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Post-caesarean endometritis-myometritis (PCEM) was diagnosed in 49 Mozambican women. They were compared with 47 control women without signs of PCEM after caesarean section. The patients and controls were matched for age, parity and days post partum. Features of the socio-economic background and of past and current obstetric history were registered. Endocervical, intracavitary and blood cultures were carried out. Screening for syphilis seropositivity and HIV-1 and HIV-2 antibodies was performed. Socio-economic and obstetric background factors were similarly distributed in cases and referents, though previous caesarean section was less frequent among cases than among referents (OR 0.12). Moderate high-risk factors in existing antenatal card tended to be more frequent among cases than among referents (OR 3.29). Microbiological findings indicated more anaerobes in the vagina, in the endocervix and in the uterine cavity, though the differences only approached significance. It is concluded that women with PCEM in the setting studied expose few characteristic background features discriminating them from women with uneventful post-caesarean outcome. Further research efforts should be directed towards case-control studies with focus upon surgical factors and on a more comprehensive microbiology and serology approach.

PIP: A case control study included 49 women diagnosed with post-cesarean endometritis-myometritis (PCEM) and 47 controls who had also undergone a cesarean section but had no PCEM. Controls were matched with cases by age, parity, and days postpartum. All cases and controls delivered at Maputo Central Hospital in Mozambique. The study aimed to define potential background PCEM risk factors of socioeconomic and obstetric origin and serological and microbiological correlates. Health workers took blood samples, endocervical swabs, and intracavitary cultures from all cases and controls. They administered intraoperative prophylactic antibiotics to all cases and controls. Cases were more likely to live in a household of at least 6 persons (odds ratio [OR] = 4.44). Other socioeconomic factors studied were not significantly different between the 2 groups. Number of live births, stillbirths, abortions, and previous low birth weight deliveries were similar among both cases and controls. Cases were significantly less likely to have undergone a previous cesarean section than controls (OR = 0.12). Anaerobic bacteria were isolated more often from cases than controls in vaginal, endocervical, and intrauterine cultures (OR = 1.65, 1.95, and 1.77, respectively). Yet, the observed cultures were not significantly different between the 2 groups. Syphilis seropositivity and Chlamydia trachomatis rates were similar in cases and controls. These findings did not reveal any easily recognizable background risk factors for PCEM or any etiologic agent for PCEM. Additional case control studies are needed to focus on surgical factors. They also need to take on a more comprehensive microbiology and serology approach.

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We studied the effect of antiprogesterone RU 486 on spontaneous uterine contractility and PGI2 release with human myometrial strips superfused "in vitro". A decrease of PGI2 release into the superfusion medium was observed after 20 min superfusion. The inhibition was dose-dependent and reversible. After 20 min washing with tyrode medium without RU 486, the uterine strips recovered their initial rate of release. R5020, a progesterone agonist, did not affect PGI2 release nor dexamethasone and testosterone. Parallel to the decrease of PGI2 observed during RU 486 superfusion, the uterine spontaneous contraction frequency decreased, while the amplitude and duration of contractions increased. The alteration of uterine contractility was also rapid, dose-dependent and reversible. Modification of uterine strip spontaneous contractility, similar to those induced by RU 486, were also observed with superfusions of R5020 at concentrations as low as 10(-9)M, dexamethasone (10(-8)M), but not with superfusions of testosterone. These observations are not in favour of a progesterone-receptor mediated effect of RU 486 in our model. The mechanism of action may be related to the antiprogesterone specific structure i.e. the bulky substituent at the C-11 position. The RU 486 effect on uterine strip contractility, mimicked by other steroids, could point to a non-specific lipid/membrane interaction. However, the fact that testosterone did not affect motility, may indicate a possible specificity of steroids having a 3 oxo pregnene structure.

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We found that the incidence of post-cesarean puerperal morbidity at Srinagarind Hospital, Khon Kaen University was 5.5 per cent, which is very low compared to other reports. Statistically significant risk factors for post-cesarean puerperal morbidity included having less than 4 antenatal care visits, duration of labour longer than 12 hours and absence of prophylactic antibiotics.

