[Prophylactic use of prostaglandin synthesis inhibitors in connection with IUD insertion]. / Profylaktisk brug af prostaglandinsyntesehaemmere ved oplaegning af spiral.

In a double-blind, randomized, placebo-controlled study conducted at a contraception clinic, 55 women (three nulliparous) were given either ibuprofen 600 mg or placebo 1-4 hours prior to insertion of IUD, 4-6 hours after insertion of IUD and the following morning. Pain was assessed by ten point Numerical Rating Scales during insertion, in the first 4-6 hours and in the following three days. No benefit of ibuprofen was demonstrated at insertion or at any other time during the first three days. The patients were further randomized to type of IUD: TCu-380A and Nova T (R.). No difference in pain scores was evaluated between these.

PIP: In a double-blind, randomized, placebo-controlled study conducted at a family planning clinic in Herlev, County of Copenhagen, during the period of May 1994 to May 1995, a total of 55 women were randomized in the following 4 groups according to treatment: 1) ibuprofen and the Gyne T 380 IUD, 2) ibuprofen and Nova T IUD, 3) placebo and Gyne T 380 IUD, and 4) placebo and Nova T IUD. All women were given either ibuprofen 600 mg or placebo 1-4 hours prior to insertion of an IUD, 4-6 hours after insertion, and the morning after insertion. Pain was assessed by a 10-point Numerical Rating Scale during insertion, in the first 4-6 hours, and over the following 3 days. The median values of pain intensity for Nova T and Gyne T were 3.0/2.9 at insertion, 1.6/1.9 during the first 4-6 hours, 1.3/1.5 during the first day, 1.1/1.3 the next day, and 1.1/1.1 on the third day after insertion. The median values of pain intensity for the ibuprofen/placebo groups were 3.3/2.5 at insertion, 1.7/1.8 during the first 4-6 hours, 1.4/1.3 during the first day, 1.3/1.1 the next day, and 1.1/1.1 on the third day after insertion. Among the women who had just given birth only 6% had intensity of pain over point 3 after 4-6 hours and none of them had it beyond the first day. 38% had significantly more pain (3) at insertion; this problem could be prevented by local anesthesia. No benefit of ibuprofen was demonstrated at insertion or at any other time during the first three days. The patients were further randomized according to the type of IUD: TCu-380A and Nova T. No difference in pain scores was ascertained between these groups.

[Birth statistics for "standard populations". A basis for obstetric quality development]. / Fødselsstatistik for "standardpopulationer". Et grundlag for obstetrisk kvalitetsudvikling.

Using standard populations like "standard-primipara" (normal pregnancy, singleton term delivery and cephalic presentation) and "caesarean secundapara" (previous caesarean section and second birth) as the basis for interunit comparisons of maternity care will control for differences in casemix that may be seen at different units, thereby increasing the validity of comparisons. Focusing on clinically meaningful subsets of the population may have the additional benefit of clarifying the relationship between everyday clinical decision making, and the statistics from medical birth registration. Birth registry data from Rigshospitalet, Hvidovre Hospital and Herning Centralsygehus 1993-1994 have been used to illustrate the association between local quality improvement activities, on the one hand, and rates of interventions and foetal outcome in "standard-primipara" on the other.

Estrogen receptor determination in endometrial carcinoma: ligand binding assay versus enzyme immunoassay.

We compared concentrations of cytosolic estrogen receptors (ERc) measured in 35 postmenopausal endometrial carcinomas by ligand binding method (LBA) (dextran-coated charcoal assay) and enzyme immunoassay (EIA). Correlations between ERc, nuclear estrogen receptors (ERn) determined by EIA, and cytosolic progesterone receptors (PR) measured by LBA were also studied. While ERc concentrations determined by LBA and EIA were highly correlated (r: 0.94), ERc values detected by LBA were approximately twice those found by EIA (median values of ERc: 155 vs. 64 fmol/mg cytosol protein, DCC vs. EIA). The percentages of ERc positive tumors were 89% by LBA and 77% by EIA. The median fraction of total ER present as ERn was 63%. PR levels correlated positively with ERn concentrations (r: 0.73). We explore possible reasons why greater concentrations of ERc are determined by estradiol binding than by the ER-EIA kit in endometrial cancer.

Induction of labour by balloon catheter with extra-amniotic saline infusion (BCEAS): a randomised comparison with PGE2 vaginal pessaries.

