Responsiveness of the Endometriosis Health Profile-30 questionnaire in a Swedish sample: an observational study.

OBJECTIVE: The objective was to evaluate the responsiveness of the Endometriosis Health Profile-30 (EHP-30) questionnaire in a Swedish sample. MATERIALS AND METHODS: Forty-two patients with endometriosis were included in a prospective observational study. MAIN OUTCOME MEASURES: The changes on the EHP-30 questionnaire after pertubation treatment were compared with the patients' self-estimated change in pain intensity. The responsiveness to change was evaluated with effect sizes and significance of change (paired t-test). The changes in scores between those who improved / not improved were compared with independent t-test. RESULTS: The changes in the scores were significant for all dimensions on the core questionnaire (p = 0.04-0.0002) for improved patients in contrast to the patients in the stable group where there were no significant changes in any dimension (p = 0.16-0.63). The effect sizes were large (> 0.8) on all core scales except for self-image (0.51) for the improved patients and small on all scales in the non-improved (stable) group (- 0.17-0.35). There were significant differences between the improved and the stable group considering change in most of the core EHP-30 scores. CONCLUSIONS: The EHP-30 is responsive to improvement on all core scales and is acceptable, understandable, and applicable in this Swedish sample.

Pertubation with lignocaine as a new treatment of dysmenorrhea due to endometriosis: a randomized controlled trial.

BACKGROUND: Endometriosis is a chronic inflammatory disease of unknown aetiology that can cause severe dysmenorrhea. Lignocaine has anti-inflammatory properties and exerts effects on nerve endings and intra-peritoneal macrophages. The objective of this study was to evaluate the effect of pertubation with Ringer-Lignocaine on dysmenorrhea in women with endometriosis. METHODS: A double-blind randomized controlled trial (RCT) was carried out at three sites in Stockholm, Sweden. Eligible patients had endometriosis as diagnosed by laparoscopy, dysmenorrhoic pain >VAS 50 mm (visual analogue scale) and patent Fallopian tubes. The study patients were randomized sequentially to preovulatory pertubations with placebo (n= 18) or study treatment (n= 24) during three consecutive menstrual cycles. The pertubation procedure comprised passing study solution through the uterine cavity and the Fallopian tubes via an intra-cervical balloon catheter. The effect on pain was evaluated with VAS scales before and after the treatments and up to nine menstrual cycles after the last pertubation. Success was defined as a reduction of ≥ 50% on the VAS scale after the third pertubation. The success rate between the treatment and the placebo group was compared with Fisher's exact test. RESULTS: In the intention-to-treat analysis, the success rate was 41.7% (10 of 24) in the treatment group compared with 16.7% (3 of 18) in the placebo group (P= 0.10, 95% CI -7.3 to 36.2%). In the per protocol analysis, the success rate in the treatment group was 45% (9 of 20) compared with 7.1% (1 of 14) in the placebo group (P= 0.024, 95% CI -2.6 to 44.8%). Of the nine patients in the lignocaine group who fulfilled the criteria for success after three pertubations, 4 (44%) had an effect persisting after nine months. The treatments were well tolerated. CONCLUSIONS: This small RCT indicates that pertubation with lignocaine is a non-hormonal treatment option for patients with dysmenorrhea and endometriosis. ClinicalTrials.gov identifier: NCT01329796.

Human chorionic gonadatropin (hCG) during third trimester pregnancy.