PIP: All patients who delivered by Cesarean section at Srinagarind Hospital, Khon Kaen University, from June 1, 1988 to May 31, 1989 were studied to determine the incidence and risk factors of puerperal morbidity. Variables included age, parity, gestational age at delivery, blood concentration before delivery, number of antenatal care visits, duration of labor, duration of rupture of membranes before delivery, number of vaginal examinations, history of previous Cesarean section, type of Cesarean section, type of anesthesia, estimated blood loss, operative time, fetal birth weight, and the use of antibiotics. Puerperal morbidity was defined as a temperature of 38 degrees Celsius or higher, occurring on any 2 of the first 10 days post partum exclusive of the first 24 hours. Univariate and multiple logistic regression analyses were used for the assessment of the risk factors. There were 548 Cesarean sections, but 42 patients were excluded, leaving 506 patients. There were 132 elective and 374 emergency Cesarean sections. The incidence of post-Cesarean puerperal morbidity was 5.5%, which is very low compared to other reports, and it was 6.5% in patients who did not receive antibiotics. The causes of puerperal morbidity included endomyometritis (35.7%), wound infection (25.0%), urinary tract infection (10.7%) and unknown cause (28.6%). Only duration of labor for more than 12 hours was found to be a statistically significant risk factor. Other factors including parity, number of antenatal care visits, history of previous Cesarean section, estimated blood loss during operation, and the use of antibiotics were found to be almost statistically significant. Further analysis by multiple logistic regression with all statistically significant and almost statistically significant variables found that statistically significant risk factors for post-Cesarean puerperal morbidity included having less than 4 antenatal care visits, duration of labor longer than 12 hours, and absence of prophylactic antibiotics.

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Termination of pregnancy because of fetal abnormalities is a physically and emotionally painful event. Prostaglandin E2 (PGE2) intravaginal suppositories are an effective method for inducing labor. Patient care and pain management require both knowledge and sensitivity on the part of the nurse.

PIP: Nursing management of second trimester abortion by PGE2 suppository after cervical dilatation with laminaria or Lamicel focuses on monitoring and treating side effects, managing pain, and supporting the patient emotionally. Mean abortion time by this method is 15-17 hours, within 24 hours in 80% of women. The side effects expected from PGs are nausea, vomiting, abdominal cramps, and diarrhea. Premedication with transdermal scopolamine, and ancillary methods such as giving ice chips, airing the room, keeping the patient clean are helpful. Acetaminophen is given orally or rectally for fever, headache, or chills. A beta-adrenergic tocolytic drug such as ritodrine HC1 is given if uterine contractions become tetanic, contractions 2-3 per minute or lasting longer than 6-90 seconds, detected by palpation. This drug must be used with caution in patients with asthma. Pain management in midtrimester abortion depends solely on the woman's comfort. Meperidine, morphine, epidural anesthesia with bupivacaine, lidocaine or morphine SO4, or patient-controlled anesthesia may be used. The nurse should monitor side effects such as hypotension, allergic responses, arrhythmias, and inability to void. Midtrimester abortion is often a stress-filled experience, since women may be ambivalent upon learning of fetal abnormalities. The women should be monitored after delivery to ensure that her uterus remains contracted, and assisted if surgical removal of retained products is necessary. Patients teaching for discharge, including medication to prevent lactation, is described. A care plan is suggested for assisting the family with bereavement, based on that used in case of stillbirth or neonatal deaths.

