty-eight primigravid women undergoing surgical termination of pregnancy before 12 weeks of gestation. METHODS: The women were randomised to receive per vaginam before surgery either the nitric oxide donor isosorbide mononitrate, the nitric oxide donor glyceryl trinitrate, the prostaglandin analogue gemeprost, or no treatment. MAIN OUTCOME MEASURES: The cumulative force required to dilate the cervix to 8 mm was measured objectively and the cervical diameter before surgical dilatation was recorded. RESULTS: Following isosorbide mononitrate or gemeprost, a lower cumulative force was required to dilate the cervix to 8 mm and a higher cervical diameter before dilatation was recorded. Pretreatment with glyceryl trinitrate reduced the cumulative force required to dilate the cervix but had no effect on cervical diameter. CONCLUSIONS: Like the prostaglandin analogue gemeprost, the nitric oxide donors isosorbide mononitrate and glyceryl trinitrate can effect cervical ripening. Nitric oxide donors may provide an alternative to prostaglandins for cervical ripening before surgical procedures in the first trimester.     

Iron deposits and catabolic properties of synovial tissue from patients with haemophilia

OBJECTIVE: Our purpose was to investigate whether prostaglandin E2-induced cervical ripening can be related to changes in fetal fibronectin levels and whether fetal fibronectin can be detected by immunohistochemistry in amniotic and cervical tissue. STUDY DESIGN: Fetal fibronectin levels in cervical mucus were quantitated in 28 nulliparous term pregnant women with unfavorable cervical states before and after intracervical application of prostaglandin E2 gel. The concentration of fetal fibronectin was determined with use of an enzyme immunoassay. Cervical biopsy specimens and amniotic tissue for immunohistochemical analysis were obtained from three term pregnant women and after parturition in three women. Cervical biopsy specimens from two nonpregnant women served as controls. Immunohistochemical analysis was performed with antibodies directed toward fetal fibronectin. RESULTS: The fetal fibronectin level in cervical mucus was low in all women before prostaglandin E2 application. In women with a successful prostaglandin E2-induced ripening (i.e., an increase of cervical score with > or =3 points), a tenfold increase in the fetal fibronectin level was registered. In women with an insufficient cervical ripening after prostaglandin E2 treatment no significant increase in the fetal fibronectin level was registered. The immunohistochemical analyses have identified fetal fibronectin in the epithelial cells of the cervix uteri. CONCLUSION: Successful prostaglandin E2-induced cervical ripening seems to be related to a significant increase in cervical fetal fibronectin levels. Fetal fibronectin can be detected immunohistochemically in the pregnant human cervix.     

Cervical ripening with prostaglandin E2 in a scarred uterus during the third trimester of pregnancy. Report of 82 cases

AIM: To study the feasibility, the results and the complications of cervical ripening using PG2 in scarred uterus in the third trimester of pregnancy. METHOD: A retrospective study of 82 cases of which 10 had ruptured membranes. The administration of 0.5 mgs of PG2 by the intracervical route after Beta-mimetic drugs by the intramuscular route. RESULTS: In 78% of the cases it was possible to improve the condition of the cervix so that labour could be induced or that it would start spontaneously. It was possible to deliver the baby vaginally in 67% of cases. There was no case of ruptured uterus. CONCLUSION: It seems possible that when there is a medical indication to induce labour to ripen the cervix using PG2 in a scarred uterus in the third trimester of pregnancy. The administration of beta-mimetic drugs for ripening and the use of tocometry to monitor labour seemed to be important precautions that have to be taken.     

Proinflammatory cytokines with free oxygen radicals in septic syndrome

In this paper authors presented the advantages of measuring the fibronectin levels in several diseases occurring during the pregnancy. They established usefulness of evaluating the fibronectin concentration in premature rupture of the amniotic membranes, preterm delivery, postdate pregnancy, preeclampsia, and intrauterine growth retardation.     

Comparative evaluation of abnormal cytology, colposcopy and histopathology in preclinical cervical malignancy during pregnancy

The results of a two-and-a half-year study on cytodetection of preclinical cervical malignancy during pregnancy are presented. Of 3,534 pregnant women, 125 (3.5%) had cytologic diagnoses of dysplasia, carcinoma in situ or microinvasive carcinoma of the uterine cervix. These results are compared with those obtained from colposcopy and from tissue diagnosis following biopsy, cervical conization and hysterectomy. They are also analyzed in relation to the patients' age, parity and age at first sexual intercourse. The management of these patients during pregnancy is discussed, especially with regard to the authors' experience in dealing with patients from very poor socioeconomic and cultural backgrounds.     