OBJECTIVE: Separate reference values were recently established for routine blood samples during last trimester pregnancy. Previously, these were based on blood samples from healthy men or non-pregnant women. Normal changes in variation in the levels of steroid hormones in the last weeks of pregnancy before delivery are also incompletely investigated. This study of the preterm hormone levels was carried out in the search for events leading to increased contractility that might occur in the predelivery weeks and potentially influence the initiation of delivery. MATERIAL AND METHODS: Blood samples during pregnancy weeks 33, 36 and 39 as well as 1-3 h postpartum were collected from pregnant women (19-39 years, mean age 30) with at least one previous pregnancy without hypertension or pre-eclampsia. All women (n = 135) had had a vaginal delivery and spontaneous start of labour. The blood samples were analysed for serum hCG, oestradiol and progesterone. Postpartum, the values were retrospectively rearranged to correspond with the actual week before the day of delivery. RESULTS: During the last trimester of normal pregnancy, a gradual increase was found in oestradiol (median 45980 to 82410 pmol/L), progesterone (median 341 to 675 nmol/L) and a gradual decrease in hCG (median 31833 to 19494 IU/L). Furthermore, a significant (p<0.03) decrease in hCG was found from the third to the second week before delivery, while oestradiol and progesterone continued to increase. CONCLUSIONS: Hormone levels during third-trimester pregnancy have not previously been systematically investigated. Recent data suggest that hCG may have a role as an endogenous tocolytic in normal pregnancy by directly promoting relaxation of uterine contractions. In the present study a significant decrease in serum hCG level was found 2-3 weeks before the spontaneous start of labour. This might contribute to increasing the contractility in the uterine muscle and gradually initiate the onset of labour.

Reference intervals for plasma levels of fibronectin, von Willebrand factor, free protein S and antithrombin during third-trimester pregnancy.

During pregnancy, significant changes occur in the hemostatic system and in the plasma levels for several plasma proteins, especially towards term. In this study changes occurring during normal pregnancy and immediately postpartum were investigated to establish adequate reference intervals for important hemostatic parameters. Blood samples were collected during pregnancy weeks 33, 36, 39 and 1-3 h after delivery from 153 healthy pregnant women with at least one previous normal pregnancy. The plasma samples were analyzed for antithrombin, von Willebrand factor (vWf), free protein S and fibronectin. Fibronectin and vWf are contact-promoting proteins responsible for adhesion and aggregation during primary hemostasis, but are also released from thrombocytes during activation of the coagulation process. Antithrombin is the most important primary physiological inhibitor of activated serine proteases related to the coagulation cascade. Protein S is a co-factor to protein C and in cooperation is also an important inhibitor of the coagulation cascade. During third-trimester pregnancy, vWf was higher than in non-pregnant women, and continued to increase postpartum. The fibronectin plasma level was mostly unchanged in comparison with non-pregnant values. Within this reference interval it gradually increased during the third trimester, but fell slightly postpartum. Antithrombin decreased slightly during the third trimester and even further, postpartum. Free protein S decreased markedly but to a stable level from week 33 to 39, decreasing even more postpartum. The present results are concordant with clinical knowledge of increased risk of thrombosis during pregnancy and early puerperium, with increased levels of vWf and fibronectin and decreased levels of antithrombin and free protein S. Clearly, current reference values based on healthy non-pregnant subjects are not usable during late pregnancy and immediately postpartum.

Retrograde migration of glove powder in the human female genital tract.

BACKGROUND: This study in humans was undertaken to evaluate earlier results from animal research showing a retrograde migration of glove powder from the vagina into the intra-abdominal cavity. METHODS: One study group was gynaecologically examined with powdered gloves the day before an abdominal hysterectomy and another group 4 days pre-operatively. There were two control groups similarly examined with powder-free gloves. Cell smears were taken from the peritoneal fluid and during the operation further smears were taken from the Fallopian tubes, uterine cavity and cervical canal. RESULTS: Statistically significant differences were found for large starch particles at all locations between the study and control groups examined 1 day pre-operatively. Considering small starch particles, there were significant differences in cervix (P < 0.001), uterus (P < 0.01) and the Fallopian tubes (P < 0.01). The combined results also show significant differences between both large and small starch particles in cervix, uterus and the Fallopian tubes. There were also differences between the study and control groups examined 4 days pre-operatively, but these were not statistically significant except for small and large starch particles in uterus (P < 0.01, P < 0.05) and cervix (P < 0.05, P < 0.05). CONCLUSIONS: This study has pointed out a retrograde migration of starch also in humans after a gynaecological examination with powdered gloves. Consequently, powder or any other potentially harmful substance that can migrate from the vagina should be avoided.