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Magnetic Resonance Imaging of the pelvis has lead to a new radioanatomical description of the uterus. Variations in the anatomical zones of the uterus were noted with different sequences used in MRI. There was also structural and signal variation depending on hormonal impregnation. Twenty seven MRIs of pelvices were carried out on 16 female volunteers. Eight of them were on oestroprogesterone as the method of contraception (Group I) and had a single MRI. Six were not taking contraceptives (Group II) and had different MRI's during the same cycle. Two women already had already gone through the menopause (Group III). Results showed differences in the size of the uterus (uterine height, length of the uterine body and cervix, diameter of the cervix) between groups I and II but no cyclic changes were observed within group II. The myometrium was found to be thicker in group I and in the luteal phase of group II females in comparison to the follicular phase in the same group. The endometrial cavity was seen in 40% of cases on T1 weighted sequences; on T2 weighted sequences it was seen in all the cases. It was thicker during the second phase in group II than in group I and III. The myometrial signal compared to that of the bladder content (urine) showed a significant increase between early and late echoes on T2 weighted sequences in group I and during the second phase of the menstrual cycle in group II. No variations, or at times a decrease in signal, were observed during the first phase of the cycle in group II.(ABSTRACT TRUNCATED AT 250 WORDS)

PIP: 16 healthy 20-71 year old women underwent magnetic resonance imaging (MRI) in Marseille, France so the radiologists could better understand the anatomy of the uterus under various hormonal states. Group I included 8 women who were taking oral contraceptives (OCs) and underwent only 1 MRI. Group II were 6 women who did not take OCs and underwent 2-4 MRIs during 2 phases of the same menstrual cycle. Group III included 2 postmenopausal women. Uterine height, cervix diameter, and uterine body length were greater in group II than group I (76.9 mm vs. 80 mm; 25.6 mm vs. 28.3 mm; and 49.1 mm vs. 46.25 mm respectively). Cervix length was greater in group I than group II (30.6 mm vs. 29.7 mm). The radiologists did not notice any cyclic changes within group II. The myometrium was thicker in group I (16.9 mm) and in the luteal phase of group II (15.8 mm) compared to the follicular phase of group II (13.75 mm). T2 weighted sequences revealed the endometrial cavity of all cases, but T1 weighted sequences revealed the cavity in 40% of cases. The endometrial cavity was thicker in group II women (6.5 mm [1st phase] and 9.9 mm [2nd phase]) than either group I (2.4 mm) or group II (1 mm) women. T2 weighted sequences in group I and during the 2nd phase of the menstrual cycle in group II showed a great increase in the myometrial signal compared to bladder content between early and late echoes. Further only T2 weighted sequences uncovered the junctional zone. The junctional zone was thickest during the 1st phase of the cycle of group II women than during the 2nd phase. T2 weighted sequence could only reveal the junctional zone in only 1 woman in group III. Knowing the zonal anatomy of the uterus and its changes is helpful in diagnosing adenomyosis, myometrial extension of endometrial carcinomas, extension of cervical carcinomas.

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A double-blind placebo-controlled trial was performed in 20 primigravidae to assess the physiological and clinical effects of oral mifepristone on myometrial contractility and sensitivity in the second trimester. Ten women received 600 mg of oral mifepristone and 10 women a placebo 24 h before abortion was induced in both groups, with extra-amniotic PGE2 instillation. Intrauterine pressure recordings demonstrated increased spontaneous uterine activity and increased sensitivity to PGE2 and ergometrine, but no change in oxytocin sensitivity after mifepristone treatment. There were no significant differences in PGE or PGF metabolite concentrations in peripheral maternal plasma over the 24-h study period after treatment between the mifepristone and placebo groups. The mean induction abortion interval in the mifepristone group was 512 (SD 321) min compared with 1128 (SD 606) min in the placebo group (P less than or equal to 0.02). The mechanism whereby mifepristone provokes enhanced uterine contractility and sensitivity to prostaglandins, with a reduction in abortion times, does not appear to be through endogenous production of PGE or PGF.

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The present case report illustrates the hormonal sensitivity of adenomyosis. Administration of an estrogen-progestin combination for what was felt to be symptomatic endometriosis resulted in exacerbation of symptoms and growth of adenomyomas. Histopathologic examination of the hysterectomy specimen revealed a pattern of decidualization previously unreported, but consistent with current theories of experimental in vivo and in vitro decidua formation.

