Mast cell involvement in human cervical ripening.

OBJECTIVE: Cervical ripening resembles an inflammatory process in many aspects, involving invasion of inflammatory cells, collagen breakdown and remodelling of the extracellular matrix. Mast cells produce a variety of inflammatory agents and are attributed a functional role in cervical ripening. The aim of this study was to examine if cervical mast cells are increased in number and stimulated during pregnancy. STUDY DESIGN: Cervical biopsies were obtained with a biopsy needle prior to surgical termination of pregnancy in the first trimester, surgery for first-trimester miscarriage, elective caesarean section, and benign gynaecological surgery in non-pregnant women. After fixation, semithin sections were prepared and stained with toluidine blue. The number of mast cells was counted under a light microscope and their secretory activity was scored (0.5-4) according to specified criteria and further visualised with electron microscopy. For pairwise comparison between groups Fisher's nonparametric permutation test was used. RESULTS: The number of mast cells was increased from 3.4 ± 1.65 mast cells per 10 visual fields in non-pregnant women to 7.70 ± 0.35 per 10 visual fields in first trimester control women (p < 0.05). The highest number of mast cells was observed at term with 10.8 ± 2.1 per 10 visual fields, a number that was significantly higher than in first trimester control women (p < 0.05). At term mast cell activity scores were 3.39 ± 0.37 compared with 2.69 ± 0.27 in control first trimester women and 2.21 ± 0.86 in women with missed miscarriage (p < 0.05). The percentage of mast cells with activity score 4 was significantly higher at term compared with in the first trimester. Free mast cell granules were predominantly observed in areas with disorganized collagen fibres. CONCLUSION: The findings confirm that an increased influx of mast cells to the cervix occurs during pregnancy. The stimulated mast cell secretory activity in conditions associated with cervical tissue remodelling, such as term pregnancy and symptomatic miscarriage, provides further evidence that mast cells play a physiological role in cervical ripening.

Low Prevalence of Active Tuberculosis among High-Risk Pregnant and Postpartum Women in Sweden: A Retrospective Epidemiological Cohort Study Using and Evaluating TST as Screening Method.

Objective: Studies on the prevalence of active tuberculosis (TB) and latent tuberculosis infection (LTBI) among high-risk pregnant and postpartum women are few and prevalence is not well known. The methods used for diagnosing and treating TB and LTBI also differ both within and between countries. The aim of the study was to investigate the prevalence of TB and LTBI among high-risk pregnant and postpartum women in a Western Region of Sweden using tuberculin skin test (TST) as screening method. Secondary aims were to evaluate the effectiveness of the screening method and possible negative labour and neonatal outcomes among TST-positive women. Methods: Pregnant women attending an antenatal care unit (ACU) allocated for TST screening were investigated and followed up for two years postpartum. Results: Only one woman out of 902 screened women in the study group was diagnosed with active TB because of TB symptoms and not because of positive TST. 36% of the skin-tested women fulfilled criteria for LTBI. No difference in perinatal outcome was found between women with and without positive TST. Conclusions: Our findings suggest that TST screening of high-risk women may not be an effective strategy, since the prevalence of active TB is low. Investigating pregnant and postpartum women with TB symptoms instead of TST for screening could be an option in low TB prevalence areas. The criteria for diagnosing and treating LTBI should be clearly stated.

A Case of Chronic Ectopic Pregnancy Manifested by Rectal Bleeding.

Ectopic pregnancy resulting in perforation of the rectum and rectal bleeding is clinically rare. We report an extremely rare case of chronic ectopic pregnancy with decreasing low levels of serum ß-HCG resulting in rectal bleeding. A 31-year-old woman, gravida 3, para 3, with moderate abdominal pain and rectal bleeding was diagnosed with a tubal pregnancy. The tube was adherent to the rectum. Following salpingo-oophorectomy, the perforation of the rectum was sutured. Biopsies from the rectum as well as the tube confirmed chronic ectopic pregnancy. This case illustrates that diagnosing ectopic pregnancy is sometimes extremely challenging and it underlines the importance of follow-up consultations when the final diagnosis has not yet been reached.

Cervical tissue changes in women with miscarriage: a morphological and biochemical investigation.