Pertubation with lignocaine--a possible new treatment for women with endometriosis and impaired fertility.

The causal relationship between reduced fertility and early stage endometriosis without pelvic adhesions is unclear. Peritoneal fluid from patients with endometrial peritoneal implants contains more leukocytes with an increased capacity to phagocytose spermatozoa. Peritoneal fluid supplemented with lignocaine has a reduced sperm phagocytosis capacity. The present clinical study with low-dose lignocaine pertubation sought to evaluate any clinical effect on fertility. An overall pregnancy rate of 30% was noted in contrast to the natural pregnancy rate for women with endometriosis which is <5%. To confirm these findings a larger study and further dose-ranging are in progress. Up to now the most effective way of increasing fertility for women with endometriosis or unexplained infertility is in vitro fertilisation (IVF). The pertubation treatment with lignocaine is inexpensive and less invasive. Its mechanism is thought to be reduced phagocytosis of the spermatozoa. Another explanation could be a regressive effect directly on the endometriotic implants, taking into account the reduced menstrual pain and increased pregnancy rate after all treatments have been completed. The finding may provide a minimal invasive and more cost-effective alternative to current treatments.

New reference values for routine blood samples and human neutrophilic lipocalin during third-trimester pregnancy.

Reference values are usually based on blood samples from healthy men or non-pregnant women. Blood samples from pregnant women may be compared with these reference values. Correct references for pregnancy can be extremely important for clinical decisions such as ablatio placentae, appendicitis, premature rupture of membranes and preeclampsia. Previous studies of normal variations during third-trimester pregnancy are incomplete. Blood samples during pregnancy weeks 33, 36 and 39 as well as 1-3 h postpartum were collected from pregnant women with dietary iron supplement and at least one previous pregancy without a history of hypertension or preeclampsia. When the sampled values were compared with the present reference values from men and non-pregnant women, the following differences were found during normal pregnancy: Haemoglobin and ferritin were reduced, CRP was slightly elevated, WBC (white blood cell count) and HNL (human neutrophilic lipocalin) were elevated during pregnancy and significantly increased postpartum. Albumin was reduced. ALT and AST were slightly elevated and GGT was unchanged during pregnancy. ALP, D-dimer and fibrinogen were elevated. Uric acid increased during the third trimester and thrombocyte count decreased. Separate reference values for pregnant women are essential for correct diagnostic decisions during third-trimester pregnancy. Elevated levels of D-dimer do not necessarily indicate ablatio placentae. A diagnosis of progressive preeclampsia cannot be based on increasing uric acid levels and reduced platelet count in a stable clinical condition. HNL signals activation of neutrophilic granulocytes and can thereby offer a helpful tool for diagnosing infection during pregnancy and postpartum.

Post-operative consequences of glove powder used pre-operatively in the vagina in the rabbit model.

This study was undertaken to determine if a retrograde migration of glove powder (Biosorb(TM)) from the vagina into the abdominal cavity in combination with a subsequent intra-abdominal trauma could affect the development of adhesions. A rabbit model was used with one control and one test group. A total of 50 mg Biosorb(TM) was deposited intravaginally in the test cases before ovulation was induced. Three days later a laparotomy with a small standardized surgical trauma was carried out on the left Fallopian tube and the ipsilateral peritoneum. Ten days later the extent of intra-abdominal adhesions was evaluated. The presence of starch particles in cell smears and biopsies was also investigated. Significant differences in the formation of adhesions were found between the control and the test cases (P < 0.001). In the test group there were dense adhesions and in four cases the Fallopian tube was completely attached to the peritoneal wall. In the control cases only loose minor adhesions were found. This study indicates that the number of starch particles migrating from the vagina to the abdominal cavity is sufficient to enhance significantly the formation of post-operative adhesions. We therefore suggest that powder-free medical or surgical gloves should be used in obstetrics and gynaecology.