PIP: A 32 year old woman underwent exploratory surgery because she had severe dysmenorrhea, the physicians found fibroids, and they excised pelvic endometriosis. 1 year later, she sought the assistance of the Center for Fertility and Reproductive Endocrinology at the Columbia Hospital for Women in Washington, D.C. because of continual dysmenorrhea and pain. A physician at the center treated her with Ovulen, a continuous estrogen/progestin therapy, yet her pain worsened. Upon a pelvic reexamination 16 months later, a physician noted a tender, enlarged, and irregularly shaped uterus (16 cm from fundus to cervix and 726g). Further, pelvic sonography detected multiple leiomyomas, 1 being 9x7 cm. The physician did a laparotomy to perform a myomectomy and therefore preserve fertility, but could not establish cleavage planes. Thus she needed to undergo a hysterectomy. Pseudodecidualized adenomyotic islands were found in the enlarged posterior myometrial wall. The results of this woman's use of Ovulen are similar to previous research on prostaglandins' role in which they act as intermediaries in decidual metaplasia. This case report affirms that progestins do not treat adenomyosis and cause significant exacerbation of its symptoms. Based on previous research and this case, the author believes that an undefined luminal component and progestin stimulation causes development of a decidual response in the uterus. Once the stimulus is defined, be it chemical, infectious, or mechanical, researchers could identify other approaches for the symptomatic relief of this debilitating and difficult to diagnose ailment.

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PIP: Animal and human volunteer research involving the hormone antagonist Mifegyne (mifepristone) is reviewed. Studies in animals and humans show that the potent antiprogesterone, Mifegyne, causes pregnancy interruption by acting directly at the level of the endometrium. Pharmacokinetic studies indicate that gastrointestinal absorption is low (25%), but subcutaneous and intramuscular routes do not fare better than does oral administration. Experimental studies in women testing for antiprogesterone effects indicate that mifegyne does not affect menstrual cycle length in women with regular ovulatory cycles, except when using the highest doses (600 mg). Mifegyne inhibits gonadotrophin secretion in a dose-dependent way. In humans, mifegyne has some progestomimetic activity in the endometrium in the absence of progesterone. Researchers know that larger doses of mifegyne than those sufficient to induce uterine bleeding are required to cause antiglucocorticosteroid effects. Studies demonstrate that in 18% of patients studied the only significant side effect is prolonged uterine bleeding. In addition, mifegyne fails to cause an abortion in 15% of the cases. The success rate is 85% when mifegyne is given prior to the 5th week of amenorrhea. Due to the occurrence of failed abortions and prolonged uterine bleeding in some women, researchers advise close medical supervision. An added effect of mifegyne is that in both animal and human studies it is effective in inducing labor. Preliminary studies suggest that mifegyne taken once a month only on the expected date of individual menses could be used as a safe and effective form of fertility control.^ieng

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The clinical and pathological findings in 22 women with a distinctive hemorrhagic cellular (HC) leiomyoma of the uterus are described. Characterized by a dense cellularity accompanied by hemorrhage and edema, 17 occurred in women taking oral contraceptives, three occurred in pregnant women, and one was found in a woman 3 days postpartum. One woman, not pregnant or taking steroids, was using hydrochlorothiazide. Recognition of this special form of leiomyoma associated with the use of reproductive steroids is needed to avoid confusing it with leiomyosarcoma. The major differences with leiomyosarcoma are that HC leiomyomas are generally small, often multiple, and have discrete areas of hemorrhage and tearing artifact, but little or no atypia. Also, their mitotic activity is confined to a narrow zone adjacent to the hemorrhage.