Nitric oxide mediated inhibition of contractile activity in the human uterine cervix

Nitric oxide (NO) is an important modulator of contractile activity in various tissues. The aim of the present study was to investigate the possible existence of an NO system within the human uterine cervix and to study the effects of NO on the cervix in early pregnancy. Cervical tissue specimens were obtained from 24 women in connection with first trimester legal abortion. NADPH diaphorase staining was used to identify nitric oxide synthase activity within the cervical tissue. Cylindrical tissue specimens were mounted in organ bath chambers for isometric registration of contractile activity. The presence of a functional NO system in the cervix was investigated by adding either sodium nitroprusside or spermine NONOate, two different NO donors, or 8-bromo cGMP, an analogue of the second messenger cyclic guanosine monophosphate (cGMP), to the organ baths. Positive NADPH diaphorase staining was clearly observed in the walls of blood vessels, in cervical smooth muscle cells, and cells scattered in the connective tissue. The NO donating drugs sodium nitroprusside and spermine NONOate both caused a dose-dependent inhibition of spontaneous contractile activity with significant inhibition at concentrations of 10(-5) and 10(-7) M respectively. Furthermore, the participation of NO in the regulation of cervical contractility was indicated by a significant concentration-dependent inhibition of spontaneous contractions when 8-bromo cGMP (10(-5)-10(-3) M) was added to the organ baths. The study indicates the existence of an NO system within the human uterine cervix and a role of NO in control of cervical function.     

Vaginal lever pessary in patients with multiple gestation, preterm labor and low fetal station. A report of three cases

BACKGROUND: The vaginal pessary has been utilized previously in patients with cervical incompetence, resulting in improvement in pregnancy outcome. The mechanical advantages generated by the vaginal lever pessary could theoretically be applied to patients in preterm labor with low station of the presenting part to prevent cervical dilatation. CASES: One patient with twins and two with triplet pregnancies presented in preterm labor with advanced cervical dilatation and low fetal station. They were treated with tocolytic drugs, and a vaginal lever pessary was placed. The gestational age at delivery was delayed with the addition of the vaginal pessary. Based on previous experience with these difficult cases, it was judged that the use of the pessary achieved a delay in delivery that would not have occurred without the device. CONCLUSION: Vaginal pessaries can be used as mechanical adjuvants in the treatment of preterm labor. These devices work by altering the pressure dynamics on the cervix and lower uterine segment. They may also help limit cervical change by preventing engagement of the presenting part into the maternal pelvis. In these cases, a vaginal pessary appears to be beneficial in delaying delivery in multiple gestations presenting with advanced cervical dilatation and low station of the presenting part.     

Cervical assessment by magnetic resonance imaging--its relationship to gestational age and interval to delivery

The aim of this cross-sectional study was to assess the uterine cervix in late pregnancy, using MRI, and to study its relationship to the gestational age and the time interval to delivery. 91 women with a singleton cephalic presenting fetus had MRI of the pelvis between 35 and 41 weeks. All had had one prior lower segment Caesarean section and no history of prior vaginal delivery. The cervical length, internal and external os diameter, cervical signal intensity and the angulation of the cervix with the cephalocaudal axis were measured on sagittal T2 weighted images and correlated with the gestational age and the interval from the MRI examination to delivery. It was found that the signal intensity of the cervical stroma increased with the gestational age. A higher signal intensity in the cervical stroma was associated with a shorter time interval to delivery. Deliveries after 40 weeks tended to occur more commonly in those with lower signal intensity in the cervical stroma and also in those with a smaller external os diameter. It is concluded that cervical softening as assessed on MRI correlated with gestational age and the time interval to delivery.     

Clinical study on uterine cervix ripening with hyaluronidase and animal experimentation on mechanism of action

The clinical course of labor in 53 cases with cervical injection of hyaluronidase (HD) and 51 cases with intravenous infusion of oxytocin to ripen the cervix was studied. The success rate of HD group (92.5%) was significantly higher than that of control group (62.8%). HD was without adverse side effects, and did not induce uterine contraction and therefore was preferable for high risk pregnancy cases. This method needed less time for cervical priming than others. The drug is easily available, not expensive and the method is simple. The animal experiments showed the mechanism of action of cervical ripening by HD was probably as follows: (1) the dissociation of ground substance in cervical connective tissue; (2) The destruction of blood vessels permit the migrating of leucocytes to surrounding tissue and resolve collagen; (3) stimulation of cervical fibroblasts to release prostaglandin.     

Use of an on-farm progesterone test in the clinical management of parturient disorders in three cows

Measurement of blood progesterone concentrations with a rapid, on-farm test was used to guide the clinical management of 3 cows with parturient disorders. An 8-year-old cow in the third trimester of pregnancy had chronic vaginocervical prolapse with partially dilated (4 cm) necrotic cervix. Blood progesterone concentration estimated with the test kit was low (< 2 ng/ml), and the cervical dilatation was attributed to stage-1 parturition. Vaginal delivery of the calf occurred 7 hours later. A 2-year-old cow examined for dystocia had a uterine torsion. Eighteen hours after apparent correction of the torsion, the cervix had failed to dilate. Blood progesterone concentration was 2 to 5 ng/ml, suggesting parturition had not yet been initiated. Parturition was induced with dexamethasone and prostaglandin, and calving occurred 32 hours later. A pregnant, 16-month-old heifer was believed to be about to calve and was admitted because of potential need cesarean section. Examination revealed the cervix to be closed. Blood progesterone concentration was low, and calving was predicted to occur within 24 hours. The heifer was monitored, and stage-2 labor was observed 8 hours later. The calf was delivered with minor assistance. In each case, the test provided diagnostic information that was useful in making therapeutic management decisions.     