OBJECTIVE: A new method for induction of labour--balloon catheter with extra-amniotic saline infusion (BCEAS)--is evaluated in randomised comparison with prostaglandin E2 (PGE2) in vaginal pessaries. STUDY GROUP: One-hundred and nine pregnant women with unfavourable cervices. MAJOR OUTCOME MEASURES: The efficiency of inducing vaginal delivery and the level of 'disadvantages following induction of labour' (DisFIL scorings). RESULTS: Overall, BCEAS was less efficient inducing vaginal delivery than vaginal PGE2 (P < 0.01) because of a significant difference among parous women (P < 0.01). In the (larger) primiparous women group, and particularly in the subgroup of these having very low pelvic scores (Lange score, < or = 3), the efficiencies of the two methods were equal (P = 0.06) and P = 0.55, respectively). The levels of DisFIL scorings were not significantly different. However, higher rates of caesarean section followed BCEAS than PGE2 (29% and 10%, respectively; P < 0.05). Serious infectious complications were not recorded following BCEAS. No difference was apparent in the status of the neonates (judging from Apgar scores and umbilical artery pH and SBE). The women, delivering vaginally, commented the two methods equally favourably. CONCLUSION: BCEAS was less efficacious than vaginal PGE2 pessaries, though among primiparous women, especially those with very unfavourable cervices, the difference was not significant. Further refinements of the method are suggested.

Plasma oestrogens in postmenopausal women with endometrial cancer.

OBJECTIVE: To study plasma levels of estrogens and androgens, sex hormone-binding globulin (SHBG) and follicle stimulating hormone (FSH) in postmenopausal patients with endometrial cancer. DESIGN: Patients and controls were matched for age, body mass index, parity and years since menopause. SETTING: Department of Obstetrics and Gynaecology, Hvidovre Hospital, Denmark. SUBJECTS: Fifty postmenopausal patients with endometrial cancer and 54 matching controls. MEASUREMENTS: Plasma levels of SHBG, FSH, oestrone, oestradiol, oestrone-sulphate, dehydro-epiandrosterone sulphate, testosterone, and androstenedione were measured by radio-immunoassays. Free fractions of oestradiol and testosterone were calculated according to levels of SHBG and albumin. RESULTS: The levels of oestradiol, free oestradiol, and oestrone were elevated (P < 0.001) in patients compared with controls (oestradiol: 51 (45-59) vs 37 (34-41) pmol/l; free oestradiol: 0.69 (0.59-0.80) vs 0.48 (0.42-0.54) pmol/l; oestrone: 180 (159-204) vs 119 (107-133) pmol/l (mean values (95% CI) in patients vs controls)). Furthermore, an increased oestrone:androstenedione ratio (0.095 vs 0.072, P < 0.01) was found in patients. SHBG correlated negatively (P < 0.001) with body mass, while the free fractions of oestradiol and testosterone correlated positively (P < 0.01) with body mass, in both patients and controls. Multiple regression analysis showed that the differences in oestrogen levels between the two groups persisted when controlling for the effect of body mass, age, years since menopause, parity, and levels of SHBG and FSH. CONCLUSION: Patients with endometrial cancer exhibit increased plasma levels of oestradiol and oestrone. Speculatively, these oestrogens may result from an increased oestrone conversion from androstenedione, an increased ovarian and adrenal secretion of androstenedione, or alternative oestrogen production routes. The present findings support the hypothetical role for oestrogens in the aetiology of endometrial cancer.

Prediction of mode of delivery and 'DisFIL score' following induction of labor by local PGE2.

The objective of the study was to evaluate pre-induction risk factors for (i) assisted vaginal delivery (forceps or vacuum extraction), (ii) caesarean section, (iii) failed induction followed by caesarean section, and from these to evaluate a score of the 'Disadvantages Following Induction of Labour' (the DisFIL score). The study was a case-control study applied on a prospective cohort of 336 pregnant women induced by local PGE2. Assisted vaginal delivery was associated with primiparity (OR (odds ratio) = 10.7; CI, 3.6-32.0) and higher pelvic scores (Bishop score: OR = 1.9; CI, 1.4-2.6). Caesarean section was related to higher maternal age (P < 0.001) and lower pelvic scores (Bishop score: OR = 0.7; CI, 0.5-1.0, P < 0.05). When performed because of fetal distress, assisted vaginal delivery and caesarean section were both associated with lower fetal weights (P < 0.05). Failed induction followed by caesarean section was related to primiparity (P < 0.0001, Fisher's test) and lower pelvic scores (Bishop score: OR = 0.6; CI, 0.4-0.9). A higher 'DisFIL score' was associated with primiparity (OR = 4.7; CI, 2.8-8.0), higher maternal age (P < 0.01), lower pelvic scores (P < 0.01, chi 2 test) and PGE2 in intracervical gel rather than in vaginal pessaries (OR = 2.1; CI, 1.4-3.2). It is concluded that the major predictors of 'Disadvantages Following Induction of Labor' by local PGE2 are primiparity, high maternal age, low pelvic scores and the method of.