PIP: A series of hemorrhagic cellular leiomyomas of the uterus, associated with oral contraceptives (17) or pregnancy (4) is described. Another woman was taking hydrochlorothiazide only. Clinical features included, most often, abnormal uterine bleeding in 18, followed by rapid enlargement to the size of a 12-14-week gestation in 9, pain in 8, and rupture of the leiomyoma in 2 women. The duration of symptoms ranged from a few hours in 7 to 16 months in 1 woman. 13 had used combined, and 1 sequential pills, ranging from 1 month to over 5 years. The size of the leiomyomas ranged from 0.7 to 11 cm, with a mean of 4.2. 6 were hemorrhagic and cystic. Microscopically they consisted of circumscribed, densely cellular proliferations of oval and spindle- shaped smooth-muscle cells with central hemorrhage and edema. 3 to 4 mitotic figures appeared per 10 high power fields in the most active areas. These leiomyomas differ from those seen in pregnancy in their cellularity, patchy hemorrhage, and edema. They differ from leiosarcomas in their smaller cells, less atypia, fewer abnormal mitotic figures, small size, multiple arrangement, multiple discrete areas of hemorrhage and discrete periphery. It is probably the progestin in the combined oral contraceptive that causes development of leiomyoma.

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The Authors treated twenty-eight women using IUD, who suffered from increased menstrual blood loss and pelvic pain, with a prostaglandin synthetase inhibitor, Suprofen, in an attempt to reduce their symptomatology, in a double blind crossover study. The drug produced an important reduction of the menstrual blood loss and pains. These observations suggest that prostaglandins are involved in the etiology of excessive menstrual blood loss and pains, and that prostaglandin inhibitors may be useful for reducing these symptoms.

PIP: Suprofen (Suprol-Cilag S.p.A.), a prostaglandin synthetase inhibitor, was tested in a double-blind crossover design on 28 women whose IUDs caused them pain or increased menstrual bleeding. The subjects had worn either a Gravigard (18 women) or a Copper T (10) for 6 to 10 months. Each subject was observed for the first month, and took either placebo or Suprofen during the next menses, followed by the alternative for the third cycle. They took 20 mg Suprofen 4 times daily, at the first sign of bleeding and or pain, then 3 times daily thereafter, for the duration of symptoms or up to 7 days. Before treatment, 71% had severe bleeding, 18% had moderate bleeding and 11% had slightly increased bleeding. During Suprofen, 43% obtained a strong decrease in menstrual blood loss, 36% had a moderate decrease and 7% had a slight decrease. Placebo decreased bleeding moderately in 2. Pain was moderate to intense in 26 women and slight or none in 2 before treatment. With Suprofen, pain decreased moderately or greatly in 23 and slightly or not at all in 5 women. Placebo improved pain moderately in 1 subject. Reported side effects of the drug were stomach cramps in 1 and nausea and headaches in 2 women. In this study, when the subjects were categorized by degree of symptoms, the prostaglandin antagonist was more effective in those complaining of more severe bleeding and pain.

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A morphometric study was undertaken to quantitate vessel numbers in uterine biopsies from a control group of patients, patients with dysfunctional uterine bleeding and patients taking low dose norethisterone or levonorgestrel. Vessels were counted at the endometrial/myometrial junction and in the functional endometrium just below the surface epithelium. The number of arteries at the endometrial/myometrial junction was found to be decreased in patients taking norethisterone and levonorgestrel. An increase was found in the total number of veins and in the number of dilated veins in the functional endometrium of the progestogen-treated specimens. Dilated veins were frequently found close to the endometrial surface and it is possible that they may be the major cause of the irregular bleeding associated with low dose oral progestogens.

PIP: A morphometric study undertaken to quantitate vessel numbers in uterine biopsies from a control group of patients, patients with dysfunctional uterine bleeding and patients taking low dose norethisterone or levonorgestrel, in Dublin, Ireland. Vessels were counted at the endometrial/myometrial junction and in the functional endometrium just below the surface epithelium. The number of arteries at the endometrial/myometrial junction was found to be decreased in patients taking norethisterone and levonorgestrel. An increase was found in the total number of veins and in the number of dilated veins in the functional endometrium of the progestogen-treated specimens. Dilated veins were frequently found close to the endometrial surface and it is possible that they may be the major cause of the irregular bleeding associated with low dose oral progestogens.