Precautions taken to prevent adhesions--a questionnaire study among Swedish obstetricians and gynaecologists.

OBJECTIVE: To collect data on the current practice and knowledge about surgical techniques for prevention of adhesions and types of surgical gloves used by Swedish obstetricians and gynaecologists. DESIGN: Postal questionnaire during 1995. SETTING: Sweden. MATERIAL: All 1200 Swedish gynaecologists were invited to participate. MAIN OUTCOME MEASURES: Methods in use to prevent the formation of adhesions such as glove selection criteria, operative techniques, and laparoscopic surgery. RESULTS: At this time there were 72 hospitals in Sweden carrying out gynaecological operations and responses were received from obstetricians and gynaecologists at 61 of these hospitals. The response rate was 27% of gynaecologists routinely carrying out such operations. There were no consistent methods in use to prevent the formation of adhesions. The most common method used was the atraumatic technique. For laparotomy 19.5% always used powdered gloves whereas half had changed to powder-free gloves. The use of powdered gloves was highest in the university hospitals (62%). 95% always closed the visceral peritoneum for gynaecological or obstetric procedures although there is no documentation to support the benefit of doing so. CONCLUSION: There was a low percentage response, probably indicating lack of interest. Swedish gynaecologists seem unaware of the need to prevent adhesions.

Fibrinolysis in the peritoneal fluid during adhesions, endometriosis and ongoing pelvic inflammatory disease.

The concentrations of the specific activators (u-PA and t-PA) and the specific inhibitors (PAI-1 and PAI-2) of the fibrinolytic system were analyzed in the peritoneal fluid in women suffering from intra-abdominal adhesions, endometriosis or pelvic inflammatory diseases (PID). Peritoneal fluids were collected from ten women in whom a laparotomy was performed and an additional 108 in whom a laparoscopy was carried out. In comparison with the normal control patients all activators and inhibitors were significantly increased in cases of PID and when a second-look laparoscopy was performed one week after laparotomy with adhesiolysis. At laparoscopies, when adhesions were verified, u-PA in the peritoneal fluid was significantly increased and in cases of endometriosis PAI-2 was significantly reduced. The start of a laparotomy in order to remove adhesions, initiates a process, resulting in a significant increase of PAI-2 antigen in the pelvic fluid. The results imply that the fibrinolytic system is comprehensively activated in the peritoneal cavity during ongoing inflammatory reaction, and after adhesiolysis. The increase in plasminogen activators in the peritoneal fluid in established cases of pelvic adhesions or endometriosis may indicate that the fibrinolytic system is continuously active to inhibit the further formation of adhesions.

The effect of lignocaine on sperm phagocytosis in the peritoneal fluid from women with or without endometriosis.

The study was undertaken to investigate a possible mechanism for reducing the phagocytosis of spermatozoa by leukocytes in the peritoneal fluid from women suffering from endometriosis. Peritoneal fluids were collected during laparoscopy from women undergoing laparoscopic sterilization or from women under investigation for cause of infertility where the laparoscopic findings were endometriosis. Prepared spermatozoa from one healthy man were incubated in vitro with peritoneal fluid with or without lignocaine. Samples from the incubations were studied daily and the number of viable and dead spermatozoa were counted. The number of free spermatozoa, not adhered to leukocytes, was significantly increased when incubated in human peritoneal fluid supplemented with lignocaine. Thus lignocaine contributes to increasing the number of free spermatozoa and maintaining the possibility of fertilizing an oocyte. For patients with endometriosis, treatment with lignocaine might be a means of increasing the chances of conception. A clinical study is in progress to evaluate this effect in vivo and to search for alternative methods of assisting the fertilization process.

Retrograde migration of starch in the genital tract of rabbits.