Progesterone receptor content in endometrial carcinoma correlates with serum levels of free estradiol.

OBJECTIVE: To study a possible relationship between serum levels of estrogens and androgens and the tumor content of estrogen receptors and progesterone receptors in endometrial cancer. STUDY DESIGN: Fifty postmenopausal patients were included. Receptors were determined biochemically in tissue cytosol by dextran charcoal-coated assay and immunohistochemically on frozen sections. Serum sex hormones were measured by radioimmunoassays. MAIN FINDINGS: Tumor biochemical progesterone receptor content correlated positively (p < 0.05) with free estradiol serum levels. No correlations were observed between estrogen receptor content and any of the serum sex hormones. The progesterone/estrogen receptor ratio, calculated from the biochemical values, correlated positively (p < 0.05) with the serum levels of free estradiol. This relation was not affected by tumor histologic grade or stage. Furthermore, this ratio correlated positively with body mass index, probably reflecting a correlation between body mass and serum estrogens. Biochemical and immunohistochemical receptor values were correlated. CONCLUSIONS: These findings suggest that hormonal regulation of receptor levels may remain preserved in at least some endometrial cancer cells.

Estrogen and progesterone receptors in endometrial carcinoma: comparison of immunohistochemical and biochemical analysis.

In 159 endometrial carcinomas, estrogen (ER) and progesterone receptors (PR) were determined biochemically by dextran-coated charcoal (DCC) assay and immunohistochemically (ICA) on frozen sections. ICA receptor content was estimated by a total histologic score (HSCORE), including all tissue components, and by a cancer HSCORE, including malignant cells only. These scores were closely correlated. A single biopsy was found to be representative for each tumor. ER-DCC status was positive in 90.3% and PR-DCC status in 92.2% of the tumors. ER total HSCORE was positive in 47% and PR total HSCORE in 89% of tumors. ER and PR correlated inversely with tumor grade (p < 0.001). Correlations were found between ER and PR content determined by either method (DCC: r = 0.77; ICA: r = 0.50), as well as between DCC and ICA content (ER: r = 0.52; PR: r = 0.76). The association between DCC and ICA was affected by the tumor grade: the DCC values decreased relatively more than total HSCOREs with increasing grade. The sensitivity of ICA against DCC assay was 56% for ER and 86% for PR. Maximal agreement between receptor status as determined by ICA and by DCC would result from a DCC cutoff level of 130 fmol/mg for ER and 114 fmol/mg for PR.

Biochemical and immunohistochemical estrogen and progesterone receptors in adenomatous hyperplasia and endometrial carcinoma: correlations with stage and other clinicopathologic features.

OBJECTIVE: This study investigates clinicopathologic associations of estrogen and progesterone receptor content in endometrial carcinoma. STUDY DESIGN: One hundred fifty-two patients with endometrial cancer and 12 with adenomatous hyperplasia were included. Dextran-coated charcoal receptor assay and immunohistochemical analysis were used. The immunohistochemical analysis receptor content was estimated semiquantitatively by a total and a cancer immunohistochemical histologic score. Multiple regression analysis was used in testing independence of established correlations. RESULTS: Estrogen and progesterone receptor dextran-coated charcoal values and immunohistochemical histologic scores correlated inversely (p < 0.001) with International Federation of Gynecology and Obstetrics grade of tumor. An inverse correlation (p < 0.0001) between clinical stage and dextran-coated charcoal values was independent of International Federation of Gynecology and Obstetrics grade. Age of patient, years since menopause, and previous estrogen treatment were not related to receptor content. In adenomatous hyperplasia high progesterone receptor levels were seen. CONCLUSION: The inverse correlation between clinical stage of endometrial carcinoma and content of estrogen and progesterone receptors may reflect tumor biologic behavior.

Predictive value of pelvic scores for induction of labor by local PGE2.