OBJECTIVE: To evaluate morphological and inflammatory events in the uterine cervix in first trimester miscarriages. DESIGN: Experimental study. SETTING: Sahlgrenska University Hospital, Gothenburg, Sweden. POPULATION: Nulliparous women with first trimester symptomatic (n = 7) or silent (n = 11) miscarriage scheduled for surgical evacuation and nulliparous women scheduled for surgical termination of first trimester pregnancies (control group n = 11). METHODS: Before evacuation, biopsies were obtained from the cervix. The specimens were either fixed in glutaraldehyde for electron microscopy or snap-frozen in liquid nitrogen and stored at -70 degrees C until analyses of interleukin-8 (IL-8) and matrix metalloproteinases (MMPs). MAIN OUTCOME MEASURES: Ultrastructure of cervical tissue, cervical tissue levels of IL-8, immunohistochemistry of MMP-1, MMP-8, MMP-9 and IL-8. RESULTS: The organization of the cervical collagen framework was deranged, the fibroblasts were reactive and the number of activated mast cells appeared to be increased in specimens from women with miscarriage compared with controls. IL-8 was significantly increased in women with miscarriage. Immunohistochemistry of MMP-1 and MMP-8 did not demonstrate any significant difference between the groups. MMP-9 was significantly lower in specimens from women with symptomatic miscarriage compared to women with silent miscarriage and women in the control group. CONCLUSIONS: An inflammatory-like response takes place in the cervix both in women with symptomatic and silent miscarriage. The intensity of the inflammatory response seems to be similar in the two groups. Therefore, inadequate cervical remodeling does not seem to be the reason why some miscarriages remain silent.

Cervical priming in the first trimester: morphological and biochemical effects of misoprostol and isosorbide mononitrate.

OBJECTIVE: To evaluate morphological changes and inflammatory events in the uterine cervix following presurgical treatment with the prostaglandin analogue misoprostol or the nitric oxide donor isosorbide mononitrate (IMN). DESIGN: Experimental study. SETTINGS: Sahlgrenska University Hospital, Gothenburg, Sweden. POPULATION OF SAMPLE: Primigravid women (n=32) scheduled for surgical termination of first trimester pregnancy, treated vaginally overnight with either misoprostol (200 microg), IMN (40 mg) or no treatment (controls). METHODS: Before evacuation, cervical biopsies were obtained with the use of a Tru-Cut biopsy needle. Morphology was studied by electron microscopy. For assessment of inflammatory events the expression of the matrix metalloproteinases MMP-1 and MMP-9 was estimated by immunohistochemistry and interleukin IL-8 was quantified by ELISA. RESULTS: Misoprostol induced splitting and disorganization of the collagen fibres. Compared to specimens from women who had received no treatment, the granular endoplasmatic reticulum appeared enriched and dilated and the nuclear chromatin was clearly dispersed. Similar changes of a lesser degree were observed in specimens obtained from IMN-treated women. Staining intensity for MMP-1 and MMP-9 was more evident in specimens obtained from IMN-treated women compared to women who had received treatment with misoprostol or no treatment. The levels of IL-8 were higher following treatment with misoprostol compared to IMN and controls. CONCLUSION: The study demonstrates that misoprostol as well as IMN induces morphological changes and inflammatory events of the cervix. Changes of the collagen network were more pronounced in samples obtained from women treated with misoprostol compared to IMN.

Outpatient cervical ripening before first-trimester surgical abortion: a comparison between misoprostol and isosorbide mononitrate.

BACKGROUND: Vaginal administration of prostaglandin analogues as well as nitric oxide donors before first-trimester surgical abortion has been shown to induce effective cervical ripening. In addition, nitric oxide donors, such as isosorbide mononitrate and nitroglycerin, have been associated with a patient-friendly side-effect profile when administered 3 h before the surgical procedure. We wanted to compare the cervical ripening effect and possible side effects of isosorbide mononitrate and the prostaglandin analogue misoprostol when self-administered at bedtime the evening before surgical abortion. METHODS: One hundred and twenty nulliparous women scheduled for suction termination of pregnancy in the first trimester were randomly assigned to receive per vaginam either 40 mg of isosorbide mononitrate or 200 microg of misoprostol. Sixty of the women were included for assessment of cervical ripening as well as evaluation of side effects. The other 60 women were recruited for assessment of side effects only. Cervical ripening was evaluated by measuring baseline cervical dilation and the cumulative force to dilate the cervix to 9 mm by means of a cervical tonometer. For assessment of side effects, the women were asked to complete a symptom questionnaire. RESULTS: Cervical resistance was significantly higher in women treated with isosorbide mononitrate compared to misoprostol (median cumulative force 73 versus 15 N). Common side effects of misoprostol were abdominal pain (69%), nausea (44%), and vaginal bleeding (66%), while in the isosorbide mononitrate group headache was frequently experienced (79%). In both treatment groups, the frequency and intensity of side effects gradually increased during the treatment interval. CONCLUSIONS: Misoprostol induced a more pronounced cervical ripening than isosorbide mononitrate, but both regimens were associated with a high frequency of side effects.