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PIP: A sesquiterpene lactone given the trivial name leucanthanolide, from the Mexican zoapatle plant (Montanoa leucantha), long used as an herbal remedy, was isolated and was found to have cytotoxicity but no uterine activity. The compound was isolated from the fraction containing zoapatanol, a substance being investigated for its ability to induce menses, abortion and labor. The compound has a molecular formula of C19H2606, a 5-membered lactone ring, an ester group, and a germacradienolide skeleton. It was evaluated for abortifacient activity in pregnant guinea pigs by intraperitoneal injection on day 22 of gestation. 3 of 5 animals had abnormal fetuses, but there was no evidence of early uterine activity. Cytotoxic testing in vitro was done on KB and P-388 test systems in cell culture. The ED50 of leucanthanolide was 0.57 mcg/ml (KB) and 0.93 (P-388). In comparison, the ethyl acetate fraction had an ED50 of 1.35 mcg/ml and 5.2 mcg/ml respectively.^ieng

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Calcium channel blockers have been advocated as potential therapeutic agents in the management of premature labor. In the present study, the class of intracellular calcium antagonistic methylenedioxyindenes (MDIs) was investigated for potential antiabortifacient activity in mice. Pretreatment of pregnant mice from day 15 of gestation with the MDIs did not afford protection against the abortifacient effect of prostaglandin F2alpha administered from day 17 of gestation. The MDIs demonstrated embryotoxic and fetotoxic activity as shown by a significant increase in the incidence of resorptions and stillbirths. Similar embryotoxicity was previously reported for the calcium channel blockers. It appears doubtful that any of the calcium antagonists so far examined will be clinically useful in the management of premature labor.

PIP: 2 intracellular calcium antagonists with weak membrane calcium channel blocking activity were tested for antiabortifacient and embryotoxic effects in mice. The compounds were 2-n-propyl-3-dimethylamino-5,6-methylenedioxyindene (pr-MDI) and cis-2-n-butyl-3-dimethylamino-5,6-methylenedioxindan (cis-H-bu-MDI). Charles River CD-1 mice treated intramuscularly with saline (controls), or Pgf2alpha twice daily to induce premature abortion starting on day 17 of gestation, with 15 or 25 mg/kg cis-H-bu-MDI. or 70 mg/kg/pr-MDI. the LD50 for cis-H-bu-MDI was 75 mg/kg (single intramuscular dose). The compounds had no effect on premature delivery. They significantly decreased numbers of live-born pups, however, counted as the difference between implantation sites and recovered live or stillborn pups. There were no malformations, maternal toxicity or detrimental effects of survival or term-born progeny. These calcium antagonists appear to be of no value in the management of premature labor.

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The hysterometric technique has been designed to measure the pharmacological effect of active agents upon the human uterine muscle. The physiological background is the fact that smooth muscle contracts under the influence of mechanical stimulation. By applying hysterometry, the effects on the human myometrium in vivo during early pregnancy of the naturally occurring prostaglandin F2 alpha and its analogue 15(S)-15-methyl-PGF2 alpha have now been evaluated. According to the analysis of the contractile responses, the effects of the agents have been determined quantitatively. The drug effects have been characterized by changes in myometrial response between registrations under basic conditions and during the infusion of the active agent, respectively. It was found that when these drugs were given in the doses usually employed in clinical practice, the effect on contractility of the PGF2 alpha compound was more pronounced than that of the analogue. However, when describing the results on a microgram basis, the 15-methyl-PGF2 alpha was confirmed to be 10-20 times more potent than PGF2 alpha.