This study in a rabbit model simulates contamination with glove powder in association with a routine gynaecological examination. Large individual variations of powder contamination were found and there were no overall statistically significant differences between the control and experimental animals. The findings are supported by the observation that some but not all women develop adhesions after gynaecological surgery. Analyzes of variances indicate differences in the migration of starch particles in the genital tract with the highest amount of particles found three days after starch contamination of the vagina. Since no adhesions were observed, there would probably need to be an ongoing post surgical or post infectious inflammation in the tissue, when the starch particles are added. Starch powder from latex gloves can cause adhesions and increase the risk of latex allergy in healthcare workers. Retrograde migration in the genital tract cannot be excluded, powdered examination products should be eliminated from the gynecologicla examination room.

The human leucocyte antigen (HLA) DR expression and the distribution of T-lymphocytes in the fimbriae of the normal fallopian tube and during pelvic adhesion disease.

PROBLEM: Systematically to investigate the expression of human leucocyte antigen (HLA) DR on the columnar epithelium and the content of T-lymphocytes in the fimbriae specimens of the fallopian tube from healthy women and from women with infertility and pelvic adhesions. METHOD: The staining of HLA-DR expression on the columnar epithelium was judged on a four-graded scale according to the distribution of HLA-DR expression. The amount and distribution of T-lymphocytes were registered. RESULTS: The biopsies from normal fimbriae contained sparsely infiltrating T-lymphocytes. On the columnar epithelial cells a patchy HLA-DR expression was observed that was more widespread in preovulatory cases. In some biopsies from sactosalpinx, the HLA-DR expression was found completely to cover the columnar epithelial cells and was associated with a heavy infiltration of T-lymphocytes. CD4+ T-lymphocytes dominated in all but one adhesion biopsies. CONCLUSION: The findings indicate an ongoing immunological activity in pelvic adhesions that might immunologically influence fertility.

Role of eosinophilic granulocytes in women with infertility and pelvic adhesions.

Increased numbers of eosinophilic granulocytes and eosinophil degranulation have been observed in various inflammatory conditions. Biopsies from the fallopian tubes of 28 patients were examined for the content of eosinophilic granulocytes. Peritoneal fluids (PF) from 89 patients were analyzed for the concentrations of eosinophilic granulocytes and the granule protein eosinophil cationic protein (ECP). The ECP levels in the PF were substantially elevated during genital inflammation (P < 0.001). Furthermore, one week after laparotomy for adhesiolysis there were both increased PF-ECP levels (P < 0.01) and raised concentrations of eosinophilic granulocytes (P < 0.001) when compared to the reference group. Staining of the biopsies with monoclonal antibodies revealed an increased total number as well as a number of activated eosinophilic granulocytes in specimens from adhesions and sactosalpinx compared to specimens from normal fimbriae. The findings indicate that eosinophilic granulocytes may have a possible role in the fibrotic process of pelvic adhesion disease.

Hyaluronan and myeloperoxidase in human peritoneal fluid during genital inflammation.

The changes in concentration of hyaluronan (HYA) and myeloperoxidase in peritoneal fluid (PF) were studied during genital intraperitoneal inflammation. PF were collected from 111 women undergoing laparatomy for adhesiolysis and reconstructive surgery of the fallopian tubes, or laparoscopy in search of causes of infertility or low abdominal pain. When the number of leukocytes in the PF had been counted, the fluid samples were centrifuged and the supernatants analyzed for the concentrations of HYA and of myeloperoxidase. During genital inflammation, whether post-operative or postinfectious, leukocytosis and elevated levels of HYA and myeloperoxidase were found in the PF. Concentrations of these substances in the PF may be usable as clinical markers for genital inflammation.

Hyaluronan and myeloperoxidase in human peritoneal fluid during genital inflammation.