The predictive value of pelvic scores, parity, age and gestational age for induction of labor by local prostaglandin-E2 (PGE2) was examined in 336 women attempting induction of labor by intracervical or vaginal PGE2. The patient characteristics were correlated to: (1) vaginal delivery within 48 h, (2) the period from induction to onset of labor (latency period), and (3) the duration of labor. The Bishop score (P < 0.01) and even more the Lange score (P < 0.0001) were significantly inversely correlated to both latency period and induction-delivery period. This was caused by cervical dilatation (P < 0.001), fetal station (P < 0.05) and cervical length (P < 0.05), whereas position and consistency of the cervix were of no importance. All three periods studied were significantly (P < 0.0001) shorter in parous women. In primiparous women, gestational age was of no importance for the latency period; however, higher gestational age was associated with longer labor (P < 0.001). We conclude that the predictive value of pelvic scores on induction hardly differs using local PGE2 compared to conventional methods; furthermore, the Bishop score should be substituted, disregarding position and consistency of the cervix, but putting more weight to cervical dilatation. A new pelvic score is proposed.

Induction of labor by prostaglandin E2: intracervical gel or vaginal pessaries?

To investigate the best route of prostaglandin medication for induction of labor, 125 pregnant women with unfavorable cervices (Bishop scores less than or equal to 6) were randomized to induction of labor with either PGE2 (0.5 mg) in a viscous intracervical gel once daily or PGE2 pessaries (2.5 mg) 1-2 a day. As estimated by life table analysis, the pessaries were significantly more effective inducing vaginal delivery compared to intracervical gel (24 h: P less than 0.025, 48 h: P less than 0.01, logrank test) and vaginal delivery was obtained within 24 h/48 h in 50%/72% of the women in the pessary group and in 29%/55% of the women in the intracervical group. Cervical ripening was found within 3 h (P less than 0.001) and in the subsequent 3 to 24 h period (P less than 0.005) after both treatments, no difference being found between the groups. The pessaries were much more effective inducing regular contractions compared to the intracervical gel (P less than 0.005, logrank test), so the latter seems preferable if cervical ripening rather than induction is intended. No difference was found analyzing the active labor period. No difference was found in methods of delivery, neonatal parameters (Apgar scores, umbilical artery blood pH and standard base excess), and the patients' attitude towards both methods of induction were equally favorable.

[Observation and follow-up of premature rupture of the membranes. A pilot study of women at term with immature cervix and premature rupture of the membranes, without contractions]. / Ekspekterende behandling ved vandafgang. En pilotundersøgelse af fødende ved termin med umoden livmoderhals og vandafgang uden veer.

In a material of 88 patients with premature rupture of the membranes and unripe cervix, a comparative investigation was undertaken to compare the effects of prostaglandin E2 (PGE2) vaginal tablets and intravenous oxytocin on induction of labour. The patients were subdivided at random into two groups: 42 patients treatment with PGE2 and 46 treatment with intravenous oxytocin. The results did not reveal any significant differences in the numbers of successful inductions regardless of the Bishop score at the commencement of stimulation but the duration of induction was found to be briefer in the oxytocin group. No significant differences were observed in the numbers of instrumental interventions in the two groups nor in the frequencies of side effects and in the employment of analgesics. Treatment with PGE2 vaginal tablets is considered to be more acceptable by the patients and easier for the staff to use. The tablets were just as safe and reliable in use as intravenous oxytocin for induction of labour in cases of premature rupture of the membranes and Bishop scores less than 6, but the duration of induction was significantly longer.

Induction of labour: the effect of vaginal prostaglandin or i.v. oxytocin--a matter of time only?

Ninety-one pregnant women with unfavourable cervix (Bishop score no higher than 6) were randomly allocated to induction of labour with either prostaglandin E2 suppositories 2.5 mg 1-2 a day or i.v. oxytocin 4-32 mU/min. The induction procedure was carried on for 2 days. For statistical comparison of efficacy, life table analysis and the logrank test were used with vaginal delivery as the aimed 'event'. Prostaglandin suppositories were more efficient after 12 h (p less than 0.025) and 24 h (p less than 0.005), whereas no difference in efficacy was observed after 48 h. Vaginal delivery was obtained within 48 h in 74% of the women in the prostaglandin group and in 70% in the oxytocin group. No difference was observed in methods of delivery or neonatal Apgar scores, though, in neonates delivered vaginally within 2 days, lowered umbilical artery blood pH values were found after prostaglandin E2 suppositories (p less than 0.05). The patients attitude toward the method of induction was highly in favour of the prostaglandin suppositories. Prostaglandin E2 suppositories are considered excellent for induction of labour if delivery has to be within 24 h, whereas the two methods are equally effective after 48 h.