Immunohistochemistry of matrix metalloproteinases (MMP), their substrates, and their inhibitors (TIMP) during trophoblast invasion in the human placenta

The invasion of extravillous trophoblast cells into the maternal endometrium is one of the key events in human placentation. The ability of these cells to infiltrate the uterine wall and to anchor the placenta to it as well as their ability to infiltrate and to adjust utero-placental vessels to pregnancy depends, among other things, on their ability to secrete enzymes that degrade the extracellular matrix. Most of the latter enzymes belong to the family of matrix metalloproteinases. Their activity is regulated by the tissue inhibitors of matrix metalloproteinases. We have studied the distribution patterns of matrix metalloproteinases-1, -2, -3, and -9 and their inhibitors TIMP-1 and TIMP-2 as compared to the distribution of their substrates along the invasive pathway of extravillous trophoblast of 1st, 2nd, and 3rd trimester placentas by means of light microscopy on paraffin and cryostat sections as well as at the ultrastructural level (only 3rd trimester placenta). The comparison of different methods proved to be necessary, since the immunohistochemical distribution patterns of these soluble enzymes are considerably influenced by the pretreatment of tissues. All three methods revealed immunoreactivities of both, proteinases and their inhibitors, not only intracellularly in the extravillous trophoblast but also extracellularly in its surrounding matrix, the distribution patterns depending on the stage of pregnancy and on the degree of differentiation of trophoblast cells along their invasive pathway. Within the extracellular matrix, immunolocalization of matrix metalloproteinases as well as their inhibitors showed a specific relation to certain extracellular matrix molecules.     

Young people with spina bifida: transfer from paediatric to adult health care

INTRODUCTION: The method used to terminate pregnancy on medical grounds during the second trimester must be safe, rapid, psychologically feasible and associated with a minimal risk of long-term sequelae. The objective of the present work was a critical analysis of the author's standard protocol of termination of pregnancy during the second trimester. MATERIAL AND METHODS: For induction of abortion during the second trimester the authors used a synthetic prostaglandin analogue (PG) F2 alpha-Dinoprost which was administered in a single dose of 30 mg by the intraamniotic route. At the time of onset of uterine contractions the authors administered peridural anaesthesia. The authors investigated indications, mean period of induction, correlation between the period of induction of abortion and the indications for termination of pregnancy, the week of pregnancy and parity of the mother. They recorded also the type and number of complications. RESULTS: From January 1991 till June 1997 179 pregnancies were terminated by intraamniotic PG administration. After a single intraamniotic PG administration 72% women aborted within 24 hours. In 26% women the intraamniotic administration was repeated twice and in 2% women three times. The mean induction period, i.e. the interval between the administration and abortion of the foetus was 22.6 hours. The interval was significantly longer (28 hours) in foetuses where pregnancy was terminated because of a neural tube defect (p < 0.01). The authors did not detect a correlation between the period of induction and the indication, week of gestation and parity of the mother. COMPLICATIONS: once a general reaction to intraamniotic administration, in three patients a major blood loss replaced by transfusion of erythrocyte mass, no uterine rupture. CONCLUSION: In all instances the therapeutic effect was achieved and there was no need to perform section minor. The disadvantage of the method is the high price of the preparation and need of repeated intraamniotic administration of PG in 29% of the patients.     

Sonographic evaluation of the uterine cervix

Ultrasonographic evaluation of the uterine cervix has been shown to help predict patients who may be at an increased risk for preterm delivery. The use of ultrasound in at-risk patients may improve the selection of those needing obstetric intervention, which therefore, may improve outcome and lower overall health care costs. Cervical competence, once thought to be a categorical variable, should now be thought of as a continuous variable, as the shortest cervical lengths are found in those women with a history of very early preterm delivery (> 24 weeks). Adjunctive tests, such as fetal fibronectin Bishop scoring and bacterial vaginosis may help to improve the accuracy of prediction of preterm birth; therefore a multifaceted risk approach to preterm birth is suggested in this article.     

Serum immunoreactive relaxin and softening of the uterine cervix in pregnant hamsters

Serum immunoreactive relaxin levels and ripening of the cervix were measured throughout pregnancy in hamsters. RIA relaxin rose from an undetectable level on day 7 to a maximum value of 29 ng/ml on day 15 of gestation and then fell prior to parturition. The cervix became progressively more dilatable from the 12th to the 16th day of pregnancy. It is suggested that the endogenous relaxin measured by RIA may induce the cervical softening. The absolute levels of immunoreactive relaxin appear to be 10 to 15-fold higher than those previously observed in rats, mice and guinea pigs.