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PIP: Endometrial cancer is the cause of considerable morbidity among women, but the disease has been underrated and its management more casual than its virulence warrants. Endometrial carcinoma is the most frequently diagnosed invasive neoplasm of the female genital tract in the US, and is third in incidence after breast and colonic cancer. The white population of the US has the highest age standardized incidence of endometrial cancer in the world, India and Japan have the lowest, and the European countries occupy intermediate positions. Between 75% and 80% of women diagnosed with endometrial cancer are postmenopausal, and the mean age at diagnosis is about 60 years. In many cases endometrial hyperplasia is misdiagnosed as frank malignancy. The predisposing factors for endometrial cancer seem to be obesity, hypertension, diabetes mellitus or an abnormal glucose tolerance curve, and prolonged or unopposed estrogen stimulation. Raised estrogen levels may occur in the following situations: 1) women with functioning ovarian tumors that produce estrogen; 2) women with polycystic ovarian disease; 3) women with ovarian dysgensis (Turner's syndrome) managed with estrogen replacement therapy; 4) women taking high estrogen sequential oral contraceptives (OCs); and 5) women undergoing estrogen replacement therapy. There is an increased risk of endometrial carcinoma associated with nulliparity. Carcinoma of the endometrium occurs in a variety of subtypes, the most frequent being adenocarcinoma, followed by adenocanthoma, adenosquamous carcinoma, clear cell carcinoma, papillary adenocarcinoma, and secretory carcinoma. Overall 5-year survival rates are 72% for adenocarcinoma, 68% for adenocanthoma, and 26% for adenosquamous carcinoma. The true extent of endometrial cancer can be ascertained only after exploratory laparotomy and then various therapies may be used according to the stage of the disease.^ieng

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Potassium thiocyanate-extractable uterine plasminogen activator activity was determined to be highest in the endometrium surrounding intrauterine devices (IUDs). Such activity was significantly higher than that encountered in control endometrium or in the endometrium remote to IUDs. As in control cases, extracted endometrial activity fluctuated during the intermenstrual ovarian cycle. It was highest in the pre- or periovulation part of the cycle, and it rose again prior to menstruation. These peaks of activity seem to correspond to times in the cycle when metrorrhagia and abnormal menstruation are usually encountered. Possible implications of the myometrial and endometrial patterns of plasminogen activator in control and IUD-exposed uterine tissue are discussed.

PIP: This research study was designed to determine the relative activator concentration in uterine tissue depressed by, adjacent to, and remote from the IUD and to compare these concentrations to control uterine tissues. Uterine tissue used in the study was obtained following hysterectomy in 22 women wearing IUDs. All analyzed tissues were acquired from uteri containing either Lippes loop D or large Saf-T-Coils. These IUDs had been in place for a minimum of 1 year and a maximum of 8 years. Hysterectomies were performed primarily for indications related to symptomatic pelvic relaxation secondary to multiparity. No patient was taking hormonal medication or contraceptives for 12 months prior to hysterectomy. No cases included specimens with significant uterine pathology other than that related to the IUD. Ovarian cycle phase was determined for all specimens analyzed by histologic criteria on adjacent slices of the excised samples. Cases included the following phases: menstrual; early proliferative; mid to late proliferative; early to mid secretory; and late secretory. The myometrium contained considerably more extractable activator than the endometrium in terms of activity per milligram of tissue protein. Variation of endometrial plasminogen activator (PA) showed the same pattern as did previously analyzed control specimens at different stages of the intermenstrual ovarian cycle. Values reached the highest levels in mid to late proliferative endometrium with a fall during the early to mid secretroy phase to the lowest levels, followed by a rise in late secretory endometrium. Myometrium did not parallel endometrium as closely as reported for control cases. In IUD cases, the highest myometrial levels were encountered in the late follicular phase and a fall occurred in the secretory phase, as was the case with endometrium, but no myometrial rise occurred prior to menses. Comparison of mean activator results of depressed, adjacent, and remote endometrial sites from IUD cases and mean endometrial activator levels from control cases revealed the highest values in IUD depressed endometrial tissues. The next highest were in IUD adjacent endometrium. Significantly lower results occurred in IUD remote endometrial samples. These comparisons were not considered to be biased by interphase differences in activator since equal proportions of all 4 menstrual phases existed among the 3 IUD sampling sites and the total control material studied. In sum, uterine PA activity plays an important role in IUD associated menorrhagia, and the results indicate that it is also important in IUD associated metrorrhagia. The causes of cyclic physiologic fluctuation and of IUD stimulated increases in uterine PA activity are poorly understood at this time.