The changes in concentration of hyaluronan (HYA) and myeloperoxidase in the peritoneal fluid (PF) were studied during genital intraperitoneal inflammation. PF were collected from 111 women undergoing laparotomy for adhesiolysis and reconstructive surgery of the fallopian tubes or laparoscopy in search of causes of infertility or low abdominal pain. When the number of leukocytes in the PF had been counted, the fluid samples were centrifuged and the supernatants analyzed for the concentrations of HYA and myeloperoxidase. During genital inflammation, whether postoperative or postinfectious, leukocytosis and elevated levels of HYA and myeloperoxidase were found in the PF. Concentrations of these substances in the PF may be usable as clinical markers for genital inflammation.

Concentration and turnover of intraperitoneal hyaluronan during inflammation.

Aseptic peritonitis was induced in rabbits by intraperitoneal injection of irritating agents, mainly starch suspensions. The inflammatory response was followed in the peritoneal lavage fluid by cell counts (average increase about 800-fold the first day) and hyaluronan concentration (average increase about 200-fold on the second and third days). The turnover rate of hyaluronan was studied by injecting tritium-labeled hyaluronan intraperitoneally and by following the appearance of tritiated water in serum. In control animals given trace amounts of hyaluronan, half-lives of 1-14 h were recorded. When the labeled polysaccharide had been mixed with 10 mg/ml of unlabeled hyaluronan, the half-life was approximately one day. Rabbits with ongoing peritonitis exhibited half-lives between 1 and 16 h. It was concluded that there was a large individual variation in uptake kinetics, that the removal process could be receptor mediated, and that the increase in intraperitoneal hyaluronan in peritonitis mainly was due to an increased production of the polysaccharide rather than a decreased rate of removal.

Cyclic variation of major histocompatibility complex class II antigen expression in the human fallopian tube epithelium.

OBJECTIVE: To systematically investigate the expression of major histocompatibility complex (MHC) class II antigens (human leukocyte antigens, HLA-DR, -DP, and -DQ) on columnar epithelium in the fallopian tube during the menstrual cycle. STUDY DESIGN: Biopsies were collected from the fallopian tube during laparotomy sterilization and immunoperoxidase staining was performed. SETTINGS: Departments of Gynecology and Obstetrics and Clinical Immunology and Transfusion Medicine, Uppsala University, Uppsala, Sweden. PATIENTS: Twenty healthy fertile women undergoing sterilization at different times of the menstrual cycle. INTERVENTIONS: None. MAIN OUTCOME MEASURES: The staining of the columnar epithelium was judged on a 4-graded scale according to the distribution of class II antigens. RESULTS: A widespread preovulatory HLA-DR expression was observed almost completely lining the columnar epithelial cells including the luminal surface, whereas postovulatory the HLA-DR expression was withdrawn from the surface. The HLA-DP and -DQ antigens varied in a similar way, although not as pronounced. CONCLUSIONS: The MHC class II antigen variation in the fallopian tube epithelium seen in this study may indicate a hormonal regulation that could reflect variable need for local immunocompetence during the menstrual cycle: a preovulatory need for immunoreactivity against invading microbes and postovulatory an optimal survival of the foreign preimplantation embryo.

Localization of hyaluronan in regions of the human female reproductive tract.

Accumulation of hyaluronan has previously been observed in various organs as an inflammatory response. To study the presumed connection between infertility due to a tubal factor and inflammation, we performed an analysis of the hyaluronan distribution in biopsy specimens from the female reproductive tract, using a biotinylated hyaluronan binding protein (HABP) as a histochemical probe. In normal specimens hyaluronan was localized in the dense, irregular connective tissue surrounding blood vessels of various sizes. Smooth muscle and columnar epithelium were devoid of hyaluronan. The isthmic part of the normal Fallopian tube showed moderately intense staining of the entire lamina propria, whereas normal fimbriae stained weakly. No cyclic changes in hyaluronan content were observed. In biopsy specimens from women with infertility due to a tubal factor, intense staining, stronger than in normal tubes, was detected in the adhesions and in the lamina propria of sactosalpinx. This may indicate that infertility due to a tubal factor is associated with an ongoing inflammatory and/or proliferative process.