[Induction of early first trimester abortion with a prostaglandin E1 analogue. A pilot study]. / Fremkaldelse af abort tidligt i 1. trimester med prostaglandin-E1 analog. En pilotundersøgelse.

A pilot investigation employing prostaglandin (PG) induced early abortion (maximal 56 days of menostasia) was planned with the object of investigation whether this non-surgical method was as effective, safe and acceptable as vacuum aspiration. The investigation was planned to include 20 women to be treated with 1 mg PGE1-vagitories at intervals of three hours up to five times in 24 hours. If abortion did not occur after 24 hours as assessed by gynaecological examination and sonography, the uterus was evacuated. After seven women had participated, the investigation was abandoned because of complications and violent pain in several women and because very few of the woman ashed to participate desired to do so, i.e. they preferred vacuum aspiration under general anaesthesia. It is concluded that the method employed here did not prove acceptable for Danish women on account of the severe pain involved and the protracted course of the procedure.

[Endometriosis--new perspectives. 1. Pathology and physiopathology]. / Endometriose--nye perspektiver. 1. Patologi og patofysiologi.

Endometriosis is a disease characterized by the occurrence of ectopic endometrium, most frequently in the pouch of Douglas and the ovaries. The disease is diagnosed at operation and occurs practically exclusively in women of fertile age. The symptoms are, in particular, diffuse low abdominal pain, dyspareunia, infertility and dysmenorrhoea. The prevalence of the disease is unknown but has been estimated as about 1-2%. The etiology is still unknown. The classical theories about 1) retrograde implantation of endometrium from menstruation and 2) metaplasia of the coelom epithelium are still current. A series of recent observations of increased macrophage activity, reduced cellular immunity and deviations in the complement system suggest, however, that special immunological factors also play a causal role. Endometriotic tissue has great morphological and biochemical similarities with endometrium and contains, similarly, receptors for steroid sex hormones but in lower concentrations and with an increased relationship between progesterone and oestrogen receptors. The pathophysiological basis for the infertility correlated with the disease is only partially understood. Apart from obvious anatomical causes, the occurrence of the luteinized unruptured follicle syndrome and alterations in the content of steroid hormones and prostaglandins in the peritoneal fluid are possible causes.

[Endometriosis--new perspectives. 2. Classification and treatment]. / Endometriose--nye perspektiver. 2. Klassifikation og behandling.

The disease, endometriosis, occurs in very varying forms and degrees of severity. Classification of the disease is therefore important. Acosta's classification was previously most frequently employed. A more recent system of classification (R-AFS) proposed by the American Fertility Society is employed here. This system is based on scoring of various elements of endometriosis. Employing this system of classification, which is now internationally used, a more differentiated description of the disease is obtained and also improved assessment of bilateral involvement. Various therapeutic possibilities are reviewed including the question of whether minimal-mild endometriosis should be treated at all. Recent therapeutic possibilities for endometriosis with laser surgery and "medical oophorectomy" employing GnRH analogues are discussed and also employment of in vitro fertilization for patients with endometriosis is mentioned. Finally, treatment with danazol and the classical therapeutic agents such as oral contraception, gestagens and surgery are reviewed with the authors' proposals of suitable patients for each form of treatment.

Oxytocin receptor blockade: a new principle in the treatment of preterm labor?

The concentration of myometrial and decidual oxytocin receptors increases dramatically in normal women in late pregnancy, causing enhanced uterine sensitivity to physiologic levels of oxytocin. Similar increase in myometrial oxytocin receptors has been found in women in preterm labor, indicating a role for oxytocin also in idiopathic preterm labor. A newly synthesized oxytocin analogue, 1-deamino-2-D-Tyr-(OEt)-4-Thr-8-Orn-oxytocin, has been found to be a competitive inhibitor of oxytocin. The present study was conducted to test its efficacy in suppressing uterine contractions during preterm labor in women. Twelve patients with established, uncomplicated preterm labor between 27 and 33 weeks of gestational age were given intravenous infusions of the analogue for 1.5 to 13 hours during continuous external cardiotocographic monitoring. In nine patients inhibition of uterine contractions was achieved and further progression in cervical scores was arrested. In three patients, all at 27 weeks of gestational age, no significant tocolytic effect was observed during a 1.5-hour infusion of the analogue and the patients were then given ritodrine intravenously. No side effects were observed in any of the patients. These preliminary findings support the concept that an increased concentration of uterine oxytocin receptors is an important etiologic factor in uncomplicated preterm labor and therefore oxytocin receptor blockade may be a therapeutic alternative for this condition.