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Thirteen women who were scheduled for hysterectomy volunteered for the study. Nine women had a levonorgestrel-releasing intrauterine contraceptive device inserted between 36 and 49 days prior to surgery and four women were on oral levonorgestrel treatment for 7 days prior to surgery. After the surgical removal of the uterus, samples of endometrial, myometrial, fallopian tube and fat tissue were obtained. Methods for measuring tissue concentrations of levonorgestrel were developed and the uptake of levonorgestrel by fat tissue in vitro was studied. The concentrations of levonorgestrel in myometrial, fallopian tube and fat tissue were all of the same order, of between 1 and 5 ng/g of wet weight of tissue, in both the intrauterine device group and the orally treated group. In the endometrium the levonorgestrel concentrations were many-fold higher in the intrauterine device group. The in vitro experiments showed a rapid uptake of levonorgestrel and an unsaturability of the fat tissue by the steroid at the concentrations used. The fat tissue concentrations of levonorgestrel correlated with the plasma concentrations.

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In 7 primigravidae admitted for first trimester abortion by dilatation and evacuation, 0.5 mg PGE2 in viscous gel (5 patients) or placebo gel (2 patients) was applied intracervically 6 hours prior to the operation. Throughout the treatment period intrauterine pressure was recorded. Application of placebo gel induced no cervical ripening or myometrial activation. In all patients receiving active gel, a marked improvement of the cervical state was induced by the treatment. In three cases, this priming occurred in parallel to minimal changes in myometrial activity, without regular uterine contractions. In two patients, marked uterine activation was registered due to partly extraamniotic application. It is suggested, that the PGE2-gel has a direct effect on the cervical tissues. Further, the risk of partially applying the gel in the extraamniotic space, thus stimulating the myometrium, depends on the gel volume relative to the dimensions of the cervical canal and the application technique.

PIP: In 7 primigravidae admitted for 1st trimester abortion by dilatation and evacuation, 0.5 mg prostaglandin E2 (PGE2) in a viscous gel (5 patients) or placebo gel (2 patients) was applied intracervically 6 hours prior to the operation. Throughout the treatment period, intrauterine pressure was recorded. Application of placebo gel induced no cervical ripening or myometrial activation. In all patients receiving active gel, a marked improvement of the cervical state was induced by the treatment. In 3 cases, this priming occurred parallel to minimal changes in myometrial activity without regular uterine contractions. In 2 patients, marked uterine activation was registered due to partial extraamniotic application. It is suggested that the PGE2 gel has a direct effect on cervical tissue. Furthermore, the risk of partially applying the gel in the extraamniotic space, thus stimulating the myometrium, depends on gel volume relative to the dimensions of the cervical canal and the application technique.

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Eight primigravid women with a mean gestational age of 9.4 weeks (9 to 10 weeks) who were admitted for first-trimester abortion by dilatation and evacuation were preoperatively treated for 6 hours with either intravenous infusion of oxytocin or a strictly intracervical application of prostaglandin E2 (PGE2) in viscous gel. Myometrial activity was monitored by intrauterine pressure recording throughout the treatment. Contractile activity was more pronounced in the oxytocin-treated group, whereas cervical priming occurred after the PGE2 treatment only. Intracervical PGE2-gel is suggested to have direct effects on the cervical tissues, independent of uterine contractile activity. Furthermore, myometrial stimulation induced by escape of gel into the extra-amniotic space can be avoided by adjusting the volume of gel and technique of application to the dimensions of the cervix.

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